Global Consensus Guidelines on Use of Testosterone in Women

SUMMARY:

A global consensus position statement (2019) on the use of testosterone in women was published and endorsed by NAMS, RCOG, RANZCOG, The International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women’s Sexual Health, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The International Society of Endocrinology and The Endocrine Society of Australia.  The statement addresses the available evidence and states

No cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction

There are insufficient data to make any recommendations regarding the use of testosterone in premenopausal women for treatment of sexual function or any other outcome

The only evidence-based indication for testosterone therapy for women is for the treatment of HSDD, with available data supporting a moderate therapeutic effect, in postmenopausal women

There are insufficient data to support the use of testosterone for the treatment of any other symptom or clinical condition, or for disease prevention

Postmenopausal Women

  • Testosterone treatment of hypoactive sexual desire disorder (HSDD) with/or without concurrent estrogen therapy (dosing approximately physiological premenopausal levels) is beneficial for the following (Level 1, Grade A evidence)
    • Increased: Satisfying sexual event (1 per month) | Subdomains of sexual desire, arousal, orgasmic function, pleasure and sexual responsiveness
    • Decreased: Sexual concerns including sexual distress

 Note: Above recommendations and evidence for use of testosterone in HSDD in postmenopausal women are specific for approximate physiologic doses and not supraphysiological that may occur with injectables, pellets or compounded preparations

Benefit of testosterone use has not been found for the following

  • Cognition
    • Insufficient evidence
  • General wellbeing
    • No effect
  • Depression
    • No effect  
  • Bone mineral density (spine and hip at 12 months)
    • No effect
  •  Lean body mass, total body fat or muscle strength
    • No effect (physiologic dosage)

KEY POINTS:

  • HSDD diagnosis and female sexual arousal disorder (FSAD)
    • HSDD and FSAD are 2 distinct conditions with clinical overlap but distinct etiologies
  • Diagnosis of HSDD should be based on clinical assessement and diagnostic criteria (e.g., ISSWSH or ICD 11th edition)
  • Use of systemic DHEA in postmenopausal women with normal adrenal function is not recommended for HSDD
    • Does not significantly improve libido or sexual function
  • Safety

Meta-analyses of the available data show no severe adverse events during physiological testosterone use, with the caveat that women at high cardiometabolic risk were excluded from study populations. The safety of long-term testosterone therapy has not been established.

Learn More – Primary Sources:

Global Consensus Position Statement on the Use of Testosterone Therapy for Women

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions—Part III (Definitions can be found in Table 1)

Testosterone Therapy in Women: A Clinical Challenge

Does Testosterone Treatment Improve Sexual Function in Women?

BACKGROUND AND PURPOSE:

  • While testosterone treatment for the improvement of low sexual desire in women is common, data on safety is limited
  • Islam et al. (The Lancet Diabetes & Endocrinology, 2019) sought to determine the potential benefits and risks of testosterone treatment for women

METHODS:

  • Systematic review and meta-analysis
  • Data sources
    • MEDLINE, Embase, the Cochrane Central Register of RCTs and Web of Jan 1, 1990, and Dec 10, 2018
    • Drug registration applications to the European Medicine Agency and FDA was also searched for unpublished data
  • Inclusion criteria
    • Blinded RCTs (minimum single blinded)
    • Duration of testosterone treatment ≥12 weeks
  • Participants
    • Women 18 to 75 years of age
    • Premenopausal or postmenopausal (natural or surgical)
    • With or without concurrent hormone treatment
    • Intravaginal testosterone excluded
  • Primary outcomes: the effects of testosterone on
    • Sexual function
    • Cardiometabolic variables
    • Cognitive measures
    • Musculoskeletal health

RESULTS:

  • 36 RCTs | 8480 patients | Most studies appropriately excluded women with identifiable causes that should be treated with other options, and not testosterone (e.g., depression or anti-depressant use)
  • Compared with placebo or a comparator (e.g., estrogen, with or without progestogen), testosterone significantly increased sexual function in postmenopausal women
    • Satisfactory sexual event frequency: Mean difference 0.85 (95% CI, 0.52 to 1.18)
    • Sexual desire: Standardized mean difference 0.36 (95% CI, 0.22 to 0.50)
    • Pleasure: Mean difference 6.86 (95% CI, 5.19 to 8.52)
    • Arousal: Standardized mean difference 0.28 (95% CI, 0.21 to 0.35)
    • Orgasm: Standardized mean difference 025 (95% CI, 0.18 to 0.32)
    • Responsiveness: Standardized mean difference 0.28 (95% CI, 0.21 to 0.35)
    • Self-image: Mean difference 5.64 (95% CI, 4.03 to 7.26)

Note: Data limited for premenopausal women and conclusions could not be drawn

  • Compared with placebo or a comparator testosterone significantly reduced the following in postmenopausal women
    • Sexual concerns: Mean difference 8.99 (95% CI, 6.90 to 11.08)
    • Distress: Standardized mean difference −0.27 (95% CI, −0.36 to −0.17)
  • Comparing oral testosterone to non-oral (e.g., transdermal patch or cream) for postmenopausal women
    • LDL-cholesterol levels increased
    • Total cholesterol decreased
    • HDL-cholesterol decreased
    • Triglycerides decreased
  • Testosterone treatment was associated with an increase in weight in postmenopausal women
    • Weight gain mean difference 0.48 (95% CI, 0.16 to 0.79)
  • No effects of testosterone were seen for the following (authors caution small ‘n’)
    • Body composition | Musculoskeletal variables | Cognitive measures
  • Adverse events
    • Compared to placebo or comparator, testosterone was significantly associated with greater likelihood of reporting
      • Acne: Relative risk (RR) 1.46 (95% CI, 1.11o 1.92)
      • Hair growth: RR 1.69 (95% CI, 1.33 to 2.14)
    • There were no reported serious events such as alopecia or voice change

CONCLUSION:

  • Testosterone treatment is effective for improving sexual function in postmenopausal women
  • Non-oral route appears to have a superior lipid profile
  • More long-term studies are needed
  • The authors call for approved testosterone formulations, specifically for women and further state

Our comprehensive systematic review provides robust support for a trial of testosterone treatment, using a dose appropriate for women, when clinically indicated in postmenopausal women

Learn More – Primary Sources:

Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data