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Dorte Glintborg, Guy T'Sjoen, Pernille Ravn, and Marianne Skovsager Andersen

Transgender women are assigned male at birth, but identify as women. The incidence of gender dysphoria is estimated to be around 1% of the population. Gender dysphoria may be associated with depression and low quality of life, which in most cases improves during gender affirming hormonal treatment (GAHT). Feminizing hormonal treatment for transgender women or gender non-binary people typically includes natural estrogen (estradiol). Additional testosterone-blocking treatment is often needed to ensure suppression of the pituitary gonadal axis and may include cyproterone acetate, a gonadotropin releasing hormone agonist (GnRH-a) or spironolactone. The health risks of cyproterone acetate as anti-androgen treatment are debated and randomized protocols with other anti-androgen treatments are requested. Orchiectomy is performed in some transgender women after various duration of GAHT. Currently, natural progesterone is not recommended as part of GAHT due to limited knowledge on the balance between risks and benefits.

In the present article we discuss evidence regarding established and upcoming feminizing treatment for adult transgender women or for gender non-binary people seeking feminization. Data on study populations with transgender women are put into a wider context of literature regarding effects of sex steroid hormones in cisgender study populations. Relevant follow up and monitoring during feminizing treatment is debated. The review has special focus on the pharmacotherapy of feminizing hormonal therapy.