Provision of gender-affirming hormones for trans and gender-diverse adults: a systematic review of health and quality of life outcomes, values and preferences, and costs

Background: Many transgender and gender-diverse individuals take gender-affirming hormones, but the evidence for their impact on health and wellbeing has not been comprehensively synthesized. Methods: We conducted a systematic review of studies reporting health and quality of life outcomes, values and preferences, and costs associated with gender-affirming hormones. The protocol was prospectively registered in PROSPERO (CRD42024451558). We searched PubMed, Embase, CINAHL, Cochrane Central, LILACS, PsycINFO, and grey literature sources for relevant evidence published between 1 January 2013 and 31 March 2024, without language or geographical restrictions. The health and quality of life outcomes review included data from randomized controlled trials (RCT) and longitudinal studies that compared adults (age 18+) who received gender-affirming hormones within the health sector to those who did not but expressed a desire to receive such care. We synthesized outcomes data using GRADE evidence profiles and assessed risk of bias with Cochrane ROB2 and ROBINS-I. We qualitatively summarized findings on values and preferences and cost, and provided confidence ratings using GRADE CERQual. Findings: Thirteen studies, including one RCT and 12 longitudinal studies, were included in the health and quality of life outcomes review. Data from the RCT was judged to be low-certainty evidence. Uncontrolled longitudinal studies had serious to critical risk of bias. Findings from these studies suggest gender-affirming hormones may improve outcomes including depression, quality of life, and suicidality. No studies identified substantive harms. We identified an additional 17 studies on values and preferences and one study presenting cost data; data suggest that gender-affirming hormones are acceptable and affordable. Interpretation: Available evidence indicates gender-affirming hormones may improve critical outcomes, including mental health and quality of life, with no evidence of substantive harms. Further evidence from prospective, controlled studies could improve the confidence in these findings. Funding: World Health Organization through a grant from the Elton John AIDS Foundation and the Bill and Melinda Gates Foundation.