Implications of hormonal carcinogenesis for transgender and gender-diverse people undergoing gender-affirming hormone therapy: an up-to-date review.

Transgender and gender-diverse (TGD) individuals face an elevated risk of cancer in comparison with the general population. This increased risk is primarily attributed to an imbalanced exposure to modifiable risk factors and a limited adherence to cancer screening programmes, stemming from historical social and economic marginalisation. Consequently, these factors contribute to poorer clinical outcomes in terms of cancer diagnosis and mortality. A focal point of interest is the potential carcinogenic effect of gender-affirming hormone therapy (GAHT). It is crucial to recognise that GAHT serves as an essential, life-saving treatment for TGD individuals. Therefore, if a demonstrated direct correlation between GAHT and elevated cancer risk emerges, essential shared decision-making discussions should occur between oncology practitioners and patients. This narrative review aims to collect and discuss evidence regarding potential correlations between GAHT and the most prevalent tumours known to be influenced by sex hormones. The objective is to comprehend how these potential carcinogenic effects impact health and inform health interventions for TGD individuals. Unfortunately, the scarcity of epidemiological data on cancer incidence in the TGD population persists due to the absence of sexual orientation and gender identity data collection in cancer centres. Consequently, in most cases, establishing a positive or negative correlation between GAHT and cancer risk remains speculative. There is an urgent need for concerted efforts from researchers and clinicians worldwide to overcome barriers and enhance cancer prevention and care in this specific population.
Competing Interests: Competing interests: DD reports grants from Gentili, and travel expenses from Roche, Gentili and Eisai. LR reports speakers’ honoraria from AstraZeneca. ML acted in a consulting/advisory role for Roche, Novartis, Lilly, Pfizer, Merck Sharp and Dohme (MSD), Seagen, Gilead, Exact Sciences and AstraZeneca; received speakers’ honoraria from Takeda, Ipsen, Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Knight, Daiichi Sankyo and AstraZeneca; received travel grants from Gilead, Daiichi Sankyo and Roche; and a research grant (to the institution) from Gilead, all outside the submitted work. RB received honoraria and/or research grant from: BI, Eisai, MSD, Amgen, Roche, Pfizer, AstraZeneca, Lilly, GSK, BMS, Otsuka and Seagen. NLV reports consulting or advisory role from Novartis, Pfizer, Roche, MSD, AstraZeneca and Eisai; speaker bureau from Pfizer, Roche, Gentili, Lilly, Gilead, Daiichi Sankyo and Techdow; travel expenses from Pfizer and Roche; and research grants from GSK and Gilead. FPe reports institutional grants or contracts from Roche, Bayer, AstraZeneca, Pfizer, Incyte, Tesaro/GSK and Merck; and consulting fees from Bayer, Pierre Fabre, AstraZeneca, Incyte, Ipsen, Clovis, Astellas, Sanofi, Roche and Pfizer. FPi reported receiving institutional research grants from BMS, Incyte, Agenus, Amgen, Lilly and AstraZeneca; and personal fees from BMS, MSD, Amgen, Merck-Serono, Pierre-Fabre, Servier, Bayer, Takeda, Astellas, Johnson&Johnson, Rottapharm, Ipsen, AstraZeneca, GSK, Daiichi Sankyo and Seagen. The other authors declare no conflict of interest to disclose.
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