Growing numbers of transgender women are reaching old age with decades of hormone treatment behind them, and with them comes a question nobody had measured: does feminizing hormone therapy have to be continued for life? The doubt has a reasonable physiological basis, since cisgender women stop having high estradiol concentrations after menopause. Yet data on what happens when this treatment is interrupted in older transgender women were practically nonexistent. A team from the Center of Expertise on Gender Dysphoria in Amsterdam (Amsterdam UMC) has now published the first clinical trial to answer that question.
The study recruited 19 transgender women aged 55 or older, with a median age of 66 years, who had been on feminizing gender-affirming hormone therapy (fGAHT) for at least five years and a median of 23 years. The design was within-subject, meaning each participant served as her own control: the therapy was stopped for 12 weeks and then restarted for another 12. At three points —baseline, after discontinuation and after reinitiation— questionnaires measured estradiol deprivation-related symptoms, sleep quality, quality of life, mental health and body image.
The results draw a clear but nuanced pattern. After stopping fGAHT, somato-vegetative symptoms worsened —that cluster that includes hot flushes and sweats and will be familiar to anyone who knows menopause (%Δ 11.5)—, sleep disturbance increased (%Δ 10.7) and, to a lesser extent, so did the decline in happiness (%Δ 6.4). By contrast, no mean differences were found in depressive symptoms, anxiety, quality of life or body satisfaction: mood, measured with standardised instruments, held steady.
Reinitiation reversed those signals. Total estradiol deprivation-related symptoms improved markedly (%Δ 36.3), and so did overall sleep quality, sleep onset latency and sleep disturbance (odds ratio 0.1; %Δ 46.6). Participants described physical and psychological changes similar to those of menopause, and only one of the 19 said she wished to stop treatment permanently. In other words, those who decide to stop did not run into psychological or body image barriers in this study.
The reach of these data deserves caution. The sample is very small —19 people—, there was no blinding or placebo, and the authors themselves note that expectancy bias may have influenced the answers, on top of a limited generalisability to the wider population of older transgender women. Nor was the trial designed to measure long-term consequences for bone, cardiovascular risk or metabolism. What it provides is concrete information about what stopping and restarting feels like, not a treatment recommendation.
The trial, registered in the EU Clinical Trials Register (EUCTR2023-505143-39-00), touches on an issue gender medicine will face more often as the first generation of transgender people who accessed hormone therapy in adulthood grows older. The authors conclude that transgender women, like cisgender women, experience symptoms when estradiol is withdrawn, which may support continuing fGAHT in older age, and that discontinuation is feasible when someone wishes it. The decision, as almost always in endocrinology, remains a conversation between patient and clinician, now with data on the table.
Source: Psychological and physical effects of short-term discontinuation of feminizing gender-affirming hormone therapy among older transgender women: a within-subject clinical trial. van Heesewijk JO, Geels RES, den Heijer M, Dreijerink KMA, Kreukels BPC. Human Reproduction 2026;41(8):1387-1396. DOI: 10.1093/humrep/deag087.
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