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Menopause & Hormone Replacement Therapy

Focus on Bioidentical Hormones
by Jannet Huang, MD, FRCPC, FACE, North American Menopause Society Certified Menopause Clinician

You may also view this information as a slide show presentation (PDF) in "Bioidentical Hormones".

Who is taking natural hormones? Mary or Jane?

Mary and Jane are close friends, both 55 year old women with hot flashes and night sweats. They each presented to their own physician and received two very different prescriptions. Mary was given Triest orally with a progesterone cream. Jane was prescribed an estrogen patch (Vivelle Dot) and prometrium. Who is taking bioidentical hormones? Whose regimen provides a hormone milieu closer to that found in normal young woman? The answer may surprise you. Read on and find out for yourself.

What is natural? What is bioidentical?

An important discussion in the types of hormones available is regarding the meaning of “bioidentical” hormones since there are different interpretations used by different groups. “Natural” does not equal “bioidentical”. Ironically, conjugated equine estrogen isolated from pregnant mares’ urine (Premarin) is actually the only available hormone product that is truly “natural” in the sense that these estrogens are packaged in the unmodified form produced by the animal. “Bioidentical hormones” should be defined as hormones that are exact mimics of the endogenous hormones produced in humans. Truly “bioidentical” hormones, by definition, have to be synthesized in the laboratory. “Bioidentical” hormones are not necessarily custom-made or “compounded”. There are a number of FDA-approved pharmaceutical products that are actually “bioidentical”. Various preparations of transdermal estradiol (patches, gel and lotion), oral estradiol tablets, local vaginal estradiol creams / tablets, oral and vaginal progesterone preparations are examples of pharmaceutical hormone products that are identical to the human estradiol and progesterone. These pharmaceutical hormone products are actually synthesized from a weakly estrogenic plant precursor molecule, diosgenin, which is derived from yam or soy. All compounded estrogen and progesterone products are also synthetic hormones, altered through biosynthetic manufacturing processes. Estriol and estrone are commonly used in compounded estrogen products, and estriol has been widely touted to be the gentler, safer estrogen. Unfortunately, some advocates of the “bioidentical” compounded hormones capitalize on the fears of women. They claim these compounded hormones to be “natural”, not synthetic, and therefore devoid of side effects. This statement has two errors: bioidentical hormones are synthesized products, altered from natural precursor compounds. Furthermore, there is no scientific evidence to corroborate this claim of greater safety of so-called “bioidentical” compounded hormones. While I am among those who support the view that the “bioidentical” hormones estradiol and progesterone may have a different side effect and risk profile than equine estrogen (Premarin) and the synthetic progestogen Provera that were used in the WHI study, we do not have adequate solid scientific evidence to make this a factual statement. Furthermore, the important issue may actually lie in the route of administration of hormone therapy. Transdermal administration of estrogen avoids the first pass through the liver and does not increase clotting risk like oral estrogen does.

Commonly Used Regimens of Hormone Therapy

First of all, let’s try to clarify the issue of when progesterone should be used. The only absolute indication for the use of progesterone is in women with intact uterus (i.e. women who have NOT undergone hysterectomy) to reduce risk of endometrial hyperplasia and endometrial cancer that is associated with unopposed estrogen therapy. While progesterone can help ameliorate hot flashes in some women, its efficacy is not as consistent as that of estrogen therapy. Progesterone also has mild sedative effect and is considered by some to help reduce sleep disturbance often seen in perimenopause and menopause. The duration and frequency of progestin use is currently a topic of debate.

HT Regimen Route of administration Preparation Form Examples (using US trade names)
Estradiol Transdermal Patch Vivelle Dot, Climara, etc…
Estradiol Transdermal Gel Estrogel
Estradiol Transdermal Lotion Estrasorb
Estradiol Oral Tablet Estrace, Gynodiol, etc…
Conjugated or esterified estrogens Oral Tablet Premarin, Cenestin, Menest, etc…
Estradiol Vaginal Ring Femring
Estradiol and Progestin (continuous) Transdermal Patch Climara-Pro, Combipatch
Combined Estradiol and Progestin (continuous) Oral Tablet FemHRT, Activella, OrthoPrefest, etc…
Combined Conjugated Estrogens and Progestin Oral Tablet Premphase (cyclical), Prempro (continuous)

Table 1 lists examples of the available FDA approved products for systemic estrogen replacement and combined estrogen/progestin therapy.

The only FDA approved combination of estrogen and androgen replacement therapy at this time is Estratest (esterified estrogens with methyltestosterone). The only transdermal androgen preparation designed for women (transdermal testosterone patch – Intrinsa) was not approved by the FDA in December 2004. This decision has raised a lot of controversies. At present, compounded preparations of testosterone creams or gels are the only preparations available for use in women, but compounded products are not regulated by the FDA and therefore highly dependent on the individual pharmacist who is doing the compounding.

Pharmaceutical vs Compounded Hormone Products

As described in the section above “What is natural? What is Bioidentical?”, bioidentical hormones are synthesized from plant precursors in the laboratory, since human versions of estrogens and progesterone cannot be found anywhere else in nature except in a woman’s body! Pharmaceutical products which are bioidentical are derived from the same sources as compounded hormones. So when it comes to choosing between pharmaceutical vs compounded hormone therapy, the decision depends on the needs and philosophy of the individual woman. This is a decision that should be arrived at after careful consideration and discussion between her and her physician with specialized training in hormone therapy. Pharmaceutical products have quality control procedures regulated by the FDA, but only certain fixed doses are marketed. So for those women whose needs fall outside of the fixed doses of available pharmaceutical products, compounding serves as a useful alternative. The quality control (especially important is the accuracy of the formula) is entirely in the hands of the individual compounding pharmacist. It is therefore imperative to work with a pharmacist whose work is trusted by you and your physician.

Compounded hormone therapy products can be customized in ingredients and concentration for each individual woman. However, it is important to keep in mind that estrogens are active hormones that bind to the same nuclear receptors, regardless of whether they are manufactured by a pharmaceutical company, or compounded by a pharmacist. Any claim that compounded hormone therapy is natural and therefore does not have the same risk of pharmaceutical hormone therapy is invalid.

The Answer About the Hormones Regimen for Mary and Jane

Well, those of you who thought that both Mary and Jane are taking bioidentical hormones were correct! As you have seen in this article, both pharmaceutical and compounded products can be bioidentical. However, what may surprise you is that Jane is actually taking the regimen that provides her with a hormonal milieu that better mimics the young woman’s natural balance! Triest is comprised of 80% Estriol (E3), 10% Estradiol (E2), and 10% Estrone (E1). Estradiol is the predominant estrogen in a young woman’s body, whereas after menopause, all estrogen levels fall, with estrone becoming the dominant version. Estriol, on the other hand, is only present in a woman’s circulation in significant levels during pregnancy, and the logic behind using estriol as the dominant estrogen is faulty. Valid concern exists about the absorption of transdermal progesterone. Bioidentical progesterone is therefore more appropriately used orally or vaginally.

The Bottom Line

In closing this discussion regarding hormone therapy in menopause, I would like to reiterate the importance of evaluating each woman as an individual, with her unique set of symptoms, risk factors, concerns and expectations. Healthcare providers should not make any assumptions regarding an individual woman’s philosophies and attitudes towards hormone therapy. It is essential to have an in-depth and honest discussion about the potential risks and benefits so that each woman can make her own informed decision. While WHI (the Women’s Health Initiative Study) has raised a lot of concerns about potential harm of HT, the study validity has been a topic of heated debate. It is important to keep in mind that WHI does not really give us the answers regarding the use of HT in women who are in the menopausal transition who need to make the decision whether to use HT or not. For more in-depth discussion of the WHI findings, please read the accompanying article entitled “A Critical Look at the Studies on Hormone Replacement Therapy”.

Hormone therapy is only a part of the whole menopause management. HT alone cannot be expected to be the “magic bullet” to maintain youth and optimize health. It is important that we use the “whole-person approach” and address lifestyle issues, such as nutrition, exercise, stress reduction as well as sleep adequacy/quality. I look at menopause as an opportunity to review a woman’s health status. Menopause is a good time to make a cohesive action plan to prevent disease and optimize quality of life.

For more information, view the slide show "Bioidentical Hormones" (PDF), a lecture given by Dr. Huang.

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All presentations are prepared by Dr. Jannet Huang and are part of her personal collection. They are posted here for the purpose of public education. If anyone would like to use these slides for their own presentation or dissemination, please contact Dr. Huang prior to doing so. Thank you.