. 2023 Jan:167:82-89.

doi: 10.1016/j.maturitas.2022.10.003. Epub 2022 Oct 22.

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

Christine R Langton¹, Brian W Whitcomb², Alexandra C Purdue-Smithe³, Quaker E Harmon⁴, Susan E Hankinson², JoAnn E Manson⁵, Bernard A Rosner⁶, Elizabeth R Bertone-Johnson⁷

Affiliations

¹ 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. Electronic address: christine.langton@nih.gov.
² Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.
³ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁴ Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
⁵ 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.
⁶ 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.
⁷ 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.

PMID: 36308975
PMCID: PMC9712230
DOI: 10.1016/j.maturitas.2022.10.003

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

Christine R Langton et al. Maturitas. 2023 Jan.

. 2023 Jan:167:82-89.

doi: 10.1016/j.maturitas.2022.10.003. Epub 2022 Oct 22.

Authors

Christine R Langton¹, Brian W Whitcomb², Alexandra C Purdue-Smithe³, Quaker E Harmon⁴, Susan E Hankinson², JoAnn E Manson⁵, Bernard A Rosner⁶, Elizabeth R Bertone-Johnson⁷

Affiliations

¹ 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. Electronic address: christine.langton@nih.gov.
² Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.
³ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁴ Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
⁵ 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.
⁶ 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.
⁷ 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.

PMID: 36308975
PMCID: PMC9712230
DOI: 10.1016/j.maturitas.2022.10.003

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.

Keywords: Gestational diabetes; Hypertensive disorders of pregnancy; Menopause; Multiple gestation; Preterm birth; Women's health.

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Conflict of interest statement

The authors declare that they have no competing interest.

Figures

**Fig. 1. Flowchart of participant selection, Nurses’ Health Study II (NHS2).**
Of the 116,429 participants enrolled in the NHS2 cohort in 1989, a total of 69,880 who completed a reproductive grid in 2001 and/or 2009 and reported their menopause status from 1989 through 2019 were included in the analytical sample. Participants were followed from the year of their first birth (1964–2008) to 2019 for occurrence of natural menopause.

See this image and copyright information in PMC

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Shaw LJ, Patel K, Lala-Trindade A, Feltovich H, Vieira L, Kontorovich A, Ananth C, Taqueti VR, Mitrani L, Stern T, DeBolt C, Kase N, Smith RT, Narula J, Mehran R, Bianco A, Bhatt DL, Stone JL. Shaw LJ, et al. JACC Adv. 2024 May 14;3(6):100980. doi: 10.1016/j.jacadv.2024.100980. eCollection 2024 Jun. JACC Adv. 2024. PMID: 38938863 Free PMC article. Review.

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

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

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