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Associations between lifetime tobacco exposure with infertility and age at natural menopause: the Women's Health Initiative Observational Study
  1. Andrew Hyland1,
  2. Kenneth Piazza1,
  3. Kathleen M Hovey2,
  4. Hilary A Tindle3,
  5. JoAnn E Manson4,
  6. Catherine Messina5,
  7. Cheryl Rivard1,
  8. Danielle Smith1,
  9. Jean Wactawski-Wende2
  1. 1Department of Health Behavior, Division of Cancer Prevention & Population Sciences, Roswell Park Cancer Institute, Buffalo, New York, USA
  2. 2Department of Epidemiology and Environmental Health, University at Buffalo, School of Public Health & Health Professions, Buffalo, New York, USA
  3. 3Division of Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  4. 4Department of Epidemiology, Brigham and Women's Hospital, Harvard Medical School, Harvard School of Public Health, Boston, Massachusetts, USA
  5. 5Division of Behavioral and Community Health, University of New York at Stony Brook, Stony Brook, New York, USA
  1. Correspondence to Danielle Smith, Department of Health Behavior, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA; danielle.smith{at}


Background Several studies have investigated the association of tobacco use with infertility and age at natural menopause, yet few have explored secondhand smoke (SHS) exposure with these outcomes. This study offers a comprehensive, quantified secondary data analysis of these issues using the Women's Health Initiative Observational Study (WHI OS).

Purpose This study examines associations between lifetime tobacco exposure—active smoking and SHS—and infertility and natural menopause (before age 50).

Methods Information on smoking, lifetime fertility status, and age at natural menopause was collected and available from 93 676 postmenopausal women aged 50–79 enrolled in the WHI OS from 1993 to 1998 at 40 centres in the USA. Multivariate-adjusted regression models were used to estimate ORs and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories.

Results Overall, 15.4% of the 88 732 women included in the analysis on infertility met criteria for the condition. 45% of the 79 690 women included in the analysis on natural menopause (before age 50) met criteria for the condition. Active-ever smokers had overall OR's of 1.14 (95% CI 1.03 to 1.26) for infertility, and 1.26 (95% CI 1.16 to 1.35) for earlier menopause than never-smoking women. Never-smoking women with the highest levels of lifetime SHS exposure had adjusted OR's of 1.18 (95% CI 1.02 to 1.35) for infertility, and 1.18 (95% CI 1.06 to 1.31) for earlier menopause. Active-ever smokers reached menopause 21.7 months earlier than the mean of 49.4 years for never-smokers not exposed to SHS, and women exposed to the highest level of SHS reached menopause 13.0 months earlier.

Conclusions Active smoking and SHS exposure are associated with increased risk of infertility and natural menopause occurring before the age of 50 years.

  • Secondhand smoke
  • Smoking Caused Disease
  • Surveillance and monitoring

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  • Contributors KP, AH, JW-W and KMH participated in the study design. KMH completed the data analysis. All the authors participated in the data collection, data interpretation, drafting and revision of the manuscript.

  • Funding The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046 C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.

  • Disclaimer The funding source had no role in the collection, analysis, or interpretation of the data, in the preparation of the manuscript, or its submission for publication.

  • Competing interests None declared.

  • Ethics approval Human Subjects Committees at participating centres approved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.