What is the role of Anastrozole (aromatase inhibitor) in hormone therapy for a transgender woman transitioning from male to female, and what are the recommended dosing and monitoring guidelines?

Anastrozole Has No Role in Transfeminine Hormone Therapy

Anastrozole is contraindicated and should never be used in transgender women transitioning from male to female, as it works against the goals of feminizing hormone therapy by blocking estrogen production. 1

Why Anastrozole is Contraindicated in Transfeminine Transition

Mechanism Directly Opposes Treatment Goals

• Anastrozole is a selective aromatase inhibitor that blocks the conversion of androgens (testosterone and androstenedione) to estrogens (estradiol and estrone) in peripheral tissues. 1
• The drug suppresses serum estradiol by approximately 70% within 24 hours and 80% after 14 days of daily dosing, reducing estradiol to the lower limit of detection (3.7 pmol/L). 1
• Transgender women require elevated estradiol levels to achieve feminization—anastrozole would directly sabotage this therapeutic objective. 1

FDA-Approved Indications Exclude This Population

• Anastrozole is FDA-approved exclusively for postmenopausal women with hormone receptor-positive breast cancer or for breast cancer risk reduction in high-risk postmenopausal women. 1, 2, 3
• The drug has never been studied or approved for use in premenopausal individuals or for gender-affirming care. 1
• The effect of anastrozole in premenopausal women has not been studied because aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women. 1

Appropriate Gender-Affirming Hormone Therapy for Transfeminine Patients

Standard Feminizing Regimen

• The Endocrine Society 2017 guidelines recommend that transgender women receive estrogen therapy (typically estradiol) combined with an androgen blocker (such as spironolactone or GnRH agonists) to achieve hormone levels consistent with their affirmed gender identity. 4
• Gender-affirming hormone therapy is safe when used within established protocols and is associated with significant improvements in mental health outcomes, including reduction in depression, anxiety, and gender dysphoria. 5

Treatment Goals

• The therapeutic objective is to increase estradiol levels to typical female ranges (100-200 pg/mL) while suppressing testosterone to female ranges (<50 ng/dL). 4
• Patients should receive information and counseling about fertility preservation before initiating hormone therapy, as this is a key component of comprehensive transgender care. 4

Critical Pitfall to Avoid

Do not confuse anastrozole's use in cisgender men on testosterone replacement therapy (where it prevents excessive estradiol elevation from aromatization) with transgender medicine—these are opposite clinical scenarios. 6, 2 In cisgender men, anastrozole may be used off-label to reduce unwanted estrogen elevation during testosterone therapy, but in transgender women, the goal is to maximize estrogen while minimizing testosterone.