What is the recommended approach for testosterone replacement therapy in women?

Testosterone Replacement Therapy for Women

Testosterone replacement therapy in women should be administered transdermally at physiologic doses for specific indications like hypoactive sexual desire disorder, with careful monitoring for androgenic side effects.

Indications and Benefits

• Testosterone replacement therapy in women is primarily indicated for hypoactive sexual desire disorder in postmenopausal women, with demonstrated short-term efficacy in improving sexual function 1
• Women with iatrogenic premature ovarian insufficiency (POI) may experience diminished libido or impaired sexual function due to low circulating testosterone levels 2
• Benefits of testosterone therapy for women include meaningful improvements in sexual desire, arousal, orgasm, pleasure, and responsiveness, with a reduction in distress 1
• Testosterone therapy typically provides an additional satisfying sexual episode per month for postmenopausal women with hypoactive sexual desire disorder 1

Administration and Dosing

• Transdermal testosterone is the preferred route of administration for women, as it:

  • Delivers testosterone at a controlled rate into systemic circulation 3
  • Avoids hepatic first-pass metabolism 3
  • Maintains more stable serum testosterone concentrations 4
  • Has fewer androgenic side effects when dosed within premenopausal physiologic ranges 1

• Dosing considerations:

  • Testosterone should be dosed within premenopausal physiologic testosterone ranges 1
  • The dose should be adjusted according to each woman's tolerance and feeling of wellbeing 2
  • Testosterone can be used alone or with menopausal hormone therapy for postmenopausal women 1

• Important caveat: No testosterone preparation is specifically FDA-approved for women, so all use is off-label 1

  • Compounded testosterone creams or reduced dosing of male-approved therapies represent off-label use 1
  • Injections or pellets cause supraphysiological testosterone levels and are not recommended for women 1

Monitoring and Safety Considerations

• Short-term studies (up to 2 years) show that testosterone at the upper portion or slightly above the reference range for reproductive-aged women does not increase risk of:

  • Hepatotoxicity
  • Endometrial hyperplasia
  • Behavioral hostility
  • Adverse cardiovascular effects 5

• Potential side effects to monitor:

  • Mild and reversible acne and hirsutism 5
  • Changes to lipid profile with oral (but not transdermal) testosterone 5
  • Risk of secondary exposure through skin contact with application site 6

• Monitoring recommendations:

  • Regular assessment of androgenic side effects
  • Monitoring of lipid profiles, especially with oral formulations
  • For women with history of cancer, particularly breast cancer survivors, careful monitoring is essential 2
  • Annual breast imaging from age 25 years onwards for high-risk women 2

Contraindications and Precautions

• Oral testosterone preparations should be avoided due to potential hepatotoxicity 2
• When using testosterone gel, precautions should be taken to prevent unintentional transfer to others through skin contact 6
• For women with progestins as part of hormone therapy, those with anti-androgenic effects should be avoided as they could worsen hypoandrogenism 2
• In women with history of hormone-sensitive cancers, careful risk-benefit assessment is needed before initiating therapy

Duration of Therapy

• For women with iatrogenic POI, hormone replacement therapy (including testosterone if indicated) should be continued until the average age of spontaneous menopause (45-55 years) 2
• After this age, continuation should be based on individual risk assessment, family history, personal preferences, and symptom severity 2
• Lower post-menopausal doses have been associated with a more favorable risk-benefit ratio 2

Important Caveats

• Long-term data on cardiovascular, cancer, and cognitive safety of testosterone therapy in women are lacking 1
• Data regarding breast cancer risk with testosterone therapy is mixed, with some experimental studies suggesting a potential decrease in estrogen-induced breast epithelial proliferation with low-dose testosterone 5
• Transdermal testosterone gel can pose a risk of unintentional transfer to children or women through skin contact with the application site 6