Sex Hormones and Risk of Incident Dementia in Men and Postmenopausal Women
Authors' conclusion
Our findings revealed that higher SHBG and lower free testosterone concentrations seem to be associated with higher incidence of all-cause dementia and AD and further studies must be done to determine causality.
Study context
- Population
- UK Biobank: 186,296 men (mean age 56.68 years, SD 8.18) and 126,109 postmenopausal women (mean age 59.73 years, SD 5.78); total testosterone and sex hormone binding globulin (SHBG) by immunoassay, free testosterone calculated by Vermeulen method
- Exposure
- Quintiles of serum free testosterone and SHBG
- Outcome
- Incident all-cause dementia and AD from hospital inpatient data
- Follow-up
- 12.0 (IQR: 11.0-13.0)-year follow-up
Methodological detailsUK Biobank, Cox proportional hazards regression adjusted for age and other variables, restricted cubic spline dose-response models
- UK Biobank
- Cox proportional hazards regression adjusted for age and other variables
- Restricted cubic spline dose-response models
Main finding
As reported in the abstract
All-cause dementia
Hazard ratio (95% CI)
Highest quintilevs Lowest quintileMen, free testosterone
0.63(0.56–0.71)
Highest quintilevs Lowest quintileMen, SHBG
1.47(1.32–1.64)
Fourth quintilevs Lowest quintilePostmenopausal women, free testosterone; lower risk
0.84(0.78–0.95)
Higher SHBGPostmenopausal women; increased incidence
1.35(1.28–1.55)
- Men developing dementia
- 3874 (2.08%)
- Postmenopausal women developing dementia
- 2523 (2.00%)
Observational data: associations, not effects.
Further findings
| Outcome | HR (CI) | |
|---|---|---|
| AD · 12.0 (IQR: 11.0-13.0)-year follow-upHighest quintilevs Lowest quintileMen, SHBG | 1.32 (1.11–1.58) | |
| AD · 12.0 (IQR: 11.0-13.0)-year follow-upFourth quintilevs Lowest quintilePostmenopausal women, free testosterone; lower risk | 0.76 (0.63–0.91) | |
| 0.512Hazard ratio (log scale) |
Alzheimer's disease (AD) · 12.0 (IQR: 11.0-13.0)-year follow-up
| HR (CI) | ||
|---|---|---|
| Higher SHBGPostmenopausal women; increased incidence | 1.52 (1.25–1.85) | |
| 0.512Hazard ratio (log scale) |
| Outcome | HR (CI) |
|---|---|
| AD · 12.0 (IQR: 11.0-13.0)-year follow-upBetween Highest quintile and Lowest quintile · Men, free testosterone; estimate outside printed interval | 0.49 (0.60–0.72) |
Original publication
Sex Hormones and Risk of Incident Dementia in Men and Postmenopausal Women. Clin Endocrinol (Oxf). Published 11 May 2025. doi:10.
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