Testosterone and Estrogen Dosing for Females
Critical Context: Indication Determines Dosing Strategy
The appropriate dose of testosterone and estrogen for females depends entirely on the clinical indication—masculinizing gender-affirming therapy requires male-range testosterone levels (100-200 mg intramuscularly every 2 weeks), while treatment of sexual dysfunction in postmenopausal cisgender women requires dramatically lower doses (4.4 mg transdermal testosterone gel daily) combined with estrogen therapy. 1, 2
For Masculinizing Gender-Affirming Hormone Therapy
Testosterone Dosing
- Injectable testosterone enanthate or cypionate: 100-200 mg intramuscularly every 2 weeks, or 50 mg weekly 3, 1
- Testosterone undecanoate (long-acting): 750 mg initially, followed by 750 mg after 4 weeks, then 750 mg every 10 weeks 3, 1
- Target serum testosterone: 500-600 ng/dL (mid-cycle for injections), within the cisgender male reference range of 300-1000 ng/dL 3, 1
Monitoring Requirements
- Measure testosterone levels 2-3 months after treatment initiation and after any dose change; once stable, monitor every 6-12 months 3
- For injectable formulations, measure testosterone midway between injections to target mid-normal values (500-600 ng/dL) 3, 1
- Monitor hemoglobin/hematocrit—expect increase to male reference range within 3 months 1
- Assess for adverse effects including polycythemia, reduced HDL cholesterol, acne, androgenic alopecia, and pelvic pain 1
Expected Physiological Changes
- Voice deepening, facial/body hair growth, menstrual suppression, clitoral growth, increased muscle mass with decreased fat mass occur within 3-12 months 1
For Sexual Dysfunction in Postmenopausal Cisgender Women
Critical Dosing Principle: Bell-Shaped Dose-Response Curve
Women demonstrate a bell-shaped dose-response curve for testosterone—exceeding threshold doses eliminates benefits and causes virilization, unlike the linear dose-response seen in men. 4
Testosterone Dosing (Must Be Combined with Estrogen)
- Transdermal testosterone gel: 4.4 mg daily raises total testosterone to mid- to high-normal female range (average steady-state concentration approximately 51.6 ng/dL) 2
- Higher doses (8.8-13.2 mg daily) raise testosterone above physiological range and inevitably cause virilization 4, 2
- Transdermal testosterone cream: 5 mg daily restores testosterone levels to premenopausal female reference range 5
- Application site: Upper arms or shoulders for gels; avoid abdomen, genitals, chest, or axillae 6
Estrogen Dosing (Required Concomitantly)
- Conjugated equine estrogen (CEE): 0.625 mg daily 3
- 17β-estradiol: 1-2 mg daily (oral) or 0.014 mg daily (transdermal) 3
- Testosterone therapy without concomitant estrogen cannot be recommended due to lack of evidence 7
Monitoring and Safety
- Laboratory testing should monitor for supraphysiologic testosterone levels, NOT to diagnose deficiency—no testosterone level has been clearly linked to clinical hypoandrogenism in women 7
- Assess subjective sexual response, desire, and satisfaction alongside monitoring for hirsutism and acne 7
- Transdermal preparations preferred over oral formulations due to first-pass hepatic effects 7
Contraindications
- Breast or uterine cancer, cardiovascular disease, or liver disease 7
Common Pitfalls to Avoid
Dosing Errors
- Using male-formulated testosterone products risks excessive dosing in women—FDA-approved male testosterone gels deliver 20.25-81 mg daily, far exceeding appropriate female doses 6
- Custom-compounded products may have inconsistent dosing 7
Inappropriate Use
- Testosterone therapy in cisgender women is ONLY indicated for decreased sexual desire with personal distress and no other identifiable cause—NOT for bone density, hot flashes, lean body mass, or well-being 7
- Rule out physical, psychosocial factors, and medications as causes before considering testosterone 7
Monitoring Timing
- For transdermal preparations, testosterone levels can be measured at any time, though peak values occur 6-8 hours after application 3
- Avoid showering for at least 2 hours after gel application to prevent reduced bioavailability (13% decrease if showering at 2 hours) 6
Transfer Risk
- Direct skin-to-skin contact with application site increases female partner testosterone by 280%—covering site with t-shirt reduces transfer to 6% increase 6
- Wash hands immediately with soap and water after application 6
Cardiovascular Risk Considerations
- Conflicting evidence exists regarding cardiovascular safety—FDA required labeling changes in 2015 regarding potential increased risk of heart attack and stroke, though this primarily addressed age-related hypogonadism treatment in men 3, 1
- Testosterone injections may carry greater cardiovascular risk than transdermal preparations due to fluctuating serum levels 3
- For transgender individuals, some studies suggest increased myocardial infarction risk, though data remain inconclusive 1