What is the recommended approach for testosterone replacement therapy in female patients?

Testosterone Replacement Therapy in Female Patients

Testosterone replacement therapy in female patients should be limited to specific clinical scenarios such as primary adrenal insufficiency with persistent libido issues or premature ovarian insufficiency, and should not be used as a general treatment due to limited safety data and lack of FDA approval for this indication.

Indications for Testosterone in Women

Testosterone replacement in women should be considered only in specific clinical scenarios:

• Primary Adrenal Insufficiency: Women with primary adrenal insufficiency (PAI) are deficient in adrenal androgen secretion, including dehydroepiandrosterone (DHEA), which can result in severe androgen deficiency 1

• Premature Ovarian Insufficiency (POI): Patients with iatrogenic POI may suffer from diminished libido or impaired sexual function due to low circulating testosterone levels 1

• Persistent symptoms despite optimized hormone therapy: Consider in women with persistent lack of libido and/or low energy levels despite optimized primary hormone replacement 1

Diagnostic Approach

Before initiating testosterone therapy:

• Confirm underlying condition causing androgen deficiency
• Rule out other causes of symptoms not related to testosterone levels
• Ensure there is a physiologic cause for reduced testosterone levels
• Laboratory assessment should include morning testosterone levels, DHEA sulfate, androstenedione 1

Treatment Recommendations

For Primary Adrenal Insufficiency:

• First-line: Oral DHEA tablets (10–50 mg), often 25 mg as a single daily dose 1
• Monitor serum DHEA sulfate, androstenedione, and testosterone levels
• Maintain levels in the normal range when measured in the morning prior to DHEA ingestion

For Other Female Patients:

• Formulations: Transdermal preparations are preferred over oral formulations 2
• Dosing: Use low-dose regimens that maintain testosterone levels at the upper portion or slightly above the reference range for reproductive-aged women 2
• Duration: Consider as a 6-month trial if clinically indicated 1
• Monitoring: Regular assessment of clinical response and potential side effects

Monitoring and Safety

• Monitor for hirsutism and acne, which are common but generally mild and reversible side effects 2
• Monitor lipid profiles, particularly with oral testosterone formulations 2
• No evidence of increased hepatotoxicity, endometrial hyperplasia, or behavioral hostility in short-term studies (up to 2 years) 2
• No demonstrated adverse cardiovascular effects in short-term studies 2
• Data regarding breast cancer risk is mixed 2

Important Cautions

• Long-term safety studies are lacking 2, 3
• No testosterone product has FDA approval specifically for use in women 4
• The Endocrine Society recommends against making a diagnosis of androgen deficiency in women due to lack of a well-defined clinical syndrome 3
• The Endocrine Society recommends against generalized use of testosterone by women due to inadequate indications and lack of long-term safety data 3

Contraindications

• Breast or uterine cancer
• Cardiovascular or liver disease 5
• Desire for fertility in the near future

Clinical Pearls

• Use the lowest effective dose for the shortest time that meets treatment goals 5
• Transdermal patches and topical gels or creams are preferred over oral products due to first-pass hepatic effects 5
• Custom-compounded products should be used with caution due to inconsistent dosing 5
• Testosterone products formulated for men carry risk of excessive dosing even when used at lower doses in women 5

Remember that testosterone therapy in women remains largely off-label and should be approached with caution, with careful consideration of potential benefits against unknown long-term risks.