Steer Clear of "Bioidentical" Hormone Therapy

Stephen Barrett, M.D.

Pharmaceutical compounding is the combining, mixing, or altering of ingredients to create a customized medication for an individual patient in response to a licensed practitioner's prescription. The quality of a finished compounded drug product can be affected by many factors, including the quality of the active pharmaceutical ingredient used and the compounding practices of the pharmacy in which the product is created. The FDA requires drug manufacturers to meet stringent quality-control standards for the contents of each product and to document how quickly the drug dissolves in the stomach. However, compounded capsules can vary significantly in dosage and absorption characteristics, with no independent check of quality or variation [1]. In 2001, for example, the FDA analyzed a variety of 29 product samples from 12 compounding pharmacies and found that 34% of them failed one or more standard quality tests. In addition, 9 of the 10 failing products failed assay or potency tests, with all containing less of the active ingredient than expected. In contrast, the testing failure rate for FDA-approved drug therapies is less than 2% [2].

Compounded "bioidentical hormones" are plant-derived hormones that pharmacists prepare and label as drugs. The products are claimed to be biochemically similar or identical to those produced by the ovaries or body. However, the relevant chemicals (steroids) in plants are not identical to those in humans. To make products that work in humans, raw materials from the plants must be converted to human hormones synthetically. Thus, to the extent that they are potent, the "bioidentical" products would pose the same risks as those of standard hormones—plus whatever problems might be introduced during compounding.

Many promoters of bioidentical hormone products advocate saliva testing to determine who might benefit from them. In fact, some nonstandard labs encourage consumers to order tests based on whether they have various symptoms.

For many years, the scientific medical community believed that hormone replacement therapy (HRT) at any age would reduce the risk of heart attack and stroke. This hope was dashed by the Women's Health Initiative Study, which found that taking estrogen plus progestin for more than five years places postmenopausal women at risk for heart attacks, strokes, and several other serious problems [3]. HRT is now mainly prescribed for the short-term treatment of postmenopausal symptoms using low doses of an estrogen such as estradiol.

The risk involved in prescribing a hormonal product depends on its chemical composition and biochemical properties, not on how it was made. However, many offbeat physicians are prescribing compounded "bioidentical" products as though they are safer than standard prescription drug products. On October 31, 2005, the American College of Obstetricians and Gynecologists (ACOG) warned against these products and the saliva tests typically used by those who prescribe them. In strongly worded documents [4,5], ACOG stated:

There is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies.
Hormone therapy does not belong to a class of drugs with an indication for individualized dosing. Salivary hormone level testing used by proponents to "tailor" this therapy isn't meaningful because (a) salivary levels are not as accurate as blood levels and (b) they can vary within each woman depending on her diet, the time of day, the specific hormone being tested, and other variables.
Most compounded products have not undergone rigorous clinical testing for either safety or efficacy. There are also concerns regarding their purity, potency, and quality.
The FDA requires manufacturers of FDA-approved products that contain estrogen and progestins to include a black box warning that reflects the findings of the Women's Health Initiative. However, compounded products (including "bioidentical" hormones) are not approved by the FDA and have been exempt from having to provide patient package inserts that contain warnings and contraindications for estrogens and progestins.
Given the lack of well-designed and well-conducted clinical trials of these compounded hormones, all of them should be considered to have the same safety issues as those hormone products that are approved by the FDA and may also have additional risks unique to the compounding process.

In January 2008, the FDA ordered seven compounding pharmacies listed to the right to stop making illegal claims about "bio-identical hormone replacement therapy (BHRT)" products. The companies were told that the FDA regards "bio-identical" as a marketing term that implies a benefit for which there is no medical or scientific basis [6]. Some were also making unsupportable claims that their drugs are better than FDA-approved menopausal hormone therapy drugs and can be used to prevent and treat serious diseases such as Alzheimer's disease, stroke, and various forms of cancer.

Some products contained estriol as well as progesterone and estrogen. No drug product containing estriol is FDA-approved, and its safety and effectiveness are unknown [7].

The bottom line for consumers is very simple: Steer clear of anyone who prescribes "bioidentical" hormones or recommends saliva testing as the basis for evaluating hormone status.

References

Bouts BA. The misuse of compounding by pharmacists. Quackwatch, Oct 14, 2002.
FDA Center for Drug Evaluation and Research. Report: Limited FDA survey of compounded drug products. FCER Web site, Jan 28, 2003.
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. JAMA 288:321–333, 2002.
No scientific evidence supporting effectiveness or safety of compounded bioidentical hormone therapy. ACOG news release, Oct 31, 2005.
ACOG Committee on Gynecologic Practice. Compounded bioidentical hormones. Obstetrics and Gynecology 106:1139-1140, 2005.
FDA takes action against compounded menopause hormone therapy drugs. FDA News release, Jan 9, 2008.
Bio-Identicals: Sorting Myths from Facts. FDA consumer update, Jan 9, 2008.

This article was revised on January 19, 2008.