What is the approach to testosterone replacement therapy (TRT) in postmenopausal females with hypoactive sexual desire disorder (HSDD)?

Testosterone Replacement Therapy for Postmenopausal Women with HSDD

Testosterone therapy is recommended for postmenopausal women with hypoactive sexual desire disorder (HSDD) when non-hormonal treatments fail, with transdermal formulations being the preferred delivery method. 1

Diagnostic Approach for HSDD

• HSDD is characterized by absence of sexual fantasies, thoughts, and/or desire for sexual activity
• Affects approximately 4 million women with approximately 16 million women over age 50 experiencing low sexual desire 2
• Diagnosis requires:
  • Ruling out modifiable factors (relationship issues, mental health problems)
  • Excluding medication side effects (particularly SSRIs/SNRIs which can reduce libido and cause anorgasmia) 3
  • Confirming symptoms are not primarily due to vaginal dryness or pain

Treatment Algorithm for HSDD in Postmenopausal Women

First-Line Approaches

1. Non-hormonal interventions:

   • Address vaginal dryness with silicone-based lubricants and moisturizers
   • Consider sex therapy for relationship factors
   • Evaluate and discontinue medications that may affect sexual function (especially SSRIs/SNRIs) 3

2. FDA-approved medications for premenopausal women:

   • Flibanserin - results in approximately 1 additional satisfying sexual event every 2 months 3
   • Bremelanotide - increases sexual desire and reduces distress related to low desire 3
   • Note: These are only FDA-approved for premenopausal women but may be considered off-label for postmenopausal women 3

Second-Line Approach: Testosterone Therapy

• Indication: Postmenopausal women with HSDD not responding to first-line treatments 1
• Formulation: Transdermal testosterone (patches or gels) is preferred 1, 4
• Dosing: Use government-approved transdermal male formulations cautiously with dosing appropriate for women 1
• Target levels: Maintain total testosterone concentrations in the physiologic premenopausal range 1
• Efficacy: Randomized controlled trials demonstrate improved sexual function, desire, and activity 4, 2

Monitoring and Safety Considerations

Pre-treatment Assessment

• Baseline total testosterone level (not for diagnosis but for monitoring) 1
• Informed consent discussion regarding:
  • Off-label use status (no FDA-approved testosterone products for women)
  • Expected benefits: moderate therapeutic improvement in sexual desire 1
  • Potential risks and side effects

Ongoing Monitoring

• Monitor for signs of androgen excess (acne, increased hair growth) 4
• Regular measurement of total testosterone levels to maintain physiologic premenopausal range 1
• Follow-up every 3-6 months to assess efficacy and adverse effects

Safety Profile

• Short-term safety data shows no serious adverse events with physiologic testosterone use 1, 4
• Main side effects reported in clinical trials were increased hair growth and acne 4
• Long-term safety has not been fully established 1
• Available data are reassuring regarding cardiovascular, breast, and endometrial outcomes 4

Important Caveats

• Compounded testosterone products are not recommended due to lack of efficacy and safety data 1
• Testosterone may not be effective without adequate circulating estrogen 3
• Testosterone therapy is not recommended for breast cancer survivors 3
• Bupropion may be considered as an alternative for improving sexual function in breast cancer survivors, though larger trials are needed 3

Conclusion

Transdermal testosterone therapy is an effective treatment for postmenopausal women with HSDD when non-hormonal approaches fail. While not FDA-approved specifically for this indication, substantial evidence supports its efficacy and short-term safety when properly dosed and monitored.