New Guidelines for Testosterone Therapy in Women: Recent Research Context
– New position statement recommends testosterone therapy for just one condition
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While the Position Statement focuses on the use of testosterone therapy in women, the biochemical and hormonal underpinnings of the risks and benefits of testosterone therapy in women have some foundation in what we know (and do not know) about endogenous androgens in PCOS as well as exogenous testosterone in transgender men (people assigned female at birth but who have male gender identity).
Key take home points for practice include: (1) We still do not have cutoff blood levels for circulating androgens to differentiate women with and without sexual dysfunction; (2) if checking testosterone, focus on total testosterone by LC-MS/MS assays, if available, as direct assays are unreliable for measuring female-range testosterone levels (but direct assays can be used to exclude high baseline testosterone concentrations and supraphysiologic concentrations during treatment); (3) if testosterone therapy is started, blood levels of testosterone should not be higher than those seen in healthy premenopausal women; (4) data currently only support transdermal testosterone (patch, specifically, based on the cited systematic review and meta-analysis (Achilli C, et al Fertil Steril 2017) and not injectable, oral, pellet, compounded preparations or DHEA; and (5) postmenopausal women on testosterone therapy who achieve physiologic premenopausal testosterone concentrations may have mild increases in acne and body/facial hair growth, but not likely alopecia, cliteromegaly, or voice change.
We still need well-designed, randomized controlled trials with more adequate power and reliable assays. We need these studies to better assess the effects of testosterone on well-being, mood, cognition and musculoskeletal tissues in women. We need to understand cardiovascular risk in women who take long-term testosterone therapy (particularly >24 months), have higher cardiometabolic risk at baseline and are not taking concurrent estrogen therapy. We need longer-term data on breast cancer risk, especially if there is prior hormone-sensitive breast cancer. We also have not developed and licensed testosterone formulations specific to women.
The Position Statement concludes with a call for more research into all of the above but serves as an initial approach to identifying and managing women who could benefit from testosterone therapy.
A new position statement, created by a task force representing several leading organizations, outlines new recommendations for testosterone therapy in women.
According to first author Susan Davis, a researcher with the School of Public Health and Preventive Medicine at Monash University in Australia, and colleagues, writing in , the statement was created because "there are no clearly established indications for testosterone therapy for women," and that in turn is creating a vacuum in how and when testosterone treatments are used in women.
"Clinicians have treated women with testosterone for decades, with the intention of alleviating a variety of symptoms, with uncertain benefits and risks," Davis and colleagues wrote. "In most countries, testosterone therapy is prescribed off-label such that women are using either testosterone formulations approved for men with dose modification, or compounded therapies. Because of these issues, there is a compelling case for a global consensus Position Statement on testosterone therapy for women based on the available evidence from placebo/comparator randomized controlled trials."
Using evidence from randomized controlled trials of at least 12 weeks' duration, the task force intended to offer "clear guidance as to which women might benefit from testosterone therapy, to identify symptoms, signs, and conditions for which evidence does not support the prescribing of testosterone, to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm."
Following their analysis, task force members concluded that current evidence was sufficient to recommend testosterone therapy in women with only one condition: hypoactive sexual desire disorder/dysfunction (HSDD). As such, Davis and colleagues called for more research into testosterone therapy in women.
"There are insufficient data to support the use of testosterone for the treatment of any other symptom or clinical condition [other than HSDD], or for disease prevention," Davis and colleagues wrote.
In the meantime, the task force made recommendations on a variety of topics, including:
• Measuring circulating testosterone in women
• Terminology for female sexual dysfunction
• Associations between endogenous androgen concentrations and female sexual function
• Testosterone treatment for naturally or surgically postmenopausal women with HSDD, with or without concurrent estrogen therapy
• Effects of testosterone on well-being, mood, and cognition in postmenopausal women
• Musculoskeletal effects of testosterone
• Possible side effects of testosterone therapy
• Testosterone therapy and cardiovascular health
• Testosterone therapy and breast health
• Potential serious adverse events of testosterone therapy in women
• Assessing female sexual dysfunction before commencing testosterone therapy
• Testosterone therapy and postmenopausal women
• Other androgenic preparations
• Design of future trials of physiologically-dosed testosterone
Davis reported receiving honoraria from Besins and Pfizer Australia; has been a consultant to Besins Healthcare, Mayne Pharmaceuticals, Lawley Pharmaceuticals and Que Oncology; and is an investigator for Que Oncology (money paid to her institution).
Primary Source
The Journal of Clinical Endocrinology and Metabolism
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