Recent groundbreaking research out of Amsterdam University Medical Center (Amsterdam UMC) has shed new light on the safety profile of testosterone use among transmasculine and gender-diverse individuals, particularly focusing on their risk of gynecological cancer during the early years of hormone therapy. Published in the highly respected journal eClinicalMedicine, this comprehensive study offers important clinical insights that may significantly influence medical guidance and transgender healthcare practices around the globe. The findings bring a new sense of reassurance to a community that has long faced uncertainty regarding the oncological risks associated with masculinizing hormone therapy.
Transmasculine and gender-diverse people, while assigned female at birth, do not identify fully within the traditional female gender binary. Consequently, many choose testosterone hormone therapy to induce masculinizing physical changes that align more congruently with their gender identity. Testosterone administration commonly results in deepening of the voice, increased muscle mass, and changes in body hair, among other physiological effects. Despite these known physical transformations, questions about the impact of testosterone on reproductive organs such as the uterus, ovaries, vagina, and vulva have persisted — especially regarding the risk of malignancies that might arise due to hormonal modulation.
The Amsterdam UMC research team followed a cohort of 1,955 young transmasculine and gender-diverse individuals, who had been on testosterone therapy for an average duration of five years. This retrospective, single-center cohort study was designed to investigate the potential incidence of gynecological cancers and pre-malignancies during testosterone use, an area previously lacking large-scale, rigorous epidemiological data. Utilizing medical records and careful clinical monitoring, the researchers sought to determine whether exogenous testosterone increases, decreases, or otherwise alters the baseline cancer risk compared to cisgender women in the general population.
Remarkably, the study reported that no participants developed cancer of the uterus, ovaries, vagina, or vulva throughout the study period. This absence of diagnosed gynecological malignancies in a sizable cohort is a compelling indication that testosterone use in the initial years of therapy does not elevate cancer risk in these hormone-responsive tissues. Dr. Asra Vestering of Amsterdam UMC, lead researcher on the project, highlighted the profound clinical value of these findings, emphasizing that “We found no increased risk of these cancers compared to women from the general population. None of these cancers were diagnosed in the entire participant group.” This outcome challenges previously held concerns rooted in theoretical models or smaller, less controlled investigations.
One of the intriguing biological findings revealed subtle yet important physiological nuances in the group under study. Despite continuous testosterone administration, some participants exhibited active endometrial tissue or ovulatory signs. Co-researcher Wouter van Vugt explained that “this is not only relevant for long-term health but also means that despite testosterone use, there is still a chance of pregnancy.” This physiological phenomenon signifies that testosterone, although profoundly influencing secondary sex characteristics and suppressing menstruation for most, does not always fully inhibit ovarian function or endometrial cycling. These observations underscore the necessity for continued gynecological and contraceptive care in transmasculine patients commencing hormone therapy.
From a medical standpoint, these findings invite a revision of protocols for hormonal treatment and patient counseling. Prior to this research, the possibility of testosterone-induced neoplastic transformation had been a major concern, often leading to invasive surgical interventions or heightened screening regimens in transgender care. This study’s results support a more nuanced understanding that aligns with observed clinical realities, potentially alleviating undue anxiety and reducing barriers to hormone accessibility. Clinicians are thus encouraged to maintain vigilant but measured gynecological evaluations tailored to the unique physiology of transmasculine and gender-diverse patients.
Importantly, this research emerges in the context of evolving gender identity legislation in the Netherlands, where new laws have removed previous surgical requirements for legal gender change. As a consequence, a growing number of transmasculine and gender-diverse individuals initiate testosterone therapy without undergoing gonadectomy or hysterectomy, diverging from earlier clinical pathways. The Amsterdam UMC data provides timely clinical evidence to support the safety of such hormone-first approaches, which are becoming more prevalent in multiple countries thanks to more inclusive policies.
While these findings are promising, the researchers stress that conclusions regarding long-term testosterone use effects are still premature. The average follow-up period of five years, while significant, does not encompass the span needed to definitively rule out late-onset pathological transformations. Ongoing and extended surveillance studies are essential to establish the lifetime safety of androgen therapy fully. Dr. Vestering advocates for continued scientific inquiry, stating that “follow-up research into the effects of long-term testosterone use remains necessary, so that care can be further tailored to safety and quality of life.”
The study also touches on an important facet of endocrine functioning. Testosterone administered exogenously undergoes complex metabolic cascades, potentially converting to estradiol or other biologically active metabolites, which may impact target tissues differently in the context of transmasculine physiology. Understanding such biochemical pathways may reveal additional mechanisms by which hormone therapy affects tissue homeostasis and cancer risk and will be a key focus for future research.
From a social and public health perspective, this investigation helps dismantle stigmatizing narratives that previously portrayed testosterone use as inherently risky or medically experimental for trans and gender-diverse populations. By providing robust empirical evidence from a large, well-characterized cohort, the Amsterdam UMC team contributes significantly to affirming the safety and dignity of gender-affirming care. Such data-driven reassurances are invaluable for healthcare providers crafting informed consent protocols and support systems for transgender individuals.
The implications of this research extend beyond oncology into reproductive health, psychoendocrinology, and transgender medicine. Recognizing that ovulation and fertility potential may persist despite androgen therapy calls for integrated approaches to contraceptive counseling and reproductive planning within this demographic. It challenges assumptions that amenorrhea induced by testosterone equates to infertility and invites refinement of patient education to manage expectations.
Moreover, the study’s design as a retrospective cohort within a single center enables a meticulous capture of clinical variables, though it also signals a need for multicenter collaboration to broaden findings across diverse populations. Future studies incorporating genetic, environmental, and lifestyle factors will be pivotal to comprehensively map the risk landscape for gynecological cancers under hormone therapy.
In sum, this landmark study from Amsterdam UMC signifies a major advance in understanding the gynecological safety of testosterone for transmasculine and gender-diverse individuals. It offers a foundation for evolving clinical guidelines emphasizing safety, holistic care, and evidence-based reassurance. As the field progresses, integrating long-term data and multidimensional markers will ensure hormone therapy remains a cornerstone of affirming, safe, and individualized transgender healthcare.
Subject of Research: People
Article Title: Incidence of Gynaecological (Pre-)Malignancies and Endometrial Activity in Transmasculine and Gender Diverse Individuals Using Testosterone: A Retrospective, Single-Centre Cohort Study
News Publication Date: 12-May-2025
Keywords: Transsexuality, Oncology, Cancer risk, Transgender identity, Endocrinology, Testosterone, Hormones
