New choices in hormone replacement therapy are raising questions about what is safe, what is effective, and what is “natural.”
Women seeking relief from menopausal symptoms today are flooding their doctors with questions and seeking some clarity as they try to make decisions about their health. Celebrity endorsements of new, alternative therapies and concerns over the safety of traditional hormone replacement therapy (HRT) have left many women anxious about how to proceed when they reach menopause and find they need relief from the symptoms associated with hormonal changes that occur.
Recent safety concerns over traditional HRT have seen women turning increasingly to alternative hormone products that have been promoted as “natural” alternatives to the synthetic hormone replacement pills produced by the pharmaceutical industry. One such alternative gaining in popularity recently is use of so-called “bioidentical” hormones, which are an identical match to the hormones produced by the body.
However, bioidentical hormone therapy is controversial, mainly because there is so little definitive research to provide data about the potential risks and benefits of its use. Because they match naturally produced hormones, bioidentical hormones cannot be patented and are not regulated by the U.S. Food and Drug Administration (FDA). This means that they have not undergone the same degree of large-scale clinical testing that synthetic hormone pills have in order to determine their potential risks and benefits.
At the same time, synthetic hormone replacement pills are associated with their own controversy, largely the result of the side effects they can produce and the available data showing that they can increase the risk of breast cancer.1
What Are Hormones?
All hormones are powerful, bioactive compounds that affect many systems of the body. Estrogen and progesterone are essential female hormones that are produced by the ovaries and adrenal glands. These hormones serve many critical functions in the body.
Estrogen is involved in developing the female sex organs in puberty, preparing the breasts and uterus for pregnancy in adulthood, and maintaining cardiovascular and bone health. Without estrogen, the female body is unable to sustain pregnancy and is susceptible to heart disease and osteoporosis. At menopause estrogen levels fall precipitously. The purpose of HRT is to restore hormone levels to counteract the negative side effects of low hormone levels, such as hot flashes. However, estrogen can also cause some cancers to grow.
Bioidentical vs. Synthetic: Different Sources and Structures
While bioidentical hormones and synthetic hormones both undergo processing in the laboratory to produce the end product, the sources from which they are derived and the structure of the final products differ.
Bioidentical hormones are derived from plant sources, usually yams or soy, and are processed in a laboratory to make their chemical structure an identical match to the hormones made by the body. Because they are a direct match to those they are intended to replace, bioidentical hormones may also be referred to as “natural” hormone replacement.
Synthetic HRTs are derived from animal sources. (Premarin® (conjugated estrogens), for example, is produced from the urine of pregnant mares.) Synthetic hormones are intended to have a chemical structure that is slightly different from naturally produced hormones—an attribute which allows them to be patented—yet they cause many of the same effects on the body.
Delivering Hormone Replacement Therapy
In addition to differing in chemical structure, bioidentical hormones and synthetic hormones are delivered in different ways. Synthetic hormones are delivered orally, in pill form. Bioidentical hormones are not taken orally, but are instead chiefly delivered through the skin via patches, creams, lotions, or gels. The reason for this is that medicines taken orally don’t enter the bloodstream in the same form as they are swallowed. Substances taken in through the gastrointestinal tract (i.e. anything swallowed) pass through the liver first, where their chemical structures are altered. For example, when a woman takes an oral dose of the estradiol—a form of the hormone estrogen that declines precipitously at menopause—it is converted in the liver to estrone, a weaker form of estrogen. However, when estradiol is absorbed through the skin—a process called transdermal administration—it enters the bloodstream immediately as estradiol.
Where Are Bioidentical Hormones Sold?
Unlike synthetic hormones, which are patented drugs and are available at conventional pharmacies, bioidentical hormones can only be acquired through specific types of pharmacies, called compounding pharmacies. These pharmacies have access to bulk chemicals from the United States Pharmacopeia (USP), and they have the state-of-the-art equipment to ensure accurate formulation of hormone treatments from the bulk chemicals.
Based on a physician’s prescription, compounding pharmacists can prepare plant-derived bioidentical hormones in a variety of dosage forms, strengths, and combinations. This is, in fact, one of the purported benefits of bioidentical hormones—they can be formulated at individualized doses and mixtures that are not available commercially.
While compounding pharmacies have a long history of providing a wide range of compounded products, opponents of bioidentical hormone therapy claim that preparation methods vary from one pharmacist to another and from one pharmacy to another. This means that patients may not receive consistent amounts of medications.2
However, compounding pharmacists and pharmacies comply with regulations set by the boards of pharmacy in their respective states, and are monitored by these boards. They assert that this oversight and the fact that pharmacies produce products from the same bulk chemicals from the USP ensure the quality of their products. 3
The Case for Bioidentical Hormones
Proponents for bioidentical hormones claim that they are safer than synthetic hormones and can effectively alleviate the symptoms of menopause.
One bioidentical hormone preparation that is available through compounding pharmacies at the request of a physician is Triest, which contains a combination of three forms of estrogen: 10 percent estradiol, 10 percent estrone, and 80 percent estriol. Research has shown that Triest seems to be effective in controlling hot flashes, insomnia, vaginal dryness, and frequent urinary tract infections associated with menopause, but it may also have a stimulatory effect on breast and endometrial tissue.4
While Triest is used in Europe as a prescription hormone replacement therapy, it is not regulated by the FDA and has not undergone evaluation in large, well-planned, and controlled clinical trials.
Synthetic hormones, in contrast, have been studied extensively. The Women’s Health Initiative study, the largest study on HRT ever conducted, involved 16,609 women, and the researchers followed participants for an average of 5.6 years. The study was initiated in 1991, and the results published in 2002 have provided the women’s health community with the most comprehensive understanding of the impact of HRT on women’s health.1
A large review of the research on bioidentical hormones published in a 2004 issue of the official journal of the North American Menopause Society concludes that, while evidence does suggest that bioidentical hormones may decrease some symptoms of menopause, they do not appear to have a proven advantage over conventional hormone therapies and further research is needed to support their use.5
Controversy Around the Use of Bioidentical Hormones
Recent media coverage and women’s conversations have been full of the controversy surrounding bioidentical hormones. Evidence of the controversy can also be seen in the position statements issued regarding the use of bioidentical hormones by professional organizations and in the legal activities that have taken place in the past two years.
In their statement on bioidentical hormones, the North American Menopause Society “does not recommend custom-compounded products over well-tested, government-approved for the majority of women, and does not recommend saliva testing to determine hormone levels.”
Similarly, a committee opinion released by the American College of Obstetricians and Gynecologists (ACOG) in 2005 states that “there is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies.”6
Also, in October 2005, Wyeth Pharmaceuticals—maker of the synthetic hormone replacement pill, Premarin—asked the FDA to investigate the distribution of bioidentical hormones by compounding pharmacies. They claim that many compounding pharmacies are making unsubstantiated claims about the benefits and risk of bioidentical hormones.
In response, a group of compounding pharmacies filed a lawsuit seeking protection from FDA regulations on the basis that pharmacies are regulated by state laws, not federal regulations. Wyeth renewed the request to FDA in late April 2006.
Hormone Replacement Alternatives
Despite the controversy, women continue to seek an alternative to synthetic hormones, and bioidentical hormones are gaining in popularity. However, it is not necessary to go to a compounding pharmacy for these hormones. There are FDA-approved products that release the active form of estrogen produced by the body—called estradiol—which have undergone the same degree of clinical testing that synthetic hormones have.
Delivered transdermally, or through the skin, products that release estradiol include the following:
- Estrogen patches: Alora®, Climara®, Esclim®, Estraderm®, Vivelle®, Vivelle-Dot® (estradiol transdermal systems)
- Estrogen cream: Estrasorb® (estradiol topical emulsion)
- Estrogen gel: Estrogel® (estradiol gel)
- Estrogen rings: Estring® (estradiol veaginal ring)
- Femring® (estradiol acetate vaginal ring)
Many women experiencing debilitating symptoms of menopause are facing a difficult decision today when it comes to deciding on a hormone replacement strategy. Media and celebrity influences, input from friends and family, and conflicting research data might all become overwhelming. Ultimately, each woman must create a plan for herself—together with her healthcare team—by carefully weighing the risks and benefits of each option as it relates to her own health and her family history.
- Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the women’s health initiative randomized controlled trial. Journal of the American Medical Association. 2002;288:321-333.
- North American Menopause Society. Statement on Bioidentical Hormones. Menopause: The Journal of the North American Menopause Society. Available at: www.menopause.org/bioidentical.htm. Accessed July 20, 2006.
- Reed-Kane, D. Natural hormone replacement Therapy: What it is and what consumers really want. International Journal of Pharmaceutical Compounding. 2001;1(5): .
- Head KA. Estriol: Safety and efficacy. Alternative Medicine Review. 1998;3:101-113.
- Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause: The Journal of the North American Menopause Society. 2004;11(3):356-367.
- American College of Obstetricians and Gynecologists. ACOG News Release. www.acog.org/from_home/publications/press_releases/nr10-31-05-1.cfm. Accessed July 20, 2006.