Are estradiol (estrogen) tablets effective for gender affirming therapy in transgender women?

Effectiveness of Estradiol Tablets for Gender Affirming Therapy in Transgender Women

Estradiol tablets are effective for gender affirming therapy in transgender women, but they carry a higher risk of venous thromboembolism compared to transdermal formulations and should be used with caution in patients with thrombotic risk factors. 1

Effectiveness of Estradiol Tablets

Oral estradiol therapy has demonstrated effectiveness in achieving feminizing effects in transgender women, including:

• Changes in body composition (increased fat mass, reduced muscle mass)
• Breast growth
• Skin softening
• Decreased body and facial hair
• Decreased libido
• Reduced erectile function
• Decreased testicular size 2

However, certain physical characteristics induced by prior male puberty do not change with feminizing hormone therapy, such as:

• Voice pitch
• Laryngeal prominence (Adam's apple)
• Bone structure 2

Dosing and Monitoring

• Oral estradiol is effective in achieving desired serum levels of 17-β estradiol, but there is wide individual variability in the amount required 3
• Over 70% of transgender women achieve treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more 3
• Nearly a third of patients do not achieve adequate treatment goals even on 6-8 mg daily of estradiol 3
• Regular monitoring of hormone levels is essential to individualize therapy and achieve optimal results 3

Safety Considerations and Risks

Oral estradiol carries several important risks that must be considered:

1. Cardiovascular risks:

   • Increased risk of ischemic stroke and myocardial infarction compared to cisgender women 2, 1
   • Consistent increased risk of venous thromboembolism (VTE) compared to cisgender men and women 2, 1
   • This risk persists despite changes in estradiol dosing and preparations over time 1

2. Other adverse effects:

   • Weight gain
   • Potential bone structure compromise
   • Infertility 2

3. Route-specific considerations:

   • Oral formulations have higher VTE risk compared to transdermal estradiol patches 1
   • Ethinyl estradiol (a specific oral formulation) is not recommended due to its high thrombogenic potential 1

Clinical Recommendations for Oral Estradiol Use

1. Patient selection:

   • Carefully assess thrombotic risk factors including age, smoking status, BMI, personal or family history of VTE, known thrombophilia, and immobility or recent surgery 1
   • Consider transdermal estradiol patches instead of oral formulations for patients with thrombophilia or other significant risk factors 1

2. Contraindications:

   • Previous thrombotic events
   • Estrogen-sensitive malignancies
   • End-stage liver disease
   • Coronary artery disease with unstable angina
   • Uncontrolled hypertension 1

3. Monitoring:

   • Regular clinical assessment for VTE symptoms
   • Regular monitoring of estradiol and testosterone levels to guide dosing adjustments 3
   • Education about warning signs of VTE 1

Combination Therapy

• Antiandrogens are often used in combination with estradiol for optimal feminization
• Options include spironolactone, cyproterone acetate, bicalutamide, finasteride, or GnRH analogues 1
• Spironolactone may impair achievement of goal serum estradiol levels 3
• Finasteride has been associated with higher testosterone levels 3

Perioperative Considerations

• Thrombosis risk is the main concern with estradiol therapy during surgery
• The physical and mental health benefits of continuing estradiol therapy may outweigh the risk of thrombosis in many cases 2
• Discontinuation of estradiol therapy before surgery may carry negative psychological consequences 2
• The decision to continue or temporarily cease estradiol therapy requires careful assessment of individual risk factors 2

In conclusion, while oral estradiol tablets are effective for gender affirming therapy in transgender women, transdermal formulations may offer a safer profile, particularly for those with elevated thrombotic risk factors.