by A.J. Day, PharmD, PCCA Vice President of Clinical Services

By now, the compounding community should be familiar with the National Academies of Science, Engineering and Medicine’s (NASEM) report, The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use . FDA commissioned the NASEM report, at a cost of $1.3 million, as part of the agency’s efforts to better understand the clinical utility of compounding bioidentical hormone replacement therapies (BHRTs) and guide FDA in crafting policy to regulate them.

The NASEM report states their committee only identified 13 studies relevant to the safety and effectiveness of cBHT (their abbreviation for compounded bioidentical hormone therapy), leading its authors to bemoan the “severe methodological limitations” and other shortcomings of available studies.

As a compounding pharmacist who reviewed a considerable amount of clinical literature on compounded hormone therapy, I found those statements to represent boilerplate complaints about compounds in general, rather than a factual description of published data.

To better evaluate the quantity and quality of data, PCCA performed a system review and meta-analysis of existing studies related to the safety and efficacy of commonly prescribed nonsterile compounds for perimenopausal and postmenopausal women. After reviewing more than 3,000 published articles, we found 29 randomized control trials (RCTs) that collectively represented 1,808 women. We had hoped that NASEM would conduct this type of evaluation, yet given its absence, PCCA felt it was important to perform a separate review so clinicians, policy makers and patients are better informed about compounded hormones.

Criteria for studies evaluated in our meta-analysis include study duration of up to one year, double-blinded and controlled using placebo or a comparator commercially available hormone product. Hormones evaluated in these studies were estradiol, estriol, progesterone, testosterone and dehydroepiandrosterone (DHEA).

The results of our review are significant. First, we identified a large amount of data excluded from the NASEM report, which the authors claimed was a “consensus study report.” The omission raises questions about the thoroughness of the studies they reviewed and, consequently, the validity of the report’s conclusions and recommendations. Additionally, our meta-analysis provided new insights on existing safety and efficacy data. With consistent outcomes for indicators of risk and benefit (such as incidence of adverse events, impact on lipid profile and glucose metabolism, sonography for endometrial thickness, sexual function scores, and improvement of symptoms), our meta-analysis showed that, despite the heterogeneity of the studies, patients benefited from compounded hormone therapy.

Limitations to our meta-analysis exist: clinical cardiovascular events were not a focus in the studies we evaluated; none of the studies conducted endometrial sampling; and patients were not followed beyond one year. While available studies did not show an increased risk from compounded hormone therapy when compared to FDA-approved hormone therapy, additional long-term research should be conducted to measure these specific endpoints and fully evaluate risk and benefit of compounded hormone therapy.

Beyond the 29 studies included in our meta-analysis, PCCA identified other studies, many of which were well designed, powered appropriately and offered meaningful data. These studies were not included in our meta-analysis because they were not RCTs. It’s important to note that these studies were also provided to the NASEM committee and were excluded in their evaluation.

To mitigate such myopic reports, the compounding industry must engage in greater efforts to publish clinical data for all therapies. By publishing clinical data, we can and will continue to educate clinicians, policy makers and, most importantly, patients. In doing so, we help protect patient rights to access personalized, compounded medicines that meet their individual needs; we retain the rightful integrity of compounding professionals; and we secure the future for compounding pharmacists and pharmacies.

A version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.