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Abstract
Context:Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment.Objective:The objective of the study was to investigate age at menopause, length of reproductive life, and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size, and strength in women aged 60–64 years.Design:This was a birth cohort study that followed up for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories.Setting:The study was conducted in England, Scotland, and Wales.Participants:Participants included 848 women with a known type of menopause and bone measures at 60–64 years.Main Outcome Measures:Peripheral quantitative computed tomography measurements of the distal radius total and trabecular vBMD were measured. Diaphyseal radius total and medullary cross-sectional area, cortical vBMD, and polar strength strain index (SSI); dual-energy x-ray absorptiometry measurements of aBMD at the lumbar spine and total hip were also measured.Results:A 10-year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% confidence interval [CI] 1.3%–15.1%, P = .02) greater trabecular vBMD and a 6.0% (95% CI 0.51%–11.5%, P = .03) greater total vBMD; findings were similar for length of reproductive life. A 10-year difference in HRT use was associated with a 6.0% (95% CI 2.6%–9.3%, P < .001) greater polar SSI and a 0.9% (95% CI 0.4%–1.5%, P = .001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for peripheral quantitative computed tomography.Conclusions:The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI and aBMD.
Highlights
Context: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment
A 10-year increase in age at natural menopause was associated with 8.2% (95% confidence interval [CI] 1.3%–15.1%, P ϭ .02) greater trabecular volumetric BMD (vBMD) and a 6.0% greater total vBMD; findings were similar for length of reproductive life
A 10-year difference in HRT use was associated with a 6.0% greater polar strength strain index (SSI) and a 0.9% greater cortical vBMD
Summary
Sample The NSHD is a prospective study of 2547 women and 2815 men followed up 24 times since their birth in a week in March 1946 [23], with a further nine postal questionnaires to women during midlife [19]. At age 60 – 64 years, 2856 study members (of whom 1460 were women) still alive and living at a known address in England, Scotland, or Wales were invited to one of six clinical research facilities (CRFs) across the country; the remaining women were not invited because they had already died (n ϭ 312), were living abroad (n ϭ 258), had previously withdrawn from the study (n ϭ 284), or had been lost to follow-up (n ϭ 233). The study received Multi-Centre Research Ethics Committee approval and informed consent was provided by participants. Of those attending a CRF, 866 women underwent a DXA scan (QDR 4500 Discovery; Hologic Inc), of whom 697 had a pQCT scan (XCT 2000; Stratec). The bone outcomes were pQCT-derived measures at the radius distal 4% site of total and trabecular vBMD and at the 50% site of diaphysis and medullary cross-sectional area (CSA), cortical vBMD and polar strength strain index (SSI), an estimate of torsional bone strength [26], and DXA-derived measurements of aBMD for lumbar spine (L1L4) and total hip
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