Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women

Gender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person's sexual characteristics to their desired sex is called 'transition.' Current guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body's male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these transgender women, surgery may then be used to support transition.

We aimed to assess the efficacy and safety of hormone therapy with antiandrogens, estradiol, or both, compared to each other or placebo, in transgender women in transition.

We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Biosis Preview, PsycINFO, and PSYNDEX. We carried out our final searches on 19 December 2019.

We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cohort studies that enrolled transgender women, age 16 years and over, in transition from male to female. Eligible studies investigated antiandrogen and estradiol hormone therapies alone or in combination, in comparison to another form of the active intervention, or placebo control.

We used standard methodological procedures expected by Cochrane to establish study eligibility.

Our database searches identified 1057 references, and after removing duplicates we screened 787 of these. We checked 13 studies for eligibility at the full text screening stage. We excluded 12 studies and identified one as an ongoing study. We did not identify any completed studies that met our inclusion criteria. The single ongoing study is an RCT conducted in Thailand, comparing estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment. The primary outcome will be testosterone level at three month follow-up.

We found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition. This lack of studies shows a gap between current clinical practice and clinical research. Robust RCTs and controlled cohort studies are needed to assess the benefits and harms of hormone therapy (used alone or in combination) for transgender women in transition. Studies should specifically focus on short-, medium-, and long-term adverse effects, quality of life, and participant satisfaction with the change in male to female body characteristics of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.