What is the approach to testosterone replacement therapy (TRT) in women?

Testosterone Replacement Therapy in Women

Primary Indication

Testosterone therapy should be prescribed specifically for postmenopausal women with hypoactive sexual desire disorder (HSDD) who have completed a biopsychosocial assessment ruling out modifiable factors such as relationship problems, mental health disorders, or other treatable comorbidities. 1, 2

Patient Selection

Appropriate Candidates

• Postmenopausal women with HSDD represent the sole evidence-based indication for testosterone therapy 1, 2
• Limited data support use in late reproductive age premenopausal women, though this remains less established 1
• Women must have distressing decreased sexual desire not primarily attributable to relationship dysfunction, depression, or other modifiable factors 1, 3

Absolute Contraindications

• Breast cancer survivors should not receive testosterone therapy 4
• Women with cardiovascular disease history should avoid testosterone-containing hormone therapy 5
• Patients with low-grade serous epithelial ovarian cancer, granulosa cell tumors, certain sarcomas (leiomyosarcoma, stromal sarcoma), or advanced endometrioid uterine adenocarcinoma 4

Diagnostic Approach

Key Clinical Points

• Do NOT use total testosterone levels to diagnose HSDD - the diagnosis is purely clinical based on symptoms and distress 1
• Obtain baseline total testosterone level before initiating therapy for monitoring purposes only 1
• Assess for vasomotor symptoms, vaginal dryness, and other menopausal complaints that may require estrogen therapy 4
• Screen for depression, relationship issues, and medications (SSRIs, antihypertensives) that impair sexual function 1

Treatment Protocol

Formulation and Dosing

• Transdermal testosterone is the recommended route - patches, gels, or creams 1, 3
• Start with 5 mg transdermal testosterone daily or less using male formulations applied cautiously 3
• Government-approved transdermal male formulations can be used with appropriate dosing adjustments for women 1
• Compounded products cannot be recommended due to lack of efficacy and safety data 1

Informed Consent Requirements

• Discuss off-label use of testosterone in women 1
• Explain moderate therapeutic benefit with increased satisfying sexual episodes and sexual desire 1, 3
• Review lack of long-term safety data beyond short-term trials 1, 6
• Document shared decision-making discussion 1

Monitoring Protocol

Initial Follow-up

• First visit at 1-2 months to assess efficacy and tolerability 1
• Evaluate for signs of androgen excess: acne, hirsutism, voice deepening, clitoromegaly 1
• Measure total testosterone level to ensure physiologic premenopausal range 1

Ongoing Monitoring

• Follow-up visits every 3-6 months during the first year 1
• Annual visits thereafter with continued assessment 1
• At each visit: assess symptomatic response, signs of virilization, and testosterone levels 1
• Maintain testosterone concentrations in the physiologic premenopausal range - do not exceed normal female levels 1

Dose Adjustments

• Increase dose if inadequate clinical response with suboptimal testosterone levels 1
• Decrease or discontinue if signs of androgen excess develop or testosterone levels exceed premenopausal range 1

Combination with Estrogen Therapy

For Women with Intact Uterus

• If prescribing estrogen for menopausal symptoms, add progestin (micronized progesterone) to protect against endometrial hyperplasia and cancer 5
• Transdermal estradiol is preferred over oral for better cardiovascular risk profile 5

For Women After Hysterectomy

• Estrogen alone without progestin is appropriate 4
• Consider estrogen therapy for vasomotor symptoms, vaginal dryness, and bone health 4

Special Populations

Surgically Menopausal Women

• Women with bilateral oophorectomy often have more severe androgen deficiency 4
• These patients may particularly benefit from testosterone therapy for HSDD 1
• Hormone therapy is recommended until at least the average age of natural menopause for women with early or premature surgical menopause 4

Gynecologic Cancer Survivors

• No contraindication for testosterone in cervical, vaginal, or vulvar cancer survivors 4
• Favorable risk/benefit profile for most non-epithelial and epithelial ovarian cancers (high grade, clear cell, mucinous) 4
• May consider in early-stage endometrial cancer patients, though caution advised 4

Common Pitfalls

• Avoid using testosterone levels to diagnose HSDD - approximately 40% of postmenopausal women have decreased sexual desire, but there is no clear correlation between sexual desire and circulating testosterone levels 3
• Do not prescribe for cardiovascular disease prevention - hormone therapy increases stroke, venous thromboembolism, and coronary heart disease risk 5
• Recognize that testosterone therapy remains significantly underprescribed - only 2.54% of women diagnosed with HSDD receive testosterone prescriptions 7
• Ensure proper dosing - male formulations contain high concentrations requiring careful dose reduction for women 3
• Monitor for virilization - though adverse effects are typically mild with physiologic dosing 1, 3

Alternative Approaches

When testosterone is contraindicated or declined, consider:

• SSRIs or SNRIs for persistent symptoms, though these may paradoxically worsen sexual function 4
• Cognitive behavioral therapy, yoga, acupuncture for menopausal symptoms 4
• Vaginal estrogen therapy for local genitourinary symptoms 4
• Referral to sexual health specialists or multidisciplinary onco-sexuality clinics 4