Insulin Sensitivity and Associated Plasma Proteomics During Sex Hormone Therapy
Authors' conclusion
Feminizing 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.
Study context
- Population
- Individuals initiating feminizing or masculinizing sex hormone therapy
- Participants
- 29 individuals
- Exposure
- Feminizing vs masculinizing sex hormone therapy
- Feminizingn = 16
- Masculinizingn = 13
- Outcome
- Change in insulin sensitivity by hyperinsulinemic-euglycemic clamp (M-value adjusted for lean body mass; M/I ratio) and associated plasma proteome change
- Follow-up
- 3 months
Main finding
As reported in the abstract
Insulin sensitivity (clamp)
| Group | M-value change | M/I ratio change |
|---|---|---|
| Feminizing | + 23.3% | + 20.2% |
Feminizing
M-value change+ 23.3%
M/I ratio change+ 20.2%
- Insulin sensitivity increased with feminizing therapy
- P < 0.05
Observational data: associations, not effects.
Further findings
Events
| Outcome | Feminizing | Masculinizing |
|---|---|---|
| Differentially expressed plasma proteins · 3 months | 49 | 356 |
- Differentially expressed plasma proteins — Proteins correlated with changes in insulin sensitivity
- 16
Differentially expressed plasma proteins · 3 months
- Involved in immunoregulation/inflammation (VEGF-D, 5'-nucleotidase), iron homeostasis/erythropoiesis (hepcidin, transferrin receptor protein 1), oxidative stress (superoxide dismutase 3)
Original publication
Insulin Sensitivity and Associated Plasma Proteomics During Sex Hormone Therapy. J Clin Endocrinol Metab. Published 22 October 2025. doi:10.
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