Hormone Therapy: Does It Lead to Increased Incidence of Diabetes in Trans Men and Women?

Studies have found that there may be a connection between hormone therapy use and type 2 diabetes, putting trans individuals at an increased risk.  

Transgender individuals commonly use hormone therapy to generate the person’s desired physical characteristics. In addition to transforming the individuals’ physical characteristics, hormone therapy can also alter metabolism and body composition. Studies have found that insulin resistance or sensitivity has developed in transgender individuals receiving hormone therapy. However, there is still uncertainty about whether type 2 diabetes is more commonly present in trans men and women using hormone therapy than in adults in the general population. Therefore, a study in the Netherlands compared the incidence of type 2 diabetes amongst adult transgender individuals receiving hormone therapy to the incidence of type 2 diabetes amongst individuals in the general population. 

This cohort study included 4,099 patients (2585 trans women and 1514 trans men) who visited the gender identity clinic of the Amsterdam University Medical Center between 1972 and 2018. Hormone therapy for trans women was composed of anti-androgens with estrogens. Estradiol patches (50 – 150 µg/24 hours twice a week), oral estradiol valerate (2 – 4 mg daily), or estradiol gel (0.75 – 1.5 mg daily) were the most regularly prescribed estrogens. The most prescribed anti-androgen was cyproterone acetate (25 – 100 mg daily). Hormone therapy was only composed of testosterone in trans men. It was administered as either testosterone gel (20 – 60 mg daily), intramuscular or oral testosterone undecanoate (1000 mg per 12 – 14 weeks, or 40 – 240 mg daily, respectively), or intramuscular testosterone esters (250 mg or 125 mg every 2 – 3 weeks). To compare the incidence of type 2 diabetes in trans women and trans men from the general population, standardized incidence ratios were used. In addition, age and sex-specific incidence rates for type 2 diabetes within the adult Dutch population were also calculated. The characteristics of trans women and trans men were presented as mean with SD, median with interquartile range (IQR), or percentages. Determinants of type 2 diabetes risk amongst trans women and trans men were studied using Cox regression analyses. Stata Statistical Software was used to perform the statistical analyses and estimate the standardized incidence ratios. 

When assessing the cumulative incidence of type 2 diabetes during the observation period amongst transgender individuals, trans women’s incidence was 4.5 per 1000 person-years with a standardized incidence ratio of 0.94 (95% CI, 0.76-1.14). Trans men’s incidence was 3.4 per 1000 person-years with a standardized incidence ratio of 1.40 (95% CI, 0.96-1.92). The cumulative incidence of type 2 diabetes was then assessed in different age categories at the start of hormone therapy. Trans women incidence who started hormone therapy from 18 – 30 years old was less than 10 with a standardized incidence ratio of 1.12 (95% CI 0.75–1.56). Trans men incidence who started hormone therapy from 18 – 30 years old was 20 with a standardized incidence ratio of 2.00 (95% CI 1.22–2.96). Similar results were found, and no differences between groups were observed for all age categories studied and groups for calendar years in which hormone therapy was initiated. When it came to risk factors, BMI at the beginning of hormone therapy was a critical risk factor for type 2 diabetes in trans women (hazard ratio [HR] 1.12 [95% CI, 1.06-1.19]) and trans men (1.09 [95% CI, 1.01-1.18]). However, risk factors such as smoking and the use of alcohol did not show any increased risk. In patients with type 2 diabetes, there were no commonly prescribed comedications or significant comorbidities present at the beginning of hormone therapy associated with an increased risk of diabetes. 

In this study, there were no differences in the incidence of type 2 diabetes in trans women and trans men after beginning hormone therapy. After comparing transgender individuals to general population men, there was no increase in the incidence of type 2 diabetes seen in trans women. Additionally, the risk of type 2 diabetes tended to be higher in trans men compared with general population women (however not statistically significant). These results oppose the worry of an increased risk of type 2 diabetes in trans women and counter the expected decrease in risk of type 2 diabetes amongst trans men. It is not recommended to do any additional screening for type 2 diabetes among trans women and men because incidence rates did not change between them and the general population. Prior studies that have attributed changes in insulin sensitivity to hormone therapy did not specifically connect the change to estrogen versus cyproterone acetate, an anti-androgen agent. Thus, the results of prior studies could have been due to the cyproterone acetate rather than estradiol.  

This study was intense due to its large study population and follow–up duration. However, the lack of individual patient data for the general population served as a study limitation due to the inability to control potential confounding variables. More studies could be done in the future to assess other factors affiliated with the development of type 2 diabetes (ex: metabolic syndrome) and how hormone therapy affects those factors.  

Practice Pearls: 

• The incidence of type 2 diabetes in trans women and men after hormone therapy was not different compared to the general population. 
• Increased screening for type 2 diabetes amongst transgender individuals is not recommended. 
• The main focus in transgender care should stay on the patient counseling of patients with overweight regarding the importance of lifestyle management. 

Daan van Velzen, Chantal Wiepjes, Nienke Nota, Daniel van Raalte, Renée de Mutsert, Suat Simsek, Martin den Heijer, Incident Diabetes Risk Is Not Increased in Transgender Individuals Using Hormone Therapy, The Journal of Clinical Endocrinology & Metabolism, 2021;, dgab934, https://doi.org/10.1210/clinem/dgab934 

Amanda Roberts, PharmD Candidate, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences Institute of Public Health