Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies

Dongshan Zhu, Hsin Fang Chung, Nirmala Pandeya, Annette J. Dobson, Janet E. Cade, Darren C. Greenwood, Sybil L. Crawford, Nancy E. Avis, Ellen B Gold, Ellen S. Mitchell, Nancy F. Woods, Debra Anderson, Daniel E. Brown, Lynnette L. Sievert, Eric J. Brunner, Diana Kuh, Rebecca Hardy, Kunihiko Hayashi, Jung Su Lee, Hideki MizunumaGraham G. Giles, Fiona Bruinsma, Therese Tillin, Mette Kildevæld Simonsen, Hans Olov Adami, Elisabete Weiderpass, Marianne Canonico, Marie Laure Ancelin, Panayotes Demakakos, Gita D. Mishra

Research output: Contribution to journalArticle

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Abstract

Background: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. Methods and findings: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40–44 (early), 45–49, 50–51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73–2.44) (p < 0.001) and early menopause (1.80; 1.66–1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04–1.23; p = 0.006) and 1.15 (1.05–1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45–49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15–20 years, the risk was markedly higher for premature (15.58; 11.29–19.86; p < 0.001) and early (6.55; 5.04–8.52; p < 0.001) menopause. Also, current smokers with 11–15 pack-years had over 4-fold (4.35; 2.78–5.92; p < 0.001) and 3-fold (3.01; 2.15–4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98–1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. Conclusions: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

Original languageEnglish (US)
Article numbere1002704
JournalPLoS Medicine
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2018

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Menopause
Observational Studies
Smoking
Premature Menopause
Odds Ratio
Logistic Models
Confidence Intervals
Poisons
Reproductive Health
Smoking Cessation
Denmark
Sweden
France
Meta-Analysis
Japan
Chronic Disease

ASJC Scopus subject areas

  • Medicine(all)

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Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause : A pooled analysis of individual data from 17 observational studies. / Zhu, Dongshan; Chung, Hsin Fang; Pandeya, Nirmala; Dobson, Annette J.; Cade, Janet E.; Greenwood, Darren C.; Crawford, Sybil L.; Avis, Nancy E.; Gold, Ellen B; Mitchell, Ellen S.; Woods, Nancy F.; Anderson, Debra; Brown, Daniel E.; Sievert, Lynnette L.; Brunner, Eric J.; Kuh, Diana; Hardy, Rebecca; Hayashi, Kunihiko; Lee, Jung Su; Mizunuma, Hideki; Giles, Graham G.; Bruinsma, Fiona; Tillin, Therese; Simonsen, Mette Kildevæld; Adami, Hans Olov; Weiderpass, Elisabete; Canonico, Marianne; Ancelin, Marie Laure; Demakakos, Panayotes; Mishra, Gita D.

In: PLoS Medicine, Vol. 15, No. 11, e1002704, 01.11.2018.

Research output: Contribution to journalArticle

Zhu, D, Chung, HF, Pandeya, N, Dobson, AJ, Cade, JE, Greenwood, DC, Crawford, SL, Avis, NE, Gold, EB, Mitchell, ES, Woods, NF, Anderson, D, Brown, DE, Sievert, LL, Brunner, EJ, Kuh, D, Hardy, R, Hayashi, K, Lee, JS, Mizunuma, H, Giles, GG, Bruinsma, F, Tillin, T, Simonsen, MK, Adami, HO, Weiderpass, E, Canonico, M, Ancelin, ML, Demakakos, P & Mishra, GD 2018, 'Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies', PLoS Medicine, vol. 15, no. 11, e1002704. https://doi.org/10.1371/journal.pmed.1002704
Zhu, Dongshan ; Chung, Hsin Fang ; Pandeya, Nirmala ; Dobson, Annette J. ; Cade, Janet E. ; Greenwood, Darren C. ; Crawford, Sybil L. ; Avis, Nancy E. ; Gold, Ellen B ; Mitchell, Ellen S. ; Woods, Nancy F. ; Anderson, Debra ; Brown, Daniel E. ; Sievert, Lynnette L. ; Brunner, Eric J. ; Kuh, Diana ; Hardy, Rebecca ; Hayashi, Kunihiko ; Lee, Jung Su ; Mizunuma, Hideki ; Giles, Graham G. ; Bruinsma, Fiona ; Tillin, Therese ; Simonsen, Mette Kildevæld ; Adami, Hans Olov ; Weiderpass, Elisabete ; Canonico, Marianne ; Ancelin, Marie Laure ; Demakakos, Panayotes ; Mishra, Gita D. / Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause : A pooled analysis of individual data from 17 observational studies. In: PLoS Medicine. 2018 ; Vol. 15, No. 11.
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title = "Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies",
abstract = "Background: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. Methods and findings: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95{\%} confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40–44 (early), 45–49, 50–51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9{\%} and 7.3{\%} of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95{\%} CI 1.73–2.44) (p < 0.001) and early menopause (1.80; 1.66–1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04–1.23; p = 0.006) and 1.15 (1.05–1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45–49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15–20 years, the risk was markedly higher for premature (15.58; 11.29–19.86; p < 0.001) and early (6.55; 5.04–8.52; p < 0.001) menopause. Also, current smokers with 11–15 pack-years had over 4-fold (4.35; 2.78–5.92; p < 0.001) and 3-fold (3.01; 2.15–4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98–1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. Conclusions: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.",
author = "Dongshan Zhu and Chung, {Hsin Fang} and Nirmala Pandeya and Dobson, {Annette J.} and Cade, {Janet E.} and Greenwood, {Darren C.} and Crawford, {Sybil L.} and Avis, {Nancy E.} and Gold, {Ellen B} and Mitchell, {Ellen S.} and Woods, {Nancy F.} and Debra Anderson and Brown, {Daniel E.} and Sievert, {Lynnette L.} and Brunner, {Eric J.} and Diana Kuh and Rebecca Hardy and Kunihiko Hayashi and Lee, {Jung Su} and Hideki Mizunuma and Giles, {Graham G.} and Fiona Bruinsma and Therese Tillin and Simonsen, {Mette Kildev{\ae}ld} and Adami, {Hans Olov} and Elisabete Weiderpass and Marianne Canonico and Ancelin, {Marie Laure} and Panayotes Demakakos and Mishra, {Gita D.}",
year = "2018",
month = "11",
day = "1",
doi = "10.1371/journal.pmed.1002704",
language = "English (US)",
volume = "15",
journal = "PLoS Medicine",
issn = "1549-1277",
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TY - JOUR

T1 - Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause

T2 - A pooled analysis of individual data from 17 observational studies

AU - Zhu, Dongshan

AU - Chung, Hsin Fang

AU - Pandeya, Nirmala

AU - Dobson, Annette J.

AU - Cade, Janet E.

AU - Greenwood, Darren C.

AU - Crawford, Sybil L.

AU - Avis, Nancy E.

AU - Gold, Ellen B

AU - Mitchell, Ellen S.

AU - Woods, Nancy F.

AU - Anderson, Debra

AU - Brown, Daniel E.

AU - Sievert, Lynnette L.

AU - Brunner, Eric J.

AU - Kuh, Diana

AU - Hardy, Rebecca

AU - Hayashi, Kunihiko

AU - Lee, Jung Su

AU - Mizunuma, Hideki

AU - Giles, Graham G.

AU - Bruinsma, Fiona

AU - Tillin, Therese

AU - Simonsen, Mette Kildevæld

AU - Adami, Hans Olov

AU - Weiderpass, Elisabete

AU - Canonico, Marianne

AU - Ancelin, Marie Laure

AU - Demakakos, Panayotes

AU - Mishra, Gita D.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. Methods and findings: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40–44 (early), 45–49, 50–51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73–2.44) (p < 0.001) and early menopause (1.80; 1.66–1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04–1.23; p = 0.006) and 1.15 (1.05–1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45–49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15–20 years, the risk was markedly higher for premature (15.58; 11.29–19.86; p < 0.001) and early (6.55; 5.04–8.52; p < 0.001) menopause. Also, current smokers with 11–15 pack-years had over 4-fold (4.35; 2.78–5.92; p < 0.001) and 3-fold (3.01; 2.15–4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98–1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. Conclusions: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

AB - Background: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. Methods and findings: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40–44 (early), 45–49, 50–51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73–2.44) (p < 0.001) and early menopause (1.80; 1.66–1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04–1.23; p = 0.006) and 1.15 (1.05–1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45–49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15–20 years, the risk was markedly higher for premature (15.58; 11.29–19.86; p < 0.001) and early (6.55; 5.04–8.52; p < 0.001) menopause. Also, current smokers with 11–15 pack-years had over 4-fold (4.35; 2.78–5.92; p < 0.001) and 3-fold (3.01; 2.15–4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98–1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. Conclusions: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

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