Transdermal Thyroid Treatment? Huh?

I love to write about the Wiley Protocol because it is so wildly controversial. Perhaps best known for mimicking the estrogen and progesterone levels of a 20-something, with peak estradiol on day 12, and peak progesterone on day 21 given in a rhythmic fashion, did you know that you can get the Wiley Protocol for your thyroid?

T. S. or Susie Wiley is the creatrix of the Wiley Protocol. She is a medical theorist with a background in molecular biology. That'll become more relevant in a moment. But know that she is not a medical doctor.

Susie has been an avant garde thought leader in the realm of hormones for years. Her main contribution? That of RHYTHM – meaning that specific patterns of hormone levels are needed for harmony between sex hormones (estrogen, progesterone, testosterone), thyroid and adrenal hormones. There is a rhythm to our light/dark cycle, our food supply, families, plants, hypothalamus, pituitary, ovaries, thyroid and adrenals -- why not, as Wiley fan and oncologist Julie Taguchi, MD suggests -- mimic the buzzing and humming of our glands which send signals to grow, bloom, seed, hibernate or die? She has applied the concept of rhythm to the dose and timing of externally-applied transdermal hormones.

Say more.

Susie believes that we have to really understand each hormone in a woman’s body and how it acts both alone and as part of the symphony, rather than simply whether you are getting too much or too little Synthroid.

It makes sense theoretically: we know that there’s a see-saw relationship between thyroid hormone and estrogen levels, so when estrogen is up, thyroid is down. So in the Wiley Protocol, the idea is that you adjust your thyroid dosage with where you are in your menstrual cycle (in Wiley Land, that concept applies equally to pre- and post-menopausal women, with and without a uterus). In other words, static dosing of thyroid medication (same dose daily) deranges both estrogen and progesterone receptors.

Let me describe it another way: when you are cycle day 1-5, your estrogen is really low. On the standard Wiley Protocol Thyroid, that means you take 6 lines  (0.6mL as measured on their handy syringes) of T4 (21.8 mcg/line) + T3 (7.4mcg/line). The reason? T3 provokes an estrogen receptor, so you will improve estrogen turnover and make more estrogen receptors on target tissues. You then adjust down to a nadir of 1 line on peak estradiol day 12, and spike back up to 6 lines day s 14-16. And so on.

What positive things can I say about the Wiley Protocol Thryoid? I like the transdermal approach. As you know, absorption of your thyroid pills through your gut… well, it sucks. That’s why you are told to wait 20-60 minutes to eat or drink anything after you take your morning pills. So it makes sense that a transdermal approach is more convenient, and perhaps absorbed better.

I also like the adjustment with the menstrual cycle, especially for my patients who are exquisitely sensitive to the steady up/down of their estrogen (estradiol). Many of my patients find that they bloat like crazy at ovulation and just before/during their menses. Sometimes more thyroid hormone is the fix (but you must see your doc on this one – I do not recommend reckless experimentation in the service of bloat prevention).

Final positive are these: apoptosis and receptor turnover.

What the heck is apoptosis, you might ask.

Apoptosis is “Programmed Cell Death.” Now, before your eyes glaze over, let me point out why this is cool, important and relevant. Apoptosis is good – it’s designed to keep you young and vibrant. It’s a way of getting rid of the debris in your body without damaging you – it gets rid of receptors you no longer need, for instance. It confers advantages and is completely different from necrosis, which is cell death as a result of traumatic injury or cancer. In your body today, 50-70 billions will die as a result of apoptosis.

Receptor turnover is another important aspect of your glandular goodness. As an example, when women are given PremPro (estrogen from PREgnant MARe urINe and synthetic progesterone, proven to cause heart disease and breast cancer in women aged 50-79), the same dose every day makes your progesterone receptors stagnate. According to Susie and the data she cites, this results in inadequate cell apoptosis and a higher chance of disease such as breast cancer. In other words, chronic, same-dose-daily leads to down-regulation of progesterone receptors, and tissue badness downstream.

If you take the WP Thyroid Transdermal Restoration for Women, you check your thyroid function tests on day 13 or 14 because that is when your endogenous thyroid levels are at their maximum.

Negative feedback? There’s the absolute lack of randomized clinical trials, the gold standard for deciding if something is safe or even just a good idea. Recall all the trouble we got into with prescribing estrogen (1950-1999: take it! 1999-2002: never take it! Dangerous & risky! 2002-now: take it if you really need it, however you best define that! Confusing)? That was because we based our recommendations for estrogen on biased data (observational studies or worse quality), and randomized, controlled trials have the least bias.

Truth be told, I tried WPT for a few months. Actually, I try almost everything before considering it for my patients. I didn’t notice much difference in my bloating or hypothyroid symptoms (the usual: fatigue, easy weight gain – such as looking at a muffin, constipation).

Problem is this: we’ve got limited options as we augment or completely replace the function of our thyroid. I welcome new kids on the block. I find that selecting the right thyroid treatment is a lot like shoe shopping – it can often take nearly forever to find the right fit. So keep the faith and know there’s choices available. Check it out if you must, but buyer beware: no (unbiased) data, no data, no data.

Hormone Therapy: Continuous Progesterone Safer

Which is better: to take progesterone continuously or sequentially (e.g., day 12-26 each month)? There are arguments on both sides, but this latest study shows that continuous progesterone has a 76% lower risk of endometrial cancer after 3-5 years. That is why I recommend regular uterine monitoring every 6+ months in women on sequential progesterone. -- SG

The long-term safety of different hormone therapy regimens has not been adequately studied in the context of endometrial cancer risk. In a national cohort study, investigators followed 224,000 Finnish women (age, >50) who used oral or transdermal estrogen-progestin (E+P) HT from 1994 to 2006. HT regimens were considered to be sequential if daily estradiol was accompanied by 10 to 14 days of progestin monthly or, in long-cycle regimens, during each 3-month interval. In continuous regimens, both estradiol and progestin were used nonstop. Incidence of endometrial cancer in E+P users was compared with that in all Finnish women.

A total of 1402 cases of incident endometrial cancer were identified. Compared with the general population, E+P users overall had 54% and 23% higher relative risk for type I and type II endometrial tumors, respectively. Monthly sequential E+P HT was associated with 69% (5 years' use) and 156% (10 years' use) higher risk for type I tumors. At 5 and 10 years of use, long-cycle sequential HT was associated with substantially higher risk for type I tumors than was monthly sequential HT. The endometrial safety of transdermal and oral sequential HT was similar; sequential HT with medroxyprogesterone acetate and norethindrone acetate also exhibited similar endometrial safety. Use of continuous E+P HT was associated with lower risk for type I tumors than in the overall population (76% risk reduction after 3–5 years' use).

Comment: Unopposed estrogen therapy or E+P hormone therapy with inadequate progestin raises risk for low-grade endometrial adenocarcinoma (i.e., type I) in menopausal women. Risks for high-grade serous papillary carcinoma and clear-cell adenocarcinoma (i.e., type II) are less clearly associated with HT use. These results are important in clarifying that, although long-term continuous E+P HT is protective, sequential therapy substantially raises risk for endometrial adenocarcinoma. The authors estimate that among 1000 women who use E+P HT for 10 years, eight additional cancer cases will be diagnosed if HT is sequential and monthly, whereas three to four fewer cases will be diagnosed if HT is continuous. For women who use sequential E+P HT long term, endometrial monitoring is appropriate.
— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health December 17, 2009

Citation(s):
Jaakkola S et al. Endometrial cancer in postmenopausal women using estradiol–progestin therapy. Obstet Gynecol 2009 Dec; 114:1197.

Are Those Pearls on your Ovary?

Polycystic Ovarian Syndrome (PCOS) is a problem of hormonal imbalance that creates sputtering ovulation and hyperandrogenism (too much male hormones, which causes increased male-pattern hair growth and acne). Most important in the diagnosis is exclusion of other causes, as no single lab result leads to the diagnosis. Over 6-10% of women have PCOS.

Other findings include multiple cysts on the ovary (called the “string of pearls” sign on ultrasound - see image below), overweight or obesity, high blood pressure, and acanthosis nigrans – a weird skin finding of darker, velvety skin on the back of the neck.



While the cause is unknown, we mostly consider PCOS to be a metabolic problem. About half of women with PCOS have high insulin levels (or hyperinsulinemia). Lowering insulin levels with exercise, eating low-glycemic foods, and other measures can correct erratic ovulation. Some of the natural therapies that have been shown to be helpful in PCOS include bioidentical progesterone use and cinnamon. Tieraona Low Dog, MD, showed in a small study published in Fertility and Sterility in July 2007 that cinnamon (0.5 teaspoon per day) lowers insulin resistance in PCOS.

I want to emphasize the role of exercise – it’s essential in PCOS, no exceptions! I recommend 30 minutes per day, 4 to 5 days per week, of cardio exercise at a minimum as the primary treatment.

One of the findings of PCOS is estrogen dominance – too much estrogen versus progesterone. Reducing estrogen levels can be very effective and I suggest the following measures:

• Meat/Dairy: avoid conventionally raised meat and dairy products, which contain growth promoters that act as xenoestrogens - these stimulate estrogen receptors in the body and disrupt normal hormonal signaling. Omnivores should choose organic products.

• Cruciferous Veggies: increasing consumption of cruciferous vegetables, such as broccoli and brussel sprouts, which increase metabolism of estrogens.

• Gluten-free: reducing gluten lowers your estradiol levels by 30% or more.

Finally, natural progesterone, prescribed and monitored by a knowledgeable provider, can also help balance estrogen dominance.

Women with PCOS are at greater risk of type 2 diabetes and metabolic syndrome, and should be additionally screened with glucose testing and a full fasting lipid profile.

Hormone Therapy Lowers Colon Cancer 25-36%

Here's another post from North American Menopause Society. Seems cyclic progesterone was associated with the greatest risk reduction of colon cancer. Check it out.

Does hormone therapy decrease colorectal cancer risk?

Johnson JR, Lacey JV Jr, Lazovich D, et al. Menopausal
hormone therapy and risk of colorectal cancer. Cancer
Epidemiol Biomarkers Prev 2009;18:196-203.

We evaluated colorectal cancer risk associated
with the duration and recency of specific
menopausal hormone therapy formulations (ie,
unopposed estrogen versus estrogen plus
progestin) and regimens (ie, sequential versus
continuous estrogen plus progestin use) among
56,733 postmenopausal women participating in
the Breast Cancer Detection Demonstration
Project follow-up study. Hormone therapy use
and other risk factors were ascertained through
telephone interviews and mailed questionnaires
from 1979 to 1998. The final cancer group
included 960 women who were identified from
self-report, medical records, state registry data,
and the National Death Index. Poisson regression
was used to generate multivariable rate ratios
(RR) and 95% confidence intervals (95% CI).
We observed a decreased risk of colorectal
cancer among ever users of unopposed estrogen
therapy (RR, 0.83; 95% CI, 0.70-0.99). Among
estrogen users, the largest reduced risk was
observed for current users (RR, 0.75; 95% CI,
0.54-1.05) and users of ≥ten years duration
(RR, 0.74; 95% CI, 0.56-0.96). We found a
reduced risk among users of estrogen plus
progestin therapy (RR, 0.78; 95% CI, 0.60-
1.02), with sequential regimen users (progestin
<15 days per cycle) having the largest risk
reduction (RR, 0.64; 95% CI, 0.43-0.95). Past
users of ≥5 years ago (RR, 0.55; 95% CI, 0.32-
0.98) had the largest risk reduction. In this
study, estrogen plus progestin use, especially
sequential regimen use, was associated with the
largest overall reduction of colorectal cancer
risk.

Comment. This is a retrospective study, the
stated purpose of which was to identify
separate risk estimates for colon cancer
according to menopausal hormone form-
ulations. A paper published 9 years earlier1
from the same database found a suggested
inverse relationship between the use of HT and
colon cancer. The current paper analyzed
postmenopausal women divided into groups of
never users, those who had ever used estrogen,
and those who had ever used estrogen plus
progestogen (EPT), and then further divided
them by sequential hormone use and length of
time exposed to HT. What the current authors
found was that those who had ever used
unopposed estrogen had a decreased risk of
colon cancer. Those who had used sequential
EPT had the largest risk reduction. What does
this information add to our knowledge of this
topic?

Estrogen receptors have been detected on colonic
cells, with estrogen-receptor β being over-
expressed in healthy colon cells and reduced in
colon cancer cells. This overexpression, coupled
with negligible expression of estrogen-receptor α,
is thought to provide protection by HT against
colon cancer. What is also known is that
prescribing patterns for HT vary among race,
with African-American, Asian, and Latina
women receiving less treatment than Caucasian
women. An evaluation of how many women
were represented in each group rather than a
designation of “nonwhite” and a designation of
“person-years” only would have been
informative. It would also have been beneficial if
the groups had been matched by age, ethnicity,
and HT use (perhaps this is a paper that will be
published later).

African-American women have the highest risk
for colon cancer, higher even than white males;
and colon cancer in these women is often
detected at a more advanced stage. If HT really
does reduce the risk of colon cancer, all women
should have a discussion with their healthcare
provider about the potential benefits of HT for
them. A prospective study of matched groups of
women would be very informative regarding risk
reduction across ethnic groups in which there is a
dearth of comparative information available.
Women who use HT are more likely to have
mammograms, as well as Pap smears and
colonoscopies. Colonoscopy, however, is still at
the bottom of the list even for women who
regularly undergo other types of health screening.
It would be helpful if healthcare providers
encouraged women to have a colonoscopy. It has
been shown that if a healthcare provider strongly
recommends a test, a patient will often agree.

As March is National Colon Cancer Awareness
Month, this might be a good time to consider a
large-scale prospective randomized trial of HT
use with timed colon cancer screening across
ethnic groups by those in this field.
Michelle Inkster, MD, PhD
Department of Gastroenterology and Hepatology
Cleveland Clinic
Cleveland, OH

Reference:
1. Troisi R, Schairer C, Chow WH, et al. A prospective
study of menopausal hormones and risk of colorectal
cancer (United States). Cancer Causes Control 1997;

Bioidentical Homornes: Are They for You?

by Guest Editor 

Dr. Marsha Nunley, MD

Are you confused about bioidentical hormones and just hormones in general? Well, that is because it is a somewhat confusing story and there are many players in the game who stand to make or lose a lot of money. This, of course, always muddies the water and we have no long term randomized controlled trials (which is the gold standard in the medical literature but very difficult to do with natural substances and hormones) on bioidentical hormones. To further complicate matters, hormones such as estradiol and progesterone are natural substances and cannot be patented and sold as a drug unless they are altered in some way. Synthetic estrogens such as Premarin and progestins such as Provera are made by pharmaceutical companies. Vivelle and other patches are “natural and bioidentical” estradiol but can be sold as a drug because they are in a “special form” ie the patch delivery system. Prometrium is natural progesterone in “micronized form” that is sold as a drug. The drug companies have made billions of dollars and are still making billions of dollars from synthetic hormones and have a great stake in stopping the trend toward compounding “natural bioidentical hormones.” In fact, the Women’s Health Initiative, though flawed in many respects, clearly showed unacceptable risks with oral synthetic hormone therapy. However, the final conclusion was to continue to give synthetic hormones…just not for too long. If you search Pub Med you will find hundreds if not thousands of articles on hormonal therapy, all with their own biases and conclusions and if you search carefully you will frequently find a financial tie that helps explain the conclusions. Compounding pharmacies are not blameless and have rushed to cash in on the bonanza in bioidentical hormone treatment. There is very little regulation of compounded products (though one could argue that the FDA is more interested in protecting Wyeth than women).

A recent review published in Postgraduate Medicine, volume, 121, Issue 1, January 2009, p.73-85 by Dr. Kent Holtorf, MD from Torrance, CA is a meta analysis and literature review of 163 articles. He looked at all types of hormone therapy including synthetic therapies (i.e., The Women’s Health Initiative and Premarin and Prempro) as well as everything he could find on bioidentical hormones including in vitro studies.

Looking at the combined results of these studies, he concluded that “bioidentical hormones (meaning estradiol and progesterone) are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal derived counterparts…and of course that we need randomized controlled trials to delineate these differences.”

Bottom line:
1. If you think you may be a candidate for hormonal therapies, choose bioidentical and choose a physician that is knowledgeable in all fields of hormonal therapies including adrenal, thyroid, and insulin issues. The hormones of your body function in a complex network affecting each other and almost every bodily process. This requires a physician who is knowledgeable and experienced in utilizing bioidentical hormones. With the recent feature of hormonal therapy on Oprah, the interest has exploded and the search engines are hot. This is an area in which physicians are self taught. It is not a standard part of physician training, and I suggest you look for physicians that have received additional training in hormonal therapy such as that received through the Antiaging and Functional Medicine Fellowship offered through the A4M or talk to your friends. They may be your best resource in finding a physician
2. There is no conclusive data that bioidentical hormones are safe. Each woman should discuss her personal risks and symptoms with a knowledgeable physician and decide if it is the right decision for her. There is data that suggests that bioidentical hormone therapy may carry a somewhat less risk and does have a positive impact on quality of life.
3. The only FDA approved treatment for menopause is Premarin and Provera. Don’t rely on the government to protect you. Educate yourself, find a doctor that you trust and make informed choices.
4. Medical research is currently funded primarily by pharmaceutical companies. Many prominent physicians and researchers rely on them for the money to do their research and are on their payroll as speakers. It was recently disclosed that a prominent physician who was paid thousands of dollars by a drug company was instrumental in recommending and greatly expanding the role of using powerful antipsychotic medications in the treatment of psychiatric illness and the use of these drugs in children had interpreted his data in favor of the drugs when in fact, the benefit was minimal at best and dangerous at worst. The research is only as good as the researchers. Money corrupts the process.

Hear Better with Hormones

Here are some recent articles showing that women on hormone therapy have better hearing than women who do not take hormones. What?! This is part of my crusade to make sure women are careful to get a nuanced view of whether they would benefit from hormones, rather than the over-simplified view that all hormones are bad. Hormones, taken at the lowest doses and preferably bioidentical, can be safe and life-altering. They've been proven to help mood, libido, vasomotor symptoms, and now HEARING!
SG

Acta Otolaryngol. 2007 Feb;127(2):149-55. Hearing in women at menopause. Prevalence of hearing loss, audiometric configuration and relation to hormone replacement therapy. Hederstierna C, Hultcrantz M, Collins A.

Department of Audiology, Karolinska University Hospital, Stockholm, Sweden. christina.hederstierna@karolinska.se

CONCLUSION. Hormone replacement therapy (HRT) may have a protective effect on hearing impairment in postmenopausal women. New guidelines for classification of audiometric configuration in age-related hearing loss are suggested. OBJECTIVES. To describe prevalence of hearing loss and audiometric configuration in a group of middle-aged women with respect to menopausal stage and HRT. SUBJECTS AND METHODS. A total of 143 women around menopause were sampled through the Swedish population register. The mean hearing threshold levels were compared according to menopausal status. The audiograms in the 57 women with hearing loss were classified according to audiometric configuration. RESULTS. In all, 57 women (40%) had any kind of hearing loss; 42 had very minute hearing loss; 15 had a 4FA (average of thresholds at 0.5, 1, 2, and 4 kHz) of at least 20-39 dB HL in at least one ear. Two of these had a 4FA of 40-69 dB HL in at least one ear. The most common configurations were: gently sloping (47%), steeply sloping (14%), and high-frequency U-shaped (14%). The postmenopausal women who were not on HRT had poorer hearing mainly at 2 and 3 kHz, compared with pre- and perimenopausal women, and postmenopausal women on HRT.

Acta Otolaryngol. 2006 Jan;126(1):10-4. Estrogen and hearing: a summary of recent investigations.
Hultcrantz M, Simonoska R, Stenberg AE.

Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden. malou.hultcrantz@karolinska.se

Is the female sex steroid estrogen the key to preserved hearing in the aging human? This question remains unanswered, but hearing loss is more profound in elderly males than females. There are also well-known sex differences in the auditory brainstem response (ABR), i.e. women have shorter latencies than men. Moreover, menopausal women who are administered hormone replacement therapy have slightly better hearing than those who are not, and women with Turner's syndrome (45,X), who are biologically estrogen-deficient, show longer ABR latencies and early presbyacusis. These findings are also supported by animal experiments. When boosted with estrogen or testosterone the non-reproductive female midshipman fish alters its inner ear auditory mechanism so that it can hear the male's hum-like call. If estrogen receptor beta is knocked out in mice, severe progressive hearing loss occurs, leading to early deafness. In apparent contradiction to these findings, there have been case reports suggesting that hormone replacement therapy and oral contraceptive use can lead to hearing loss, but of another type, namely acute sudden deafness. Such contradictory aspects of the action of estrogen are commonly found and may spring from the fact that there are two estrogen receptors, alpha and beta, both of which are present in the inner ear of mice, rats and humans. Knowing how sex steroids can alter hearing ability may give important clues as to how estrogen can preserve hearing in humans. In this review we present a summary of current knowledge about hearing and estrogen.