Is there evidence for using testosterone therapy in women for Hormone Replacement Therapy (HRT)?

Evidence for Testosterone Therapy in Women for HRT

Testosterone therapy in women for hormone replacement therapy has limited evidence supporting its use for specific indications such as low libido, but lacks long-term safety data and is not FDA-approved specifically for women. 1, 2

Current Evidence and Indications

• Testosterone therapy has shown benefit primarily for treating low sexual desire/libido in women, especially postmenopausal women who are adequately estrogenized 2
• Short-term studies (up to 2 years) suggest that testosterone at doses that maintain levels at the upper portion or slightly above the reference range for reproductive-aged women appears relatively safe 1
• Most clinical trials in postmenopausal women have demonstrated that adding testosterone to estrogen significantly improved multiple aspects of sexual functioning including:
  • Libido and sexual desire
  • Arousal
  • Frequency of sexual activity
  • Sexual satisfaction 2

Safety Considerations

Potential Side Effects

• Mild and reversible androgenic effects:
  • Acne
  • Hirsutism (unwanted hair growth)
  • Changes to lipid profile (with oral, but not transdermal testosterone) 1

Short-term Safety Data (up to 2 years)

• No increased risk of hepatotoxicity
• No endometrial hyperplasia
• No behavioral hostility
• No adverse cardiovascular effects observed including:
  • No changes in blood pressure
  • No changes in blood viscosity
  • No changes in arterial vascular reactivity
  • No hypercoagulable states
  • No polycythemia 1

Breast Cancer Risk

• Data is mixed regarding breast cancer risk
• Some experimental studies suggest a decrease in estrogen-induced breast epithelial proliferation with low-dose testosterone
• Models of superphysiologic testosterone levels (such as polycystic ovarian disease) have not shown increased risk of breast cancer 1

Limitations and Gaps in Evidence

• No testosterone preparation has been specifically FDA-approved for women's sexual interest/desire disorder or for androgen insufficiency in women 2
• Long-term safety studies (beyond 2 years) are lacking 1
• Most testosterone use in women is in the form of compounded preparations or off-label use of formulations designed for men 3

Practical Considerations

When to Consider Testosterone Therapy

• Women with symptoms of androgen insufficiency:
  • Absent or greatly diminished sexual motivation/desire
  • Persistent unexplainable fatigue or lack of energy
  • Lack of sense of well-being 2
• Most appropriate for postmenopausal women who are already on estrogen therapy 2

Monitoring

• Monitor for androgenic side effects (acne, hirsutism)
• Regular lipid profile assessment, particularly with oral formulations
• Maintain testosterone levels within or slightly above the normal female reference range 1

Conclusion

While short-term evidence suggests testosterone therapy may be beneficial for specific symptoms in women (particularly sexual dysfunction), the lack of long-term safety data and FDA-approved formulations specifically for women means it should be used with caution. The decision to use testosterone therapy should be made after considering potential benefits against the limited long-term safety data available.