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Transgender People Have Varying Insulin Sensitivities After Taking Gender Affirming Sex Hormone Therapy 

Mar 17, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Mia Flowers, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy

Examining the complex relationship between incretin hormones and sex hormones in patients undergoing gender transition. 

In this longitudinal prospective cohort study, 90 Caucasian transgender people ranging from 18 to 64 years of age in Ghent, Belgium were given a year’s worth of sex hormone therapy to determine their effects on incretin responses and, ultimately insulin sensitivity. Previous studies reported somewhat conflicting results of decreasing or unchanged insulin sensitivity after short-term masculinization of birth-assigned women and feminization of birth-assigned men.  


In 2010 to 2013, insulin resistance via the homeostatic model assessment (HOMA), fasting blood glucose, plasma blood glucose after oral glucose tolerance tests (OGTT), body weight, waist-tohip ratio, and fat-free mass were measured in 55 transgender women and 35 transgender men from the European Network for the Investigation of Gender Incongruence (ENIGI) study. The tests were taken at baseline and oneyear postgenderaffirming sex hormone therapy. Version seven of the World Professional Association for Transgender Health Standards guidelines were followed by administering cyproterone acetate 50 mg once daily as the antiandrogen of choice concomitantly given with estradiol valerate 2 mg by mouth twice daily in patients undergoing male-to-female gender transition. Transwomen patients older than 45 years of age received estradiol patches or transdermal gels 1.5mg twice a day to serve as a prophylactic measure to deep vein thrombosis. Females transitioning to males or transgender men were given long-acting testosterone 1,000 mg intramuscularly once every 12 weeks.  

Normally distributed data were analyzed utilizing paired t-tests, while the non-normally distributed data were analyzed via nonparametric Wilcoxon signedrank tests. ANOVA and independent ttests were used to assess differences amongst the different groups, which also involved a significance level of 0.05 and Bonferroni-Holm correction for numerous comparisons. All the data was computed with IBM SPSS 24.0 software.  

Generally, the group composed of transgender women were older and made for a larger cohort with a p-value of less than 0.001. This group experienced better fat distribution in their midsections and an increase in body weight. The transgender men experienced an increase in body weight, including more fat-free mass and a larger waist-to-hip ratio (P < 0.01). The 2019 American Diabetes Association (ADA) guidelines were used to classify two transmen and three transwomen as pre-diabetic with impaired fasting glucose before the initiation of year-long hormone therapy. The remaining of both cohorts had normal insulin and fasting plasma glucose levels. None of the subjects met the criteria for type 2 diabetes at baseline.  

Post-treatment with testosterone, transgender men had unchanged fasting plasma glucose levels, but the fasting insulin levels and insulin resistance lowered with p-values of 0.08 and 0.06, respectively. Despite these changes, they were not found statistically significant. OGTTs results were unchanged regarding insulin and glucose AUCs. The significant finding of statistical significance was an increase in cholesterol levels, specifically in HDL (P < 0.05) and LDL (P < 0.05). Female-to-male transitioning patients post-treatment had higher insulin resistance and higher fasting insulin levels (P <0.001) despite reports of continuous fasting plasma glucose. Lipid panels revealed a statistically significant decrease in HDL (P<0.001), LDL (P,0.001) and triglycerides (P<0.05). The primary outcome being the AUCs from the OGTTs, depicted a decrease in glucose with unchanged insulin levels.  

This research following people who are transitioning found a positive correlation between increased masculinization via testosterone treatment and post-OGTT incretin levels as well as insulin sensitivity, while there was a positive correlation between insulin resistance and increased feminization with estrogen treatment. The relationship between these hormones is complex and reported to be inconclusive despite these findings. Circumstances may be confounded by varying physiological variables such as smoking, age, genetics, or physical activity.  Also, incretin dynamics should be further evaluated in various populations and in more extended periods to bring forth more insight in order to understand the possible correlation. More studies could allow for a mechanism to be established amongst the hormones and comprehension of whether there is a difference in insulin sensitivities amongst women and men regardless of gender transformation.  

Practice Pearls: 

  • The relationship between incretin hormones and sex hormones requires further investigation. 
  • Monitoring parameters, including a lipid panel, should be conducted at baseline for anyone undergoing gender transformation. 
  • Masculinization via testosterone treatment tends to precipitate increased incretin responses in contrast to feminization by estrogen therapy. 


Shadid, Samyah, et al. “Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People.” Diabetes Care, vol. 43, no 2, Feb. 2020, pp. 411 LP – 417, doi:10.2337/dc19-1061. 

Mia Flowers, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy 


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