A fundamental issue with safe prescribing of testosterone in women has been the lack of clearly established indications and guidelines for testosterone therapy. In addition, there has been a wide variance of uses and intentions with uncertain benefits and risks. Despite this, clinicians have been prescribing testosterone to women for decades, with an absence of clear indications and approved products. To address this concern on current testosterone prescribing practices, a task force was established including representatives from the International Menopause Society, the European Menopause and Andropause Society, the International Society for Sexual Medicine, and the Endocrine Society to conduct a systematic review and meta-analysis of the risks and benefits of testosterone therapy in women. The task force met in May 2019 and drafted a consensus position paper that was published simultaneously in several journals: Climacteric, Maturitas, Journal of Sexual Health, and the Journal of Clinical Endocrinology and Metabolism.   

The task force developed the consensus position statement of the known benefits and potential risks of testosterone therapy with the purpose of providing guidelines for treatment, considering benefit and risk. They addressed conditions for which the published evidence does not support the use of testosterone and wherever possible, based recommendations on the results from randomized controlled trials (RCTs) of at least 12 weeks’ duration. They also reported findings with Levels of Evidence, which can be found by reading one of the original consensus position papers.  

In the following, I have attempted to highlight a summary of their recommendations: 

• The only evidence-based indication for testosterone therapy for women is for the treatment of hypoactive sexual desire disorder (HSDD), and evidence suggests a moderate therapeutic effect. This is true for natural menopause and surgical menopause women. 
• According to the evidence, a diagnosis of HSDD involves a complete clinical assessment and does not involve the measurement of testosterone levels. Diagnostic criteria used can be found from the International Society for the Study of Women’s Sexual Health.  
• Only doses that approximate physiological testosterone concentrations in premenopausal women should be used. The maximum being 10 mg per day of transdermal testosterone. 
• The benefit of testosterone therapy on sexual function includes an increase of an average of one satisfying sexual event per month, in addition to increases in sexual desire, arousal, orgasmic response, pleasure and sexual responsiveness. 
• Severe adverse events with these physiological testosterone doses are not evidenced in meta-analyses of short-term data. However, long-term safety of testosterone therapy in women has not been established. 
• Systemic testosterone therapy for postmenopausal women, in the doses that approximate levels in premenopausal women, is associated with increases in acne, body and facial hair growth. In these physiological doses, alopecia, clitoromegaly, or voice changes do not occur. 
• Transdermal or injectable non-oral testosterone deliveries are preferred due to a lack of adverse effects on lipid profiles, and possibly efficacy. 
• Randomized controlled trials of testosterone therapy have not included women at high cardiometabolic disease risk. Therefore, we cannot make recommendations regarding the effect of physiologic doses on cardiovascular risk in those women who are at risk; nor, can we make recommendations about long term use and cardiovascular risk.   
• Randomized trials for HSDD and testosterone therapy did not include women with a prior diagnosis of breast cancer. Caution is advised for testosterone treatment in women with hormone sensitive breast cancer. 
• In the U.S., there is no approved female testosterone product. The task force chose to advise formulations for men, at one tenth the dose to be used in women and they chose to not recommend compounded testosterone preparations. This is my main disagreement with the task force guidelines. Compounded testosterone cream, or even oral or sublingual deliveries, can be precisely formulated. Compounded cream is preferred.   

You might be surprised at the recommendation that testosterone is only for HSDD. However, in a review of the evidence, with the focus on RCTs, I want to highlight the following with a bit of redundancy to ensure clarity: 

• There is insufficient evidence to support the use of testosterone therapy to enhance cognitive performance or to delay cognitive decline in postmenopausal women. 
• Data is inconclusive about improving wellbeing in premenopausal women, but the data does not show an effect of testosterone on general well-being in postmenopausal women. Data also does not show an effect of testosterone on depression.  
• The reported effects of testosterone therapy on musculoskeletal outcomes is problematic in that the studies were very small, all participants were also taking estrogen therapy, and no studies have been in women with osteoporosis.  
• The current data do not support an effect of testosterone on bone mineral density of the spine, total hip or femoral neck at 12 months evaluation. 
• Readers might be surprised to hear that there is no significant effect of testosterone therapy, when physiological doses are used, on lean body mass, total body fat or muscle strength. 
• Oral testosterone therapy is associated with negative lipid profiles with adverse effects on HDL-cholesterol and LDL-cholesterol levels. Transdermal or injectable testosterone therapies have shown no significant adverse effects on lipid profiles, at least over the short term.  
• No effect on increases in blood pressure or blood glucose or HbA1c has been seen with testosterone therapy in women.  
• There has been a non-significant trend in an increased risk of deep venous thrombosis (VTE) (even with transdermal use), however, the role of the concurrent use of estrogen complicates any clear conclusion.  
• Testosterone therapy does not increase mammographic breast density. 
• The current available data suggest that short term transdermal testosterone therapy does not impact breast cancer risk but data from RCTs are insufficient to assess long term breast cancer risk. 
• There is no data to support the use of testosterone therapy as a strategy to prevent breast cancer and caution is advised in the use of women with a history of hormone sensitive breast cancer.  

Practical Clinical Recommendations to Consider

• Test total serum testosterone as the main biomarker rather than free testosterone.  Total testosterone can be measured with enhanced accuracy using liquid/gas chromatography and tandem mass spectrometry assays (LC/GL-MS/MS) (Davis, S, Baber R, Panay N, et al.) (Grade B). Total testosterone is the main biomarker, rather than free testosterone. The guidelines recommend LC/GC-MS/MS of total testosterone over immunoassay for improved accuracy.  
• Test total serum testosterone prior to prescription. This is not for the purpose of diagnosing anything, but rather to be used as a guide for not overdosing.   
• Supraphysiologic doses are not recommended. 
• Measure SHBG: if above normal range, less likely to benefit. 
• Measure baseline total testosterone prior to treatment and repeat 3-6 weeks later. 
• Total testosterone after treatment should not exceed 27-38.6 ng/dL (may vary depending on individual laboratory reference ranges used). 
• Monitor for signs of androgen excess: most common are acne, hirsutism, alopecia, clitoromegaly, voice changes. 
• Monitor testosterone levels every 4-6 months. 
• Typical response time: 6-8 weeks; as early as 4; maximum effects at 12 weeks. 
• Discontinue treatment at 6 months if no sexual function benefits. 
• Lower the dose of testosterone if the levels are above the normal reference range for a premenopausal woman, or if they are having adverse effects. 
• Dosing should be targeted to achieve total serum testosterone concentration in the physiologic premenopausal range. The starting daily dose for women should be one-tenth of the 1% testosterone tube or packet approve for daily use in men, which generally equates to three tubes or three packets per month.  You can pick one tenth of the lower packet or one tenth of the higher dose packet, depending on your decision to start lower or to start at the maximum dose for women.  
• The other option, which I prefer, is a compounded cream from a compounding pharmacy.  
• Maximum daily dose of testosterone for postmenopausal women for HSDD is 10 mg/day. 
• Common compounded cream prescriptions: Half upper end of dosing: Testosterone 20 mg/gm cream; apply one quarter gram (5 mg) per day to inner arms.  
• I discourage the use of testosterone pellet or injectable, for use in peri and postmenopausal women who want to maintain their female characteristics.  Seriously elevated supraphysiological levels occur, and the lack of ability to adjust the dose in the short term is often problematic. 

Closing Comments

I know that some of my colleagues will be challenged by the information shared here.  However, with the current popularity and climate and culture of perimenopause/menopause information and prescribing, I have concerns about the high and naïve expectations women have as to what testosterone can do for them. I have additional concerns and sometimes serious concerns about the lack of adequate training and education in safe and effective prescribing of testosterone by clinicians. I have seen many women in my practice having previously been prescribed much higher than physiological doses of testosterone and experiencing blood levels over 10 times the recommended range, side effects, and sometimes permanent side effects such as voice changes. Let’s be well informed as to the reliable published scientific evidence.  When straying from that evidence and the guidelines, know the risks, monitor, and be in good communication with our patients, sharing always, the best of what is known and not known.  

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Resources: 

Davis, S, Baber R, Panay N, et al.  Global Consensus Position Statement on the Use of Testosterone Therapy for Women.  J Sex Med 2019;16:1331-1337.