What are the guidelines for oral hormone therapy with testosterone in women?

Oral Testosterone Therapy in Women: Not Recommended

Oral testosterone therapy should not be prescribed to women due to significant hepatotoxicity risk and lack of FDA approval for female use. 1

Critical Safety Concerns with Oral Testosterone

Hepatotoxicity Risk

• 17-alpha-alkylated oral testosterone preparations (including methyltestosterone) are associated with severe liver toxicity, including abnormal liver function tests, cholestasis, jaundice, and both benign and malignant hepatic tumors. 1
• The use of oral testosterone formulations in the United States is strongly discouraged and should be avoided. 1
• The AUA explicitly states that clinicians should not prescribe alkylated oral testosterone due to hepatotoxicity concerns. 1

Regulatory Status

• The FDA recently approved oral testosterone undecanoate for men, but specifically contraindicated its use in men with age-related hypogonadism and has not approved it for women. 1
• Oral testosterone undecanoate, while showing less hepatotoxicity than other oral preparations, is not available for women and lacks efficacy data in female populations. 1

Recommended Alternatives: Transdermal Testosterone

Preferred Route of Administration

• Transdermal testosterone (patches or gels) is the recommended route for women when testosterone therapy is indicated, as it avoids first-pass hepatic metabolism and associated liver toxicity. 1, 2, 3
• Transdermal preparations maintain more stable serum levels and have a neutral lipid profile compared to oral formulations. 3

Specific Indications for Testosterone in Women

• Testosterone therapy in women is only recommended for postmenopausal women with hypoactive sexual desire disorder (HSDD) causing distress, after ruling out modifiable factors like relationship problems or mental health issues. 2, 4, 3
• The Endocrine Society recommends against making a diagnosis of "androgen deficiency syndrome" in women due to lack of a well-defined clinical syndrome. 4, 5
• Evidence does not support testosterone use for infertility, cognitive function, cardiovascular health, metabolic health, bone health, or general well-being. 4

Dosing and Monitoring for Transdermal Testosterone

• Use physiological doses that maintain total testosterone levels in the upper physiological range for premenopausal women (approximately 300-400 ng/dL). 2, 3
• Government-approved male transdermal formulations can be used cautiously with appropriate dose adjustments for women (typically 1/10th of male dose). 2
• Monitor for signs of androgen excess including acne, hirsutism, voice deepening, and clitoromegaly at each visit. 2, 4
• Check baseline total testosterone before initiating therapy, then monitor levels 3-6 weeks after starting to ensure levels remain in physiological range. 2

Critical Pitfalls to Avoid

Compounded Products

• Do not prescribe compounded testosterone preparations due to lack of quality control, variable potency, and absence of efficacy and safety data. 1, 2
• Individual pharmacies operate without direct FDA oversight, resulting in considerable variation in potency even between batches from the same pharmacy. 1

Contraindications

• Active liver disease (absolute contraindication for any testosterone formulation). 1
• Current or history of breast cancer or hormone-sensitive malignancies. 1
• Pregnancy or women attempting to conceive. 4
• Cardiovascular disease within the past 3-6 months. 1

Long-term Safety Concerns

• Long-term safety data (>2 years) for testosterone therapy in women are lacking. 2, 4, 3
• Short-term studies (up to 2 years) show no increased risk of cardiovascular events, endometrial hyperplasia, or behavioral changes when testosterone levels are maintained in physiological ranges. 6
• Data on breast cancer risk remain mixed and inconclusive. 6

Clinical Algorithm for Testosterone Consideration in Women

1. Confirm postmenopausal status (premenopausal use has limited data). 2, 4
2. Diagnose HSDD based on persistent distressing low sexual desire not explained by relationship issues, medications, or psychiatric conditions. 2, 4
3. Rule out contraindications: liver disease, breast cancer history, recent cardiovascular events. 1
4. Obtain informed consent discussing off-label use, limited long-term safety data, and potential adverse effects. 2
5. Check baseline total testosterone level (not for diagnosis, but for monitoring reference). 2
6. Prescribe transdermal testosterone only (never oral formulations). 1, 2, 3
7. Reassess at 3-6 weeks: check testosterone level and signs of androgen excess. 2
8. Continue monitoring every 3-6 months for efficacy, adverse effects, and testosterone levels. 2, 4