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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to MaturitasAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Prevalence and risk factors of premature ovarian insufficiency/early menopause.Semin. Reprod. Med. 2020; 38: 237-246https://doi.org/10.1055/s-0040-1722317
- Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data.Lancet Public Health. 2019; 4: e553-e564https://doi.org/10.1016/s2468-2667(19)30155-0
- Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: a systematic review and meta-analysis.JAMA Cardiol. 2016; 1: 767-776https://doi.org/10.1001/jamacardio.2016.2415
- Births: final data for 2020.Natl. Vital Stat. Rep. 2022; 70https://doi.org/10.15620/cdc:112078
- Evaluation of US state-level variation in hypertensive disorders of pregnancy.JAMA Netw. Open. 2020; 3e2018741https://doi.org/10.1001/jamanetworkopen.2020.18741
- Pregnancy: an underutilized window of opportunity to improve long-term maternal and infant health - an appeal for continuous family care and interdisciplinary communication.Front. Pediatr. 2017; 5: 69https://doi.org/10.3389/fped.2017.00069
- SMFM special statement: state of the science on multifetal gestations: unique considerations and importance.Am J Obstet Gynecol. 2019; 221: B2-B12https://doi.org/10.1016/j.ajog.2019.04.013
- Pregnancy and reproductive risk factors for cardiovascular disease in women.Circ. Res. 2022; 130: 652-672https://doi.org/10.1161/CIRCRESAHA.121.319895
- Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis.Diabetologia. 2019; 62: 905-914https://doi.org/10.1007/s00125-019-4840-2
- Preterm delivery and future risk of maternal cardiovascular disease: a systematic review and meta-analysis.J. Am. Heart Assoc. 2018; 7https://doi.org/10.1161/JAHA.117.007809
- Preeclampsia and future cardiovascular health: a systematic review and meta-analysis.Circ Cardiovasc Qual Outcomes. 2017; 10https://doi.org/10.1161/CIRCOUTCOMES.116.003497
- 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the american College of Cardiology/American Heart Association task force on clinical practice guidelines.J. Am. Coll. Cardiol. 2019; 74: 1376-1414https://doi.org/10.1016/j.jacc.2019.03.009
- Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from european cardiologists, gynaecologists, and endocrinologists.Eur. Heart J. 2021; 42: 967-984https://doi.org/10.1093/eurheartj/ehaa1044
- The use of sex-specific factors in the assessment of women's cardiovascular risk.Circulation. 2020; 141: 592-599https://doi.org/10.1161/CIRCULATIONAHA.119.043429
- Serum AMH levels in women with a history of preeclampsia suggest a role for vascular factors in ovarian aging.J. Clin. Endocrinol. Metab. 2014; 99: 579-586https://doi.org/10.1210/jc.2013-2902
- Risk factors for atonic postpartum hemorrhage: a systematic review and meta-analysis.Obstet. Gynecol. 2021; 137: 305-323https://doi.org/10.1097/AOG.0000000000004228
- Risk factors for uterine atony/postpartum hemorrhage requiring treatment after vaginal delivery.Am. J. Obstet. Gynecol. 2013; 209 (e1–6): 51https://doi.org/10.1016/j.ajog.2013.03.011
- Hypertensive disorders of pregnancy increase the risk of future menopausal hot flashes in japanese women: results from the Japan Nurses' health study.Menopause. 2021; https://doi.org/10.1097/GME.0000000000001889
- More vasomotor symptoms in menopause among women with a history of hypertensive pregnancy diseases compared with women with normotensive pregnancies.Menopause. 2013; 20: 1006-1011https://doi.org/10.1097/GME.0b013e3182886093
- Hypertensive disorders of pregnancy and menopausal symptoms: a cross-sectional study from the data registry on experiences of aging, menopause, and sexuality.Menopause. 2020; 28: 25-31https://doi.org/10.1097/GME.0000000000001638
- Impact of nulliparity, hypertensive disorders of pregnancy, and gestational diabetes on vasomotor symptoms in midlife women.Menopause. 2020; 27: 1363-1370https://doi.org/10.1097/GME.0000000000001628
- Life-course reproductive history and cardiovascular risk profile in late mid-life: the CARDIA study.J. Am. Heart Assoc. 2020; 9e014859https://doi.org/10.1161/JAHA.119.014859
- Common diseases as determinants of menopausal age.Hum. Reprod. 2016; 31: 2856-2864https://doi.org/10.1093/humrep/dew264
- Origin, methods, and evolution of the three Nurses' health studies.Am. J. Public Health. 2016; 106: 1573-1581https://doi.org/10.2105/AJPH.2016.303338
- Chan School of Public Health.Health Study History, Nurses'2016 (Accessed July 29, 2022)
- Hypertensive disorders of pregnancy and maternal cardiovascular disease risk factor development: an observational cohort study.Ann. Intern. Med. 2018; 169: 224-232https://doi.org/10.7326/M17-2740
- Preterm delivery and maternal cardiovascular disease in young and middle-aged adult women.Circulation. 2017; 135: 578-589https://doi.org/10.1161/CIRCULATIONAHA.116.025954
- Association of history of gestational diabetes with long-term cardiovascular disease risk in a large prospective cohort of US women.JAMA Intern. Med. 2017; 177: 1735-1742https://doi.org/10.1001/jamainternmed.2017.2790
- Multiple birth resulting from ovarian stimulation for subfertility treatment.Lancet. 2005; 365: 1807-1816https://doi.org/10.1016/s0140-6736(05)66478-1
- Association of parity and breastfeeding with risk of early natural menopause.JAMA Netw. Open. 2020; 3e1919615https://doi.org/10.1001/jamanetworkopen.2019.19615
- Ovarian reserve and anti-mullerian hormone (AMH) in mothers of dizygotic twins.Twin Res Hum Genet. 2013; 16: 634-638https://doi.org/10.1017/thg.2013.4
- Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women.Eur. J. Epidemiol. 2019; 34: 235-246https://doi.org/10.1007/s10654-019-00490-w
- Does accelerated reproductive aging underlie premenopausal risk for cardiovascular disease?.Menopause. 2013; 20: 1139-1146https://doi.org/10.1097/GME.0b013e31828950fa
- Heart disease risk determines menopausal age rather than the reverse.J. Am. Coll. Cardiol. 2006; 47: 1976-1983https://doi.org/10.1016/j.jacc.2005.12.066
- Twin pregnancy: is it a risk factor for long-term cardiovascular disease?.J. Matern. Fetal Neonatal Med. 2016; 29: 1626-1630https://doi.org/10.3109/14767058.2015.1057491
- Cardiovascular mortality risk a decade after twin and singleton pregnancies complicated by hypertensive disorders of pregnancy.Pregnancy Hypertens. 2022; 28: 9-14https://doi.org/10.1016/j.preghy.2022.01.009
- Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study.CMAJ. 2021; 193: E1448-E1458https://doi.org/10.1503/cmaj.202837
- Multi-fetal pregnancy, preeclampsia, and long-term cardiovascular disease.Hypertension. 2020; 76: 167-175https://doi.org/10.1161/HYPERTENSIONAHA.120.14860
- Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses.BMC Pregnancy Childbirth. 2021; 21: 449https://doi.org/10.1186/s12884-021-03938-8
- Hypertension and early menopause after the use of assisted reproductive technologies in women aged 43 years or older: long-term follow-up study.J. Obstet. Gynaecol. Res. 2016; 42: 1782-1788https://doi.org/10.1111/jog.13141
- Association of infertility with atherosclerotic cardiovascular disease among postmenopausal participants in the Women's Health Initiative.Fertil. Steril. 2022; 117: 1038-1046https://doi.org/10.1016/j.fertnstert.2022.02.005
- Effect of internal iliac artery ligation on ovarian blood supply and ovarian reserve.Climacteric. 2011; 14: 54-57https://doi.org/10.3109/13697130903548916
- Reproductive performance after conservative surgical treatment of postpartum hemorrhage.Int. J. Gynaecol. Obstet. 2014; 124: 248-252https://doi.org/10.1016/j.ijgo.2013.08.018
- Excessive follicular recruitment and growth in mothers of spontaneous dizygotic twins.Acta Genet. Med. Gemellol. 1991; 40: 291-301https://doi.org/10.1017/s0001566000003470
- The paradox of declining fertility but increasing twinning rates with advancing maternal age.Hum. Reprod. 2006; 21: 1531-1532https://doi.org/10.1093/humrep/del009
- Pregnancy, perinatal and childhood outcomes in women with and without polycystic ovary syndrome and metformin during pregnancy: a nationwide population-based study.Reprod. Biol. Endocrinol. 2022; 20: 30https://doi.org/10.1186/s12958-022-00905-6
- The association between chronic diseases and the age at natural menopause: a systematic review.Women Health. 2021; 61: 917-936https://doi.org/10.1080/03630242.2021.1992067
- Validity and reproducibility of self-reported age at menopause in women participating in the DOM-project.Maturitas. 1997; 27 (doi:10.106/s0378-5122(97)01122-5): 117-123
- Reproducibility and validity of self-reported menopausal status in a prospective cohort study.Am. J. Epidemiol. 1987; 126: 319-325https://doi.org/10.1093/aje/126.2.319
- Variability in diagnostic evaluation and criteria for gestational diabetes.Diabetes Care. 1996; 19: 12-16https://doi.org/10.2337/diacare.19.1.12
- Association of adverse pregnancy outcomes with risk of atherosclerotic cardiovascular disease in postmenopausal women.JAMA Cardiol. 2020; 5: 1390-1398https://doi.org/10.1001/jamacardio.2020.4097
- The menopause transition and women's health at midlife: a progress report from the study of Women's health across the nation (SWAN).Menopause. 2019; 26: 1213-1227https://doi.org/10.1097/GME.0000000000001424
- Factors related to age at natural menopause: longitudinal analyses from SWAN.Am. J. Epidemiol. 2013; 178: 70-83https://doi.org/10.1093/aje/kws421
- H. Eunice Kennedy Shriver National Institute of Child, N. Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, Racial disparities in adverse pregnancy outcomes and psychosocial stress.Obstet Gynecol. 2018; 131: 328-335https://doi.org/10.1097/AOG.0000000000002441
- E. American Heart Association Council on, Prevention, T. Council on Arteriosclerosis, B. Vascular, C. Council on, N. Stroke, C. the Stroke, Adverse pregnancy outcomes and cardiovascular disease risk: unique opportunities for cardiovascular disease prevention in women: a scientific statement from the American Heart Association.Circulation. 2021; 143: e902-e916https://doi.org/10.1161/CIR.0000000000000961
Article info
Publication history
Published online: October 21, 2022
Accepted:
October 16,
2022
Received in revised form:
September 2,
2022
Received:
June 30,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
