Transgender Health: Gender-Affirming Hormone Therapy and Diabetes Risk

New research published in The Journal of Clinical Endocrinology & Metabolism shows that transgender women may be at higher risk for type 2 diabetes compared to cisgender women, but not to cisgender men. However, there is little evidence that hormone therapy is the culprit.

As of 2016, 1.4 million adults identify as transgender or gender diverse (TGD). Transfeminine (TF) individuals were assigned male gender at birth, and transmasculine (TM) individuals were assigned female gender at birth. In the subsequent six years, the number of people identifying as TGD has likely increased significantly, as the 2022 U.S. Trans Survey (USTS) is expected to show.

Not surprisingly, as the number of those individuals who identify as transgender increase, healthcare providers are encountering more transgender and gender-diverse patients in their practices. An important priority of transgender health research is to better understand the metabolic changes induced by gender-affirming hormone therapy, and a specific area of interest is the occurrence of type 2 diabetes.

Diabetes and the Transgender Population

The growth of this population has implications for clinicians, chief among them being the need to understand the healthcare issues TGD people uniquely face. A study published in the November issue of The Journal of Clinical Endocrinology & Metabolism (JCEM) charts new territory in beginning to uncover what these might be and how clinicians might approach them. In “Is There a Link Between Hormone Use and Diabetes Incidence in Transgender People? Data From the STRONG Cohort,” Noreen Islam, MD, MPH, of the Emory University School of Medicine, in Atlanta, Ga., and team investigated whether the TGD population faces particular risks of prevalent (present at study initiation) or incident (not present at study initiation) type 2 diabetes.

“Although our data shows GAHT does not seem to increase the risk for type 2 diabetes in transgender individuals compared to cisgender controls, clinicians should continue to monitor the cardiometabolic status of transgender individuals.”

Noreen Islam, MD, MPH, Emory University School of Medicine, Atlanta, Ga.

Many TGD people opt for GAHT, which involves increasing estrogen and lowering testosterone in TF individuals and increasing testosterone in TM individuals. Thus, the need to understand how GAHT affects metabolism and the endocrine system is clear.

Islam, a third-year pediatric endocrinology fellow at Emory University, explains, “A part of receiving certification in the subspecialty of pediatric endocrinology is engaging in scholarly activities in addition to the core curriculum. I was interested in participating in an epidemiologic study as part of my scholarly activity during fellowship and was introduced to Michael Goodman, MD, MPH, a professor in the department of epidemiology at Rollins School of Public Health of Emory University. Dr. Goodman is part of the team who gathered data for The Study of Transition Outcomes and Gender (STRONG), the data set used for the study, and was my research mentor.”

Participants selected from the STRONG cohort included 5,002 TGD adults ages 18 years and older matched to a reference group. Of that number, 2,869 (57%) were TF and matched to 28,300 cisgender females (CFs) and 28,258 cisgender males (CMs); the 2,133 (43%) TM individuals were matched to 20,997 CFs and 20,964 CMs. At study initiation in 2006, 32% of TF individuals and 24% of TM individuals were on GAHT. The study continued through 2014 or follow-up through 2016.        

In the TF group, type 2 diabetes was prevalent in 175 cases, compared to 77 cases in the TM group. Of these, 56 (32%) and 19 (34%), respectively, were on GAHT. The team found that baseline prevalence of type 2 diabetes was 61 per 1,000 participants (approximately 6%) both in the overall TF group and among TF participants on GAHT. The TM group showed 36 per 1,000 participants overall and 37 per 1,000 participants for those on GAHT (approximately 4%).

As for incident type 2 diabetes, the TF group had 94 cases, 17 (18%) of which were diagnosed after initiation of GAHT, and the TM group had 44 cases, 12 (27%) of which developed after starting GAHT. (The other incident cases occurred in TGD individuals either not on GAHT during the study period or who started GAHT after type 2 diabetes diagnosis.)

When the team compared type 2 diabetes cases in the TF group overall to the CF reference group, logistic regression analyses showed that TF individuals have higher odds of having prevalent type 2 diabetes (adjusted odds ratio estimate of 1.3) and higher risk of incident type 2 diabetes. Results of comparisons of other groups were not significant.

Good News for GAHT

These findings that type 2 diabetes is more common among TF individuals compared with CFs but not CMs possibly reflects the known gender disparity in type 2 diabetes risk in the general population, with males being nearly twice as likely as females to develop the disease. While this may be related to the fact that TF individuals were assigned male at birth, the team did not specifically investigate this association. Rather, they were primarily concerned with whether GAHT affects diabetes risk, and, here, the news is encouraging. Although they hypothesized that they would see increased risk of type 2 diabetes with GAHT in both the TF and TM cohorts compared to cisgender controls, their results show that, when the analysis was restricted to TGD participants on GAHT, type 2 diabetes risk did not increase.

“However,” Islam says, “although our data shows GAHT does not seem to increase the risk for type 2 diabetes in transgender individuals compared to cisgender controls, clinicians should continue to monitor the cardiometabolic status of transgender individuals.” Meanwhile, data from STRONG will continue to be analyzed with the goal of improving the health status of TGD individuals.

“There is little evidence that type 2 diabetes occurrence in either transgender women or transgender men is attributable to gender-affirming hormone therapy, at least in the short term.”

Noreen Islam, MD, MPH, Emory University School of Medicine, Atlanta, Ga.

Islam adds that although more research is needed, “there is little evidence that type 2 diabetes occurrence in either transgender women or transgender men is attributable to gender-affirming hormone therapy, at least in the short term.”

Other authors of the study include: Rebecca Nash, Qi Zhang, and Michael Goodman of Emory University in Atlanta Ga.; Leonidas Panagiotakopoulos, Tanicia Daley, and J. Sonya Haw of Emory University School of Medicine; Shalender Bhasin of Brigham and Women’s Hospital and Harvard School of Medicine in Boston, Mass.; Darios Getahun of Kaiser Permanente Southern California and Kaiser Permanente Bernard J. Tyson School of Medicine in Pasadena, Calif.; Courtney McCracken of Kaiser Permanente Georgia in Atlanta, Ga.; Michael J. Silverberg of Kaiser Permanente Northern California in Oakland, Calif.; Vin Tangpricha of Emory University School of Medicine and the Atlanta VA Medical Center in Atlanta, Ga.; and Suma Vupputuri of Kaiser Permanente Mid-Atlantic States in Rockville, Md.

The research received funding from the Patient-Centered Outcomes Research Institute and the National Institute of Health’s Eunice Kennedy Shriver National Institute of Child and Human Development.

The manuscript, “Is There a Link Between Hormone Use and Diabetes Incidence in Transgender People? Data from the STRONG Cohort,” was published online, ahead of print at: https://bit.ly/3nboo3e.

Horvath is a freelance writer based in Baltimore, Md. In the December issue, she researched, compiled, and wrote the annual Eureka! article that detailed the top endocrine science discoveries of 2021. 

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