Sex differences of endogenous sex hormones and risk of XXXX 2 @entity6 : a systematic review and meta-analysis.

@entity1 @entity251 @entity6 @entity3428 @entity53 @entity164 @entity443
CONTEXT: Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of @entity164 2 @entity6 , such that @entity3428 may increase risk in @entity1 while decreasing risk in @entity1 . OBJECTIVE: To systematically assess studies evaluating the association of plasma levels of @entity251 , @entity443 ( @entity443 ), and @entity53 with risk of @entity164 2 @entity6 . DATA SOURCES: Systematic search of EMBASE and MEDLINE (1966-June 2005) for English-language articles using the keywords @entity6 , @entity251 , sex-hormone-binding-globulin, and @entity53 ; references of retrieved articles; and direct author contact. STUDY SELECTION: From 80 retrieved articles, 43 prospective and cross-sectional studies were identified, comprising 6974 @entity1 and 6427 @entity1 and presenting relative risks (RRs) or hormone levels for cases and controls. DATA EXTRACTION: Information on study design, @entity1 characteristics, hormone levels, and risk estimates were independently extracted by 2 investigators using a standardized protocol. DATA SYNTHESIS: Results were pooled using random effects and meta-regressions. Cross-sectional studies indicated that @entity251 level was significantly lower in @entity1 with @entity164 2 @entity6 (mean difference, -76.6 ng/dL; 95% confidence interval [CI], -99.4 to -53.6) and higher in @entity1 with @entity164 2 @entity6 compared with controls (mean difference, 6.1 ng/dL; 95% CI, 2.3 to 10.1) (P<.001 for sex difference). Similarly, prospective studies showed that @entity1 with higher @entity251 levels (range, 449.6-605.2 ng/dL) had a 42% lower risk of @entity164 2 @entity6 (RR, 0.58; 95% CI, 0.39 to 0.87), while there was suggestion that @entity251 increased risk in @entity1 (P = .06 for sex difference). Cross-sectional and prospective studies both found that @entity443 was more protective in @entity1 than in @entity1 (P< or =.01 for sex difference for both), with prospective studies indicating that @entity1 with higher @entity443 levels (>60 vs < or =60 nmol/L) had an 80% lower risk of @entity164 2 @entity6 (RR, 0.20; 95% CI, 0.12 to 0.30), while @entity1 with higher @entity443 levels (>28.3 vs < or =28.3 nmol/L) had a 52% lower risk (RR, 0.48; 95% CI, 0.33 to 0.69). @entity53 levels were elevated among @entity1 and postmenopausal @entity1 with @entity6 compared with controls (P = .007). CONCLUSIONS: This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of @entity164 2 @entity6 in @entity1 and @entity1 . High @entity251 levels are associated with higher risk of @entity164 2 @entity6 in @entity1 but with lower risk in @entity1 ; the inverse association of @entity443 with risk was stronger in @entity1 than in @entity1 .
