Age of menopause and fracture risk in postmenopausal women randomized to calcium plus vitamin D, hormone therapy, or the combination: results from the Women's Health Initiative Clinical Trials

Objective: We previously reported that in the absence of hormone therapy (HT) or calcium/vitamin D (Ca/D) supplementation, earlier menopause age was associated with decreased bone mineral density and increased fracture risk in healthy postmenopausal women. Treatment with HT and Ca/D is protective against fractures after menopause. In this analysis, we asked if the age of menopause onset alters fracture risk in healthy postmenopausal women receiving HT, Ca/D, or a combination. Methods: Hazard ratios (HRs) for any fracture among 21,711 healthy postmenopausal women enrolled in the Women's Health Initiative Clinical Trial, who were treated with HT, Ca/D, or HT + Ca/D, and who reported age of nonsurgical menopause of <40, 40 to 49, and >= 50 years, were compared. Results: Women with menopause <40 years had significantly higher HR for fracture than women with menopause 40 to 49 or >= 50 years, regardless of treatment intervention (HR [95% CI]: menopause <40 y vs >= 50 y, 1.36 [1.11-1.67]; menopause <40 y vs 40-49 y, 1.30 [1.06-1.60]). Conclusions: In the overall Women's Health Initiative Clinical Trial cohort and within each treatment group, women with younger menopause age (<40 y) had a higher risk of any fracture than women reporting older menopause ages. The effect of menopause age on fracture risk was not altered by any of the treatment interventions (HT, Ca/D, HT + Ca/D), suggesting that early age of menopause is an independent contributor to postmenopausal fracture risk.