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By Robert W. Rebar, MD
Founding Chair Emeritus and Professor, Department of Obstetrics and Gynecology, Western Michigan Homer Stryker M.D. School of Medicine, Kalamazoo, MI
Dr. Rebar reports no financial relationships relevant to this field of study.
SYNOPSIS: Exogenous testosterone is currently indicated only for women with documented hypoactive sexual desire disorder/dysfunction.
SOURCE: Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. J Clin Endocrinol Metab 2019;104:4660-4666.
Although there are no definitive indications for the use of testosterone in women and there are no FDA-approved products containing testosterone for women, clinicians have used several different preparations of testosterone to alleviate a variety of symptoms despite uncertain benefits and risks. The need for clarity in the management of women asking or using exogenous testosterone led to the establishment of a task force of representatives from several leading international societies. The purpose of this task force was to make recommendations based on a systematic review and meta-analysis based only on findings from blinded placebo/comparator randomized controlled trials of at least 12 weeks’ duration. The international panel produced several recommendations:
Whether these recommendations will be observed remains to be determined. They were formulated by a distinguished panel and endorsed by several international societies. Still, I say this because clinicians have administered androgens to women for many reasons for decades; yet the analysis of the available data does not justify widespread use at this time. Perhaps the last recommendation of the panel is the most important: Additional research is badly needed to determine if there are other uses for physiologic doses of testosterone in women. If so, then the appropriate products need to be developed, tested, and approved for use.
Several years ago, one commercial FDA-approved product combined esterified estrogens (0.625 or 1.25 mg) with methyltestosterone (1.25 or 2.5 mg) (Estratest). It also was marketed in a form containing only esterified estrogens (Estratab). These products were approved because their effects were broadly equivalent to products containing conjugated estrogens. They are no longer produced, and it is unlikely that the same products containing methyltestosterone would be approved today without additional studies.
Randomized studies with the estrogen-only and the combined estrogen-methyltestosterone preparation indicated that those containing androgen produced nonsignificantly greater improvements in well-being and sexual interest.3 Somatic symptom relief in the low-dose preparation containing methyltestosterone was the same as with those containing the higher dose of esterified estrogens.4
It is possible that the effects of the methyltestosterone added to the esterified estrogens may be due, at least in part, to higher doses of circulating estrogens. This is true because methyltestosterone is efficiently aromatized to estrogens. In fact, in a study supported by the manufacturer but never published because of the untimely death of the first author, the study showed that more than 90% of the effect of esterified estrogens plus methyltestosterone was due to the estrogen alone, making it possible that the entire effect on well-being and sexual satisfaction was merely due to estrogen.5
Women with primary ovarian insufficiency (POI) are documented to have lower levels of circulating androgens than do age-matched controls. Yet in a 12-month randomized, placebo-controlled, parallel-design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy in 128 women with POI, the addition of physiologic amounts of testosterone failed to have any significant effects on quality of life, self-esteem, and mood.6
The conclusion from studies published to date can be summarized succinctly: Until we have additional data, the long-term administration of testosterone in women should be discouraged except in the treatment of women with documented HSDD.
Financial Disclosure: OB/GYN Clinical Alert’s Editor Jeffrey T. Jensen, MD, MPH, reports that he is a consultant for and receives grant/ research support from ObstetRx, Bayer, Merck, and Sebela; he receives grant/research support from AbbVie, Mithra, and Daré Bioscience; and he is a consultant for CooperSurgical and the Population Council. Peer Reviewer Catherine Leclair, MD; Nurse Planner Andrea O’Donnell, RN, FNP; Editorial Group Manager Leslie Coplin; Editor Jason Schneider; and Executive Editor Shelly Mark report no financial relationships relevant to this field of study.