Discuss Alternatives to Estrogen Therapy
Estrogen therapy is the mainstay treatment in trans female patients. However, estrogen therapies are associated with side effects. For example, Ethinyl estradiol (oral formulation) is associated with an increased incidence of deep venous thrombosis. Thus, there is a strong recommendation against its use in transgender patients (Swe et al., 2022). In addition, estrogen has been associated with cardiovascular disease in transgender women with a trend toward an increased risk of heart disease. The use of oral Ethinyl estradiol seems to be strongly associated with cardiovascular events and should thus be avoided as mainstay therapy for patients.
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Due to the adverse effects of estrogen therapy, various alternatives to estrogen therapy have been recommended. Spironolactone is one of the most common estrogen alternatives used to suppress endogenous testosterone secretion in trans female patients. It inhibits the binding of dihydrotestosterone to its androgen receptor, thus inhibiting androgen effects (Glintborg et al., 2021). However, it is associated with a high risk of hyperkalemia, and therefore patients should be closely monitored. In addition, Cyproterone acetate (CPA) is used as an alternative since it inhibits the testosterone receptor. It also acts as synthetic progesterone, which suppresses the hypothalamic-pituitary-gonadal axis (Glintborg et al., 2021).
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Another alternative is 5α-reductase inhibitors such as finasteride and dutasteride, which impede the conversion of testosterone to the more active dihydrotestosterone. However, they are associated with liver toxicity and are less effective than spironolactone (Glintborg et al., 2021). Gonadotropin hormone-releasing hormone (GnRH) is an alternative to estrogen, which inhibits the pituitary-gonadal axis and causes suppressed gonadal sex hormone levels while keeping the adrenal androgen production intact (Glintborg et al., 2021). Nonetheless, GnRH is expensive and is not often a good option for patients. In addition, some patients are prescribed Progestins, but they should be used with caution since there is a theoretical risk of breast cancer connected with long-term exogenous progesterone use.
References
Glintborg, D., T’Sjoen, G., Ravn, P., & Andersen, M. S. (2021). Management of endocrine disease: Optimal feminizing hormone treatment in transgender people. European Journal of Endocrinology, 185(2), R49-R63.
Swe, N. C., Ahmed, S., Eid, M., Poretsky, L., Gianos, E., & Cusano, N. E. (2022). The effects of gender-affirming hormone therapy on cardiovascular and skeletal health: A literature review. Metabolism Open, 100173. https://doi.org/10.1016/j.metop.2022.100173
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