Fig. 5

Summary findings of sex-specific risk factors across the lifespan for dementia or cognitive decline. Across the lifespan in females, meta-analyses indicated 8 risk factors across life stages associated with increased dementia or cognitive decline: late menarche, nulliparous, per child increase in parity, grand parity, bilateral oophorectomy, short reproductive period, early menopause, and higher total estradiol. Three protective factors were identified: long reproductive period, late menopause, and HRT. Individual studies also found higher SHBG increased risk, while infertility, oophorectomy with hysterectomy, and higher free estradiol decreased risk. Across the lifespan in males, meta-analyses showed ADT and higher SHBG increased dementia/cognitive decline risk. ED and BPH also elevated risk based on individual studies. The X-axis stands for the specific age at which the factor occurred or the average age of pooled studies. The Y-axis stands for the value of RRs. The colored spots represent the pooled RR from meta-analyses, while the uncolored spots indicate the RR from individual studies. Lines across the spot or rhombus represent the 95% CI. On the right edge of the figure are 19 clock plots. Each clock plot contains three concentric 3/4 circles, the innermost circle covers from − 1 to 2, it reflects RR and 95% CI, the arrow points at RR, and the colored range represents the pooled 95% CI from meta-analyses of more than 2 studies. Red ranges denote the factor as a risk, while green ranges indicate a protective effect. Unfilled ranges signify 95% CIs from individual studies. The middle circle represents the number of studies included for each factor, covering a range of 0–15. The outmost circle represents weigher NOS scores with a range of 5–8. The results will be more reliable when the arrows of the outer 2 circles point further to the right part. The results will be more significant when the arrows of the innermost circle point further to either the left (protective) or right (risk) part. Abbreviations: ADT: androgen deprivation therapy, BPH: benign prostate hyperplasia, CI: confidence interval, ED: erectile dysfunction, HRT: hormone replacement therapy, PCa, prostate cancer, RR: relative risk, SHBG: sex hormone–binding globulin, WQS: weighted-NOS score. * The result of HRT was indicated by E S LeBlanc