Appeal type: Experimental/Investigational
Decision: Upheld

A 69-year-old female enrollee has requested compounded topical cream (estradiol and progesterone) for treatment of her menopausal symptoms.  Findings:  Three physician reviewers found that compounded drugs are agents that are prepared, mixed, assembled, packaged, or labeled as a drug by a pharmacist. Unlike drugs that are approved by the U.S. Food and Drug Administration (FDA) to be manufactured and sold in standardized dosages, compounded medications often are custom made for a patient according to a physicians specifications. The steroid hormones most commonly compounded include dehydroepiandrosterone, pregnenolone, testosterone, progesterone, estrone, estradiol, and estriol. These hormones are made by a compounding pharmacist from a provider's prescription and are available in various routes of administration, including oral, sublingual, and transdermal or as implants, injectables, and suppositories. The patient in this case has been prescribed compounded transdermal estradiol and progesterone. Most compounded products have not undergone any rigorous clinical testing for either safety or efficacy, and issues of quality assurance regarding the purity, potency, and quality of compounded products are a concern. From June 2001 to December 2001, the FDA analyzed 29 product samples from 12 compounding pharmacies. Although none of the compounded products failed identity testing, 10 of the 29 products (34%) failed 1 or more standard quality tests performed. Nine of the ten failing products failed assay or potency tests, with all products failing potency testing demonstrating sub-potent results. That is, the products analyzed contained less of the active ingredient than expected. In comparison with these results, the analytical testing failure rate for drug therapies approved by the FDA is less than 2%.Currently, the FDA requires manufacturers of products approved by the FDA that contain estrogen and progesterone to use class labeling reflective of the findings of the Womens Health Initiative. However, because compounded products are not approved by the FDA and have no official labeling, they are exempt from including the contraindications and warnings required by the FDA in class labeling for hormone therapy. Given the lack of well-designed and well conducted clinical trials of these alternative therapies, compounded hormone products should be considered to have the same safety issues as those associated with hormone therapy agents that are approved by the FDA. They also may have additional risks intrinsic to compounding. There is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens. The only available reports for compounded hormone replacement preparations have attempted to confirm their efficacy in relieving menopausal symptoms. These studies are few and small in size. As such, there is a clear need for additional large, randomized placebo-controlled studies in this area. Without clear evidence in the peer-reviewed medical literature to support this compounded medication as within the standard of care, its use is not likely to be more beneficial than standard alternatives.