Physiological Effects of Gender-Affirming Hormone Therapy

    Gender-affirming hormonal treatment (GAHT) causes significant increases in the physiological and psychological well-being of transgender individuals. Transgender people are faced with gender dysphoria (GD), which increases anxiety, stress, and depression due to their physical appearance not matching their gender identity. GAHT is used to inhibit or reduce androgen synthesis of either testosterone or estrogen, and there are three types of antiandrogen. There are the antiandrogens that impede on androgen-receptor signaling, the ones that limit conversion of testosterone to dihydrotestosterone (DHT), and those that lessen the androgen production. To decide which one to take, it ultimately depends on how the medications will be administered.

    Testosterone therapy in transmen will start to show signs in around three months, which includes the lack of menstruation, an increase in body hair, acne, changes in skin, alterations in fat distribution and muscle mass, and voice deepening. Estrogen therapy in transwomen will show signs gradually throughout 18 to 24 months, which includes breast growth, increased body fat, and reduced body and facial hair growth. GAHT increases the quality of life and causes positive effects on mood. It has been found that the serotonin reuptake transport binding (SERT) in transwomen that take estrogen and antiandrogen medications is lowered, while SERT in transmen is increased in different brain regions. This provides reasonable data that hormone treatment alleviates physiological stress, especially due to the significantly lower cortisol levels and stress in transgender individuals within 12 months of treatment. Transgender people have had reduced anxiety, perceived stress, and social distress after GAHT, as well as improvements in mental health, quality of life, self-esteem, and mood. 

    GAHT has also been found to increase certain health issues in transwomen, due to the increase of estrogen in the body. Specifically, estrogen therapy has caused an increase in venous thromboembolic events (VTE), which includes heart attacks, strokes, pulmonary embolisms, and cardiovascular mortality. This mostly occurs when taking estradiol orally, due to the “first-pass” effect in the liver, which increases prothrombotic factors. Transwomen may also experience bone loss due to the introduction of more estrogen in the body, which impedes on the body’s natural distribution of testosterone to help bone health and muscle mass. Transmen receiving exogenous testosterone in physiological amounts creates an anabolic effect on cortical bone and can be sufficient in preventing bone demineralization in transgender patients. Transmen may also experience more executive dysfunction due to the importance of estrogen in the prefrontal cortex. 

Reference: Moustakli, Efthalia, and Orestis Tsonis. “Exploring Hormone Therapy Effects on Reproduction and Health in Transgender Individuals.” MDPI, Multidisciplinary Digital Publishing Institute, 29 Nov. 2023, www.mdpi.com/1648-9144/59/12/2094.