Does Gender-Based Hormone Therapy Affect the Risk of T2DM?

People with transfeminine (TF) may be at greater risk of Type 2 diabetes (T2D) compared to cisgender women (CF), according to the results of a cohort study. However, the corresponding difference in risk of T2D was not discernible compared to cisgender (CM) men, and there is little evidence attributing T2D in TF or transmasculin (TM) people to gender-affirming hormone therapy ( GAHT), the researchers discovered.

The manuscript was published online in The Journal of Clinical Endocrinology & Metabolism.

“The results of our study reassure us that gender-affirming therapy does not increase the risk of [T2D], but our analysis was not designed to assess more subtle subclinical changes. For this reason, healthcare providers should continue to monitor the metabolic status of people receiving gender-affirming therapy, ” noted study author Noreen Islam, MD, MPH, of Emory University School of Medicine in Atlanta, Georgia.

Almost one million people in the United States identify as transgender, and the number of those who report identifying as transgender and gender diverse (TGD) is increasing. As providers are increasingly likely to encounter TGD patients in their practice, a better understanding of the health issues these people face becomes increasingly important, the authors explained.

One of the priorities of TGD health research is to elucidate the metabolic changes induced by GAHT, because “there is some evidence that GAHT can affect glucose metabolism and body weight, but how these changes influence risk. of [T2D] is not clear, ”they added.

To assess the occurrence of T2DM in a cohort of TGD people receiving GAHT, the researchers assessed data from the Transition Outcome and Gender Study (STRONG). This cohort is made up of electronic health records of TGD patients receiving care in 3 Kaiser Permanente health systems in California and Georgia.

TGD patients were matched with up to 10 cisgender males and 10 females based on race / ethnicity, year of birth, and other characteristics. All study participants were at least 18 years old on the index date, and data reported between 2006 and 2014 were included in the analysis; an extended follow-up period until the end of 2016.

Of the 5002 TGD individuals included, 2869 (57%) were TF and 2133 (43%) were MT; patients were matched with 28,300 CF patients and 28,258 CM patients, and 20,997 CF patients and 20,964 CM, respectively.

The analyzes revealed:

• Members of the MT cohort were on average younger than their TF counterparts, and more than half of the participants (54% for TF and 60% for TM) were not Caucasian Hispanic.
• The proportions of participants with a normal baseline body mass index were about the same in the TF and TM cohorts (36% vs. 34%).
• About 32% of TF people and 24% of MT people were under GAHT on or before the index date.
• Prevalent and incident T2DM was more common in the TF cohort compared to the CF referents with odds ratio (OR) and HR estimates of 1.3 (95% CI, 1.1-1.5) and 1 , 4 (95% CI, 1.1-1.8), respectively.
• 175 (61%) of 287 TF patients and 77 (59%) of 131 MT patients had a diagnosis of T2DM at baseline (on or before baseline) and the rest developed diabetes sometime after baseline.
• No significant difference in the prevalence or incidence of T2DM was observed in the remaining comparison groups, both overall and in people with TGD with evidence of reception of GAHT.
• Previous studies have explored the impact of GAHT on laboratory markers of insulin resistance and glucose metabolism. One study found that GAHT can induce insulin resistance in TM and TF individuals, but only if insulin levels remained within physiological limits. An additional study “reported that TF individuals experienced an increase in glucose use after initiation of GAHT, while the same result for participants in the MT study demonstrated no discernible change from the baseline “. However, both studies included small sample sizes.

“Published literature indicates that measurements of glucose metabolism and insulin resistance do not appear to be negatively influenced by testosterone in MT individuals but may be affected by estradiol therapy in TF individuals”, the researchers explained. They continued, “Despite these observations, the clinical significance of the reported associations is unclear, and it is possible that small GAHT-related changes in laboratory parameters do not translate to an increased risk of overt T2DM. “

In the present analysis, data was not collected at specified intervals and the algorithm used did not explicitly distinguish between T2DM and type 1 diabetes (T1D), although cases with codes diagnoses specific to T1D were excluded. Some classification errors may have occurred, marking a limit to the study.

Data on other risk factors for T2DM such as family history, socioeconomic status, and adverse childhood experiences were also not included. Previous research has indicated that stress in sexual and gender minorities is associated with a higher incidence of cardiovascular disease, while data links stressful experiences to T2DM and poor blood sugar control, the researchers explained. authors.

“Given the apparent lack of association between reception of GAHT and incidence of T2DM in our study, further research should focus on the hypothetical effect of gender minority stress and its interaction with factors of stress. lifestyle-related metabolic risk in people with TGD, ”they concluded. Future larger and more detailed studies with longer follow-up periods are warranted.

Reference

Islam N, Nash R, Zhang Q et al. Is there a link between hormone use and the incidence of diabetes in transgender people? Data from the STRONG cohort. J Clin Endocrinol Metab. Published online November 30, 2021. doi: 10.1210 / clinem / dgab832