Is testosterone therapy safe for women?

Safety of Testosterone Therapy in Women

Testosterone therapy in women has limited safety data and should not be routinely prescribed due to insufficient evidence regarding long-term safety and the lack of FDA-approved formulations specifically for women.

Current Evidence on Safety

The safety profile of testosterone in women varies based on dosage, administration route, and duration of treatment:

Short-term Safety (up to 2 years)

• When used at physiologic doses (maintaining levels in the upper normal range for premenopausal women), short-term studies show:
  • No increased risk of hepatotoxicity
  • No endometrial hyperplasia
  • No adverse cardiovascular effects including blood pressure changes, blood viscosity alterations, or hypercoagulable states 1
  • No polycythemia when used transdermally at appropriate doses for women 1

Potential Side Effects

• Common and generally mild side effects include:
  • Acne (reversible)
  • Hirsutism (reversible)
  • Lipid profile changes (with oral, but not transdermal formulations) 1

Major Safety Concerns

1. Cardiovascular Risk:

   • Long-term cardiovascular safety data in women is lacking 2
   • Unlike in men, where testosterone therapy has been extensively studied, the cardiovascular effects in women remain uncertain

2. Cancer Risk:

   • Breast cancer risk data is mixed 1
   • Long-term safety studies regarding cancer risk are insufficient 2

3. Virilization:

   • Risk of virilization with supraphysiologic doses 3
   • Injections or pellets can cause supraphysiological levels and are not recommended 2

Formulation Considerations

• Transdermal formulations are preferred as they:

  • Produce more stable hormone levels
  • Have fewer effects on lipid profiles compared to oral formulations 1
  • Can be dosed more appropriately for women

• Inappropriate formulations:

  • Injections and pellets are not recommended due to supraphysiological levels 2
  • Compounded products cannot be recommended due to lack of efficacy and safety data 4

Monitoring Recommendations

If testosterone therapy is initiated despite limited safety data:

• Baseline total testosterone level should be obtained before treatment 4
• Monitor for signs of androgen excess:
  • Acne
  • Hirsutism
  • Voice changes
  • Clitoromegaly
• Maintain testosterone concentrations in the physiologic premenopausal range 4
• Regular follow-up to assess for adverse effects

Important Caveats

• No testosterone preparation is FDA-approved specifically for women 2
• Current use represents off-label prescribing
• The International Society for the Study of Women's Sexual Health notes that access to properly dosed testosterone therapy for women remains an unmet need 4
• Unregulated prescribing practices have led to potentially dangerous outcomes 5

Clinical Decision Algorithm

1. Consider testosterone only if:

   • Patient has hypoactive sexual desire disorder not primarily related to modifiable factors
   • Other causes (relationship issues, mental health problems) have been addressed
   • Benefits may outweigh risks for the individual patient

2. If proceeding:

   • Use only transdermal preparations
   • Dose appropriately to maintain physiologic premenopausal levels
   • Monitor closely for adverse effects
   • Discontinue if virilizing side effects occur
   • Inform patient of off-label use and limited long-term safety data

3. Absolute contraindications:

   • History of hormone-sensitive cancers
   • Pregnancy or breastfeeding
   • Untreated polycythemia
   • Severe acne or hirsutism

The Endocrine Society previously recommended against the generalized use of testosterone in women due to inadequate indications and lack of long-term safety data 6, highlighting the need for caution in clinical practice.