Q&A: Experts' advice on bioidentical hormones and oral contraceptives for perimenopausal women

The following questions and answers summarize cases discussed in a recent issue of Menopause e-Consult, a newsletter of the North American Menopause Society (NAMS).

The ethics of bioidentical hormone therapy

A colleague has expressed concern about the ethics of prescribing bioidentical hormone therapy (BHT)-specifically, about the lack of a black box warning on BHT product packages, like the one on hormone therapy (HT) products approved by the Food and Drug Administration (FDA). Should my practice be making more of an effort to educate our patients about the risks and benefits of BHT? Should we prescribe these products at all?¹

BIOIDENTICAL HORMONES ARE exogenous hormones that are chemically identical to the hormones produced by the ovaries (such as estrone, estradiol, estriol, progesterone). Many FDA-approved prescription products contain bioidentical hormones. BHT, however, usually refers to custom-compounded hormones in the form of topical creams, gels, lotions, sublingual tablets, subdermal implants, and suppositories.^2,3

Unlike FDA-approved products containing bioidentical hormones, custom-compounded BHT products are not tested for purity, potency, efficacy, and safety, so dosing and purity can vary, and safety and efficacy are unknown.^2,3 A 2001 review by the Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists reported that 34% of 29 product samples from 12 compounding pharmacies analyzed by the FDA failed one or more standard quality tests. Ninety percent of the failed samples contained less of the active ingredient than expected, compared with 2% of FDA-approved products.⁴

SCIENTIFIC EVIDENCE LACKING. No peer-reviewed, randomized, controlled trials have studied compounded BHT products, and no scientific evidence supports claims that such products are safer and more effective than conventional prescription HT. No large studies show that BHT reduces the risk of osteoporosis or prevents breast cancer, as is sometimes claimed; nor has custom topical progesterone cream been found to prevent estrogen-induced endometrial hyperplasia.⁵

Testing salivary hormone levels to "tailor" the dose of BHT is meaningless because of poor reproducibility and large variations among assays. Levels may fluctuate within each woman depending on variables such as diet, time of day, and the hormone being measured.²

ETHICAL ISSUES. Clinicians should keep in mind two ethical goals when considering prescribing BHT: inform and do no harm. The lay literature often makes unsubstantiated claims that compounded BHT carries less risk than conventional HT and uses misleading terms such as "cutting-edge therapy," "individually tailored," "safer than or superior to synthetic hormones," and "dosed upon salivary testing to individualize and provide safe therapy."

A 2007 review of ethical problems with BHT notes that "patients do not have the background to decipher credible sources from noncredible sources."⁶ Self-education by patients using inaccurate, misleading information or inflated results interferes with informed consent. The review identifies symptomatic postmenopausal women or those who fear breast cancer or heart disease as a "vulnerable population."

When discussing BHT with a patient, start by finding out what the patient has read or heard. Present the risks and anticipated benefits reasonably and truthfully. Warn the patient that so-called experts in the field of BHT may be "self-identified" and lack training in endocrinology, an academic affiliation, or published work; they may be selling their own products. Practitioners who both prescribe and market or sell BHT may have a conflict of interest.

All HT formulations-whether FDA-approved or "bioidentical" compounded products-come from the same precursor compound and, in the absence of evidence to the contrary, are presumed to have the same risks and benefits. Anyone who writes a prescription for compounded BHT is responsible for educating the patient about those risks and benefits.

THE BOTTOM LINE. BHT compounds can be considered unproven, experimental, innovative, and not the standard of care. On January 9, 2008, the FDA sent letters to seven compounding pharmacies warning that medical evidence does not support claims that BHT is superior to approved HT and that such claims are considered false and misleading.⁷

The decision whether or not to prescribe custom-compounded BHT should always be based on the evidence and options as they pertain to the individual patient. Offer FDA-approved products if they are available and effective. If the patient cannot tolerate approved HT products or requests only compounded BHT, you can meet your ethical obligation by explaining the lack of scientific data on BHT and alerting the patient to misleading claims in the media and on the Web. Be sure to document your discussion.

DISCLOSURE: Dr. Pinkerton reports: Boehringer-Ingelheim, Duramed, Merck, NovoNordisk (consultant); Solvay, Wyeth (research support); Merck (speaker).