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Risk for hormone-dependent tumors unclear with gender-affirming HT
A systematic review revealed a lack of well-designed, long-term studies examining an association between gender-affirming hormone therapy and an increased risk for hormone-dependent tumor development, despite the fact that HT is typically started at a young age and continues for life, according to data published in Clinical Endocrinology (Oxford).
“We performed this systematic review based on a clinical question that arose: Do we need to do things differently when it comes to tumor screening in transgender individuals on hormone therapy? As transgender research is in its infancy, it wasn’t overly surprising that there is insufficient evidence to support specific screening,” Ada Cheung, MBBS (Hons), FRACP, PhD, National Health and Medical Research Council Early Career Fellow in the Department of Medicine (Austin Health) at The University of Melbourne in Victoria, Australia, told Endocrine Today. “Further research is very much needed. There is insufficient data to support screening for tumors specifically for transgender individuals on hormone therapy.”
Cheung and her colleagues aimed to assess the risk for tumor development in transgender adults to guide clinical screening recommendations. Based on the Preferred Reporting Items for Systematic Review and Meta-Analysis reporting guidelines, the researchers searched the Ovid MEDLINE, Ovid PsycINFO and Embase electronic databases for studies examining tumor incidence or prevalence or cancer-related mortality in transgender adults. They included all peer-reviewed publications that assessed histological type and temporal relation to gender-affirming HT, including case studies with two or more cases of the same histological type.
The database search yielded observational, retrospective cohort studies (n = 7), one-time cross-sectional studies (n = 2) and case reports and case series (n = 39); researchers did not identify any randomized, controlled trials or prospective observational studies.
Four of the retrospective cohort studies focused on the incidence rates of breast or prostate cancer in the transgender population, and three focused on causes of mortality or morbidity in individuals receiving gender-affirming HT with cancer as a subcategory. Only two of the studies included participants who had been taking gender-affirming HT for more than 10 years, and none of the studies showed a significant association with HT.
Of the two cross-sectional studies, one was an initial report of 100 transgender adults with no cancer diagnoses after a mean of 10 years on HT. However, when additional participants with a mean of 6 or 7 years on HT were included, researchers found several cancers in only the male-to-female group, although the findings were not significantly different from those in the general male population.
Researchers reported tumor development after HT use in many of the case studies. Breast cancer was the only type of cancer reported in more than one case after initiation of testosterone therapy, and all cases were ductal carcinoma of the breast with variable hormone receptor status. Overall, breast cancer was reported in 12 cases after a mean of 16 years on HT, and prostate adenocarcinoma was reported in patients aged a mean of 66 years.
Multiple case studies also revealed meningioma and prolactinoma following HT use in individuals older than 40 years.
“Based on low-level evidence, case reports of meningioma and prolactinoma were only reported in the setting of high-dose cyproterone acetate (used as an anti-androgen), and the inference would be that low doses (< 50 mg daily) should be used, if required,” Cheung said.
The researchers recommended in their discussion that until more conclusive evidence is available, the minimum dose of HT should be used to achieve masculinization or feminization. They called for future well-designed prospective, population-based studies with a longer duration of HT use to inform evidence-based guidelines for the transgender population.
“Tumor screening can be a sensitive area for many transgender individuals who may have dysphoria to their secondary sexual characteristics,” Cheung said. “The presence of organs may not be apparent from the outset. For example, even after genital reassignment surgery, transgender women will have a prostate, and breast cancer can still occur in transgender males. Tumor screening should be based on guidelines for the general population, and the presence of organs in transgender individuals rather than gender identity or hormonal therapy status.” – by Tina DiMarcantonio-Brown
For more information:
Ada Cheung, MBBS (Hons), FRACP, PhD, can be reached at the Department of Medicine (Austin Health), The University of Melbourne, Level 2, Centaur Building, 300 Waterdale Road, Heidelberg West, Victoria 2081, Australia; email: adac@unimelb.edu.au.
Disclosure: The authors report no relevant financial disclosures.