Climacteric : the journal of the International Menopause Society · 2026
Female reproductive factors, genetic susceptibility and incident osteoporosis risk.
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Liu Zhong-Qiang, Xiong Yu-Jun, Yu Xiao, Lv Tian, Xu Hang-Yang
Аннотация
OBJECTIVE: Osteoporosis risk is shaped by both reproductive factors and genetic predisposition, yet their combined effects remain insufficiently studied.
METHOD: A total of 49,885 women from the UK Biobank were analyzed, excluding those with baseline osteoporosis or missing reproductive data. Reproductive factors included age at menarche, menopause time/status, history of stillbirth, hysterectomy, oophorectomy and oral contraceptive (OC) use. Genetic susceptibility was assessed using the polygenic risk score (PRS). Cox models estimated associations, with restricted cubic splines testing non-linear trends. Kaplan-Meier curves and sensitivity analyses were performed.
RESULTS: Late menarche, premature ovarian insufficiency, menopausal status, stillbirth, hysterectomy and oophorectomy were linked to higher osteoporosis risk, while OC use was protective. Women with high PRS combined with adverse reproductive histories had the greatest risk. Additive interactions were evident between genetic risk and menopause, stillbirth, hysterectomy and oophorectomy, whereas other factors acted largely independently. Sensitivity analyses supported robustness.
CONCLUSION: Both reproductive history and genetic susceptibility contribute to osteoporosis risk in women. Joint assessment of these factors may enhance risk stratification and inform personalized prevention.
METHOD: A total of 49,885 women from the UK Biobank were analyzed, excluding those with baseline osteoporosis or missing reproductive data. Reproductive factors included age at menarche, menopause time/status, history of stillbirth, hysterectomy, oophorectomy and oral contraceptive (OC) use. Genetic susceptibility was assessed using the polygenic risk score (PRS). Cox models estimated associations, with restricted cubic splines testing non-linear trends. Kaplan-Meier curves and sensitivity analyses were performed.
RESULTS: Late menarche, premature ovarian insufficiency, menopausal status, stillbirth, hysterectomy and oophorectomy were linked to higher osteoporosis risk, while OC use was protective. Women with high PRS combined with adverse reproductive histories had the greatest risk. Additive interactions were evident between genetic risk and menopause, stillbirth, hysterectomy and oophorectomy, whereas other factors acted largely independently. Sensitivity analyses supported robustness.
CONCLUSION: Both reproductive history and genetic susceptibility contribute to osteoporosis risk in women. Joint assessment of these factors may enhance risk stratification and inform personalized prevention.