2016 Update on menopause

FDA-approved HT is preferable to compounded HT formulations
_{Pinkerton JV, Santoro N. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women. Menopause. 2015;22(9):926-936.}

_{Pinkerton JV, Constantine GD. Compounded non-FDA-approved menopausal hormone therapy prescriptions have increased: results of a pharmacy survey. Menopause. 2016;23(4):359-367.}

_{Gass ML, Stuenkel CA, Utian WH, LaCroix A, Liu JH, Shifren JL.; North American Menopause Society (NAMS) Advisory Panel consisting of representatives of NAMS Board of Trustees and other experts in women's health. Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey. Menopause. 2015;22(12):1276-1284.}

Consider how you would manage this clinical scenario: During a well-woman visit, your 54-year-old patient mentions that, after seeing an advertisement on television, she visited a clinic that sells compounded hormones. There, she underwent some testing and received an estrogen-testosterone implant and a progesterone cream that she applies to her skin each night to treat her menopausal symptoms. Now what?

The use of HT for menopausal symptoms declined considerably following the 2002 publication of the initial findings from the WHI, and its use remains low.⁴ Symptomatic menopausal women often find that their physicians are reluctant to consider prescribing treatment for menopausal symptoms because of safety concerns regarding HT use. Further, confusion about HT safety has opened the door to the increasing use of compounded bioidentical HT formulations, which are not approved by the US Food and Drug Administration (FDA).³ Since the publication of my 2015 Update on menopause (OBG Manag. 2015;27(6):37−40,42−43), several reports have addressed the use of "custom compounded" bioidentical menopausal HT in US women.

Millions use compounded HT for menopausal symptoms
A recent study by Pinkerton and Santoro that analyzed data from 2 national surveys suggested that as many as 2.5 million US women currently use non−FDA-approved custom-compounded HT. The authors also found that more than three-quarters of women using compounded HT are unaware that these medications, which include oral, topical, injectable, and implantable (pellet) formulations, are not FDA approved. In a study by Pinkerton and Constantine, total annual sales of compounded HT were estimated at approximately $1.5 billion. The dramatic growth in the use of compounded HT appears to have stemmed from celebrity endorsements, aggressive and unregulated marketing, and beliefs about the safety of "natural" hormones.⁵

Spurious laboratory testing. Women seeking care from physicians and clinics that provide compounded HT are often advised to undergo saliva and serum testing to determine hormone levels. Many women are unaware, however, that saliva testing does not correlate with serum levels of hormones. Further, in contrast with conditions such as thyroid disease and diabetes, routine laboratory testing is neither indicated nor helpful in the management of menopausal symptoms.⁶ Of note, insurance companies often do not reimburse for the cost of saliva hormone testing or for non-FDA-approved hormones.⁵

Inadequate endometrial protection. Topical progesterone cream, which is not absorbed in sufficient quantities to generate therapeutic effects, is often prescribed by practitioners who sell bioidentical compounded hormones to their patients.7 According to a report by the North American Menopause Society, several cases of endometrial cancer have been reported among women using compounded HT. These cases may reflect use of systemic estrogen without adequate progesterone protection, as could occur when topical progesterone cream is prescribed to women with an intact uterus using systemic estrogen therapy.

What this evidence means for practice
Clinicians should be alert to the growing prevalence of use of compounded HT and should educate themselves and their patients about the differences between non−FDA-approved HT and FDA-approved HT. Further, women interested in using "natural," "bioidentical," or "custom compounded" HT should be aware that FDA-approved estradiol (oral, transdermal, and vaginal) and progesterone (oral and vaginal) formulations are available.

Because the FDA does not test custom compounded hormones for efficacy or safety and the standardization and purity of these products are uncertain, the American College of Obstetricians and Gynecologists has stated that FDA-approved HT is preferred for management of menopausal symptoms.⁸ Similarly, the North American Menopause Society does not recommend the use of compounded HT for treatment of menopausal symptoms unless a patient is allergic to ingredients contained in FDA-approved HT formulations.⁹

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