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Special Features: Margaret E. Wierman, Rosemary Basson, Susan R. Davis, Sundeep Khosla, Karen K. Miller, William Rosner, and Nanette Santoro Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2006; 91: 3697-3710 [Abstract] [Full text] [PDF]

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Re: E-Letter to the Editor: A Different Perspective on Androgen Therapy In Women

Margaret E. Wierman, Rosemary Basson, Susan R. Davis, Sundeep Khosla, Karen K. Miller, William Rosner, and Nanette Santoro   (6 February 2007)

E-Letter to the Editor: A Different Perspective on Androgen Therapy In Women

Andre T Guay, Abdulmaged Traish, Irwin Goldstein, Richard Spark, Ricardo Munarriz, Jacques Buvat, Ridwan Shapsigh, Martin Miner, Rossella Nappi, Alessandra Graziottin, Salvatore Caruso, Antonio Aversa, Lila Nachtigall, James Simon, Emmanuele Jannini   (30 November 2006)

Re: E-Letter to the Editor: A Different Perspective on Androgen Therapy In Women 6 February 2007
Margaret E. Wierman, professor UCDHSC, Rosemary Basson, Susan R. Davis, Sundeep Khosla, Karen K. Miller, William Rosner, and Nanette Santoro Send letter to journal: Re: Re: E-Letter to the Editor: A Different Perspective on Androgen Therapy In Women margaret.wierman{at}uchsc.edu Margaret E. Wierman, et al.	Guay et al express concern about the conclusions of the recent guidelines on Androgens in Women, which recommend against the diagnosis of androgen deficiency syndrome and against the treatment of women with testosterone. They assume there is definitive link between endogenous androgens and sexual motivation, which has not been established. The Princeton Conference was based upon clinical consensus and not published data. The authors suggest we failed to appreciate the data showing a drop in testosterone levels after oophorectomy. These data are described in the guideline, as well as the controlled studies that show short term benefit of replacement of testosterone to high-normal levels in oophorectomized women with sexual dysfunction. The authors of the letter discount our distrust of current assays for testosterone in female plasma. We refer them to the recently published (online), “Utility, Limitations and Pitfalls In Measuring Testosterone: An Endocrine Society Position Statement” (1), which documents in detail the problems in the measurement of testosterone in women. We agree that the Davison paper was a laudable attempt to define normative testosterone ranges in women across the lifespan (2). However, there is evidence that current RIAs for testosterone developed for measurement in men lack accuracy below 200 ng/ml and that improved assays are needed to define normal levels in pre- and post-menopausal women (3). While we agree with Guay et al., that women have the right to sexual health care, the majority of women are not in need of androgen therapy. The evidence for this therapy, beyond treatment of oophorectomized women, is lacking. We applaud continued clinical investigation in this area and encourage the funding of non-industry sponsored trials. As we have learned from the Women’s Health Initiative, assumption of benefit should be proven before any hormonal therapy is endorsed for the large populations. When not appropriately targeted, they can do harm. Until there is a definable androgen deficiency syndrome that includes biochemical and clinical criteria tested prospectively, and evidence of safety of prolonged androgen therapy (because such treatment is often open-ended), we stand by the conclusions of our guideline. References 1. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H 2006 Utility, Limitations and Pitfalls in Measuring Testosterone: An Endocrine Society Position Statement. J Clin Endocrinol Metab doi:10.1210/jc.2006-1864 2. Davison SL, Bell R, Donath S, Montalto JG, Davis SR 2005 Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 90:3847-3853 3. Holownia P, Conway GS, Shrivastava U, Round J, Honour JW 1993 A clinical evaluation of a direct radioimmunoassay of testosterone. Clin Chim Acta 214:31-43
E-Letter to the Editor: A Different Perspective on Androgen Therapy In Women 30 November 2006
Andre T Guay, Endocrinologist Lahey Clinic/Harvard Medical School, Abdulmaged Traish, Irwin Goldstein, Richard Spark, Ricardo Munarriz, Jacques Buvat, Ridwan Shapsigh, Martin Miner, Rossella Nappi, Alessandra Graziottin, Salvatore Caruso, Antonio Aversa, Lila Nachtigall, James Simon, Emmanuele Jannini Send letter to journal: Re: E-Letter to the Editor: A Different Perspective on Androgen Therapy In Women andre.t.guay{at}lahey.org Andre T Guay, et al.	The Endocrine Society’s Clinical Practice Guideline on androgen therapy in women (1) is, in reality, more a position paper than a guideline, for the only recommendation to emerge from this document is that physicians not treat androgen deficient women with androgens. The dual pillars of this premise are invalid: 1) that female androgen deficiency is neither definable nor amenable to quantitative analysis because existing androgen assays are inaccurate or lack precision, and 2) there are no normative data regarding androgen levels in women. The Committee chose to ignore the undisputed observation that total circulating androgen levels decline by more than 50% following bilateral oophorectomy and in so doing trivialized the plight of women who experience characteristic symptoms after this surgery. The seminal paper by Davison et al. (2) clearly defined normative female androgen levels in over1400 women from ages 18 to 75. The clinical syndrome of female androgen deficiency was defined in the Princeton Consensus Conference (3). Like androgen deficiency in men, both clinical symptoms and biochemical marker of low androgen levels must be present to establish the diagnosis of female androgen deficiency. Debate about which assay best identifies the female androgen deficient state is welcome, but the recommendation to put on hold further evaluation with currently available assays and withhold treatment from the individual symptomatic androgen deficient woman seems inappropriate. The Guideline’s Committee implied that there are not yet sufficient safety data on androgen supplements in women, citing the WHI study, an inaccurate analogy because that study specifically excluded postmenopausal women with vasomotor symptoms. This was because those designing the study knew that symptomatic estrogen deficient women would not tolerate placebo assignment, drop out, and compromise that report’s credibility. Even in men, there is as yet only one three-year study with generalized chronic safety data (4). While recent guidelines for diagnosis and treatment of androgen treatment in men illustrate gaps in our current knowledge (5), they do not discourage diagnosis and treatment of androgen deficient men. The current report reinforces a persistent bias in addressing the interaction between female sexual dysfunction and hormone levels. This contradicts the World Health Organization's mandate that women have the right to sexual health care, which could include using hormones. There is a considerable body of evidence on the important role of androgens in women’s health. The call for more animal studies is well taken, however the recommendations against use of androgen therapy in symptomatic androgen deficient women, until all the biological, clinical and psychological research is complete, is inappropriate. We will always know more in the future than we do now, but that never justifies not doing the best we can with currently available diagnostic and therapeutic resources to help our patients. References 1. Wierman ME, Basson R, Davis SR, Khosla S, Miller KK, Rosner W, Santoro N. 2006. Androgen therapy in women: an Endocrine Society clinical Practice Guideline. J Clin Endocrinol Metab. 91:3697-3710 2. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. 2005. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 90:3847-3853 3. Bachman G, Braunstein G, Burger H, Davis S, Dennerstein L, Goldstein I, Guay A, Leiblum S, Lobo R, Notelovitz M, Rosen R, Sarrel P, Sherwin B, Simon J, Simpson E, Shifren J, Spark R, Traish A. 2002. Female androgen deficiency: the Princeton consensus statement on definition, classification, and assessment Fertil Steril 77:660-665 4. Wang C, Cunningham G, Dobs A, Iranamesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS. 2004. Long-term testosterone gel (Androgel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men J Clin Endocrinol Metab 89:2085-2098 5. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto Am, Snyder PJ, Swerdloff RS, Montori VM. 2006. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 91:1995-2010