What is the recommended dosing for testosterone replacement therapy in postmenopausal women with low testosterone levels?

Testosterone Therapy Dosing for Postmenopausal Women

Critical Upfront Statement

Testosterone therapy is NOT FDA-approved for women, and current major guidelines (AUA, USPSTF) do not provide specific dosing recommendations for postmenopausal women because the evidence focuses on male testosterone deficiency. 1 However, off-label testosterone therapy has been used for over 40 years in postmenopausal women with sexual dysfunction, and research evidence supports its efficacy when used appropriately. 2

Primary Indication for Testosterone in Postmenopausal Women

Testosterone therapy should be considered specifically for postmenopausal women with hypoactive sexual desire disorder (HSDD) who are adequately estrogenized, NOT for general symptoms of menopause or chronic disease prevention. 2, 3

• The primary indication is absent or greatly diminished sexual motivation/desire (libido), persistent unexplainable fatigue, and lack of sense of well-being in the context of documented low testosterone levels. 2
• Women must be adequately estrogenized before adding testosterone—this typically means concurrent estrogen therapy in postmenopausal women. 2, 4

Dosing Recommendations Based on Research Evidence

Transdermal Testosterone (Preferred Route)

Start with low-dose transdermal testosterone formulations designed to maintain levels within the normal female physiological range (approximately 300 μg/day patch or equivalent). 3, 4

• Transdermal patches releasing 150-300 μg of testosterone daily have demonstrated efficacy in clinical trials lasting up to 2 years. 2, 3
• The goal is to achieve testosterone levels in the mid-to-upper normal range for premenopausal women, NOT male reference ranges. 3

Alternative Formulations (Off-Label)

• Compounded bioidentical testosterone preparations are NOT recommended due to lack of standardization, quality control, and safety data. 5
• Methyl testosterone (oral) has been studied but carries significant risk of HDL cholesterol reduction and should be avoided. 4
• Injectable testosterone formulations designed for men are inappropriate due to supraphysiologic dosing. 3

Monitoring Requirements

Monitor total and free testosterone levels 3-6 weeks after initiation, targeting the mid-to-upper normal range for premenopausal women (total testosterone approximately 30-70 ng/dL). 3

• Baseline lipid panel required, with repeat monitoring every 6 months due to risk of HDL cholesterol reduction. 4
• Monitor for androgenic side effects (hirsutism, acne, voice deepening) at each visit—these are reversible with discontinuation. 2, 6
• Liver function tests should be monitored if using oral formulations, though transdermal is preferred. 4

Duration of Therapy

Use the lowest effective dose for the shortest duration necessary to control symptoms, with reassessment every 6-12 months. 5, 3

• Long-term safety data beyond 2 years is lacking in women. 2, 3
• Attempt periodic discontinuation to assess ongoing need. 3

Absolute Contraindications

Do NOT prescribe testosterone to women with:

• History of breast cancer or hormone-sensitive malignancies 5, 7
• Active liver disease 5, 7
• Pregnancy or breastfeeding 6
• Cardiovascular disease or active thrombotic disorders 7

Critical Clinical Pitfalls to Avoid

• Do not use male testosterone formulations or dosing regimens—these result in supraphysiologic levels and increased adverse effects. 3
• Do not prescribe testosterone without concurrent adequate estrogen replacement in postmenopausal women—testosterone works synergistically with estrogen for sexual function. 2, 4
• Do not use testosterone for general menopausal symptoms, fatigue, or osteoporosis prevention—the indication is specifically HSDD with documented androgen deficiency. 3
• Do not rely on total testosterone measurements alone—free testosterone is more physiologically relevant, though measurement accuracy is problematic with standard assays. 6, 3
• Do not prescribe compounded "bioidentical" testosterone pellets or creams—these lack standardization and safety data. 5

Evidence Quality Assessment

The evidence for testosterone dosing in women comes primarily from research studies rather than formal guidelines, as the AUA guideline specifically addresses male testosterone deficiency only. 1 The USPSTF guideline addresses estrogen/progestin therapy but not testosterone. 1 Multiple controlled trials demonstrate efficacy for sexual dysfunction with low-dose testosterone (150-300 μg/day transdermal) in adequately estrogenized postmenopausal women, with good tolerability up to 2 years. 2, 3, 4 However, no FDA-approved testosterone product exists for women, necessitating off-label use with careful monitoring. 3