23 July, 2012:

A recent 21-year follow-up prospective study was designed to analyze the association between smoking and the onset of menopause at an earlier age in a large cohort of middle-aged women after adjustment for a number of potential confounders [1]. The main outcomes were age of menopause measured at the 21-year follow-up, smoking and menopausal status. This study was based on 3545 women who provided data on their menopausal status at the 21-year follow-up of the study and prospective as well as concurrent data on smoking. In univariate analysis, tobacco smoking during the reproductive life course, socioeconomic status and gravidity were significantly associated with earlier age of menopause. In multivariate analyses, women who smoked cigarettes were more prone to develop earlier menopause than non-smokers. Compared to current smokers, risk of early menopause was significantly lower in those women who were former smokers. In summary, data from this study suggest that the impact of smoking is independent of other covariates associated with both smoking and age of menopause. These findings raise the possibility that effective programs for smoking cessation may lead to a later age of menopause and reduce the risk of adverse health consequences of early menopause.

Comment

The analysis by Hayatbakhsh and colleagues [1] using a very large series of Australian middle-aged women adds evidence to the hypothesis that women who smoked cigarettes were more prone to develop a menopausal status earlier than those who did not smoke [2,3] and supports the possibility that effective quit-smoking interventions may lead to a later onset of menopause, diminishing, therefore, the risk of adverse health consequences of early menopause.

As expected, like other conditions linked to the smoking habit [4,5], the risk of earlier menopause in smokers is related to the numbers of cigarettes smoked. The magnitude of association between prospective cigarette smoking, both at the baseline and 14-year follow-up, is stronger for the 20+ cigarettes group than those who smoked less than 20 cigarettes per day (hazard ratio (HR) 1.48, 95% confidence interval (CI) 1.16–1.88; HR 1.67, 95% CI 1.29–2.16, respectively). Moreover, the risk of earlier menopause in women who cease smoking, quitting before or after 14 years of use (HR 1.00, 95% CI 0.78–1.30; HR 1.19, 95% CI 0.77–1.85, respectively) is similar to those who were never-smokers. The effect of smoking on age of menopause remained unchanged after adjusting the association for women's socioeconomic status, ethnicity, body mass index, use of oral contraceptives and gravidity.

A significant contribution of the present study to the existing literature is that it suggests a reversible effect of smoking on age of natural menopause. This finding is similar to that observed in the skin where former users have less wrinkles than current users [4]. Indeed, the data indicate that effective quit-smoking in the early stages of the reproductive period can, at least, minimize the impact of tobacco consumption on early menopause.

There are several hypothetical mechanisms to explain the effect of tobacco on reproductive function. Tobacco smoke contains polycyclic hydrocarbons, which affect ovarian germ cells and lead to follicular exhaustion and lower levels of estrogen [6]. In addition, substances such as nicotine, cotinine and anabasine, present in tobacco, inhibit androstenedione conversion to estrogen [7] and smoking can also have an effect on hypothalamic–pituitary function [8], delaying the surge in the luteinizing hormone level. However, most of these effects have not been demonstrated in humans.

Finally, and most important, given the link between early menopause and several physical health problems, including cardiovascular diseases, urogenital atrophy, and osteoporosis, the results of the study by Hayatbakhsh and colleagues, that risk of earlier menopause in women who quit smoking is lower than those who continue smoking, suggest the importance of developing programs focussed on smoking cessation.

Camil Castelo-Branco

Ob Gyn Senior Consultant, Hospital Clínic Barcelona, and Full Professor, University of Barcelona, Spain

References

1. Hayatbakhsh MR, Clavarino A, Williams GM, Sina M, Najman JM. Cigarette smoking and age of menopause: A large prospective study. Maturitas 2012 Jun 11. Epub ahead of print.

http://www.ncbi.nlm.nih.gov/pubmed/22695707 

2. Amigoni S, Morelli P, Chatenoud L, Parazzini F. Cross-sectional study of determinants of menopausal age and hormone replacement therapy use in Italian women. Climacteric 2000;3:25-32.

http://www.ncbi.nlm.nih.gov/pubmed/11910606 

3. Blanck HM, Marcus M, Tolbert PE, et al. Time to menopause in relation to PBBs, PCBs, and smoking. Maturitas 2004;49:97-106.

http://www.ncbi.nlm.nih.gov/pubmed/15474753 

4. Castelo-Branco C, Figueras F, Martínez de Osaba MJ, Vanrell JA. Facial wrinkling in postmenopausal women. Effects of smoking status and hormone replacement therapy. Maturitas 1998;29:75-86.

http://www.ncbi.nlm.nih.gov/pubmed/9643520 

5. Lubin JH, Purdue M, Kelsey K, et al. Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies. Am J Epidemiol 2009;170:937-47.

http://www.ncbi.nlm.nih.gov/pubmed/19745021 

6. Jurisicova A, Taniuchi A, Li H, et al. Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri. J Clin Invest 2007;117:3971-8.

http://www.ncbi.nlm.nih.gov/pubmed/18037991 

7. Barbieri RL, Friedman AJ, Osathanondh R. Cotinine and nicotine inhibit human fetal adrenal 11 beta-hydroxylase. J Clin Endocrinol Metab 1989;69:1221-4.

http://www.ncbi.nlm.nih.gov/pubmed/2584357 

8. Tziomalos K, Charsoulis F. Endocrine effects of tobacco smoking. Clin Endocrinol (Oxf) 2004;61:664-74.

http://www.ncbi.nlm.nih.gov/pubmed/15579179 

Content updated 23 July 2012