Observational studyThe Journal of clinical endocrinology and metabolism2026
Insulin Sensitivity and Associated Plasma Proteomics During Sex Hormone Therapy.
Observational study in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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Who cites it
3 citing papers in PubMed.
- Challenges and knowledge gaps in sex differences in cardio-kidney-metabolic syndrome across the lifespan.Biology of sex differences · 2026Review
- Sex differences in the association of the CRP-TyG index with coronary artery disease and long-term mortality in MASLD.Frontiers in endocrinology · 2026Article
- The impact of sports supplements on metabolism, glycemic control, and lipid profile in adolescents and young adults: a narrative review.Pediatric endocrinology, diabetes, and metabolism · 2026Review
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Authors and funding
11 authors.
Funding
Abstract
purposeWomen are generally protected against insulin resistance and related comorbidities when compared with men, potentially due to the role of sex hormones. While epidemiological and animal studies suggest that sex hormones may impact insulin sensitivity, studies in humans on the effects of estradiol and testosterone treatment on insulin sensitivity assessed by gold-standard measures remain limited. The molecular mechanisms involved are also not well understood. Therefore, we aimed to investigate changes in insulin sensitivity and associated change in plasma proteome following 3 months of sex hormone therapy.
methodsThis prospective, observational study included 29 individuals initiating feminizing (estradiol with GnRH analogue; n = 16) or masculinizing (testosterone; n = 13) therapy. Measurements at baseline and after 3 months included insulin sensitivity, assessed via hyperinsulinemic-euglycemic clamp (M-value: adjusted for lean body mass and M/I ratio: M-value adjusted for plasma insulin concentrations), along with plasma proteomics.
resultsDuring feminizing hormone therapy, insulin sensitivity increased (M-value: + 23.3%, M/I ratio: + 20.2%; P < .05), whereas during masculinizing hormone therapy, no changes were observed. Of the differentially expressed plasma proteins (49 during feminizing and 356 during masculinizing hormone therapy), 16 correlated with changes in insulin sensitivity. Several were involved in immunoregulation and inflammation (vascular endothelial growth factor D, 5'-nucleotidase), iron homeostasis and erythropoiesis (hepcidin, transferrin receptor protein 1:cytoplasmic domain), and oxidative stress (superoxide dismutase 3).
conclusionFeminizing hormone therapy, characterized by high serum estradiol and low serum testosterone concentrations, enhanced insulin sensitivity. These findings highlight the impact of sex hormones on insulin sensitivity and may inform sex-specific precision medicine.
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