What is the recommended strength of testosterone therapy for women?

Testosterone Dosing for Women

For women with confirmed androgen deficiency and sexual dysfunction, testosterone therapy should target serum testosterone levels in the upper portion of the normal reference range for reproductive-aged women (approximately 300-600 ng/dL total testosterone), using the lowest effective dose to achieve symptom relief. 1, 2

Recommended Formulations and Dosing

Transdermal Delivery (Preferred Route)

• Transdermal testosterone patches or gels are the preferred delivery method as they provide physiologic testosterone levels and avoid first-pass hepatic metabolism 3, 1
• Investigational testosterone matrix patches designed specifically for women are in advanced clinical development, though not yet FDA-approved 3
• Transdermal formulations avoid the adverse lipid profile changes seen with oral testosterone 1

Dosing Strategy

• Start with low-dose regimens and titrate to achieve testosterone levels at the upper portion of the normal female reference range 1, 2
• Target total testosterone levels should remain within or slightly above the reference range for reproductive-aged women 1
• The goal is symptom improvement (particularly libido and sexual function) while maintaining testosterone in physiologic ranges 2, 4

Clinical Context and Limitations

Current Regulatory Status

• No testosterone preparation has been specifically approved by the FDA for treatment of female sexual dysfunction or androgen insufficiency 2, 5
• Testosterone therapy in women remains off-label use, despite over 40 years of clinical experience 2
• The Endocrine Society recommends against generalized use of testosterone in women due to inadequate long-term safety data 5

Evidence-Supported Populations

• Postmenopausal women with hypoactive sexual desire disorder (HSDD) show the strongest evidence for benefit, particularly surgically menopausal women 2, 5, 4
• Clinical trials up to 2 years duration demonstrate efficacy for improving libido, sexual desire, arousal, frequency, and satisfaction when testosterone is added to estrogen therapy 2, 4

Safety Monitoring Requirements

Short-Term Safety Profile (Up to 2 Years)

• Mild and reversible acne and hirsutism are the most common side effects 1
• No evidence of hepatotoxicity, endometrial hyperplasia, or behavioral hostility at appropriate doses 1
• No adverse cardiovascular effects including blood pressure changes, blood viscosity alterations, or polycythemia have been demonstrated 1

Critical Monitoring Parameters

• Monitor serum testosterone levels regularly to avoid supraphysiologic dosing 4
• Assess for virilization signs (acne, hirsutism, voice deepening) 1, 4
• Lipid profile monitoring, particularly with oral formulations 1

Long-Term Safety Concerns

• Long-term effects on cardiovascular risk and breast cancer incidence remain unknown 5, 4
• Data on breast cancer risk are mixed, with some experimental studies suggesting decreased estrogen-induced breast epithelial proliferation with low-dose testosterone 1

Important Clinical Considerations

Contraindications and Cautions

• Avoid oral alkylated testosterone preparations due to hepatotoxicity risk (this applies to male guidelines but principle extends to women) 6
• Oral testosterone causes adverse lipid profile changes not seen with transdermal administration 1

Patient Selection Criteria

• Confirm symptoms of androgen insufficiency: absent or diminished sexual motivation/desire, persistent unexplained fatigue, lack of well-being 2
• Ensure adequate estrogenization in postmenopausal women before adding testosterone 2
• Address other contributors to sexual dysfunction before initiating testosterone 4

Interaction with Estrogen Therapy

• Oral estrogen therapy significantly reduces free testosterone levels compared to transdermal estrogen 3
• Women on oral estrogen may require higher testosterone doses to achieve therapeutic levels 3
• Consider switching to transdermal estrogen if testosterone supplementation is planned 3

Clinical Decision Algorithm

1. Confirm clinical syndrome: Document symptoms of low libido/sexual dysfunction and androgen insufficiency 2, 4
2. Exclude other causes: Rule out relationship issues, depression, medications, and other medical conditions 4
3. Consider patient population: Strongest evidence exists for surgically menopausal women 2, 5
4. Counsel extensively: Discuss off-label use, lack of FDA approval, and unknown long-term safety 5, 4
5. Initiate low-dose transdermal testosterone: Start with lowest effective dose 1, 3
6. Target physiologic levels: Aim for upper normal range for reproductive-aged women 1
7. Monitor closely: Regular clinical and laboratory assessment to prevent supraphysiologic dosing 4