In a woman with documented low serum testosterone and hypoactive sexual desire unresponsive to non‑pharmacologic measures, when is testosterone therapy indicated, what starting dose and formulation should be used, and how should treatment be monitored and duration limited?

Testosterone Therapy for Hypoactive Sexual Desire Disorder in Women

Testosterone therapy is indicated for postmenopausal women with documented hypoactive sexual desire disorder (HSDD) that causes personal distress and has not responded to non-pharmacologic interventions, when serum testosterone is low and other causes of low libido have been excluded. 1, 2

Diagnostic Confirmation Required Before Treatment

Establish the diagnosis of HSDD:

• Persistent or recurrent deficiency of sexual fantasies and desire for sexual activity that causes marked personal distress 1, 2
• Symptoms must be present for at least 6 months and not better explained by relationship problems, psychiatric conditions, medications, or other medical conditions 2

Measure baseline testosterone:

• Obtain morning total testosterone and calculate free testosterone (using total testosterone and SHBG) 2
• Document low serum testosterone, though no universally accepted threshold exists for women; clinical context matters more than absolute values 1, 2
• Free testosterone by equilibrium dialysis is preferred when available, though calculated free testosterone is acceptable 2

Exclude other causes of low libido:

• Depression, anxiety, relationship discord, medications (SSRIs, antihypertensives), inadequate estrogen status, thyroid dysfunction, and chronic illness 2

Patient Selection Criteria

Appropriate candidates:

• Postmenopausal women (natural or surgical menopause) with confirmed HSDD 1, 2
• Failure of non-pharmacologic measures (relationship counseling, addressing modifiable factors) 2
• Adequate estrogen status if the woman has a uterus (concurrent estrogen-progestin therapy) 1

Limited or no evidence for:

• Premenopausal women (insufficient data) 2
• Perimenopausal women (only limited research supports use) 2
• Women without sexual distress (testosterone should not be used for energy, cognition, or bone health) 2

Starting Dose and Formulation

No FDA-approved testosterone formulation exists for women in the United States. 2 Off-label use of male formulations at reduced doses is current practice:

Transdermal testosterone gel (preferred):

• Start with 5 mg daily (approximately 1/10th of the typical male dose) applied to non-genital skin 1, 2
• Target physiologic to slightly supraphysiologic free testosterone concentrations 3
• Transdermal delivery provides more stable serum levels than injections 4

Alternative formulations:

• Testosterone cream compounded at 1-2% concentration, applied daily 1
• Avoid oral testosterone due to adverse effects on HDL cholesterol 3
• Injectable testosterone is not recommended due to difficulty achieving stable physiologic levels in women 5

Expected Benefits and Realistic Expectations

Modest improvements in sexual function:

• Small but statistically significant increases in sexual desire, arousal, frequency, and satisfaction 6, 1
• Benefits typically emerge after 3-6 months of therapy 1
• Effect sizes are modest; not all women respond 2

Bell-shaped dose-response curve unique to women:

• Unlike men, excessive testosterone doses do not produce greater benefits and may worsen outcomes 5
• Supraphysiologic doses can cause aggression, virilization, and emotional side effects that counteract sexual benefits 5
• This explains why moderate doses are optimal and higher doses should be avoided 5

No proven benefits for:

• Energy, fatigue, or sense of well-being (despite historical claims) 2
• Bone density or fracture prevention 2
• Cognitive function or brain health 2

Monitoring Protocol

Initial follow-up at 6-8 weeks:

• Measure total and free testosterone 3-4 hours after gel application 1, 2
• Target mid-normal female range for free testosterone (avoid supraphysiologic levels) 1, 3
• Assess for androgenic side effects (acne, hirsutism, voice changes) 1, 2

Ongoing monitoring every 3-6 months during first year:

• Repeat testosterone levels to ensure stable dosing 1, 2
• Monitor lipid profile (HDL cholesterol may decrease with oral but not transdermal testosterone) 3
• Assess clinical response: improvement in sexual desire and distress 1, 2
• Screen for virilization (facial hair, clitoromegaly, voice deepening) 1, 2

Annual monitoring once stable:

• Testosterone levels, lipid panel, liver function tests 1, 2
• Clinical assessment of sexual function and side effects 1, 2

Duration of Treatment and Discontinuation

Trial period:

• Assess response at 6 months; if no improvement in sexual desire or distress, discontinue therapy 1, 2
• Continue only if clear benefit is documented 1, 2

Long-term use:

• No long-term safety data beyond 2 years exist 6, 2
• Ongoing risk-benefit assessment is mandatory 2
• Consider periodic treatment holidays to reassess need 1

Discontinue if:

• No symptomatic improvement after 6 months 1, 2
• Development of significant androgenic side effects 1, 2
• Patient no longer desires treatment 2

Safety Considerations and Contraindications

Absolute contraindications:

• Pregnancy or breastfeeding 2
• Androgen-sensitive cancers (breast, endometrial) 2
• Cardiovascular disease (insufficient safety data) 2

Relative contraindications:

• Untreated sleep apnea 2
• Severe acne or hirsutism 2
• Polycystic ovary syndrome 2

Common side effects (mild and dose-dependent):

• Acne and oily skin 6, 3
• Mild hirsutism 6, 3
• Weight gain 1

Serious risks (rare at physiologic doses):

• Virilization (voice deepening, clitoromegaly) if doses are excessive 5, 1
• Potential cardiovascular effects (data insufficient) 2
• Unknown long-term cancer risk 2

Critical Pitfalls to Avoid

Do not prescribe testosterone for:

• Women without documented HSDD and personal distress 1, 2
• Premenopausal women (insufficient evidence) 2
• "Anti-aging," energy, or cognitive enhancement (no proven benefit) 2

Do not use excessive doses:

• Women exhibit a bell-shaped dose-response curve; higher doses worsen outcomes 5
• Target physiologic female levels, not male levels 1, 3

Do not skip baseline evaluation:

• Always exclude depression, relationship issues, medications, and inadequate estrogen before attributing symptoms to testosterone deficiency 2

Do not continue indefinitely without reassessment:

• Lack of long-term safety data mandates ongoing risk-benefit evaluation 2
• Discontinue if no benefit is documented at 6 months 1, 2