Long-Term (Multi-Year/Adult) Outcomes of Pediatric Gender-Affirming Hormone Therapy

What the evidence says

The strongest and most consistent evidence in this set concerns continuation of treatment, not health outcomes: in a Dutch cohort of 720 people who began gender-affirming medical treatment in adolescence following puberty suppression, 98% (704 of 720) were still using gender-affirming hormones (GAH) at follow-up, and no tested factor — age at first clinic visit, age at start of puberty suppression or GAH, puberty stage, year of treatment initiation, or prior gonadectomy — was associated with discontinuation. Among the small number who did discontinue in a separate pediatric cohort, only 1 stopped permanently, and none expressed regret about having received therapy or retransitioned to the gender congruent with sex assigned at birth.

Cardiovascular and cardiometabolic outcomes show a measured, direction-consistent signal. A systematic review rated the evidence for increased cardiovascular events in transmen treated with testosterone as high certainty — the highest certainty rating in this evidence set for any outcome. A separate cross-sectional study (Klaver et al., 2018) of patients who took puberty blockers for at least 2 years followed by GAH for 2–3 years found increased body mass index, high blood pressure, elevated LDL and triglycerides, decreased HDL, and higher obesity rates as adults compared with population norms, though this is medium-confidence, cross-sectional evidence rather than the high-certainty rating given to cardiovascular events specifically.

Sexual function outcomes in adulthood are measured but with weaker confidence. A retrospective cohort of 37 transfeminine individuals who received puberty blockers and vaginoplasty (mean age 20.9 at vaginoplasty) found 67% of sexually active participants regularly experienced one or more sexual difficulties such as low desire, low arousal, difficulty achieving orgasm, premature orgasm, or pain during intercourse. A separate cross-sectional comparison found sexual dysfunction reported in 58% of transmasculine and 50% of transfeminine individuals who began transition before age 18, based only on descriptive statistics with no inferential testing and small subgroup samples the source describes as likely underpowered.

Long-term mental health and psychological well-being improvement from adolescent GAH therapy has the weakest evidentiary backing of any outcome in this set: it is rated very low or low certainty across multiple reviews, with observed effect sizes described as small and of potentially little clinical significance. Case reports and small studies additionally report associations between long-term GAH use and several serious morbidities — granulosa cell tumors, invasive breast cancer, thyroid cancer, pelvic floor dysfunction, and idiopathic intracranial hypertension — but this evidence is rated low confidence in both direction and magnitude.

A notable absence: the only prospective cohort study that followed patients from puberty suppression through GAH into adulthood (the original Dutch cohort, de Vries et al., 2014) did not examine long-term physical health outcomes at all. This means the highest-quality longitudinal design in this evidence set — the one capable of tracking the same individuals from adolescent treatment initiation to adulthood — has no data on physical health endpoints; the cardiovascular, cardiometabolic, and cancer-association findings above all come from separate, generally weaker-design studies.

Where the evidence splits

Two sources measuring sexual dysfunction in adulthood among people who began puberty suppression before 18 report different magnitudes for transfeminine individuals: 67% of sexually active participants in a study of 37 people who had vaginoplasty (van der Meulen et al., 2024) versus 50% in a separate cross-sectional comparison against adult-onset transition cohorts. The claims do not state a shared methodology between these two studies — the first is restricted to a post-vaginoplasty, sexually-active subset with a specific set of symptom categories, while the second compares broader transmasculine and transfeminine subgroups against adult-onset cohorts using only descriptive statistics. The sources do not explicitly reconcile the two figures; both are individually flagged as constrained by small sample size, so the split in magnitude is unexplained by the sources beyond these population and measurement differences.

The certainty ratings for cardiovascular events (high certainty) versus mental health and psychological well-being improvement (very low to low certainty) both come from the same body of systematic-review literature but arrive at very different confidence levels for different outcomes. This is not a contradiction — the two ratings describe different outcome domains — but the sources present it as a deliberate contrast: the systematic review is described as finding "high certainty evidence for cardiovascular events in transmen treated with testosterone and very low certainty evidence for improvement in gender dysphoria, global function, and depression" in the same review.

Thresholds and dose-response

No threshold established in the current sources.

Open empirical questions

• Whether the increased cardiometabolic risk factors and obesity observed in the Klaver et al. (2018) cohort persist, worsen, or improve over follow-up longer than the periods measured.
• Whether the case-report-level associations with cancers (granulosa cell tumors, invasive breast cancer, thyroid cancer) and idiopathic intracranial hypertension reflect elevated population-level risk, since no longitudinal epidemiologic study of this is present in the current sources.
• What accounts for the different sexual dysfunction rates (67% vs. 50%) reported for transfeminine individuals across the two cited studies, since the sources do not directly compare their populations or methods.
• Whether the high-certainty cardiovascular event finding extends to age ranges beyond those under 26 covered in the cited review, since the sources note a need for longer follow-up in broader age ranges.