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Association of adverse pregnancy outcomes and multiple gestation with natural menopause: A population-based cohort study

  • Christine R. Langton
    Correspondence
    Corresponding author at: P.O. Box 12233, Research Triangle Park, NC 27709, USA.
    Affiliations
    Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA
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  • Brian W. Whitcomb
    Affiliations
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA
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  • Alexandra C. Purdue-Smithe
    Affiliations
    Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
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  • Quaker E. Harmon
    Affiliations
    Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
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  • Susan E. Hankinson
    Affiliations
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA
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  • JoAnn E. Manson
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA

    Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
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  • Bernard A. Rosner
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
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  • Elizabeth R. Bertone-Johnson
    Affiliations
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA

    Department of Health Promotion and Policy, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA
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      Highlights

      • In this study, multiple gestation was associated with increased risk of early natural menopause.
      • Preterm birth with spontaneous labor was associated with younger age at natural menopause.
      • Gestational diabetes and hypertensive disorders of pregnancy were associated with older age at natural menopause.

      Abstract

      Objective

      Adverse pregnancy outcomes (APOs) and early menopause are each associated with increased risk of cardiovascular disease (CVD); whether APOs are associated with age at menopause is unclear. We examined the association of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and multiple gestation with age at natural menopause.

      Study design

      Observational, prospective study within the Nurses' Health Study II cohort (1989–2019).

      Main outcomes measures

      Risk of early natural menopause, defined as occurring before the age of 45 years, and age at onset of natural menopause (hazard ratio (HR) >1 indicates younger age at menopause).

      Results

      The mean [SD] baseline age of 69,880 parous participants was 34.5 [4.7] years. Compared with participants who had a term singleton first birth, those with a term multiple-gestation first birth had higher risk of early menopause (HR: 1.65, 95% CI: 1.05, 2.60) and younger age at natural menopause (HR: 1.46, 95% CI: 1.31, 1.63). Estimates for preterm multiple gestation were of similar magnitude. Menopause occurred at a younger age for those with a preterm birth with spontaneous labor (HR: 1.08, 95% CI: 1.03, 1.14) compared to those with a term birth with spontaneous labor. Conversely, estimates for GDM (HR: 0.95, 95% CI: 0.89, 1.02) and HDP (preeclampsia, HR: 0.93, 95% CI: 0.89, 0.97) suggested an association with older age at menopause.

      Conclusions

      In this large cohort study, several statistically significant associations between APOs and age at natural menopause were observed. A deeper understanding of the relationships among APOs, menopause, and CVD is needed to help identify people at higher risk for early menopause and later CVD.

      Abbreviations:

      APO (adverse pregnancy outcome), ART (assisted reproductive technologies), BMI (body mass index), CI (confidence interval), CVD (cardiovascular disease), GDM (gestational diabetes), HDP (hypertensive disorders of pregnancy), HR (hazard ratio), HT (hormone therapy), NHS2 (Nurses' Health Study II cohort), OC (oral contraceptive), PCOS (polycystic ovary syndrome)

      Keywords

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