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“When you come to a fork in the road, take it.” —Yogi Berra Clinicians are faced with a therapeutic dilemma resulting from the publication of two guidelines/position statements regarding the use of testosterone for menopausal women from two respected societies: The Endocrine Society and the North American Menopause Society (NAMS) (1, 2). The authors of both of these scholarly works are highly accomplished academic clinician-scientists who carefully analyzed the data that were available using an evidence-based approach. As would be expected, there was much upon which they agreed including the data concerning the physiology of androgen production in women, the fact that most assays that are used to measure total and free testosterone in women are neither accurate nor precise, and that reliable, age-matched normative data that can be used clinically are, at best, sparse (see The Endocrine Society’s more recent position statement on testosterone measurements for additional detail) (3). They agree that despite these limitations, there are several conditions that have been shown to be associated with low testosterone levels in women. These include surgical menopause, hypopituitarism, adrenal insufficiency, systemic glucocorticoid or oral estrogen therapy, and chronic illness. They further agree that there is no clear association between circulating levels of testosterone and sexual function. Both acknowledge that the administration of testosterone to surgically menopausal women receiving concomitant estrogen therapy who had developed distressing loss of sexual desire after their oophorectomy is efficacious in improving libido and an increasing the number of satisfying sexual events. This significant improvement in sexual function occurred with doses of testosterone that raised the serum free testosterone levels to within the normal range for premenopausal women. Agreement was also present concerning the dearth of high-quality data and conflicting information surrounding androgen treatment effects on cognition, mood, bone, cardiovascular function, and body composition. Finally, both groups point out that long-term ( 6 months) safety data under controlled circumstances are unknown and that data concerning efficacy and safety in postmenopausal women who are not receiving estrogens were unknown at the time that the papers were submitted to the journals. The major area of disagreement concerned the recommendation regarding treatment of women with testosterone. The authors of the NAMS position stated: “Although data are limited, there is consistent evidence that in postmenopausal women with sexual concerns, adding either oral or nonoral testosterone to estrogen therapy results in a positive effect on sexual function, primarily an increase in sexual desire. Data are inadequate to support the therapeutic use of testosterone for any other indication, including bone preservation, menopause symptoms, well-being, body composition or cognition. . . . In selecting postmenopausal women for testosterone therapy, clinical factors are generally of much greater importance than serum hormone levels, especially given the relative unreliability of most clinically available testosterone assays for women and the multiple causes of sexual desire disorders.” In contrast, The Endocrine Society Clinical Practice Guideline states: “Although evidence exists for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, we recommend against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking.” Thus, we have two committees composed of highly respected scientists diverging in an important clinical recommendation. I believe that there are three fundamental reasons for these differences. First, there are conceptual differences about what is being treated. Part of this problem derives from the Princeton Consensus Conference held in 2001, which defined female androgen insufficiency. Their definition was based on review of the peer-reviewed literature and the experience of the assembled experts who manage women with symptoms that include a diminished sense of wellbeing or dysphoric mood; persistent, unexplained fatigue; and sexual dysfunction such as decreased libido, sexual receptivity, and/or pleasure (4). They noted that although there were no specific biochemical abnormalities, pathology, or objective findings that confirmed the diagnosis, both controlled and uncontrolled trials demonstrated that testosterone therapy was efficacious in improving the symptoms in the women. The consensus committee also stated that a serum testosterone level in an individual with the disorder Abbreviation: NAMS, North American Menopause Society. 0021-972X/07/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 92(11):4091–4093 Printed in U.S.A. Copyright © 2007 by The Endocrine Society doi: 10.1210/jc.2007-1709

the journal of clinical endocrinology and metabolism/journal of clinical endocrinology and metabolism

The Endocrine Society Clinical Practice Guideline and The North American Menopause Society Position Statement on Androgen Therapy in Women: Another One of Yogi’s Forks