Compounded Bioidentical Hormones Therapy

An Endocrine Society Position Statement

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INTRODUCTION

Compounded “Bioidentical” Hormone Therapy (cBHT), particularly estrogen and progesterone, have been promoted by some as safer and more effective alternatives to manufactured FDA-approved hormone therapies (HT) for relief of symptoms of the menopause. In fact, little or no scientific evidence exists to support such claims about cBHT.1 Additionally, preparation of cBHT formulations is not subject to FDA oversight, and can be inconsistent in dose and purity.2 As a result of unfounded but highly publicized claims, patients have received incomplete or incorrect information regarding the relative safety and efficacy of cBHT preparations.

“Bioidentical” hormones are defined as substances that have exactly the same chemical and molecular structure as hormones that are produced in the human body. Any hormone can be made to be “bioidentical,” and there are many FDA-approved hormone preparations that are “bioidentical.” However, the term has also been used to describe compounded formulations containing estrogens, progesterone, and androgens (cBHT). Administration of estrogen and progesterone (in women with a uterus) is an effective treatment for relief of symptoms associated with menopause, but may carry some risk of potentially serious side effects.3 As women seek safer treatments, they often request cBHT from their physicians.

BACKGROUND

In 2002, the Women’s Health Initiative (WHI), a long-term randomized trial of over 10,000 women aged 50 to 79 years taking oral conjugated equine estrogens 0.625 mg with 2.5 mg daily medroxyprogesterone acetate or placebo, raised concerns about the safety of HT. Increased risks (cardiovascular events and breast cancer) outweighed preventive benefits (reduced fractures and colon cancers). Many clinicians stopped prescribing and women stopped taking these preparations. This created an environment for the propagation of the scientifically unproven idea that cBHT might be safer and more effective than FDA-approved HT. No comprehensive trial has examined the safety or efficacy of cBHT for symptom relief; no clinical outcomes trials have been completed.

Since the initial publication of the WHI, additional analyses of outcomes by age and time since menopause have determined that risks are very small when HT is initiated in women less than age 60 years or fewer than 10 years since menopause.4 Current experts now recommend that a symptomatic perimenopausal or post-menopausal woman discuss her individual risks and anticipated benefits of HT with her physician. If they decide that HT would overall be beneficial and safe, then the physician could prescribe a regimen and closely monitor.5

CONSIDERATIONS

If dosage and purity were equal, then all estrogenprogesterone containing HT (cBHT or FDA-approved ‘bioidentical” preparations), would be expected to carry essentially the same risks and benefits. Therefore, regardless of the source or structure of the hormone administered therapeutically, all HT regimens—even those that are so-called “customized”—must be carefully controlled.

Hormone customization is very difficult to achieve, because blood hormone levels are difficult to regulate accurately due to normal physiologic and pharmacokinetic variations and limitations of readily available assay methods. Nonetheless, proponents of cBHT assert that simple tests of saliva can provide the information necessary to customize hormone doses. These claims are not supported by scientific data confirming assay quality control, standardization, or clinical correlations.

Hormone therapy with structures identical to endogenous hormones can be obtained as FDA-approved preparations (oral estradiol, transdermal estradiol patches, gels, sprays, lotions, estradiol vaginal creams, tablets, and rings, and micronized oral or vaginal progesterone). These products are formulated with strict manufacturing oversight and dispensed by retail pharmacies. Prior to approval, efficacy for treatment of symptoms of menopause has been established in 12-week placebo controlled RCT per FDA guidance.

Alternatively, products dispensed from compounding pharmacies may contain combinations of different forms of estrogen and/or progesterone with different potencies. Since the final hormone formulations of most compounding pharmacies are not subject to FDA monitoring for dose, purity, safety, or efficacy, there may be additional and at this point unknown risks associated with them. Postmarket surveys of such hormone preparations have uncovered inconsistencies in dose and quality.6

Table 1 compares FDA-approved hormone therapy with compounded “bioidentical” hormone therapy.

The controversies surrounding the safety and efficacy of cBHT illustrate the need for further scientific and medical scrutiny of these substances. Until such studies are completed, physicians should exercise caution when prescribing cBHT and counsel their patients about the controversy over the use of these non-FDA approved preparations. Additionally, patients should educate themselves about HT and engage in candid discussions with their doctors. Thoughtful consideration should be given to the decision to undergo any HT, and cBHT presents unique and additional concerns because of the process by which many of them are made.

POSITIONS

The Endocrine Society is concerned that patients are receiving potentially misleading or false information about the benefits and risks of cBHT. Therefore, the Society supports FDA regulation and oversight of all hormones regardless of chemical structure or method of manufacture. This should include, but not be limited to, the following:

  • Surveys for purity and dosage accuracy
  • Mandatory reporting by drug manufacturers of adverse events
  • A registry of adverse events related to the use of hormone preparations
  • Inclusion of uniform information for patients, such as warnings and precautions, in packaging of hormone products

Originally issued October 26, 2006; reissued February 5, 2009; reissued September 26, 2017.

Table 1

FDA-approved Hormone Therapy Compounded "Bioidentical" Hormone Therapy
Molecular structure Similar or identical* to human Identical to human
FDA oversight Yes No
Dosage Monitored; accurate and consistent Not monitored; may be inaccurate or inconsistent
Purity Monitored; pure Not monitored; may be impure
Safety Tested; risks known Not FDA tested; risks unknown
Efficacy Tested and proven Not FDA tested; unproven
Scientific evidence Existent; conclusive Insufficient

* A few “bioidentical” hormones—those available from retail pharmacies, such as estradiol and progesterone—are produced under FDA supervision and are monitored for dosage and purity. However, even FDA-monitored “bioidentical” hormones have not been examined in head-to-head RCT with clinical outcomes such as cardiovascular events and fracture, and, therefore, have unproven safety and efficacy.

September 2017



  1. Santoro N., Braunstein G.D., Butts C.L., et al. Compounded Bioidentical Hormones in Endocrinology Practice: an Endocrine Society Scientific Statement. J Clin Endocrinol Metab 2016; 101:1318-1343.
  2. ibid
  3. Stuenkel C.A., Davis S.R., Gompel A., et al. Treatment of Symptoms of the Menopause.An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:3975-4011.
  4. Manson J.E., Chlebowski R.T., Stefanick M.L., et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 2013;310:1353-1368.
  5. Stuenkel C.A., Davis S.R., Gompel A., et al. Treatment of Symptoms of the Menopause. An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:3975-4011.
  6. FDA Center for Drug Evaluation and Research. Report: Limited FDA Survey of Compounded Drug Products. January 2003. Available at http://www.fda.gov/cder/pharmcomp/survey.htm.