Are estradiol (E2) blood levels of severely elevated estradiol safe for a trans female?

From the Guidelines

Estradiol blood levels of 900 pg/ml are considered excessively high and potentially hazardous for transfemale individuals, necessitating a discussion with a healthcare provider to adjust the hormone regimen and mitigate associated health risks. The optimal target range for estradiol in transgender hormone therapy is typically between 100-200 pg/ml, akin to levels found in cisgender women during the follicular phase of their menstrual cycle 1. Levels as high as 900 pg/ml substantially exceed physiological ranges, potentially increasing the risk of adverse effects such as venous thromboembolism, cardiovascular issues, and liver problems.

Key considerations for transfemale individuals undergoing hormone therapy include:

• The use of estrogen and adjunct antiandrogen therapy to achieve feminine physical attributes, such as increased breast development and decreased facial and body hair 1
• The importance of regular blood monitoring to maintain appropriate hormone levels and minimize health risks 1
• The potential for adverse effects, including weight gain, compromised bone structure, infertility, and cardiovascular disease, which necessitate careful management and monitoring 1

In terms of management, healthcare providers may recommend:

• Reducing the estradiol dosage or changing the administration method to achieve a more physiological level 1
• Utilizing common estradiol formulations, such as oral tablets, transdermal patches, or injectable estradiol valerate or cypionate, to achieve the desired feminization effects while minimizing health risks
• Regularly monitoring blood levels every 3 months initially, then every 6-12 months once stable, to ensure optimal hormone levels and minimize adverse effects 1

From the Research

Estradiol Blood Levels and Safety for Transfemales

• The provided studies do not directly address the safety of estradiol blood levels of 900 pg/ml for transfemales 2, 3, 4, 5, 6.
• However, study 3 suggests that different clinical endpoints have different response thresholds to estradiol levels, and that a very low concentration of estradiol (<15 pg/ml) is sufficient to suppress serum LH and FSH levels and relieve vasomotor symptoms.
• Study 6 reports that the serum estradiol level with estradiol 2 mg (107.6 pg/mL) was significantly higher than with estradiol 1 mg (65.8 pg/mL) or conjugated estrogen 0.45 mg (60.1 pg/mL), but does not provide information on the safety of levels as high as 900 pg/ml.
• Study 4 mentions that adverse effects associated with estradiol use include thromboembolic disease, macroprolactinoma, breast cancer, coronary artery disease, cerebrovascular disease, cholelithiasis, and hypertriglyceridemia, but does not specify the estradiol levels at which these effects occur.

Comparison of Estradiol Levels

• The studies provide information on the effects of estradiol levels in the range of 15-107 pg/ml, but do not address the safety of levels as high as 900 pg/ml 2, 3, 6.
• Study 3 suggests that higher estradiol levels may be required to achieve certain clinical effects, such as increasing bone mineral density (minimum concentration of 15 pg/ml) or reducing total cholesterol and low-density lipoprotein-cholesterol (level of estradiol required is more than 25 pg/ml).

Hormone Replacement Therapy for Transfemales

• Study 4 discusses the use of estradiol and anti-androgen agents for hormone replacement therapy in transfemales, but does not provide information on the safety of estradiol blood levels of 900 pg/ml.
• Study 5 describes the use of anti-androgens in hormone replacement therapy, but does not address the safety of high estradiol levels.