What is the role of testosterone replacement therapy in women, particularly for hypoactive sexual desire disorder (HSDD)?

Testosterone Replacement Therapy in Women

Testosterone therapy can be considered for postmenopausal women with hypoactive sexual desire disorder (HSDD) who have not responded to addressing modifiable factors, using low-dose transdermal formulations with careful monitoring, though this remains an off-label use without FDA approval for women. 1

Patient Selection and Diagnosis

Appropriate Candidates

• Postmenopausal women with HSDD are the primary candidates supported by evidence, particularly those with surgically induced menopause who show the strongest response to treatment 1, 2
• Limited data support use in late reproductive age premenopausal women, though evidence is less robust 1, 3
• HSDD must not be primarily related to modifiable factors such as relationship problems, mental health disorders, or other treatable comorbidities 1

Diagnostic Approach

• Total testosterone levels should NOT be used to diagnose HSDD - no single testosterone level predicts low sexual function in women 1, 2
• Obtain baseline total testosterone level before treatment initiation for monitoring purposes only, not diagnosis 1
• The diagnosis of HSDD is clinical, based on distressing low sexual desire that causes personal distress 1, 3

Treatment Protocol

Formulation and Dosing

• Systemic transdermal testosterone is the recommended route of administration 1
• Government-approved transdermal male formulations can be used cautiously with dosing adjusted appropriately for women (typically 1% testosterone 5g twice weekly has been reported) 1, 4
• Compounded products cannot be recommended due to lack of efficacy and safety data 1

Expected Benefits

• Moderate therapeutic benefit with improvements in sexual desire, arousal, frequency of sexual activity, orgasm, and overall satisfaction 1, 2
• Response typically occurs within 3 weeks to 3 months of initiating therapy 4
• Current data show no benefit for bone health, brain health, energy, or cognition - testosterone should only be used for HSDD 3

Monitoring and Safety

Required Monitoring

• Monitor total testosterone levels to maintain concentrations in the physiologic premenopausal range (not supraphysiologic levels) 1
• Assess for signs of androgen excess at each visit, including hirsutism, acne, voice deepening, and clitoromegaly 1, 4
• Laboratory monitoring every 3 months should include: complete blood count, lipid profiles, liver function tests, and free and total testosterone levels 4
• Once stable, monitoring intervals can be extended to every 6-12 months 5

Safety Profile

• Short-term safety data show no serious adverse events with physiologic testosterone use 1, 6
• Most common side effects are mild facial acne and hirsutism, which are typically reversible upon discontinuation 4, 2
• Long-term safety has not been established, particularly regarding cardiovascular risk and breast cancer incidence 1, 6, 3

Critical Clinical Considerations

Informed Consent Requirements

• Clinicians must provide informed consent before initiating therapy 1
• Shared decision-making must include comprehensive discussion of:
  • Off-label use (no FDA-approved testosterone formulation for women in the United States) 1, 3
  • Moderate expected benefits 1
  • Lack of long-term safety data 1, 6
  • Need for ongoing monitoring 1

Treatment Duration and Discontinuation

• If no improvement in sexual function after 12 months, discontinue treatment 5
• Side effects like acne typically resolve within 2 months after completing treatment 4

Important Limitations

• Testosterone is NOT indicated for women with normal sexual function - it should only be used for documented HSDD 1
• No role for testosterone in treating energy, vitality, cognitive function, or physical functioning in women 3
• The lack of FDA-approved formulations makes proper dosing challenging and requires careful titration using male formulations 1, 3