Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People

Diabetes Care. 2020 Feb;43(2):411-417. doi: 10.2337/dc19-1061. Epub 2019 Nov 18.

Abstract

Objective: The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study.

Research design and methods: Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated.

Results: In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01) increased. Fasting insulin (-1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (-1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (-1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (-0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] × min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] × min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (-2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (-1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] × min; P < 0.01), but fasting glucose (-0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] × min) remained unchanged.

Conclusions: In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.

Trial registration: ClinicalTrials.gov NCT01072825.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cohort Studies
  • Europe
  • Female
  • Glucagon / metabolism
  • Glucose Tolerance Test
  • Gonadal Steroid Hormones / administration & dosage
  • Gonadal Steroid Hormones / pharmacology*
  • Hormone Replacement Therapy* / methods
  • Humans
  • Incretins / metabolism*
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion / drug effects
  • Male
  • Prospective Studies
  • Sex Reassignment Procedures / methods
  • Time Factors
  • Transgender Persons
  • Transsexualism / chemically induced
  • Transsexualism / metabolism*
  • Young Adult

Substances

  • Blood Glucose
  • Gonadal Steroid Hormones
  • Incretins
  • Insulin
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT01072825