Testosterone, Estradiol, and Sex Hormone-Binding Globulin in Alzheimer's Disease: A Meta-Analysis

Background: Previous studies suggested that plasma sex hormones may be implicated in the pathogenesis of Alzheimer's disease (AD). However, the relationship between sex hormones and AD remains unclear. Objective: To systematically review and quantitatively analyze studies observing plasma total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels among AD patients. Methods: Medline, EMBASE, the Cochrane Library, and PsycINFO (R) were searched for studies published prior to March 28 th, 2014. Published studies that reported plasma levels of TT, E2, and SHBG in AD and matched controls were included in the present meta-analysis. Results: Meta-analysis was performed using the random effects model, expressing continuous outcomes as the mean difference (MD) between AD and control populations. The 95% confidence intervals (CI) were also calculated. No differences were found in plasma levels of TT and E2 between AD and matched controls (TT MD -0.17 nmol/l, 95% CI -0.54, 0.20; E2 MD -1.16 pmol/l, 95% CI -9.85, 6.83). Plasma levels of SHBG were significantly increased in AD patients compared to healthy controls (SHBG MD 12.94 nmol/l, 95% CI 2.68, 23.20). Conclusion: Patients with AD had higher plasma levels of SHBG. The up-regulated levels of plasma SHBG show preliminary supportive evidence that SHBG and the bioavailability of functional sex hormones in plasma may be linked to the pathogenesis of AD.