Meta-analysis Suggests That Smoking is Associated with an Increased Risk of Early Natural Menopause

Sun, Lu MSc; Tan, Lijun PhD; Yang, Fang PhD; Luo, Yi MSc; Li, Xi PhD; Deng, Hong-Wen PhD; Dvornyk, Volodymyr PhD


Menopause. 2012;19(2):126-132. 

In This Article

Abstract and Introduction


Objective: Age at natural menopause (ANM) is usually defined as the age at the last menstrual bleeding followed by the absence of menses for 12 consecutive months. Although many studies have suggested an association between smoking and early age at natural menopause, evidence remains conflicting because some studies reported inconsistent or contrasting results. To resolve this ambiguity and to quantitatively evaluate the effect of smoking on ANM, we conducted a meta-analysis of the available data about smoking and ANM.
Methods: After extensive searching of public literature databases, a total of 11 studies were selected for this meta-analysis. Among them, the phenotype of the participants in five studies (dichotomous studies) was classified as early or late ANM, and odds ratio (OR) was used to evaluate the effect of smoking on early ANM. For the other six studies (continuous studies), mean and SD were provided for smoking and nonsmoking samples, and weighted mean difference (WMD) was used as the effect size.
Results: We found that smoking was significantly associated with early ANM in both dichotomous and continuous studies. The pooled effect was OR = 0.74 (95% CI, 0.60-0.91, P < 0.01) in the dichotomous studies. For the continuous studies, the pooled effect estimated by WMD was -1.12 (95% CI, -1.80 to -0.44, P = 0.04). After adjustment of the original data for heterogeneity, the pooled results changed only a little: OR = 0.67 (95% CI, 0.61-0.73, P < 0.01) for dichotomous studies and WMD = -0.90 (95% CI, -1.58 to -0.21, P = 0.01) for the continuous studies.
Conclusions: The results of our study suggest that smoking is a significant independent factor for early ANM.


Menopause marks the end of a woman’s menstrual cycle and reproduction period. It is usually defined as the absence of menses for 12 consecutive months. The normal process of menopause occurs when ovaries cease the production of estrogen and progesterone, and a woman’s lifetime supply of oocytes is depleted.[1] The age at natural menopause (ANM) is closely related to women’s physical and psychological health. Early ANM was associated with a higher risk of several complex diseases, such as osteoporosis,[2,3,4] genital tract cancers,[5,6,7] and cardiovascular diseases.[8,9,10] For example, early menopause may increase the risk of venous thrombosis and association with cardiovascular diseases through changes in the concentration of female sex hormones such as estrogen and progesterone.[11,12] On the other hand, late ANM may be a factor for an increased risk of breast cancer[13,14] and endometrial and hepatocellular cancers.[15,16,17] In summary, although early ANM may lower the risk of some disorders like breast cancer, overall mortality is increased by about 2% with each reducing year of age at menopause.[18,19] Therefore, from a clinical point of view, determining the potential factors that influence ANM may contribute to the prophylaxis of these diseases.

ANM is affected by various social, genetic, and environmental factors such as smoking,[20,21] alcohol consumption,[22] nutrition,[23] race,[24] maternal age at menopause,[25] and others. Tobacco smoking is one of the factors accelerating the process of human senescence. Many studies suggested smoking as a potential factor for early menopause,[26,27,28] but some studies did not support this view.[29,30] Furthermore, the effect sizes of smoking on ANM varied greatly in these studies.

So far, two reviews summarized the published reports on the association of smoking and ANM,[31,32] but none used a systematic statistical technique to quantitatively analyze the aggregated data. A meta-analysis is a powerful tool that can sum up results of different studies and produce a single estimate of the major effect with increased accuracy.[33,34,35,36] To systematically review the published data, we performed a meta-analysis from all eligible studies to quantitatively estimate the association between smoking and ANM.[37]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.