The ZRT Laboratory Blog

Fertility Mapping: Navigating Fertility with PCOS and Insulin Resistance Part II

Fri, 05 Jul 2024 16:02:12 -0700

PCOS is a multifactorial condition impacted by alterations in receptors, metabolism and functionality of hormones, neurotransmitters and nutrients. It is a lifelong condition that contributes to infertility, weight gain, cardiometabolic symptoms and diseases. In this blog, we look at laboratory testing and what can and should be tested in all women where you suspect PCOS.

Lab Testing for PCOS

Polycystic ovarian syndrome (PCOS) diagnosed through the Rotterdam criteria, a comprehensive framework that encompasses a variety of indicators, including clinical symptoms, laboratory findings of elevated testosterone levels, ovulatory dysfunction, and ultrasound evidence of ovarian cysts. Women do not have all the criteria to be diagnosed. In general, PCOS is a clinical diagnosis. For further details on the Rotterdam criteria please refer to the following resource: NCBI Article.

Recommended lab testing:

Women with PCOS are recommended to test the following hormones
17 OH Progesterone – rule out congenital adrenal hyperplasia
Cortisol – rule out Cushing's syndrome
DHEAS
Glucose
Hgb A1c
hsCRP
Insulin
LH/FSH on day 3 or 4 of the cycle (during the period) is usually 1:1 but can be 2:1 or higher.
Lipids/Cholesterol
Prolactin – high prolactin can also stimulate irregular periods and polycystic ovaries
SHBG – if doing total hormone levels.
Testosterone
TSH

In both saliva and bloodspot testing, it is common to observe elevated levels of testosterone and DHEAS, alongside reduced progesterone levels. Although women with PCOS may exhibit symptoms of estrogen dominance, estrogen levels are rarely high. Results from salivary laboratory assessments typically look like this although this patients DHEAS is not elevated.

Due to the tight ranges measuring bio-available testosterone and DHEAS utilized in saliva testing, elevated testosterone levels are often more clearly identified in saliva testing as compared to serum testing.

In this individual you can see that the total testosterone in bloodspot is at the top of the normal range, but the insulin is very high in this fasting sample. The optimal fasting insulin should be less than 10. Although not reported, this individual’s hemoglobin A1c was optimal.

Similarly, in urine analysis, indications of PCOS may include heightened levels of testosterone, androstenedione, DHEA, and DHT. A profile suggestive of PCOS is shown below. Notice the very high DHT as well as the other androgens.

Treatment of PCOS

The first goal for PCOS is to lower insulin levels which then decreases androgen levels and increases progesterone levels via ovulation. Ideally women will have 6 months of health optimization before attempting pregnancy and especially if utilizing assisted reproduction therapies. However, if discontinuing oral contraceptives conception should be attempted the first month after stopping contraceptives.

Insulin Reduction

Interventions encouraging lower simple carbohydrates, increasing complex carbohydrates, and increasing dietary fiber should be a basis for all women with PCOS. Medications like metformin and GLP1s, herbs like Berberine, and nutrients like inositol should be considered in women with higher insulin levels even in with normal body weight.

Inositol, otherwise known as vitamin B8, is a sugar that the body uses in receptor functionality. Inositol also acts as a secondary insulin messaging, therefore reducing insulin resistance. Its action on cellular receptors is not limited to insulin but is involved in the neurotransmitters and all hormones. In women with PCOS, inositol fails to be recycled in the cells and is overall deficient (1). Inositol supplementation has been shown to decrease insulin and glucose, improve menstrual cycles and has improved pregnancy rates. Inositol levels are high in ovum follicular fluid and ovum with higher levels of inositol are associated with higher quality.

Other therapies such as melatonin and vitamin D may be appropriate for many patients. Usage of some of these supplements and medications throughout pregnancy for women with PCOS especially metformin and inositol suggest that optimizing insulin may lead to better pregnancy outcomes (2, 3).

Achieving pregnancy with PCOS may require additional effort. Diligently managing insulin levels and optimizing weight and overall health significantly contribute to success of conception, even when assisted reproductive technologies may be necessary. Incorporating lifestyle optimization into treatment plans for preconception, conception, pregnancy, and postpartum care is essential for nurturing the healthiest eggs, embryos, and babies. ZRT extends heartfelt wishes for success to all.

References:

Fertility Mapping: Navigating Fertility with PCOS and Insulin Resistance: Part I

Wed, 26 Jun 2024 12:52:10 -0700

While it sometimes seems that babies are everywhere, for many people the process of becoming a parent can be a long and heart-wrenching journey. Infertility affects 1 out of 6 people with one-third of the cases due to female issues, one-third due to male issues, and one-third due to the couple together (1).

It is estimated that approximately 10% of all women have polycystic ovarian syndrome (PCOS) and that around 80% of them will struggle with infertility (2). While many women with PCOS will achieve pregnancy on their own, others will need medical assistance to become pregnant.

In the last couple of years, the research world has dramatically expanded our comprehension of PCOS. It has long been known that PCOS involves elevated levels of female androgens particularly testosterone and DHEA. Newer research has provided deeper knowledge into the interplay between environmental, immunological, inflammatory, hormonal, and genetic factors. This rise of knowledge underscores the reality that PCOS is a more systemic imbalance far beyond the ovaries and presenting a more comprehensive challenge to those it affects. As we delve into the conversation about PCOS and its impact on fertility, it's essential to highlight several recent key insights that have emerged:

Hormonal Imbalances: Women with PCOS struggle with higher androgens (testosterone and DHEA/S), but research shows variances in hormone receptors may be to blame. This intricate dance of hormones and their movement in and out of cells play a central role in the condition's development and its myriad of symptoms.
Beyond the Ovaries: While PCOS manifests with ovarian symptoms, it is also a lifelong mental health and cardiometabolic condition. This perspective is crucial, as it emphasizes the importance of a holistic approach to management; recognizing that PCOS affects much more than reproductive health.
Genetic Variances: The field of DNA research is revealing significant genetic variants present in women with PCOS. These include alterations in the cellular functions of adipose tissue, insulin, melatonin, adrenal function, and androgens (notably testosterone and DHEAS). This genetic backdrop contributes to the condition's complexity and individual variability in symptoms and responses to treatment.
A Lifelong Journey: It's important to understand that PCOS is a lifelong condition persisting even if the ovaries are removed. This reality highlights the need for ongoing management and support for those affected.
A Family Affair: PCOS runs in families. Many women with PCOS report having family members who also struggle with the condition reflecting how genetic predispositions play a role in its symptom development.

These insights into PCOS illuminate the condition's multifaceted nature, encouraging a compassionate, informed approach to care and support for those navigating its challenges.

Physiology of PCOS is Complex

Before exploring how PCOS affects fertility, it’s helpful to understand that PCOS embodies a complex physiological condition. In PCOS we find genetic variances in hormone levels, neurochemistry, cell receptor numbers, decreased receptor functionality, and altered hormone metabolism within the cells which all contribute to a variety of patient symptoms. Analogous to cell doorways, receptors serve as entry points for hormones, each requiring a specific key. These "doors" and their mechanisms are inherited and may differ in size, efficiency, and quantity among individuals. In PCOS, receptor dysfunction arises when these keys fail to operate correctly, leading to improper use, recycling, and opening of the receptor "doors."

Many receptors are altered in PCOS including those for norepinephrine, estrogen, vitamin D, adiponectin, cortisol, and testosterone; all which underscores the systemic nature of PCOS. Focusing on the role of insulin, identified as a key factor in approximately 70% of women with PCOS, sheds light on how this condition transcends an isolated ovarian disorder to implicate systemic challenges (3). Insulin levels are generally elevated in women with PCOS independent of weight or carbohydrate intake. Newer research is showing that this is due to anormal insulin receptors and likely abnormal insulin metabolism. Higher insulin then sets off a cascade affecting various hormones including LH, DHEAS, DHEA, androstenedione, and testosterone, contributing to weight gain, abdominal obesity, reduced sex hormone-binding globulin (SHBG), and heightened inflammation. These hormonal imbalances manifest as hallmark symptoms of PCOS, such as:

Weight-gain especially in the abdomen
Acne
Excessive hair growth on the face and body
Scalp hair loss
Irregular or absent menstrual cycles

Furthermore, sustained high insulin levels elevate risks for lifelong conditions including:

Fatty liver disease (NASH/NAFLD)
High blood pressure (hypertension)
Insulin resistance
Diabetes Type 2

High Insulin Impacts Fertility

Elevated insulin levels and higher androgens (testosterone and DHEAS) in PCOS are problematic for fertility. This hormonal landscape often results in a proliferation of immature ovarian cysts, impeding the maturation process of ovum (eggs), and decreasing the progression to ovulation. In scenarios where insulin and testosterone levels are significantly elevated, women may experience challenges in achieving routine ovulation, with some women not experiencing menstrual periods without pharmacological support. On occasions where ovulation is successful, the eggs produced by women with PCOS tend to be of lower maturity, which may affect fertilization, embryo quality, and decrease implantation rates. Despite these challenges, many women with PCOS achieve pregnancy on their own. Others find fertility success through ovulation stimulants or in vitro fertilization (IVF). Treatments such as letrozole or clomiphene are known to elevate gonadotrophin hormones (FSH and LH), fostering the development of more mature ovum. Some women may achieve pregnancy swiftly with these treatments, while others might observe significant benefits from a regimen extending over 3-4 months, which promotes a hormonal environment conducive to healthier egg development.

Semaglutide, GLP1 and Fertility with PCOS

The introduction of GLP1 medications has been notable for individuals with type 2 diabetes, but usage in women with PCOS has shown remarkable weight loss in women who have struggled to lose weight with other medications or regimens. Recently, a flood of reports of “Ozempic babies” has been noted as women have gotten spontaneously pregnant after starting a GLP1 for weight loss including among women who have done IVF unsuccessfully in the past. These occurrences underline the strong negative impact of insulin on fertility even in the face of assisted fertility technologies. Questions remain if the main impact of the GLP1s is to lower overall insulin levels thereby improving egg quality and fertilizations or if the GLP1s have separate action on egg maturity, fertilizations or implantations. What is clear however, is that GLP1s should be considered in women with high insulin levels especially if weight is also an issue, before or as part of a plan to do assisted reproduction.

On "The Pill” for PCOS and Want to Get Pregnant

Many people with PCOS turn to oral contraceptives to regulate menstrual cycles and address symptoms associated with elevated testosterone levels. These medications not only facilitate regular uterine bleeding but also play a significant role in reducing ovarian testosterone production, decreasing adrenal androgens, and fostering an environment rich in estrogen. Additionally, oral contraceptives increase the levels of sex hormone-binding globulin (SHBG) and cortico-binding globulin (CBG), additionally lowering androgens. This control of testosterone effectively alleviates acne, excessive facial and body hair, scalp hair loss, and aids in the maintenance of regular menstrual cycles. Furthermore, for numerous women, the use of oral contraceptives contributes positively to weight management. Although a slight increase in insulin resistance may occur, the overall reduction in androgen levels typically leads to decreased insulin and cortisol levels, and subsequently, weight stability.

However, when the pursuit of fertility becomes a priority, discontinuing oral contraceptives becomes necessary, reintroducing previous challenges. Stopping oral contraceptives prompts the ovaries to resume their natural cycle. While many women are under the belief that they should allow their cycle to happen for several months before attempting pregnancy, the initial 1-2 months post-discontinuation of oral contraceptives may present the highest fertility potential for women with PCOS. This phenomenon contradicts common expectations, as the resumption of natural ovulation commonly and quickly leads to increased testosterone levels which may reduce ovulation frequency and, consequently, reduce the chances of conception. Therefore, for women with PCOS wishing to conceive may wish to attempt pregnancy as soon as possible after discontinuing the contraceptives to optimize fertility opportunities.

Pregnancy and Beyond

Upon achieving pregnancy, it is prudent for women with PCOS to be mindful of the high likelihood of developing gestational diabetes. It is advisable to monitor not only blood sugar levels and hemoglobin A1C but also insulin levels; testing both fasting and those following meals or a glucose challenge. Elevated insulin and glucose levels during pregnancy can lead to various complications, including accelerated growth and increased size of the baby, heightened risk of hypertension in the mother, premature deliveries, neonatal blood sugar complications, and possibly an elevated risk of diabetes in the child later in life. Moreover, increased insulin levels have been implicated in reducing development of breast ducts, potentially complicating lactation post-delivery (4). Embracing a diet rich in protein, low in simple carbohydrates, and abundant in fiber can significantly contribute to maintaining optimal blood sugar and insulin levels throughout pregnancy.

While all of these challenges make pregnancy difficult in women with PCOS, it is important to once again stress that most women with PCOS are able to become pregnant. For providers who are caring for women with PCOS, it is the aim to optimize health for the woman before, during and after pregnancy. With our growing knowledge of this condition, we can appreciate that PCOS is a much more systemic condition than ever before. The next blog on PCOS will look at lab testing and some of the treatments that may wish to be considered.

Figure 1. A summary of the most representative impact of IR and HI in women with PCOS. Abbreviations: SHBG: sex hormone-binding globulin; LH: luteinizing hormone; IGF1: insulin growth factor 1; GnRH: gonadotropin-releasing hormone; ACTH: adrenocorticotropic hormone; HPO: Hypothalamus-pituitary-ovary; HPA: Hypothalamus–pituitary–adrenal (5).

Image credit: Zhao, Han, Zhang, Jiaqi, Cheng, Xiangyi, Nie, & He, Bing, "Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment." Biomed Central. Journal of Ovarian Research, Jan 11, 2023, Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment | Journal of Ovarian Research | Full Text (biomedcentral.com).

References:

Periods: The Miracle of Bleeding for 7 Days Without Dying

Fri, 27 Sep 2019 13:27:32 -0700

ZRT is a company made up mostly of women. It’s not that we don’t have men working here, but 80% of our employees happen to be women. A combination of a company mostly of women, working in the health field, and having gone to medical school which tends to take away that filter that says “perhaps certain topics are off limits,” can lead to hilarious conversations like our one today on the favorite of all lady topics – periods! I am going to give you an inner look at a woman’s conversation about this topic, so if you are squeamish you might want to look away.

We’ve been talking about how times have changed with respect to how women culturally handle periods, how young girls learn to deal with them, how many funny misunderstandings are out there (sorry men, this usually reflects on you), and how things have changed with our own comfort with our periods and in general, society’s willingness to acknowledge that they exist.

What’s up with This Bleeding?

So, what are periods all about? The period is “that time (or period) of the month” where the lining of the uterus is shed due to the lack of a fertilized embryo and therefore does not need to support a pregnancy. The lining of the uterus is made up of mucosal tissue and has 2 layers that attach to the smooth muscle layer of the uterus. Estrogen makes it grow; progesterone helps it mature. Only a small group of mammals including humans, apes, monkeys, bats and elephant shrews shed this lining when pregnancy doesn’t occur. If pregnancy does occur, the endometrium serves as a nourishing pillow where the embryo is implanted and starts to grow.

A myth out there, that apparently needs to be addressed, is a woman cannot “hold” her uterine lining inside for a convenient time.

Shedding of the uterine lining usually occurs at an average rate of 2-3 tbsp (40 mL) per cycle, although some women may have a much heavier flow (up to 540 mL). I don’t know about anyone reading this, but honestly, sometimes periods seem like you are just losing cups! If you have ever dropped food coloring into a bowl of water, you can imagine that even a small amount can look startling. So, that’s why when doctoring, we ask so many questions about how many pads, tampons, etc. a woman needs. A myth out there, that apparently needs to be addressed, is a woman cannot “hold” her uterine lining inside for a convenient time. Sadly, nature gave us a cervix, but didn’t give the uterus a sphincter. Thus, women have absolutely no control over when or how long they bleed. It’s totally normal to soak 1-7 normal sized tampons or pads per period. Seriously though, there are women that do that on only the first day!

Too Much Bleeding

Which leads me to the fun topic of “why the heck am I bleeding so much?” Ladies, I hear you!!! Let’s just say it together – periods can suck. Heavy periods can suck A LOT; as in suck everything out of you! So, first, if you are bleeding so much that you are saturating a pad/tampon every hour please talk to your doctor. There are a couple of things that can be going on – well, there are more, but we are going to talk about just a couple.

Too much endometrium, usually due to too much estrogen and/or not enough progesterone. ZRT tests this a couple of ways – we do saliva/blood spot at the peak of the luteal phase when progesterone should be at its highest. Guess what, a significant number of you have totally normal estrogen and too little progesterone. When we do our menstrual cycle mapping (28-day test) we see that some women make a TON of estrogen before ovulation and don’t produce very much progesterone after ovulation. This means that the endometrium has tons of growth, but not enough differentiation or maturing to stop the growth.
Uterine structure issues. Hey, building a person is tricky and for some women, well, our moms didn’t get it quite right. Two uteruses, heart shaped, with septal divisions are unusual, but not rare. Add some fibroids (balls of muscle) or polyps (think skin tags) and our poor little uterus, which should clamp down and squeeze to help stop bleeding, can have problems. This leads to heavy flow as the uterus needs to be a round shape to be the most efficient at this. A lot of times these problems are picked up when we are teenagers, but sometimes come up later. Fibroids are super common and are one of the most common reasons for hysterectomies because of heavy bleeding. Where and how big these fibroids are can really influence bleeding.
Adenomyosis. This is where the endometrium invades into the muscle. The uterine muscles have little influence on this bleeding, which can be prolific and painful. The uterine lining can also be much thicker than usual. Women are prone to this if they had an invading placenta during childbirth, if they have had multiple pregnancies, or if they’ve had uterine procedures (C-sections, surgical terminations, myomectomies).
Bleeding disorders. I mention this one because sometimes the period is the first time a young lady might have been considered to have a risk. Von Willebrand’s is not uncommon and can cause profound bleeding.
Anemia. What! You might be saying, how can anemia make me bleed more? Yes, nature’s cruel joke is that the more you bleed, the more anemic and iron deficient you are, which can make you bleed more. How’s that for a punch line? Turns out iron is needed to have good contractility of the muscles, so when you are losing blood, you are losing the ability to clamp down on that uterine lining and stop too much blood loss.

What Do We Do with All This Blood?

How to handle this bleeding is such a challenge. Holy cow, this takes time my friends. I’m an old pro at having periods; I have long and heavy periods, a history of gigantic fibroids (shout out to Dr. Jenna Murray for reconstructing my uterus and letting me have my daughter), and I am still figuring things out. Which leads me to the funny conversation today at ZRT – MENSTRUAL CUPS. I’m a bit obsessed—seriously, I’ve bought 3 different brands in the last week. As a woman who really struggles with periods, I really, really love menstrual cups. They changed my period experience from something I dreaded to just a blip on the calendar.

What are menstrual cups? Well, they are little cups (about 1 inch in diameter, 1 inch long) that are inserted into the vagina and form a seal with the vaginal walls and catch the blood. You guys – ok ladies, if you haven’t tried one – DO IT! Now let’s dive into your options! We have a lot more available to us now than the original soft cup/Instead™ and the Diva™. The Soft cup™/Instead™/Flex cup™ has worked for me for years. It’s made it so that my period doesn’t consume my life. I recently found a company that is making a silicone version of one called the Lumma Cup™ from Brazil and I bought it. I love that it’s not disposable and it was great. Now, this led me to looking at all the true cups – the Lumma™ is more of a disk – and there are SO, SO MANY! Check out www.putacupinit.com for a forum and resources. I want to have lunch with these ladies – they are great and boy, we could have such great period conversations. They have a quiz that can help you figure out what one might work for you.

Cups are getting so popular that we are even seeing Tampax™ get into the game. Diva cup™ and Saalt™ are both available at Target, so really you can easily find one to try (Putacupinit has coupons; use them because you might have to try a couple). Why do I love them? They easily catch 2-4 times the blood volume as a tampon. Which means instead of changing a tampon every 2-3 hours, you might get away with dumping them every 6-12 hours. Less bathroom time – hurray! Less vaginal dryness and irritation – double hurray! Plus, sex is possible in some of these versions – so hurray for less period hassles in general!

A Couple of Menstrual Cup Myths That I Want to Address

Yes, you can use one with your IUD, but make sure to break the suction before pulling it out and take care not to pull on the strings.
Yes, you can use the cups if you have never had sex. As soon as a girl has a sense of her period and has comfort with her body, she can use a menstrual cup. She might want to experiment with different folds to make the cup smaller upon insertion and fold it a bit upon removal, but it will work.
No, the cup can’t get lost up there. Now, if you have a high cervix it might seem like it, but I promise, it won’t be lost. Try bearing down like you are having a bowel movement and/or squatting, to push your cervix and the cup lower into the vagina. Also, don’t panic; it will come out.
Yes, you can poop with them in and you are not going to force them out. If that is a concern, you are likely constipated and need to take some magnesium, fiber, or vitamin C and drink more water, but hey, that’s a different blog.
Yes, you might have less cramping with the menstrual cups. What? I KNOW! I’m not sure of the mechanism, but my guess is that some cervixes just hate being poked by tampons. Since the cervix is not bothered by the cups, I’m thinking that is why many women notice less cramping. Have I convinced you yet?

No plastics, no herbicides or pesticides in the cotton (yes, that is a real thing), decrease in waste, cheaper over time, less vaginal microflora disruption.

There are other benefits with the cups as well – no plastics, no herbicides or pesticides in the cotton (yes, that is a real thing), decrease in waste, cheaper over time, less vaginal microflora disruption. Now, you must be willing to try a couple of cups. You might need a different one for your heavier days vs. your lighter days to start with. You might also find some really don’t work for you. For instance, you might find that you have a very high or very low cervix that can cause some discomfort or some very funny contortions as you learn to insert or remove them. You might find that you hate the little stem or that you really like one cup for working out, but another for days that are more mellow. Basically, you have to learn, but once you find one that works, I think that most women can successfully incorporate them into their period gear.

Underwear That Can Help

Have you tried period underwear? I haven’t tried these yet but hear great things about THINX™ as well as Modibodi™ underwear. I think these would have been amazing for me as a young girl and absolutely great for a woman who is perimenopausal and dealing with surprise periods. There are more and more brands out there, so let me know your favorites. For me, they would be back-ups, but for those of you lucky enough to have light periods I hear you can go an entire day. Get some for your young teens in your life who are figuring things out.

So, I’m with you with the heavy periods. Check your hormones, get help if you need it, and change how you handle them. I haven’t addressed therapeutics on things to try to decrease the flow – that will be another blog. But in the meantime, you can imagine all the docs here at ZRT having a laugh over the shapes, colors and stories of dealing with periods and lady-land. We have to be in it together because boy, it really can be a bear. Treat yourself to a nice new pair of period panties and, as for me, I have an eye out to try a rainbow-colored menstrual cup next cycle. I’ll let you know how it went.

Related Resources:

5 Tips to Getting Started with ZRT Testing

Fri, 06 Jul 2018 10:05:00 -0700

Health care providers (HCPs) who want to get started with ZRT Laboratory need only take a few easy steps to begin using our saliva, dried blood spot and dried urine tests. Simply set up an account, order kits and then identify the patients who can benefit from hormone, neurotransmitter, heavy metal, and cardiometabolic testing. Best of all, when HCPs have questions about reports and treatment plans, they can simply call our team of clinicians for answers.

Want more details on using ZRT? Read on to learn Dr. Alison McAllister’s 5 tips for successfully integrating ZRT testing into your practice.

1. Identify Patients Who Can Benefit

Not all practitioners commonly run tests, and some even worry about patients being upset about paying for them, but Dr. McAllister (who oversees her own private practice) finds that most patients really want this information. It gives them evidence about why they feel the way they feel, and test results also serve as the report card that validates their improvement.

Some of the common presenting symptoms that should identify patients who can benefit from testing include:

Women with
- Irregular cycles, PMS/PMDD, infertility, endometriosis, thyroid problems, stress
- Menopause symptoms like hot flashes, night sweats, insomnia, vaginal atrophy
Men with
- Changes in muscle mass or libido, anxiety, stress, abdominal weight gain

ZRT offers Patient Checklists, which can also be a helpful tool for identifying who can benefit from testing.

2. Pick the Right Profile(s)

ZRT offers a range of profiles, but there are 5 recommended by Dr. McAllister:

Saliva Hormone Profile III

This is ZRT’s most popular profile and a good baseline to see where a patient’s hormone levels are. For follow up, Dr. McAllister recommends Saliva Profile I, which includes the same hormones but only morning cortisol instead of all 4 diurnal samples.

Comprehensive Profile I

This is another popular profile and a good baseline to see where a patient’s hormone levels are. It includes a range of thyroid markers.

NeuroAdvanced Profile

This is ZRT’s neurotransmitter profile, which includes a range of 14 parent and metabolite neurotransmitters, including dopamine, serotonin, epinephrine, norepinephrine, GABA and 9 others. Test neurotransmitters for cases of severe fatigue, anxiety, OCD or ADD, depression or insomnia. Hormones and/or elements can also be added for additional detail.

Urine Hormone Testing

ZRT is the lab that first developed the Dried Urine Hormone Test and is expert at deciphering the complexities of what these levels mean. ZRT tests more estrogens than any other lab, and has unmatched expertise in evaluating these levels for breast cancer risk.

Heavy Metals & Essential Elements

ZRT’s panels focus on testing the 4 most toxic heavy metals – lead, mercury, cadmium, arsenic – and essential elements that include iodine, selenium, zinc, magnesium and copper using the convenient sample collection of dried blood spot and dried urine.

3. Dispense Test Kits

When handing out test kits during an office visit, Dr. McAllister has noticed that providers who are most successful will spend some time showing the kit components to patients. Once they understand how easy the collections are, and how they can all be done at home, they have more confidence – and are more likely to complete their test kits.

4. Collect Samples

ZRT offers detailed instructions and collection videos to help patients with sample collection. Once samples and paperwork are complete, patients can easily return their kits to ZRT via the enclosed 2-day UPS label (US only). Dried samples are shelf-stable for 30 days – over weekends, holidays, and even when it’s hot – and saliva samples can be kept frozen until mailing.

5. Retrieve Results

ZRT offers the secure, online portal www.myZRT.com for results delivery. Reports can also be faxed or mailed for providers who request it. For HCPs who have questions after receiving patient results, don’t hesitate to call the ZRT clinicians at 1.866.600.1636. They’re available Mon-Fri from 9am-5pm PT – no cost, no appointment necessary and no time limits. They can help decipher tough cases and discuss treatment options.

Bonus! Educational Resources

As a bonus, ZRT also offers a wide array of educational resources for both HCPs and patients that range from webinars and videos to articles and brochures. Many of these materials are available for download online at www.zrtlab.com/resources, but we also have some printed booklets and brochures for patients that are available free of charge to providers. Just ask our customer service team or complete and return this form.

Hopefully these tips will prove useful in getting the hormone testing part of your practice up-and-running quickly and successfully. If you have questions or have ideas that you want to share, feel free to chime in with comments.

Lithium - Medication or Micro-Nutrient?

Mon, 02 Apr 2018 12:46:00 -0700

Lithium is an element that, at the present time, is considered non-essential to the human body. However, it is getting a lot of attention as a therapy, and there are interesting reports of beneficial actions of lithium.

You might have seen our blog by Dr. James Greenblatt or one of the NY Times articles mentioning lithium. It is also coming up with frequency because of increasing awareness on mental health issues. There are lots of questions still to be answered, but we are excited about delving into them with you.

For this blog, I wanted to take a moment to introduce a new test for ZRT that ties in with our nutritional elements testing – lithium in dried urine.

Lithium Carbonate as a Medication

Most docs know of the prescription medication lithium carbonate, which has long been used for the treatment of manic-depression/bipolar disorder. It contains 18.8 mg of elemental lithium per 100 mg of lithium carbonate and was first used medically in 1871 to treat mania. Lithium carbonate treatment can be extremely successful, but does come with numerous adverse reactions depending on a person’s sensitivity to the medication as well as the dosage of lithium that they take.

Lithium carbonate commonly causes these side effects: changes to thirst and urination, vomiting, muscular weakness, changes to appetite, heart issues, skin and hair changes, fatigue, and thyroid disorders. In some cases, these adverse reactions are offset by the benefits that the patients might appreciate with the medication. So, it makes sense that there is a great deal of caution regarding other lithium salts.

Other Forms of Lithium

The most popular non-prescription form of lithium is lithium orotate, although many other salts of lithium have been researched and articles can be found on Pubmed by searching “microdose lithium” or “micro-dose lithium.” Lithium orotate is the primary form available over the counter in America.

So why is it different from the medication? Well, honestly, it might not be, except in the dosage and better availability to brain tissue [1]. This idea that lower dosages may have benefits and fewer adverse reactions is not a new one. In fact, many elements or medications work this way with a low dose causing no problems, while toxicity is seen at higher dosages; or we might find benefits in naturally occurring elements that are not essential for life, such as gold. The use of low dose naltrexone vs. high dose naltrexone is another example. Lithium orotate contains 3.83 mg of lithium per 100 mg of the salt, significantly lower than in lithium carbonate.

Lithium is a naturally occurring element. Many communities around the world have lithium in drinking water at significant levels and there are some positive associations with lithium intake. In the US, tap water levels seem to fluctuate from undetectable to 0.170 mg/liter. You can even buy lithium-containing water – Lithia spring water is available online containing 0.450 mg/liter and our “local town” of Ashland, Oregon itself has a Lithia water fountain right downtown, where from the early 1900s “drinking the waters” was thought to be good for you.

In the early 1900s, it was also possible to purchase 7-UP with lithium – originally called “Bib-label Lithiated Lemon-Lime Soda” then “7-UP Lithiated Lemon Soda” joining other “good for you drinks.” It was known anecdotally, even then, that lithium was used to improve mood and was a constituent of many patent medicines of the day. In 1948 lithium was banned from soft drinks, likely due to the increasing use of the prescription lithium.

Current Research in Lithium Microdosing

There is new interest in low “microdosing” of lithium. Current research has been looking at Alzheimer’s disease and dementia, depression and suicidology, and mood stability.

Alzheimer’s & Dementia

Lithium intake at 10 µg per liter of water showed a 17% lower rate of dementia; however, lithium levels of 5-10 µg per liter were linked with a 22% increase in dementia, showing that the dosage is sensitive and that we have much to learn about this element [2]. However, there are some hints of neuroprotection and protective stress responses.

Depression & Suicidology

It is amazing to think that trace levels might actually influence behavior, but in fact lithium levels in community water does appears to be directly tied to levels of suicide, violence, and depression [3]. How does that work? Well, the idea that we are influenced by our environment is something that we commonly take for granted; for example, if we are exposed to carcinogens, we get increased cancer rates; lead dust in our houses or ground can decrease brain function; and trace perchlorate in our water increases hypothyroidism.

Mood Stability

Mood stability is the most common usage for prescription lithium. It often comes at a cost of managing adverse reactions by adjusting dosage. The breadth of mechanisms regarding lithium’s mode of action to create stability is largely unknown, although one specific target of lithium’s action involves glycogen synthase kinase-3 (GSK3) [4]. By inhibiting GSK3, lithium curbs brain inflammation, protects existing neurons and promotes the growth of new ones [5]. Additional ongoing research is suggestive of lithium’s role in regarding sodium transport and metabolism of catecholamine. There is also research indicating that phenylethylamine (PEA) stimulant activity is suppressed by lithium. Future studies can hopefully tell us how microdosing and prescription dosing work and when one form is warranted over the another.

Like Selenium, Lithium Could be Reclassified as Essential

In the 1930s, selenium was considered highly toxic to humans. It is still considered toxic at high doses, but an essential trace element for thyroid hormone synthesis and the catalytic metal of antioxidant enzymes at physiological doses. The Swiss alchemist Paracelsus is quoted as saying: “Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.” The scientific literature is now pointing to the importance of low-dose lithium in maintaining health and preventing disease. It is not inconceivable that one day soon it will, like selenium, become an essential trace element.

Lithium Testing

ZRT’s urine lithium test is not a test geared for managing prescription lithium dosing. This test is aimed at giving people a way to assess their intake through their drinking water or supplementation. This is a growing topic of research and it will be fascinating to see where the research takes us in the next 10 years or so. We will continue, as always, to bring you interesting articles and things to ponder as you are helping your patients.

Many people have been getting some answers and help through ZRT's Heavy Metals & Nutritional Elements testing. We are excited that this test is already helping so many people and hope that the new lithium add-on assessment helps further.

Related Resources

References

[1] Kling MA, et al. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. J Pharm Pharmacol. 1978;30(6):368-70.

[2] Kessing LV, et al. Association of Lithium in Drinking Water with the Incidence of Dementia. JAMA Psychiatry. 2017;74(10):1005-1010.

[3] Vita A, et al. Lithium in drinking water and suicide prevention: a review of the evidence. Int Clin Psychopharmacol. 2015;30(1):1-5.

[4] Luca A, et al. Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy. Oxid Med Cell Longev, 2016;2016:3030547.

[5] Chiu CT and Chuang DM. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2011;36(6):461-76.

Menstrual Cycle Mapping – Your Questions Answered

Fri, 02 Feb 2018 14:14:00 -0800

ZRT has launched a month-long hormone assessment in dried urine called the Menstrual Cycle Mapping test. This is what some call the 28-day hormone test. In our profile, we test estrogen, progesterone, and LH levels throughout a month.

This article tackles some frequent questions providers might have regarding the purpose of the testing and who the ideal patient is.

TESTING SPECIFICS

Why urine testing instead of saliva?

Saliva testing is what ZRT was founded on, and we have tested over 1.8 million individuals at this point. We are celebrating 20 years of hormone testing this year! Hurray! We love saliva testing. But, what we don’t love is having you collect every other day for 15 samples. Urine testing has the benefit of a super easy collection – wake up and pee on the strip! If you forget that time, you do your second morning urine. Easy.
Urine testing is also well established in the medical literature for the purpose of this test, which is determining ovulation, LH, estrogen, and progesterone levels. Saliva would also work, but we can’t test LH to help pin-point LH; Bloodspot works really well, but ouch, too many finger pokes. Since we are looking for patterns more than absolute levels, urine is the perfect, easy collection tool.

Blood on the strip – is this a problem?

No! We are testing metabolites of estrogen and progesterone that are generated by the liver and rapidly eliminated in urine. Thus, the levels in any blood contamination will not skew the patterns.

Can I change the time my patient collects the samples?

Absolutely! Our default is 15 strips provided in the kit. We encourage starting on day 7 and continuing on alternate days until the period appears. For many women that means that about 11 samples will be collected. If your patient has a 28-day cycle, that means you have an additional 4 strips that you could have collected when the patient’s symptoms are at their worst or when you would like to see more data points. ZRT will be plotting all information relative to the actual days of the cycle when the samples were collected.

Pooling samples? Other labs pool the samples but have the patient collect every day; do you do this?

ZRT does not pool samples. It is not in the interest of patients to have averages of hormone levels over 2 or more days reported back to them. Pooling a sample that is low on day 10 with a sample that is high on day 12, for instance, would produce a “normal” result, yet the highs and low are what could be behind the patient’s symptoms – i.e., drops in estrogen that can trigger migraines. Assessing levels on the actual days gives the best information for the patient.

Miss a day?

If a patient misses a morning, they can do it later that same day OR just collect the next day as well as the following day to get back on the same pattern. For example, if Sunday was missed, they would collect Monday to compensate, and then test on Tuesday as originally planned.

Card damaged?

If a patient damages a card (e.g. drops in the toilet etc), just have them use another card to collect the second morning sample or collect the next day. Most women (with average cycle of 28 days) will only expect to use 11-12 cards, so there should be several extra urine cards for them.

PATIENT CONDITIONS

Who is the ideal patient?

I think any woman would enjoy the information that they get from this test. It’s fun to see how much our hormones fluctuate, when ovulation happens, and what progesterone is doing in the luteal phase. So, given all of that, I think the woman who is having symptoms associated with menstrual hormone changes throughout the month, women dealing with infertility, irregular spotting or migraines are the women most likely to benefit from this information.

View the complete Menstrual Cycle Mapping Sample Report here.

Ablations

Yes, this test might be great for women who have had an ablation, are having symptoms, and have no idea where their cycles are. It would generally be able to help them determine at what stage of their cycles they are.

Amenorrhea/No Periods

If you want to do Menstrual Cycle Mapping on amenorrheic patients, just have them choose a random day and collect every other day until all 15 cards are collected. If they have had an ablation or hysterectomy and have symptoms associated with their “period time,” then they can count that as the period and start collecting after that until all cards are filled.
Saliva or blood spot testing is another way of testing these patients with a single collection.

Is this kit the same as ZRT's Fertility kit?

This kit is not the same as ZRT's Fertility Profile which measures estradiol, progesterone, testosterone, DHEAS, FSH, diurnal cortisol, and thyroid hormones. It’s designed to help a patient evaluate for ovarian potential as well as screen for many conditions that inhibit fertility like hypothyroidism, PCOS, and low vitamin D. When used for fertility purposes, the Menstrual Cycle Mapping kit is designed to help a woman understand the fluctuations in her hormones during the month that may contribute to inadequate uterine lining, the lack of ovulation, or inadequate luteal progesterone levels. While the Cycle Mapping kit will show if a woman has ovulated, it doesn’t give the full range of hormones that the Fertility kit does.
I think of these as synergistic to each other – both providing excellent, but not interchangeable information.

Can we test people on IUDs?

As a lab, we can test anyone, but it might not clinically be helpful. Copper IUDs (not containing any hormones) will still show ovulation (or attempts to ovulate), estrogen, and progesterone levels. Progestin IUDs will show a flat progesterone level since the progestin won’t be seen by the assay, but it will still show estrogen fluctuations and potentially LH fluctuations. For many women who don’t cycle at all on their progestin IUD, we may not see any progesterone or even LH fluctuations. I’ll update this information if we can show what these women’s patterns tend to look like.
For someone who has symptoms with the progestin IUD and has no periods, a single salivary or blood spot test should be adequate. If symptoms are fluctuating throughout the month with “good and bad” times then this test may be beneficial, but please understand the limitations of the test.

Oral contraceptives?

I do not think this is a good test for women on hormonal contraceptives, even if they are symptomatic. If women are still getting heavy periods on contraceptives you might consider looking at tranexamic acid or use of NSAIDS as therapy. The ethinyl estradiol and progestins in the oral contraceptives will flatten the hormones in the test.

PCOS – Polycystic Ovarian Syndrome

About 50% of women with PCOS will have a higher LH throughout the cycle. Women will tend to have anovulatory cycles and oligomenorrhea (few cycles). A single sample with saliva or blood spot is likely adequate, but women may enjoy checking to see if they are having any surges in progesterone or LH, or if they are ovulating, checking to see if they are having adequate progesterone levels in the luteal phase.

Progesterone supplementation: can I use this test to look at my progesterone dosages?

We do not recommend using this test to look at supplementation. Topical supplementation isn’t going to be well represented in urine and oral supplementation is going to be overly represented due to progesterone metabolism in the liver. As a lab, we of course can test it, but this test might not answer the question that you need answered.

HORMONES QUESTIONS

Is it normal to have very strong, painful ovulation cramps?

This is known as Mittelschmerz and is not uncommon. While many women have no symptoms of ovulation, some women will experience twinges of pain, cramping, spotting or any number of symptoms for minutes to hours around ovulation. This is thought to be due to the prostaglandin changes associated with ovulation.

TREATMENT QUESTIONS

Iron levels

Iron supplementation is generally 325 mg/capsule or tablet in which 25 mg is elemental iron. While many anemic patients will have good replacement with as little as 1 capsule, many women with heavy periods will require much higher levels of iron supplementation. In my experience, if ferritin is very low and women have heavy bleeding they will often require or benefit from either IV iron infusions or injections and/or therapy to stop their heavy bleeding, even if that means using a progestin IUD or oral contraceptive to get on top of the blood loss and restore ferritin levels.
Iron is required to optimize uterine cramping which is part of how the uterus stops the period, so women with low iron levels tend to bleed more because they can’t stop the period, thus leading to even more iron deficiency.

Curcumin for heavy bleeding?

Sadly, there has been no research published on this topic. Curcumin is known to be a fibrinolytic, so if heavy bleeding is thought to be due to a blood disorder such as Von Willebrand’s, it should be used cautiously or avoided, just like NSAIDS which could contribute to increased bleeding. However, curcumin also manipulates prostaglandin production, like NSAIDS, and as such would be expected to help many women with heavy bleeding. Some studies suggest a 50% reduction of bleeding with NSAID usage. Many women have noted that curcumin helps decrease their heavy flows.

What about Tranexamic acid/Lysteda (oral)/Cyklokapron (injection) for heavy bleeding?

Tranexamic acid is a relatively new medication for bleeding or I should say that it’s still relatively newish in using it for heavy bleeding in most practices. Tranexamic acid has been used by women with Von Willebrand’s to control bleeding disorders for many years. It is a non-hormonal treatment for heavy periods and is a synthetic lysine amino acid derivative. It reduces bleeding by 40% and was tested in women with a variety of causes of heavy periods including fibroids. The medication is only used for 1-5 days and only at the time of bleeding. Tranexamic acid works by slowing the action of fibrinolysis which can contribute to heavy periods. Sadly, it’s not suggested for women on hormonal contraceptives or who have a history of blood clots, as the therapy will increase clotting risk. Studies have shown that it can work as well as hormonal contraceptives for heavy bleeding at all age groups, so I think it’s a nice option to have especially for people intolerant to contraceptives. It is prescribed as 2 tabs (650 mg) TID for 1-5 days. Cash price is about $150/30 tablets. As a fun fact, this product is available over the counter in Britain and Japan for about $14 US/18 tablets. Totally try it for your patients!

I’m super excited to share with you examples of cycles as we review more and more of these. Don’t hesitate to contact us if a question hasn’t been answered. I hope you get lots of great information from this test.

Related Resources

Hormones, the Menstrual Cycle & Cycle Maps

Thu, 14 Dec 2017 11:55:00 -0800

The menstrual cycle is a symphony of hormones coordinated to yield an egg and to prepare the uterus and breast tissue for pregnancy. For most women, pregnancy will only take place in a very small percentage of cycles.

However, the monthly surge and fall of hormones starting in menarche and ending in menopause influences the brain, breast and uterus of women and may result in numerous symptoms throughout the month.

Menarche – The Beginning

The menstrual cycle will start with menarche around the average age of 12.5 years — down from approximately 17 years of age approximately 100 years ago. [1] Most young girls will start with very irregular cycles, progressing to regular cycles within 2-7 years, although anovulatory cycles are not uncommon especially when first cycling. [2] During early menarche, the coordination of the hypothalamus, pituitary and ovarian axis is maturing and the ovaries become fully developed. The negative and positive feedback loops are being established and the amplification of cyclical surges of hormones, particularly hypothalamus and pituitary hormones, is stimulated.

The menstrual cycle is divided into 4 main sections:

The menses – or “period”
The follicular phase
Ovulation
The luteal phase

Menses – "The Period"

During menses, the endometrial lining is shed (about 2 tablespoons). Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are expected to be in approximately a 1:1 ratio. Hormones are all at their lowest level of the month and the body tissues are given a rest from higher levels of hormones. During the period, the ovaries go through “follicular selection” when a small number of follicles approximately 5-10 mm in size become hormonally sensitive. The rest of the follicles regress or undergo atresia.

Symptoms common during this time:

Migraines and headaches
Menstrual cramping
Heavy bleeding / Lack of the menses
Fatigue
Pelvic pressure
Mood disorders - depression

The Follicular Phase – Growing the Ovum and Endometrium

During this phase of the cycle, the rise of estrogen acts to stop menses. The endometrium is thickened, increasing from approximately 4 mm to 10 mm within 10 days. LH and estrogen cycle in a positive feedback loop that contributes to enlargement of the dominant follicle by 2-3 mm per day, growing it to approximately 18-25 mm in size at the time of ovulation. During this time there is a dramatic increase in estrogen and LH. Symptoms during this time are usually minimal. But migraines and headaches are common with the rise of estrogen.

Symptoms common during this time:

Migraines and headaches
Persistent spotting or prolonged menstrual bleeding.
Lack of endometrial growth
Inadequate follicle growth

Ovulation – Releasing the Egg

During this phase of the cycle estrogen and LH peak, heralding the egg’s arrival. Within 10-12 hours of the LH peak (34-36 hours after the start of the surge), the egg is released from the dominant follicle. Ovulation often alternates between the left and right ovaries and some, but not all, women might notice ovulatory pain mid-cycle called Mittelschmerz, which is German for "middle pain." Women might also notice "ovulatory mucus" which tends to have the consistency of egg-whites – stretchy, watery, and abundant.

Symptoms during this time include:

Migraines and headaches
Increased libido
Ovarian pain
Ovulatory spotting

The Luteal Phase – Enriching the Endometrium

This is the stage of the menstrual cycle which generally produces the majority of problematic symptoms.

The release of the egg (ovum) triggers the involution and development of the corpus luteum. The corpus luteum is essentially a hormonally active scar left on the ovary after the trauma of ovulation. It is the corpus luteum that will produce the progesterone and much of the estrogen in the second phase of the cycle. The ovum, after ovulation, moves through the fallopian tubes and is either fertilized or not. Meanwhile, the endometrium is changing reaching approximately 10-16 mm in thickness. The rise in progesterone stops the thickening of the lining and instead initiates the secretory phase. The dramatic rise in progesterone increases the blood flow to the uterus and endometrium. The endometrial glands in the uterine lining increase and start secreting glycogen, fructose and glucose into the endometrium to nourish any fertilized ova. The blood vessels within the endometrium become coiled. If pregnancy occurs, the rise in human chorionic gonadotropin (hCG) from the developing placenta will maintain the corpus luteum. But, in most cases, the corpus luteum will start to degenerate, the ovum dies and the lining of the uterus is completely shed. Estrogen and progesterone drop dramatically and the start of the next cycle begins. The luteal phase is very consistent in length from woman to woman and averages 14 days.

This is the stage of the menstrual cycle which generally produces the majority of problematic symptoms.

Symptoms common during this time — often just grouped as Pre-Menstrual Syndrome (PMS):

Migraines and headaches
Persistent spotting
Mood disorders – irritability, premenstrual dysphoric disorder (PMDD)
Acne
Change in appetite – cravings, increased food intake
Fibrocystic breast changes and breast pain
Water retention
Bloating
Weight gain

Peri-Menopause – The Last Hurrah

Menopause is rarely the quick event of periods stopping and never having them again. For most women, up to 10 years prior to menopause, ovulation stops being so dynamic, with less progesterone being produced from the corpus luteum and anovulatory cycles occurring more often. The progesterone becomes relatively deficient compared to the peak reproductive years and women start noticing more symptoms of estrogen dominance. In the cycle, the luteal phase may shorten showing less overall progesterone production and an earlier drop in progesterone. This defines the condition commonly known as the luteal phase defect. More PMS symptoms appear and arise earlier in the luteal phase. Meanwhile, estrogen will slowly start to fluctuate more and more as the follicles fail to produce as much and the brain tries to compensate for the deficiency. This will start to contribute to more symptoms, initially only at the times when estrogen already fluctuates and then eventually to the entire month. It’s the fluctuations in estrogen that most likely contribute to vaginal atrophy and dryness, low libido, hot flashes, night sweats, memory changes, anxiety and insomnia. LH levels start to rise as the brain tries to maintain consistent estrogen levels. LH (and FSH) will become variable, but reach high levels years before menopause has truly arrived.

Menopause – The Conclusion of the Reproductive Chapter

The consequences of hormone imbalance can influence every bodily tissue including the brain throughout the cycle and even after menopause.

Menopause is the absence of menstrual bleeding for a year in women over the age of 40 (Women who have no cycles under the age of 40 are generally dealing with other underlying health conditions, medications or autoimmune disorders). The ovarian egg reserves have been depleted. The ovaries stop responding to the now very high levels of LH. Progesterone levels have dropped dramatically and are basically non-existent. Testosterone production continues from the ovaries, but the adrenal cortex will produce estrogen and progesterone for the rest of the woman’s life although at levels far lower than the ovaries did during the peak reproductive years.

The importance of a woman’s hormones from approximately age 12 until age 50 will for many women only cover approximately half of her lifetime. Yet, the consequences of hormone balance, or alternatively hormone imbalance, can influence every bodily tissue including the brain throughout the cycle and even after menopause.

Optimal hormone health requires a coordinated and elegant communication between the brain and ovaries that for many women does not occur. Testing the menstrual cycle throughout the month can allow women a peek into the times where symptoms are problematic. ZRT’s Menstrual Cycle Mapping profile gives you that peek into those levels.

Related Resources

References

[1] O’Grady 2008. Early puberty for girls. The new “normal” and why we need to be concerned. Canadian women’s health network. 11(1)

[2] Zhang,K et al. 2008. Onset of ovulation after menarche in girls: a longitudinal study. J Clin Endocrinol Metab. 93(4): 1186-1194.

Keeping Your Child Safe From Toxic Baby Food

Fri, 10 Nov 2017 12:16:00 -0800

Is there anything more endearing than the photographs of your baby eating his or her first foods? Their faces squish-up, they are covered from head to toe, their tongues protrude to catch every bite or more often to try to get the revolting taste out of their mouths.

Now, we parents are the ones squishing up our faces and showing huge grimaces of disgust at the latest report that our baby food is contaminated by metals – arsenic, lead, cadmium – none of it monitored or regulated by the FDA.

The non-profit Clean Label Project independently analyzed 500 baby formulas and prepared baby foods (formula, food, pouches, snacks, drinks, cereals) from 60 companies and found the following horrifying information.

Arsenic was found in 80% of all baby formulas – Organic baby foods had twice the levels found in conventional baby foods, and 65% of all baby products had detectable arsenic levels.
Lead was found in 36% of products.
Cadmium was found in 58% of products. Soy formulas had 7 times more than dairy formulas.
BPA was found in 60% of products claiming to be BPA free.

Looking for Common Threads

When you look at the foods that "failed," you see some definite trends. Many infant food mixes combine applesauce and rice combined with other veggies and fruit. Due to recent publicity, apples and rice are becoming more and more recognized as a source of arsenic in the diet. Much of this arsenic will be organic vs inorganic and a large portion of these metals will pass through children and won't be absorbed. However, a portion of the eaten metals will be absorbed.

In addition, metals can also harm a significant part of our bodies without being absorbed at all. Our GI system contains billions of bacteria, out-numbering our own cells significantly. Metals and chemicals that affect plants can damage our own internal "gardens" changing our own gut chemistry and changing our nutrition, GI health, and brain health, putting us at risk of autoimmune conditions as well as many other chronic health issues.

Problems Caused by Toxic Metal Exposure

So why are metals so bad? Metal exposure in young children is known to decrease IQ by several points. Although this adjustment seems small, over a population this contributes to a significant drop in the IQ of the population.

Metals may accumulate in the kidneys increasing the risk of hypertension as we age. Cadmium has a 30-year half-life, so childhood exposure persists easily into adulthood. Since cadmium is a metalloestrogen, a metal that acts like estrogen, higher levels in young children, especially girls, at the time of puberty would be expected to influence the development of breast tissue and likely, if like other xenoestrogens, would increase breast cancer risk in the future. High cadmium levels during puberty might even influence the timing of puberty, and higher levels during the reproductive years may influence testicular development in boys and future testosterone production and sperm quality and quantity, and in girls influence egg quality and influence uterine and ovarian conditions like endometriosis, PCOS, and infertility.

How Metals Get into Baby Food

One of the most disturbing facts about this reveal is that these products are being sold and not tested routinely for quality and truth in labeling.

Some of these metals are becoming increasingly present in our agricultural foods through natural occurrence or through use of pesticides and herbicides either directly being sprayed on foods or through contamination of ground water. Many of the other chemicals found the foods like BPA and its cousins (the rest of the alphabet) may be added through the processing and packing of the foods – putting hot foods into plastic containers or BPA lined tins. BPA can also interact with estrogen receptors with known implications in breast, ovarian and testicular health.

One of the most disturbing facts about this reveal is that these products are being sold and not tested routinely for quality and truth in labeling. There is little regulation and mandatory testing of foods for metals. As we become more and more aware of the science of metals, we become even more aware that there are no real safe levels of metals that have an impact on our neurological, gut microbiome, reproductive and immunological systems.

So What is a Mom to Do?

Sigh. This is the fundamental question right? We can choose organic, but in some cases they were worse than conventional products. The best answer is to make your own baby food. This doesn’t eliminate all the metal contaminations as some of these exist even in whole foods that adults are also eating, but it does mean that you control the source of these foods, where you buy them, and their processing.

A couple of things that I found helpful when I made baby food:

A small blender works great and I would steam or bake my foods and freeze them in cubes in silicone ice cube trays then transfer them to freezer bags. Meals became as easy as just taking out a couple of different flavored foods and heating them up.
As my little girl got bigger, she had blended dinner of the same foods that I was eating. This lead to meals of meat, veggies, grains with spices.
For pouches, there are some great silicone refillable make your own versions that we still like. They work well for applesauce blends as well as for other yogurts and smoothies for food on the go.
For babies that need formula, I wish I had a great answer. Definitely choose the companies that "passed" the testing and ask any company if they test their product for these metals and BPA. Choose products that have BPA free liner and ideally don't choose pre-mixed formulas which have found to have the highest levels of BPA.

Children are not just little adults. Their detoxification system is different, and their vulnerabilities are different as well. Because they are growing and developing, exposure to metals and toxins are expected to have different damaging effects depending on their growing anatomy and physiology. As our environment becomes more toxic and our control of food quality becomes more limited due to globalization and international food processing, it is becoming even more important that every person starts demanding from companies independent testing for toxins in our food. Our health and our children’s depends on it.

Related Resources

Cortisol Patterns For Graveyard (Shift) Workers

Tue, 31 Oct 2017 12:16:00 -0700

If you come by ZRT on Halloween you’re likely to be greeted by a witch, vampire, zombie or other nightcrawler. We take our decorations and dressing up seriously around here, and finding people in costume processing your labs or taking your calls is par for the course.

Laughing aside (and let me tell you, some costumes are hilarious) those who live their lives by night – on the graveyard shift – can really struggle.

Two primary challenges for people who work at night are energy and fatigue. This is largely due to the pineal gland and its interaction with light that triggers and enforces our body’s pre-programmed circadian rhythm – which produces high cortisol in the morning and then drops throughout the day until the lowest value at night. For those who work graveyard shift that normal circadian rhythm must be re-established, and for many people it doesn’t happen.

Here are a few tips that we’ve collected to help patients who are denizens of the dark:

Better to embrace the night than go back-and-forth

Workers who can fully switch to being up at night tend to do better in flipping their cortisol circadian patterns than those who go back-and-forth. We know that wake-up and bedtimes do better with consistency, so it's not surprising that keeping those constant – even if flipped – is better for our brains and cortisol levels.

Support nocturnal patterns

The trick to helping patients who are graveyard shift workers is to support them on the daily rhythm they are in.

Cortisol that is lower than optimal upon awakening and, yet, is too high at bedtime is a common pattern in individuals working nights. This often leads to fatigue during working hours and then struggling to fall asleep and stay asleep during resting hours.

The trick to helping patients in this situation is to support them on the daily rhythm they are in. This may mean that they are doing adrenal stimulant therapies at 8pm to help wake up and again at midnight, and then taking phosphatidylserine or magnolia prior to bedtime to slow down.

Observe the dark (and light)

Because melatonin production is essentially turned off by light, it makes sense that morning light helps wake us up. Likewise, when light – especially blue light – hits our eyes at night, we get more stimulated. So, using a seasonal affective disorder (SAD) light upon awakening can really help someone who has to work nights. If they can also use full spectrum lights during the day at their work or encourage the company to change their florescent bulbs to full spectrum lights, it can also make a difference in being alert throughout the day.

In opposition, around bedtime you should use dim lights, turn on your phone’s night screen, and decrease any phone, computer, tablet and TV usage to start to increase the melatonin production. Black-out curtains, ear plugs and sound proofing are all great tools. Taking melatonin at the time of desired sleep can also help the circadian switch.

Working graveyard shift can be hard, and studies have shown it is also not good for our health. Part of this is because people often live half-way between worlds when it comes to cortisol production. However, there is a series of simple measures we can take as health care providers to help our night-dwelling patients have better energy, less fatigue, better quality sleep, and improved work and social outcomes.

Happy Halloween! Don’t stay up all night.

Related Resources

Pheochromocytoma - A Rare Condition Exposed by Neurotransmitter Testing

Wed, 28 Jun 2017 11:34:00 -0700

The New York Times did a remarkable story the other day that ended with the line "When you hear hoofbeats, the chances are good that it's a horse…but we must also remember that sometimes the circus is in town. [1]"

ZRT is apparently hosting the circus this year. At the odds of 3-8 individuals per million – ZRT has been instrumental in discovering two cases of pheochromocytoma tumors in the last six months. A condition that my clinical physiology teacher, Dr. Bettenburg, said was so rare that we would never see one, and if we did, we should contact her – so I did, this week.

What is Pheochromocytoma?

Pheochromocytomas are tumors occurring primarily in the adrenal gland (85%) and the abdomen (98%), while approximately 2% occur in other parts of the body (brain excluded). While they are extremely rare, they can run in families, have been associated with other syndromes and genetic abnormalities, and can sometimes be malignant (most likely in non-adrenal tumors). A pheochromocytoma secretes catecholamines that activate a cascade of "fight or flight symptoms" without a cause.

Catecholamines

The catecholamines include epinephrine, norepinephrine, dopamine, and dopamine’s metabolite DOPAC (tested in ZRT's NeuroAdvanced profile). The catecholamines are so called because they consist of a chemical structure called a catechol, which is a benzene ring with two adjacent hydroxyl groups and an amine-containing side-chain. They are derived from the amino acid tyrosine which comes either from the diet or synthesized in the body from phenylalanine, and are produced by the adrenal medulla and the sympathetic nervous system.

Their job is to respond to acute stressors – a fear, a threat, intense sound or light, low blood sugar, or any other trauma. When the chromaffin cells of the adrenals or the postganglionic fibers of the nervous system respond to a trigger, they dump vast amounts of catecholamines into the system, acutely causing an increase in heart rate, blood pressure, blood sugar, alertness, and lung volume, changes to skin circulation, digestive slowing, dilation of the pupils, inhibition of erections, dilation of blood vessels to the muscle, and mobilization of glycogen and fat for energy production.

All of these effects happen within moments, and the entire brain system, from the amygdala – hypothalamus – pituitary – adrenal glands and the entire sympathetic nervous system are activated almost instantaneously. These catecholamines are then broken down, mostly by the enzyme monoamine oxidase (MAO), into their metabolites VMA, HVA, and normetanephrine (NMN).

Consequences of Catecholamine Production in the Absence of Stressors

So, what happens when you are producing these catecholamines when you don't have reason to? You can have symptoms that look just like panic attacks, hypertension, irregular heart rates, and headaches; all conditions that are much, much more common than a pheochromocytoma. Like these more common conditions, the symptoms of pheochromocytoma happen in "spells" that can occur at varying frequencies from daily to monthly, and thus a rare tumor is not likely to be the cause that gets considered.

Symptoms of pheochromocytomas [2] which happen episodically include:

Hypertension
Headaches
Palpitations/Irregular heart beat
Tremors
Anxiety
Nausea
Epigastric pain
Flank/back pain
Constipation
Weight loss

However, in two instances, ZRT testing found that these common symptoms were in fact indicative of pheochromocytoma. Interestingly, only one patient had the classic severe hypertension that a differential diagnosis of pheochromocytoma requires. The other patient's main symptoms were anxiety, irregular heart rhythms, tremors, and anxiety; symptoms that never suggested a pheochromocytoma in the differential diagnosis.

What is the Pheochromocytoma Test? Routine Neurotransmitter Testing.

It's extremely likely that as we do more neurotransmitter testing we will determine that these tumors are not that rare after all.

Pheochromocytomas are traditionally diagnosed by plasma metanephrine testing or by 24-hour catecholamine and metanephrine testing. It is clear that ZRT's 4-point urine testing is just as accurate. Urine testing is not as sensitive, but is very specific while plasma (blood) testing is very sensitive, but not as specific [3]. When pheochromocytoma is suspected, lab tests are followed up by abdominal CT or MRI and additional blood work to screen for genetic mutations that contribute to pheochromocytoma. Treatment is surgery with the best anesthesiologist you can find, because just touching these tumors can cause massive dumping of catecholamines and spikes of blood pressure that can be life threatening. Once removed, unless malignant, patients do extremely well.

We are so happy that the two people who were helped by ZRT in the discovery that they had pheochromocytoma will receive the care they need to finally feel better. It's extremely likely that as we do more and more neurotransmitter testing we will determine that these tumors are not that rare after all.

Related Resources

References

[1] https://www.nytimes.com/2017/06/07/magazine/she-had-never-suffered-from-anxiety-was-she-having-her-first-panic-attack.html

[2] http://emedicine.medscape.com/article/124059-clinical

[3] http://emedicine.medscape.com/article/124059-overview

A Year of Saliva Testing in Research

Fri, 23 Dec 2016 09:34:00 -0800

I wanted to share a few of the studies using saliva testing that were published in the literature in 2016.

Just a hint, if you want to search for articles on saliva testing, use pubmed.gov and search saliva estradiol (or progesterone, testosterone etc.).

Be aware that saliva hormone testing is so standard in the research world that rarely is it mentioned in the titles of the papers. Over 310 studies were published in 2016 using saliva testing – 61 studies for testosterone and 189 studies on cortisol, while poor progesterone was neglected with only 14 studies this last year.

It’s always good to know that the work that ZRT has been doing for almost 20 years in the field of saliva testing is still cutting edge and useful.

Estradiol Study

Fjeldheim FN et al. Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes. BMC Cancer. 2016;16(1):776.

Take home: Women who have genetic SNPs, even in premenopausal status, have higher estradiol levels and higher breast density. Genetic SNP for CYP19 1A1 (aromatase gene) and breast density and CYP17 was associated with increased metabolic risk factors (obesity etc). Approximately 40% of the world’s population appears to have some mutation for the CYP19A1 gene. This study also made nice mention of the fact that measuring estradiol this way measures the unbound bioavailable estradiol and that salivary immunoassays correlate nicely with LCMS levels.

ABSTRACT

Background:

Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown.

Methods:

We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7 and 12 of the menstrual cycle, and digitized mammographic density was assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol.

Results:

We observed inverse linear associations between the minor alleles of eight measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent mammographic density (p-values: 0.002-0.026), these associations were strongest in lean women (BMI, ≤23.6 kg/m^2.). The odds of above-median percent mammographic density (>28.5 %) among women with major homozygous genotypes were 3-6 times higher than those of women with minor homozygous genotypes in seven SNPs. Women with rs3020364 major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No associations between SNPs and daily cycling estradiol were observed. However, we suggest, based on results of borderline significance (p values: 0.025-0.079) that the level of 17β-estradiol for women with the minor genotype for rs3020364, rs24744148 and rs2982712 were lower throughout the cycle in women with low (<28.5 %) percent mammographic density and higher in women with high (>28.5 %) percent mammographic density, when compared to women with the major genotype.

Conclusion:

Our results support an association between eight selected SNPs in the ESR1 gene and percent mammographic density. The results need to be confirmed in larger studies.

Progesterone Study

Lovick TA et al. A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms. Psychoneuroendocrinology. 2017;75:83-90.

Take home: Women (46 of them at least) who had PMS actually had stable progesterone levels throughout the luteal phase until 3 days prior to menses, when progesterone levels sharply dropped. Women without PMS had a gradual decline in progesterone in the 8 days prior to menses. Both groups of women had approximately the same upper and lower levels of progesterone. This shows that it is likely the dramatic shift in progesterone levels that contributes to PMS symptoms rather than a drop to a certain level.

ABSTRACT

Neither maximum nor minimum concentrations of progesterone in the two groups were related to the appearance or severity of premenstrual symptoms.

There is a consensus that the development of premenstrual dysphoric states is related to cyclical change in gonadal hormone secretion during the menstrual cycle. However, results from studies seeking to link symptom severity to luteal phase progesterone concentration have been equivocal. In the present study we evaluated not only the absolute concentrations of progesterone but also the kinetics of the change in progesterone concentration in relation to development of premenstrual symptoms during the last 10days of the luteal phase in a population of 46 healthy young adult Brazilian women aged 18-39 years, mean 26.5±6.7years. In participants who developed symptoms of premenstrual distress, daily saliva progesterone concentration remained stable during most of the mid-late luteal phase, before declining sharply during the last 3days prior to onset of menstruation. In contrast, progesterone concentration in asymptomatic women underwent a gradual decline over the last 8days prior to menstruation. Neither maximum nor minimum concentrations of progesterone in the two groups were related to the appearance or severity of premenstrual symptoms. We propose that individual differences in the kinetics of progesterone secretion and/or metabolism may confer differential susceptibility to the development of premenstrual syndrome.

Testosterone Study

Afrisham R et al. Salivary Testosterone Levels Under Psychological Stress and Its Relationship with Rumination and Five Personality Traits in Medical Students. Psychiatry Investig. 2016;13(6):637-643.

Take Home: Men respond to stress by increasing testosterone; women respond to stress by decreasing testosterone. There was some correlation with emotional management, testosterone, and gender in how individuals responded to stressors that bears further study.

ABSTRACT

Objective:

The purpose of this study was to evaluate the salivary testosterone levels under psychological stress and its relationship with rumination and five personality traits in medical students.

Methods:

A total of 58 medical students, who wanted to participate in the final exam, were selected by simple random sampling. Two months before the exam, in the basal conditions, the NEO Inventory short form, and the Emotional Control Questionnaire (ECQ) were completed. Saliva samples were taken from students in both the basal conditions and under exam stress. Salivary testosterone was measured by ELISA. Data was analyzed using multivariate analysis of variance with repeated measures, paired samples t-test, Pearson correlation and stepwise regression analysis.

Results:

Salivary testosterone level of men showed a significant increase under exam stress (p<0.05). However, a non-significant although substantial reduction observed in women. A significant correlation was found between extroversion (r=-0.33) and openness to experience (r=0.30) with salivary testosterone (p<0.05). Extraversion, aggression control and emotional inhibition predicted 28% of variance of salivary testosterone under stress.

Conclusion:

Salivary testosterone reactivity to stress can be determined by sexual differences, personality traits, and emotional control variables which may decrease or increase stress effects on biological responses, especially the salivary testosterone.

DHEAS Study

Ge F et al. Concurrent and prospective associations between HPA axis activity and depression symptoms in newlywed women. Psychoneuroendocrinology. 2016;73:125-132 .

Take home: DHEAS is an important tool to assess HPA axis in regards to measuring hormones and depression and must be used in addition to cortisol. This study definitely doesn’t answer all questions regarding stress, and in fact suggested that individuals with higher levels of depression may have more HPA axis activity during stressors just as much as those with HPA axis dysfunction may be more prone to depression. One thing I liked about this study was that they pointed out that they measured DHEAS in saliva because it is the most biologically active molecule as compared to DHEA. They also pointed out that salivary flow rate was not a problem during collection which has been a common criticism of using DHEAS as a measurement tool.

ABSTRACT

We investigated the extent to which individual differences in activity of the hypothalamic pituitary adrenal axis (HPA) are associated with depressive symptoms among newlywed couples. Participants were 218 couples (M age 28.4 years; 94% White) who provided 5 saliva samples (later assayed for cortisol and DHEA-S) before and after participation in a discussion of a major area of disagreement in their relationship. Depressive symptoms were assessed initially, and approximately 19- and 37-months later. Results revealed an interactive effect suggesting that concordant levels of cortisol and DHEA-S (either both high or both low) were concurrently and prospectively associated with higher depression scores. Interestingly, this interactive effect was observed for wives only - not for husbands. These observations underscore contemporary theoretical assumptions that the expression of the association between HPA activity and depression is dependent on factors related to the interaction between characteristics of the person and features of the social environment, and moderated by co-occurring variation in endocrine milieu.

Cortisol Study

Poole L et al. Depression 12-months after coronary artery bypass graft is predicted by cortisol slope over the day. Psychoneuroendocrinology. 2016;71:155-8 .

Take home: I purposely pulled an article regarding the diurnal rhythm of testing cortisol. I believe that in the quest to understand cortisol and the HPA axis dysregulation that can occur, practitioners are commonly getting confused and thinking that diurnal rhythm testing isn’t important vs. diurnal circadian rhythms. There are several interesting articles on night shift work changing circadian rhythms of cortisol, but I wanted to pull an article on a different aspect of cortisol rhythms.

ABSTRACT

Alterations in the diurnal profile of cortisol have been associated with depressed mood in patients with coronary heart disease. The relationship between cortisol output and depressed mood has not been investigated prospectively in coronary artery bypass graft (CABG) patients before. We aimed to study the relationship between cortisol measured pre- and post-operatively and depression symptoms measured 12 months after CABG surgery. We analysed data from 171 patients awaiting first-time, elective CABG surgery from the pre-assessment clinic at St. George's Hospital, London. The Beck Depression Inventory (BDI) was used to assess depression symptoms and saliva samples were collected to measure diurnal cortisol. Baseline assessments of depression and cortisol were obtained an average 29days before surgery, short-term follow-up of cortisol occurred 60 days after surgery and long-term follow-up of depression was assessed 378 days after surgery. Baseline cortisol slope was not associated with depression at 12-month follow-up. However, a steeper cortisol slope measured 60days after surgery predicted reduced odds of depression (BDI≥10) 12 months after surgery (odds ratio 0.661, 95% confidence interval 0.437-0.998, p=0.049) after controlling for covariates. These findings suggest interventions aimed at improving adaptation in the early recovery period may have long-term benefits in this patient group.

Related Resources

Childhood Cancer – Let’s Talk About It

Fri, 30 Sep 2016 09:56:00 -0700

The month of September is known for both menopause month and children’s cancer awareness month. Many people commonly recognize the first but not the second.

I would just like to take a moment and talk about children’s cancer. This is not my typical blog about fun and the joy of science and research that I usually strive for.

Don’t worry, I'll blog about the wonders of estrogen, thyroid, or testosterone soon I’m sure. The ZRT family however, has been touched by a child of an employee with cancer – Go Regan! – and sadly 1 out of 300 children will be diagnosed with cancer (under the age of 18).

I personally have 3 friends whose children have had cancer and I’ve personally worked with families and been affected by their journeys. Without awareness, there is no drive for funding of pediatric cancer research or pediatric cancer treatments which today is only 4% of the national research budget and almost zero of the pharmaceutical companies’ budgets.

My Personal Involvement

Now, you might wonder what this has to do with me or my work here at ZRT. A legitimate question to be sure. I actually did my residency in integrative cancer care at a time when few people were acknowledging the role of diet or supplements in healthcare, let alone cancer care. I saw amazing people face difficult illnesses with a spirit of strength that continues to inspire me today. I saw people survive their cancer and their treatment to return home to their lives, surprising their doctors and families, and to live fully, although often choosing a different life path.

But I also saw people who were “cured” only to question if it was worth it, because of how they felt after treatment. Many times, these were my patients whose hormones were so dramatically changed by their cancer treatment that they no longer felt like themselves; and so began my delving into the world of endocrinology and eventually to my coming to ZRT. Over the years, I have, like many of you, been able to dramatically improve my patients’ lives through thyroid support, adrenal support or sex hormone support. But the patients that always touch me the deepest are the children.

Hormonal Effects of Cancer Treatments in Children

The children and their families, the other doctors and nurses, are like a precious metal – strong and vibrant, forged by the terrible hammer of cancer and treatment.

Now, children under the age of puberty commonly don’t have reproductive hormones, but the treatments for cancer in children are often more harsh than those used in adults because of their rapidly growing bodies and metabolism. This commonly contributes to children having lasting neurological, psychological, endocrinological, and frankly every other “–logical” part of their body, longer term consequences.

They struggle with adrenal imbalance symptoms as the high doses of steroids used impact the hypothalamic-pituitary-adrenal system that was really just starting to develop. They struggle with centralized hypothyroidism that can be missed because it’s not common, but when they’ve had radiation to the brain, that can be an unforeseen problem. Older teens struggle with infertility as the treatment will damage their uterus, ovaries or testicles leading to lifelong dependence on hormones. Other problems such as paralysis, brain damage, learning disabilities, depression, and of course PTSD, are also not uncommon badges of “winning” against childhood cancer.

Resilience of Families Affected by Childhood Cancer

It sounds like so much, and it is. It’s terribly unfair. But the children and their families, the other doctors and nurses, are like a precious metal – strong and vibrant, forged by the terrible hammer of cancer and treatment. They are some of the most amazing people you’ll meet and you wonder how they do it; but those of us who are parents know that you just “DO” when your child needs you. You face the situation and you move through. There really isn’t a choice. Sadly, too often the children dealing with cancer do not survive. As a society we don’t like to talk about that. There is no money in pharmaceuticals to treat children. Science has brought few new treatments for children’s cancers and there are few studies looking at therapies specifically geared for children, although there are some promising strides being made in immunotherapies.

So today I raise a cheer to all those children, parents, extended families and friends who have gone through cancer. Let’s raise awareness so that other children and their loved ones don’t have to walk this terrible path. Go Gold in September for children’s cancer awareness.

Additional Reading:

If you want a powerful read by a mother who lost her child to cancer and how she’s honoring his memory, I highly recommend the following. Ty’s mother Cindy puts this struggle in the most amazing way: http://tylouis.blogspot.com/2016/09/when-your-child-has-cancer.html
An organization that is doing amazing support in our area is the Children’s Cancer Association: http://joyrx.org/
If you want to donate to a charity involved in research or cancer support, I recommend that you check them out at this site: https://www.charitynavigator.org/

Related Resources:

Metal Elements on a Mineral Mission to Mars

Fri, 12 Aug 2016 12:24:00 -0700

Have you seen the movie The Martian? I highly recommend it. The premise is that an astronaut called Mark Watney goes with a team to Mars, gets left behind and has to survive.

I love semi-disaster stories and even better when it's Matt Damon playing the main character. Now, according to the book, Watney had lots of vitamins and mineral supplements to supplement his diet. But if he hadn't had those supplements, there are certain elements that he could have become deficient in that could have led to severe health problems.

Let's explore some of the metal elements - nutritional elements - that you might want to take with you if you were on a mission to Mars.

Copper

I think that most people will be surprised to learn that copper is so critical to our body systems. It is especially important in the company of iron and zinc. Many health care providers understand that if you use zinc you should use copper, but don’t truly understand why. Zinc will upregulate the synthesis of a copper binding ligand which indirectly antagonizes the absorption of copper in the GI tract. As a result, more copper is bound in the mucosal cells and prevented from entering circulation.

There was a fun case (not fun for the patient though) of a woman who was using a zinc- containing dental adhesive (>2 tubes per week) for her dentures, which caused her to develop copper deficiency symptoms. Copper is not common in the body; our body contains about 1.4-2.1 mg Cu/kg of body weight. It is concentrated in the liver, muscle and bone and it’s involved in mitochondrial functions as well as anti-inflammatory and antioxidant functions via superoxide dismutase. Copper is needed for blood vessel formation, heart health, and collagen and connective tissue growth and is also required for neurotransmitter synthesis.

Deficiency symptoms are mostly hematological (microcystic anemia) and neurological. Microcytic anemia is the result of low copper levels causing a deficiency of ceruloplasmin, which is needed for iron absorption in the digestive tract. Few iron supplements contain copper, but this is a great mechanism to understand if you are constantly fighting someone’s iron deficiency anemia.

Low copper is also now associated with, and in some cases becoming a treatment for, atherosclerosis, ALS, and osteoporosis. Too much of a good thing is problematic however, with copper excess as a known cause of Wilson's disease where it can cause cirrhosis, increased skin pigmentation, eye changes, and diabetes, but new research is also investigating high copper as a problem in epileptics, Alzheimer’s disease, and cancer (ovarian, breast, gastric, bladder, and leukemia). Research into therapies to chelate copper and also to replace copper for disease management is ongoing.

Estimated average requirements 0.7 mg/day; RDA 0.9 mg/day
RDA pregnancy 1 mg/day
Lactation 1.3 mg/day
Upper limit (UL) of safety is 10 mg/day; Europe’s UL is 5 mg/day

Magnesium

Testing magnesium level is tricky as normal serum values are found to be inadequate. That’s why we test it in a whole blood spot collection as it provides an RBC (red blood cell) magnesium level.

Amazing magnesium fact: it's the third most common element in sea water behind sodium and chloride. It's the 4^th most common element on earth and you'll be glad to know that if you go Mars, it's extremely common on that planet. Phew, no worries there, you just have to dig it up.

Magnesium is one of the most common elements in the human body, concentrating in the bones, brain and heart, but essential in all cells and used in over 600 enzymatic reactions. Anything from synthesizing proteins, to activating vitamin D, to metabolizing dopamine and glutamate requires magnesium. It’s been found useful for numerous clinical conditions such as hypertension, migraines, insomnia and leg cramps. And we are commonly deficient – about 2-15% of the population. It causes cramping in all muscles, the heart being the most important, tremors, hypertension, and neuromuscular and metabolic dysfunction.

Through our diet, we get magnesium from spices, nuts, grains, cocoa (my favorite source) and vegetables (particularly dark green leafy veggies). But high or low protein diets can inhibit absorption, and people on proton pump inhibitors are commonly deficient. Levels are also commonly lower in people with diuretic usage or kidney problems.

Medications often deplete magnesium, but some medications actions may also be inhibited by magnesium. The body contains approximately 22-26 g of magnesium (vs. copper’s average of 100 mg) – mostly in the skeleton. But testing it is tricky as normal serum values are found to be inadequate. That’s why we test it in a whole blood spot collection as it provides an RBC (red blood cell) magnesium level. In fact, only when you are severely depleted do serum levels drop.

RDA (diet + supplementation): 400-420 mg/day for men; 310-320 mg/day for women
Adult upper limit of tolerability is 350 mg/day (level at which no diarrhea or GI complaints will occur)
Toxicity has occurred at 5,000 mg/day

Selenium

Ok, so selenium isn't a metal, but it is a mineral and we really need it for the voyage. Astronauts living at the International Space Station have found that cells secrete large amounts of inflammatory cytokines and express more than 1000 different genes from being at microgravity, not to mention the exposure to space radiation; all of this creates significant oxidative stress and inflammation. The longer the voyage, the more reactive oxygen species (ROS) damage occurs which actually gets worse upon returning to earth’s gravity.

Selenium is an amazing antioxidant through the actions of selenocysteine and selenomethionine. Selenocysteine is critical in glutathione peroxidase, but is known to contribute to 25 selenoproteins at this time. Selenium is also critical in 3 iodothyronine deiodinases making selenium one of our important thyroid nutrients. In fact, selenocysteine or selenomethionine is found in high concentrations in areas that experience high ROS – sperm, thyroid, liver, kidney and muscles. Selenium is found in Brazil nuts, grains, seafood, organ meats, poultry and dairy products. You can also find it in garlic, onions, and broccoli if the soil is rich in selenium, which is thankfully plentiful in Martian dirt. Low levels of selenium are likely a contributor to rapid aging, as well as immune dysfunction, thyroid dysfunction, and cancer. High blood levels of selenium may decrease blood sugar control.

RDA: 55 mcg adults; 60 mcg pregnancy; 70 mcg lactation
Tolerable upper limit 400 mcg/day
Toxic level 800 mcg/day

Zinc

Zinc on Mars apparently warranted a news headline in 2011. So, you might be able to find it if you look hard enough, but this is one that you might want to bring with you. Zinc deficiency is estimated to affect up to 2 billion people worldwide. People with the genetic disorder acrodermatitis enteropathica, alcoholics, or those who have severe burns, prolonged diarrhea, or are on total parenteral nutrition or certain medications can become severely low. Milder deficiencies are common with children, people with malabsorption or malnutrition, strict vegetarians or vegans, or older individuals. I personally saw a patient with profound zinc deficiency who was many years post gastric bypass.

Zinc is needed for over 300 enzyme conversions just like magnesium. We also know that zinc plays a critical role in regulating genes and cell signaling (remember zinc fingers in hormone receptors? Yup, they contain actual zinc). So zinc impacts almost every system in the body including the immune system.

If you are deficient, immune dysfunction and growth restriction, failure to thrive, and neurological impacts on children may occur. Clinically, there are several exciting paths that zinc research is investigating including using it as treatment for: athletic training, copper chelation protocols, immune regulation, macular degeneration, diabetes, diarrhea, atherosclerosis, and child development in developing countries. So, when packing your food for Mars, consider packing shellfish, red meat, eggs, grains, nuts and legumes. Non-meat sources are less bioavailable due to their phytate contents, so pack extra. Note, intranasal zinc treatments have been known to cause an individual to permanently lose their sense of smell, so caution here.

RDA: 11 mg/day men; 8 mg/day women
Toxicity levels: Single dose of 225 mg or more will induce vomiting. Symptoms of nausea, diarrhea, sweating, weakness and rapid breathing can also occur. Major toxicity is caused by copper deficiency
Upper tolerable limit: 40 mg/day

There is no doubt that if we ever do undertake a trip to Mars, careful nutritional guidance is going to be needed to prevent severe deficiencies. If you bring nothing else along, pack some nuts. The trip is going to take a while.

Additional Resources:

Related Resources

7 Tips to Making Your Own Blue Zone

Sun, 21 Feb 2016 08:00:00 -0800

Did you know there are 5 places in the world where your odds of living to 100 are greater than anywhere else on the planet?

These regions are called "Blue Zones" and include Sardinia (Italy), Okinawa (Japan), Loma Linda (California, Seventh-day Adventists), Nicoya (Costa Rica), and Ikaria (Greece).

Based on the research and writings of Dan Buettner, people are studying these communities to try to find out how they have tapped into the fountain of youth and are trying to introduce these tools into new communities and towns.

What do these Blue Zone communities have in common?

A strong sense of family
They eat very little meat and processed foods, but instead eat a diet rich in complex carbohydrates, especially beans, and have a moderate caloric intake
They do moderate exercise every day as a function of living – they walk to work, garden, climb hills, etc.
They have a moderate amount of wine per day with friends and family
They have an active, strong social life
They report less stress, sleep well, and nap
They have a strong sense of purpose in their lives
They have a strong faith basis to their lives

So how can we incorporate these traits into our everyday existence and how do they make a difference to our cardiovascular health?

Social and Family Support

In most of these cultures, we find that social and family support is key. I would also argue that faith and religious gatherings are also a part of this. So how do social, family, and faith support help you live longer and, more importantly perhaps, better?

There are several studies showing that being isolated increases mortality. You are more likely not to get help when you need it, and being isolated can be stressful. But the studies by the Blue Zone group and others have found more interesting information. They found that being surrounded by groups of people who are living a certain way helps you to live that way as well.

In other words, if everyone around you is walking, eating healthily, and avoiding certain behaviors, you are likely to stay on track and do the same – the "big brother is watching" phenomenon. This can work for you or against you; as the Framingham study found, people who were overweight were much more likely to have overweight friends. But I also think that social and family support can reduce overall stress. You know that everyone is there for you when things are good, and when they are bad.

Dietary Factors

These communities also eat lower caloric foods that are high in antioxidants. They all have different diets, and I think that the research has yet to show that one of the diets is better than the other.

I believe the biggest factors are that they eat a lot of veggies, fiber, and antioxidants. Their antioxidants come from teas, wine, and fruits and veggies. They eat little to no processed foods which tend to be higher in calories, chemicals, and sodium. They eat with family and friends, which lowers stress levels multiple times per day.

Exercise

While we can’t change everyone’s behavior toward health, we can make small changes that encourage overall health.

These communities exercise in a moderate way every day as a way of life. Interestingly, although people may go to gyms, we are seeing a decline in this everyday exercise in modern America.

One of the biggest reasons cited is that areas aren’t as safe as they used to be. People limit outdoor movement and exercise according to their perception of safety. In the 1950s, most children walked to school. In fact, my mother walked to school, home for lunch, back to school and then back home again at the end of the day – as a 6 year old, by herself, in downtown Toronto.

In 1969, the National Center for Safe Routes to School found that 48% of children aged 5-14 walked or bicycled to school. In 2009, this was reduced to 13% although the numbers of children living within a mile of school was reduced by only 10% (Sirard and Slater, 2009).

This lack of walking to school or even playing in the streets is perhaps both a consequence and a cause of the change in the perception of safety in the community that impacts children, which also affects adults. How can that be? There is a self-perpetuating cycle where parents are fearful of letting their children walk to school because no one else is walking to school, therefore creating the image that walking to school or anywhere else must be unsafe. Thus adults as well as elderly people are not out in their communities watching the children, which also reduces their opportunities to socialize with each other.

The psychology of human nature tells us that if people are walking in the community, especially children, then an area must be safe. When communities encourage residents to walk by creating spaces for them to enjoy nature, people will naturally start to walk, which in turn encourages community.

An experiment to change behavior

So, the Blue Zone Community did an experiment to see if they could change the health of a community.

They used a town in Minnesota, Albert Lea, for the experiment. They found that they could change the behavior of this community by making exercise options accessible and easy, by changing the wording on menus in restaurant food to encourage people to choose the healthy option, by limiting snacking in schools, by encouraging only healthy options as impulse buys at the grocery store, and by encouraging people to engage socially in their community.

Years after the experiment, success is still evident; they changed the foundation by which people interact in their personal sphere. Now, more towns are signing up as they see that this impacts citizens’ attendance at work and school and lowers health care costs. While we can’t change everyone’s behavior toward health, we can make small changes that encourage overall health.

Stepping into the Blue Zone

Tips for ways to step into the blue zone include:

Walk your children to school 1 day a week (or more). Take turns with other parents so that it is more feasible with busy work schedules.
Let your children play in the street (with discretion). Not only will your children enjoy it, but it creates a community of neighbors, slows traffic down, and encourages elderly neighbors to come out of their houses.
Build a community. It doesn’t have to be with a religious group, although it may be for you, but it could also be around a volunteer position, your neighborhood, a hobby, or your children’s school.
Eat more vegetables – period. You don’t have to become vegan, but try to incorporate at least 1 vegetable at every meal of the day with a goal of at least 5 servings per day.
Eat with friends at work instead of at your desk. Perhaps go for a walk together every day. You’ll keep yourselves accountable and lower your stress burden.
Add more fiber to your diet. Most of these communities ate more beans per day than average.
Create a family mission statement about what you and/or your family wish for the world. Having a positive sense of purpose in how you are making a difference satisfies us and feeds our psyches.

For more information see www.bluezones.com

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Hyperinsulinemia vs Hyperglycemia - the Story of PCOS & Obesity

Wed, 20 Jan 2016 11:20:00 -0800

Many times when I am talking to a practitioner about a patient with PCOS and/or weight issues, I commonly get the response – "His/her blood sugar is normal." However, when we are looking at the health of PCOS and weight-challenged patients, their insulin response is of primary importance, and not just their blood sugar.

When we are fasting, both blood sugar and insulin levels should be at a steady state. Blood sugar is generally between 70-90 mg/dL and insulin levels between 1-8 µIU/mL. When we eat a meal, blood sugar increases. In response, insulin is produced by the pancreatic beta cells to help shepherd glucose into all cells to be used as energy.

Within 2 hours, insulin and glucose levels should have essentially returned to normal. Thus, our cells’ exposure to glucose and insulin is only for short blips of time within a 24 hour cycle. Excess glucose that is not used for energy is stored as glycogen in the liver and muscle cells to be used for energy between meals, where it is rapidly available for sudden energy needs such as "fight or flight" situations; but once these stores are full, the body stores extra glucose as fat in adipose cells and we gain weight.

If we allow this hyperinsulinemia to continue the body will lose the ability to manufacture enough insulin to control postprandial glucose levels.

Insulin Resistance

When we become insulin resistant, things change. The first tissue to become insulin resistant is generally our muscle cells. Exercise improves insulin sensitivity. But when tissues become insulin resistant, higher levels of insulin are needed to shepherd glucose into cells. In a healthy situation, the pancreas responds to higher blood glucose levels by producing larger amounts of insulin to match the higher level of glucose returning glucose levels to normal with the higher insulin. Initially, this higher insulin production occurs only after meals when glucose levels spike. If, however, glucose levels after meals continue to be elevated, eventually fasting insulin levels will be elevated to maintain normal glucose levels. This situation of high insulin is called hyperinsulinemia and all of this occurs in the presence of normal blood glucose.

If we allow this hyperinsulinemia to continue, and dietary and other lifestyle choices continue to push blood sugar higher after meals, the body will lose the ability to manufacture enough insulin to control postprandial glucose levels. If insulin levels cannot control postprandial (PP) glucose levels and lifestyle continues to favor high glucose foods, fasting glucose levels will also become chronically elevated and the patient will officially have non-insulin dependent diabetes (NIDD). In a non-controlled NIDD patient, high glucose will continue to spur high insulin levels until the pancreas no longer produces adequate levels. This will stimulate an NIDD patient into an insulin deficiency state and eventually over into an insulin dependent AND insulin resistant diabetic situation, sometimes known as type 3 diabetes.

It is easy to see as we lay out the manner in which many people become diabetic, that this is not a disease that starts all at once. There are many steps along the way when we wish that patients would empower themselves to change the course of their disease.

Women with PCOS are commonly in a hyperinsulinemic state for years. It may be that they have defective insulin receptors that do not trigger adequate glucose management even at lower glucose levels. As a result, the insulin appears to drive testosterone and DHEAS higher, since the production of these hormones is stimulated by excess insulin. This higher DHEAS and testosterone from both the ovaries and adrenal glands produce so many of the symptoms of PCOS – increased facial and body hair, loss of scalp hair, and acne. The high insulin contributes to irregular menstrual cycles and drives weight gain, both by increasing food cravings, decreasing satiety, increasing adipose deposition, and changing cortisol metabolism. Women with PCOS also have altered Cortisol and HPA axis functioning. Although the mechanisms are still under investigation, many women with PCOS are found to have altered cortisol metabolism both systemically and within adipose tissues, perhaps because of their PCOS and perhaps because of obesity.

How do You Know if Someone is Hyperinsulinemic?

Symptoms of hyperinsulinemia include fatigue which may be severe, complaints of "hypoglycemia" even in the presence of normal or high-normal glucose levels, weight gain, acne, increased facial/body hair, loss of scalp hair, browning of the skin in areas of rubbing (neck and armpits are common – known as acanthosis nigrans), skin tags, anxiety, depression, brain fog, sugar cravings, and a sensation of never being full.

So the next time you see that PCOS patient or overweight patient who tells you that they are not diabetic consider that hyperinsulinemia might still be contributing to a lot of their symptoms.

Related Resources

The Fertility Screening Tool You May Not Know About

Thu, 09 Apr 2015 15:45:00 -0700

Infertility is a heart breaking condition that affects millions of people around the world or approximately 8-12% of couples.

When a couple has been trying over a year (under the age of 35) or over 6 months (over the age of 35) screening for hormonal causes is one of the first recommended steps. This is because sometimes simple adjustments to thyroid and/or progesterone can result in fertility.

Fertility testing screens for numerous problems found in those with infertility. ZRT’s Fertility Profile looks at all the sex hormones and includes the recommended panel of tests by Resolve™, the national infertility association: Estradiol, progesterone, and testosterone – evaluating ovulation, luteal phase defect, and PCOS. It looks at the adrenal hormones – evaluating DHEAS and Cortisol which allows for PCOS, blood sugar imbalances, adrenal insufficiency. It includes a complete thyroid panel including screening for hypothyroidism as hashimotos – TSH, Free T4, Free T3, and TPO antibodies. A day 3 (day 1 = first day of period) FSH and LH allows for screening for PCOS markers as well as looking at the ovarian egg reserve. This panel was designed to be one of the first things done for someone looking at why they aren’t pregnant, but is also a good test to screen men who are also part of a couple with problems.

I’ve found this first line screening to catch many things that people really hadn’t considered and that many OB/GYNs had not looked at.

I’ve seen this information help women who are already in the process of doing clomid or letrazole where no one had fully evaluated them prior to trying these medications. I’ve also seen a lot of luteal phase/anovulatory cycles, PCOS, Hashimotos and hypothyroidism in women who really didn’t have the classical symptoms – they just couldn’t get pregnant.

As a naturopathic doctor, many people have wondered if I am against using fertility medications. The answer is no. However, I see women all the time being set up to fail these treatments. What do I mean by that? A fertility specialist will generally “allow” approximately 3 tries with oral medications before recommending IVF which is great, but very expensive.

So, of course you want to see people have success in those 3 tries. However, if a patient has Hashimotos or PCOS that is unrecognized and untreated, it makes it less likely that they will get pregnant with oral medications and/or more prone to miscarrying once pregnant. Instead, my recommendation is that women have a period of time where they are optimized for health and fertility and then use those medications or IVF knowing that their success rates are going to be much higher per cycle.

Obviously, this panel can not identify anatomical reasons for infertility and there are lots of unknowns. But I hope that you might consider this panel and be able to help a couple get pregnant. It’s one of the best feelings in the world to be a part of someone’s miracle.

Related Resources

The Pg/E2 (Progesterone/Estradiol) Ratio

Tue, 31 Mar 2015 08:56:00 -0700

When sex hormones are tested in women either in saliva or blood spot, ZRT test reports give a ratio of progesterone (Pg) to estradiol (E2). The ratio is helpful in clinical practice when both E2 and Pg are within range, yet the patient continues to have symptoms. It is not expected to be normal or used clinically when either E2 and/or Pg are outside of their expected ranges or if the patient does not have clinical symptoms.

A low ratio occurs when Pg is low relative to E2. This describes the classic situation of estrogen dominance. In general, either decreasing estrogen and/or increasing progesterone are appropriate. Women who are postmenopausal are generally in this group.

A high ratio occurs when Pg is high relative to E2. This is most common with supplementation and describes progesterone dominance. When this occurs, a patient may complain of symptoms of estrogen deficiency resuming after previous successful treatment as estrogen receptors are down-regulated by excessive progesterone. In general, either increasing estradiol and/or decreasing progesterone are appropriate. This commonly occurs in menopause after a woman has been using progesterone successfully in perimenopause and her estrogen levels finally start to decrease as menopause is reached.

How is the ratio calculated?

We report an “optimal” ratio of 100-500, however this is only valid when E2 is within a normal luteal phase range; i.e., when E2 is 1.3-3.3 pg/mL in saliva, and 43-180 pg/mL in blood spot. The ratio is calculated from the Pg value in pg/mL divided by the E2 value in pg/mL.

Saliva test example: a patient has E2 = 1.5 pg/mL and Pg = 300 pg/mL. The units are the same (pg/mL), so the ratio is 300 divided by 1.5:

300 1.5

= 200

Blood spot or serum example: a patient has E2 = 100 pg/mL and Pg = 20 ng/mL. The Pg units are first converted to pg/mL before calculating the ratio: 1 ng/mL is equivalent to 1000 pg/mL. Therefore, the ratio is 20 ng/mL x 1000 = 20,000 pg/mL Pg, divided by 100 pg/mL E2:

20 x 1000 100

= 200

Both of these examples represent normal endogenous luteal phase levels of E2 and Pg.

Is the ratio relevant in women using hormone therapy?

With some types of hormone therapy such as topical progesterone, Pg levels in saliva are much higher than endogenous luteal phase levels, ranging from 200-3000 pg/mL at 12-24 hours after dosing, and so the ratio can appear high. However, because symptoms of both estrogen dominance and progesterone dominance can look the same, testing and assessing the ratio along with clinical symptoms can help determine the next step for treatment.

Clinical Case

Mary complains of hot flashes and night sweats. She’s a 50-year–old, newly postmenopausal woman who has never been on hormones. Her BMI is normal and she has no other health issues. A saliva test finds an E2 of 1.1 pg/mL (reported as “OK”), but a Pg level of 15 pg/mL (also “OK” for a postmenopausal woman), giving a ratio of 13.6 which is low. Based on her symptoms and a low ratio you start her on topical progesterone, which immediately helps the patient symptomatically. A few months later, you test her hormone levels again in saliva. Her E2 is 1.3 pg/mL and her Pg level is now 2500 pg/mL (within range for topical treatment). Her ratio is now 1923, reported as “high”. What do you do? The patient has no symptoms, feels great and her E2 and Pg levels are within appropriate ranges – no adjustments in treatment are needed.

A year later Mary comes back reporting hot flashes and night sweats. She was doing well until about 3 months ago. She had done a detox diet and had lost about 5 lbs. A saliva test shows that her E2 has dropped to 0.5 pg/mL: still “OK”, but much lower than last year; her Pg is still within the supplementation range at 2350 pg/mL. Her ratio is now 4700, which is still high. Unlike the last visit, however, Mary is now symptomatic. You have 3 choices: add estrogen therapy, reduce progesterone therapy, or both. Why is her higher Pg making things worse? Excessive Pg when E2 is low can down-regulate estrogen receptors and worsen estrogen deficiency symptoms. If Mary chose not to start estrogen therapy, just reducing the progesterone dosage would likely normalize her symptoms.

This case example highlights a misunderstanding that topical progesterone therapy only works for a limited period. It’s not that the progesterone stops working, it’s that the patient’s E2 level has declined further and the Pg/E2 ratio is now too high.

Navigating the Challenges of Hormone Replacement Therapy Dosing

Wed, 11 Mar 2015 17:11:00 -0700

Over 25 million women a year worldwide will enter menopause and make a decision about hormone replacement therapy. For healthcare practitioners, what dosage and what formulation these hormones take is open to debate.

After many years of teaching and talking to practitioners, I’ve learned that: there are many strategies for approaching dosages, everyone thinks that theirs is the best, most of them work well for many patients but not all, and that we really, really need more research.

There is very little to no research on different dosing strategies.

Standard bioidentical hormones have research behind them, but they are looking at serum testing and usually compare themselves to placebos rather than each other. When you look at the doses of some of these products, you can see the large variation all used to treat the same condition.

For instance, in estrogens we have estradiol patches which dose from 0.025mg to 0.1mg a day. At the same time we have Estrasorb™ 4.35mg/packet with 2 packets, commonly used for a total of 8.625mg per day. There is also compounded supplementation at dosages as low as the patches, to one protocol that doses hormones at twice the dose of Estrasorb™ (16mg daily).

How can all of these doses be for the same symptoms? How can they all have the same side effects? How can the manufacturers come up with these doses and why are they so different from each other? The answer lies in the testing methods and the delivery pharmacodynamics.

The testing methods are clear.

If you only test in serum, you will tend to overdose your topical creams. But, because serum tests have been used for most of the research on hormone replacement therapy, you find that most topical creams cite absorption rates of only around 10%, which is frankly, a pretty poor product if it was true.

At ZRT, we believe that absorption rates of most topical creams are closer to 90% or above. However, when you dose topical creams, the delivery is not a steady state delivery, but is instead a “bolus” effect. Topical creams seem to absorb very quickly and release their hormones very quickly. Saliva and bloodspot testing catches these levels rather than show the baseline levels or barely elevated seen in serum values.

We need more research in how topical hormones are being delivered to tissues.

We know that serum, saliva, bloodspot and urine can all tell us different things because we test in all these mediums (serum only for our research clients). But, no one is really looking at how these hormones are passing into the different mediums through the body.

When we compound hormones, we introduce dosages, topical formulations of creams and troches and combinations that have not been well studied. We need to look at not only our dosages, but also the pharmacodynamics of our delivery system, as well as the patient’s lab results in a helpful lab matrix to determine if we are getting the optimal results for our patient.

I’m excited to hear Dr Paul Savage talk about physiological dosing in this webinar. I generally advocate for physiologic dosing trying to get good lab work within range as well as using hormones dosages as close to what the body makes as possible. It will be interesting to hear his take on this topic.

In the meantime – yay for Polonini et al, who actually looked at Biest and progesterone and how it delivered through the skin. Interestingly enough, they found approximately 90% absorption of hormone.

Related Resources

Surgical Menopause - A Doctor's Perspective

Mon, 17 Mar 2014 01:50:00 -0700

A recent study [1] found that women with BRCA1 or BRCA2 gene mutations benefit from a significantly reduced risk of ovarian, fallopian tube, or peritoneal cancers by having their ovaries removed before the age of 35.

For women with such a genetic predisposition to cancer, the decision to remove their ovaries and/or breasts can prevent cancer in the future; however, I thought it would be worth looking at the long-term repercussions of this decision.

I think it's important to be clear that this is NOT a discouragement of women considering this decision as it may be life-saving. However, as healthcare professionals, it's important to recognize that gains may be a compromise and better research and care are needed for women who make this decision.

Overview of BRCA1 & BRCA2 Concerns

As a review, BRCA1 and BRCA2 gene mutations are found in approximately 5-10% of all breast cancer patients and approximately 15% of ovarian cancers. Women who carry the BRCA1 gene have a lifetime risk (by age of 70) of breast cancer of 55-65% (vs 12% in the general population) [2]. For women with the BRCA2 gene mutation, the lifetime risk of breast cancer is 45%. The breast cancers have an increased tendency to occur in younger women under the age of 50 and are often triple negative breast cancers (ERneg/PRneg/Her2Neu neg). Treatment of breast cancers in these women does not differ from non-BRCA carriers and death risks are not increased in this population compared to other women of the same age, extent of cancer spread, or hormone status.

For BRCA1 carriers, the ovarian cancer risk rises from the general population's risk of 1.4% to 39-60%, and for BRCA2 from 1.4% to as high as a 20% lifetime risk. In many of the women with BRCA ovarian cancer, the diagnosis is commonly made by the age of 45. This information, combined with very poor screening methods to catch ovarian cancer before it has spread outside of the ovaries, have spurred the recent publicity generated by publication of the study [1] regarding removing ovaries before the age of 35.

How do people know if they have genetic mutations? Certain ethnic groups, especially people of Ashkenazi Jewish decent, are at higher risk for inheriting these genetic mutations. Families that have multiple individuals with either breast and/or ovarian cancer are also at higher risk for inheriting these mutations and can be advised to be tested. Certainly having a diagnosis can change a woman's decision making for cancer monitoring, prophylactic surgery, and child bearing (especially for young women).

Recently, individuals such as Angelina Jolie have helped remove the stigma of having prophylactic mastectomies and oophorectomies. There is no hormonal consequence to breast removal, but it does have the long term physical consequence of lymphedema; but what about the longer term consequences of ovarian removal?

Consequences of "Surgical Menopause"

Removal of a young woman's ovaries puts them into instant menopause, known as "surgical menopause." Menopause under the age of 40 dramatically increases a woman's risk of osteoporosis (approximately 70% of all women will become at least osteopenic) [3]. Peak bone mass is generally reached at the age of 30-35 at which time bone loss becomes gradual until menopause, when there is a sudden drop in hormones and bone density. For women who go into menopause at the age of 35, osteoporosis by the age of 50 or 60 is a legitimate concern. So, women who have ovarian removal at 35 face a very good chance (approximately 70%) of having osteoporosis by 60 and perhaps a severe osteopenia by the age of 7-80. Non-hormonal therapies such as weight bearing exercise and nutritional therapies such as calcium, magnesium, vitamin K, and vitamin D can certainly help reduce risk. Medications such as biphosphonates may be beneficial to increase density, but benefit in using these medications for more than 3 years is questionable and long term prevention of fractures years later is debatable. So, women who choose to remove their ovaries to prevent the devastating results of ovarian cancer are faced with a very big question of what to do about the very real risk of osteoporosis prevention and treatment.

Menopausal symptoms are also another common symptom of ovarian removal. Hot flashes, night sweats, vaginal dryness, and lowered libido are common after surgical menopause. The use of hormone replacement therapy after oophorectomy is controversial because of concerns of increasing the risk of breast cancer. However, many women will choose to use hormone replacement therapy until the age of 50 to minimize their risk of osteoporosis and to alleviate other menopausal changes.

Memory, sleep, and mood changes are common after oophorectomy. Estrogen helps up-regulate serotonin receptors, so a sudden drop in estrogen can contribute to insomnia, anxiety, depression, decreased memory, and perhaps increased dementia. These symptoms are those that generally influence a woman to decide to use hormone replacement despite the risks.

Early menopause, with its loss of cardioprotection from estrogen, increases the risk of coronary heart diseases and strokes. Estrogen has been shown to reduce IL6 thereby reducing inflammation and intimal wall hyperplasia, and promoting angiogenesis [4]. Estradiol supplementation when started years after menopause may increase cardiovascular risk, but starting at the time of menopause may be beneficial.

In summary, many women will make the decision to remove their ovaries to prevent future ovarian cancer. As someone who has worked with many ovarian cancer patients and their families, I know it is truly a cruel cancer with such poor detection methods that I completely understand and support this choice.

I think that where research needs to focus is on the longer term health of these patients. I've personally seen many women take big jumps to prevent cancer only to be shocked at the lack of sympathy and care when the symptoms become intolerable. Understanding the risk factors for using hormones and also the risk factors for avoiding hormones is a crucial discussion to have with patients prior to them making such an important decision.

Related Resources

References

Men's Heart Health & Testosterone

Thu, 20 Feb 2014 01:53:00 -0800

Men and testosterone therapy have been a hot topic in the news recently.

Stories are filled with cautions about the use of testosterone therapy in men causing heart attacks and leading many doctors to question testosterone supplementation.

A closer look at the study may provide more insight. The study released is referenced at the end of this post. (1)

This study looked at 55,593 men who started testosterone therapy. Some were over the age of 65 and a smaller number were under 65.

There are two important subgroups - those with cardiovascular disease and those without.

The study also looked at those not using testosterone and using phosphodiesterase type 5 inhibitors (e.g. sildenafil / tadalafil / Viagra). Essentially, the study was an analysis of insurance data.

This is what the study found:

Group 1 - Men > 65 years old with heart disease had 2 times increased risk of MI

Group 2 - Men > 65 years old without known cardiovascular disease (2,047) had 2 times increased risk of MI (8 cases)

Group 3 - Men < 65 years old with cardiovascular disease (n=4,006) had 2-3 times increased risk of MI (21 cases)

Group 4 - Men < 65 years old without known cardiovascular disease had no increased risk of MI

Group 5 - Men taking PT5I meds had no increase in MIs

What does this study tell us? What questions does it stimulate us to ask?

It tells us:

A man's age may be more of an indicator of cardiovascular health than a patient's previous diagnoses
Sexual activity alone is not the trigger for the increase in MI rates since there was no increase in MIs in men using circulation-increasing sexual performance drugs
Men without known diagnoses of cardiovascular disease under the age of 65 are not likely to have an MI once starting testosterone therapy. This is important since this is the highest growing population of men starting to use testosterone

It makes us ask:

What is it about starting testosterone that increases MI risk? Is it the increase in estrogen, produced when testosterone is metabolized by aromatase? Is it the change in cardiovascular tone? The increase in libido that stimulates more sexual activity than commonly seen with just PT5I medications?
What happens to men after the initial 90 days if they continue on testosterone therapy?
Does changing the way (mode of delivery - topical / injection / pellet / sublingual) we supplement testosterone change a patient's cardiovascular outcomes?
Does dosage make a difference?

One of our clinical consultants on staff, Dr. Alison McAllister, has a few main takeaways from the study:

Cardiovascular disease is extremely common, and the fact that age was a better predictor in recognizing sub-optimal cardiovascular patterns is not surprising. I was surprised that men didn't have an increase in non-fatal MIs with PT5I medications; however, in my clinical experience these medications don't enhance libido, but rather facilitate erections. Therefore, men using testosterone who may or may not also use PT5I medications seem much more likely to want to have sex and therefore may be having more sexual encounters. I also think that men using testosterone are likely to increase physical activity in multiple ways - weight lifting, running, a faster pace of moving, etc. None of these studies looked at this information. However, years ago, there was a study (2) showing that men who used L-arginine after an MI had a higher rate of recurrent MIs. In that study, one finding was that men using MIs were much more active because they felt better and basically did too much.

I do think the role of estrogen and dosage is an important consideration. Giving testosterone in ways that does not increase clotting risks, coagulation, and causing changes in RBC counts, hemoglobin or hematocrit would very likely not increase the risk of MI. To this extent, I think one could make an argument for lower dose topical testosterone therapies combined with aromatase inhibitors. If physicians are continuing to dose testosterone topically at levels that change serum values, they are more likely to see changes in estrogen and blood indices before they see changes in serum testosterone levels. That is a much larger topic, but I've seen many men using testosterone topical gel at doses of 100 mg with low serum values and yet, estrogen levels are > 50, LH is suppressed, and RBC / hemoglobin / hematocrit are elevated, suggesting that low serum values are underestimating actual serum assimilation. Because this is not an uncommon prescription, I think it is likely that a large number of the men in the study were using this dosing protocol. In fact, this article did not break down the incidence of MI by dosage or route of delivery at all.

Where do I think we stand now? The way I interpret this information is to be extremely careful in giving testosterone to men over the age of 65. Discuss easing into more activities as they start to feel better rather than jumping into the life of an 18 year old. Dose at physiological doses, watch estrogen levels, and discuss what we don't know with patients. I don't see anything in this study that suggests testosterone is too risky for men to use or try, but I do think we need to be smart in having these discussions with men. I think it's very important to re-iterate that men under the age of 65 with no reported cardiovascular disease had no increase in MI. Perhaps, because they were more likely to be exercising and having sex regularly and less likely to aromatize their testosterone, there was less strain on their heart health. In this group, I think we can feel very comfortable talking to them about testosterone support.

These are all very important questions to ask in clinical trials. This is not the first study to suggest this information, but hopefully will stimulate more studies to try and determine the answers.

Related Resources

References

(1) W. D. Finkle, S. Greenland, G. K. Ridgeway, J. L. Adams, M. A. Frasco, M. B. Cook, J. F. Fraumeni, Jr., and R. N. Hoover. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 9 (1):1-7, 2014.

(2) Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gerstenblith G. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006;295(1):58-64.

Struggling With Infertility? What Hormones to Test.

Mon, 04 Feb 2013 03:27:00 -0800

This blog explains what hormones are tested in ZRT's Fertility Profile and why each one is important.

LH & FSH are pituitary hormones, which means they affect the brain. Their communication with growing egg follicles in the ovaries is one of the only positive feedback loops in the body. On day three or four of the menstrual cycle (day one is the first day of the period) LH & FSH are at their lowest level. This relationship is normally a 1 to 1 function, but some women have LH levels that are two or three times greater than their FSH levels on day three or four of their cycle. This is a sign of polycystic ovarian syndrome (PCOS) and occurs in approximately 50% of PCOS women. The opposite problem can also occur - high FSH and LH levels.

Think of FSH and LH as calling out to the ovaries. Lower levels suggest the brain is barely whispering to call for an egg and its estrogen. Higher levels (fourteen and above) suggest the brain is shouting for eggs and estrogen. Higher levels of LH and FSH reflect that the number of eggs is decreasing. This is one of the most important tests in the fertility profile because high levels suggest that immediate assistance from a fertility specialist should be sought. Women who have very high levels can still become pregnant, but this usually requires reproductive assistance.

Sex Hormones
The ZRT Fertility Profile measures sex hormones at the mid-luteal peak, which occurs seven days after ovulation. For many women, this is generally day twenty one of the cycle; but it will fall on a different day in women with shorter or longer cycles.

Estradiol is one of three types of estrogen, and the only estrogen the ZRT Fertility Profile Tests. Estrogens are hormones that are talked about a lot with fertility because they helpto develop the uterine lining and are important for breast development. Inadequate estrogen can be a sign of lack of ovulation or low ovarian health and can impede healthy implantation of the developing embryo.

Progesterone is produced from the corpus luteum after ovulation and creates an optimally functioning uterine lining. Lower levels suggest ovulation is not occurring, an inadequate corpus luteum is being produced, or that the corpus luteum is failing before implantation occurs. Estrogen helps to build tissue and progesterone develops the tissue to accept a fertilized egg.

Testosterone is produced from the ovaries and turns into estradiol within the ovaries, which is a sign of healthy ovulation. When testosterone levels are too high, as seen in women with PCOS, the follicles and egg quality are poor. High testosterone also interferes with ovulation, which can cause cycles to become irregular. High testosterone is partially stimulated by high insulin levels.

Adrenal Hormones
DHEA-S is one of the primary hormones in the body and serves as a precursor to testosterone and estradiol. Low levels of DHEA-S can lead to lower estrogen levels and changes in the immune system. High levels of DHEA-S are often associated with higher insulin levels, higher testosterone levels, and PCOS.

Cortisol is a primary adrenal hormone, is produced in response to stress, and like all hormones, balance is critical. Low levels of cortisol prevent optimal thyroid function at the cellular receptors, but high levels can inhibit thyroid function and ovulation. The old saying, “Relax and you’ll get pregnant” comes from the role that cortisol plays in balancing ovulation. While it isn’t quite as simple as “relax”, balanced cortisol levels are important for ovulation and pregnancy. ZRT measures cortisol in a daily (diurnal) rhythm of four samples collected throughout the day.

Thyroid Hormones
Thyroid stimulating hormone (TSH) is produced in the brain’s pituitary gland and signals to the thyroid gland the need to make thyroid hormone. Because this is a stimulatory hormone, results are inversely related to the actual production of hormones from the gland; high TSH means there is low thyroid production, and low TSH means there is high thyroid production. Because it is so efficient, TSH is a great tool for assessing how happy the brain is with the amount of thyroid being produced. For fertility health, a good TSH range is generally accepted as less than 2.5. Levels of TSH greater than 2.5 are associated with poorer pregnancy and ovulation rates.

Free T4 and Free T3 are the two hormones made by the thyroid gland. They are called “free” because they are not bound to thyroid binding globulin (TBG). TBG is the protein carrier that carries thyroid all over the body. Because many things can change TBG levels, free levels are the most stable. Free T4 and Free T3 levels are important because they reveal how effective the thyroid gland is at responding to TSH stimulation.

Thyroid peroxidase antibody (TPOab or TPO) is an antibody stimulated in the gastrointestinal system by an immune reaction. The gastrointestinal immune reaction then searches for other tissue that looks like this antibody and mistakenly targets the thyroid gland. Thus, TPO is a cross-reactivity antibody, which means it is created by mistake. Thyroid autoimmunity is the most common cause of hypothyroidism. TPOab is a sign that other immune reactions are happening, which are commonly gastrointestinal parasites or food reactions. Celiac disease (the inability to process wheat gluten) is commonly found in women with TPO. Individuals with Celiac disease have a higher percentage of infertility until treated with a gluten free diet. Thyroid autoimmunity also contributes to a much higher rate of miscarriages in the first trimester.

Vitamin D3 is an optional test you can add to the existing panel. It is optional because many people have already been tested for their Vitamin D levels. If the patient has not been tested, we highly recommend women get screened. Vitamin D3 is converted in the body to a hormone that is in the same family as estradiol and thyroid. It is very important in opening receptors, or doors, in the cells. Vitamin D3 deficiency is extremely common, even in sunny climates. Vitamin D3 restoration to satisfactory levels (less than thirty two) has been found to improve fertility rates in PCOS women and women doing IVF treatments. Vitamin D3 is important in the immune system and in regulating insulin levels.

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