Endocrine Society Reading Room | Does Type 2 Diabetes Incidence Change in Trans People Undergoing Hormone Therapy?

A study in The Journal of Clinical Endocrinology & Metabolism has found that transgender people undergoing hormone therapy did not have higher incidence of type 2 diabetes than people of the same birth sex in the general population. This held true both for trans women (n=2,585, 90 cases, SIR 0.94 95% CI 0.76-1.14) and trans men (n=1,514, 32 cases, SIR 1.40 95% CI 0.96-1.92).

The first study author, Daan van Velzen, DRS, is an endocrinology researcher at Amsterdam University Medical Centre in The Netherlands, and discusses the study here with the Reading Room. The exchange has been edited for length and clarity.

What was the key knowledge gap or question this study was designed to address?

Van Velzen: Previously, several studies had suggested a strong increase in insulin resistance after starting feminizing hormone therapy. In turn, this strongly suggests an adverse effect on the risk of developing diabetes.

However, no investigation had evaluated whether the actual incidence of type 2 diabetes indeed increased or changed in transgender individuals receiving hormone therapy. That was the aim of our study.

How would you summarize your main finding?

Van Velzen: No differences in incidence rates of type 2 diabetes were found between transgender individuals and the general population, which indicates that gender-affirming hormone therapy does not meaningfully increase the risk.

Did anything surprise you about the study or its findings?

Van Velzen: The biggest surprise was the main finding of our study.

One potential explanation for this discrepancy is perhaps that the studies on insulin resistance were relatively short and were performed in the time period when trans women still received cyproterone acetate as a testosterone blocker.

However, ours was a long-term study, and in most trans people cyproterone acetate was discontinued after gonadectomy. So it is possible that the earlier reported effect on insulin resistance is not so much an effect of estrogen therapy but most likely of cyproterone acetate. This indicates that cyproterone acetate — and not estradiol as had been hypothesized — may be the cause of the increased insulin resistance observed in trans women.

How can or should endocrinologists and their care teams update their practices based on these findings?

Van Velzen: Although the finding needs to be confirmed, these data add to existing evidence of various negative health effects associated with cyproterone acetate, such as increased risk of meningioma. All of this has brought us to the decision to use GnRH analogues as our preferred testosterone blocker instead of cyproterone acetate.

We would suggest that there is no specific reason for endocrinologists to routinely measure glucose levels in transgender individuals, beyond reasons that already apply as they would in the general population. However, considering the increased cardiovascular risk and mortality observed in transgender individuals and particularly trans women, measuring glucose in at-risk individuals may help optimize cardiovascular risk in this group.

WHAT FINDINGS MAY MEAN FOR CLINICAL PRACTICE

  • No increase in type 2 diabetes among transgender individuals
  • Cyproterone acetate may be a culprit in higher insulin resistance
  • No specific reason to routinely measure glucose in transgender people
  • Glucose monitoring in high risk individuals may help optimize cardiovascular risk

Read the study here and expert commentary on the clinical implications here.

No study author disclosed any relevant financial relationships with industry.

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