1. Suggested design of future studies.

Methods	RCT or controlled cohort study
Participants	Transgender women experiencing gender dysphoria, in transition N* Age: from the age of 16 years
Intervention	Antiandrogens (cyproterone acetate or spironolactone) and estradiol Antiandrogens (cyproterone acetate or spironolactone) alone Estradiol alone All types of administration: oral, sublingual, transdermal, subdermal and intramuscular. For estradiol and bioidentical 17‐beta‐estradiol, as well as synthetic derivatives.
Comparator	Any of the active interventions listed above
Outcomes	Primary outcomes Quality of life (QoL) Satisfaction with change of male to female body characteristics, Adverse events specific to hormone therapy, including serious adverse events
Notes	* Size of study with sufficient power to detect a ~ 10% difference between the two groups for primary outcome