Joint Associations of Actual Age and Genetically Determined Age at Menarche With Risk of Mortality

Abstract

IMPORTANCE Previous studies have shown an association between actual age at menarche and risk of all-cause mortality; however, the results are inconsistent, and no study has analyzed the joint associations between genetic susceptibility and actual age at menarche with the risk of mortality in prospective cohorts.OBJECTIVES To investigate joint associations of actual age and genetically determined age at menarche with risk of all-cause mortality. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study was conducted using data from the UK Biobank population across the United Kingdom from March 13, 2006, to October 1, 2010. A total of 264 546 women aged between 39 and 71 years with actual menarcheal age were included in this study; 246 676 of these women had genetic data available. Actual age at menarche was obtained from the touchscreen questionnaire at recruitment from 2006 to 2010. Genetically determined age at menarche was assessed by a genetic risk score. Statistical analysis was performed from August 22 to December 12, 2019. EXPOSURE Age at menarche. MAIN OUTCOMES AND MEASURES A multivariable Cox proportional hazards regression modelwas used to assess associations of actual or genetically determined age at menarche with risk of all-cause mortality. RESULTSThe mean (SD) age of the study population at baseline was 56.4 (8.0) years, and the mean (SD) age at menarche included in the analyses was 13.0 (1.6) years. During a median of 9.0 years (range, 8.3-9.7 years) of follow-up, 7761 deaths were documented among the women with actual age at menarche, and 7054 deaths were documented among the women with genetically determined age at menarche. Both the actual age at menarche and the genetically determined age at menarche showed a U-shaped association with the risk of all-cause mortality (lowest actual age [<12 years] vs reference age [15 years]: hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]; highest actual age [Ն16 years] vs reference age [15 years]: HR, 1.17 [95% CI, 1.05-1.31]; P < .001 for quadratic trend; genetic risk score[GRS] of 1 vs reference score [GRS of 4]: HR, 1.10 [95% CI, 1.01-1.19; GRS of 6 vs reference score [GRS of 4]: HR, 1.09 [95% CI, 1.00-1.18]; P = .03 for quadratic trend). Significant interactions were also found between actual age at menarche and genetically determined age at menarche with all-cause mortality (HR of mortality associated with age of menarche <12 year was 1.24 [95% CI, 1.10-1.40] in the GRS of 1 group and 1.44 [95% CI, 1.21-1.72] in the GRS of 6 group; P = .001 for interaction). Women with mismatch of actual age and genetically determined age at menarche had the highest mortality risks; participants with the lowest genetic risk score and the highest age at menarche had an HR of 2.12 (95% CI, 1.58-2.83), and participants with the highest GRS and the lowest age at menarche had an HR of 1.44 (95% CI, 1.21-1.72).

Identifying risk factors for polycystic ovary syndrome in women with epilepsy: A comprehensive analysis of 248 patients

“…Further analysis on the phenotypes of PCOS implied that younger age at epilepsy onset (<13 years) was significantly associated with oligo‐ or anovulation (<13 vs. ≥13 years, 45.83% vs. 28.98%; p = .0109) and hyperandrogenism (29.17% vs. 13.07%, p = .0026), and marginally associated with polycystic ovary morphology on ultrasound (20.83% vs. 11.36%, p = .0519). These findings suggest that epilepsy onset before sexual maturation may have an impact on ovarian follicle development, ovulation, and hormone secretion, since the mean age of menarche in Chinese women has been calculated to be 13 years 34 . Therefore, early screening examinations of PCOS are beneficial for WWE with a young age of epilepsy onset (<13 years).…”

“…These findings suggest that epilepsy onset before sexual maturation may have an impact on ovarian follicle development, ovulation, and hormone secretion, since the mean age of menarche in Chinese women has been calculated to be 13 years. 34 Therefore, early screening examinations of PCOS are beneficial for WWE with a young age of epilepsy onset (<13 years). However, diagnosis of PCOS in adolescents can be challenging, especially oligo-or anovulation.…”