Our study investigated the various factors influencing the menstrual cycle and the effects of smoking on menopausal onset. In our study, the risk factors for menstrual cycle irregularity were perceived stress, obesity, smoking, and marital status. Furthermore, early initiation of smoking and high cigarette consumption were significantly associated with premature menopause based on the results of analyses using both logit and linear regression models. This study focused on modifiable risk factors, such as smoking, obesity, and perceived stress, and revealed the importance of these factors in the improvement of women’s health.
With regard to stress, our study showed that high level of perceived stress was associated with high probability of menstrual cycle irregularity. A previous study conducted among 696 women aged 20–40 years revealed that menstrual cycle irregularity was associated with high chronic stress level [29]. Moreover, past studies that utilized special tools to check the stress level (i.e., > 20 in the Perceived Stress Scale or Global Severity Index) of university students also indicated that stress was correlated with irregular menstruation [30, 31]. One theory that explained the mechanism through which stress affects the menstrual cycle involves the HPA axis. This theory suggests that a reduction in the HPA axis activity leads to the occurrence of menopause. When the stress level is high, the HPA axis activity is interrupted. Thus, women who are suffering from considerable stress may experience more irregularities in menstruation than those who are not under stress [32].
In the present study, women who had BMI of 25–30 or ≥30 have high possibility of developing irregular menstruation. This finding is also consistent with those of previous studies on the association between irregular menstruation and obesity. For instance, one study that involved 14,779 women who were 19–23 years old showed that those with BMI of < 17, 17–18.5, 18.5–20, 25–30, and > 30 had 1.6, 1.2, 1.2, 1.1, and 1.4 times higher probability of developing menstrual cycle irregularity, respectively, than those with BMI of 20–25 BMI [33]. Furthermore, another study conducted among 1095 female students in childbearing years (18–25 years old) in Taiwan demonstrated that women with BMI of > 27 had 18.48 times higher risk of developing menstrual cycle irregularity than those with BMI of 18.5–23.9 [20]. Additionally, a study on irregular menstruation, which was defined as > 15 days of menstrual cycle difference, that was conducted among 726 women showed that women with BMI of > 30 had 2.61 times higher risk of developing irregular menstruation than those with BMI of 25–29.9 [22]. The mechanism behind the association between BMI and irregular menstruation may be attributed to low SHBG level and high testosterone and FAI levels. The present study showed that women who had higher BMI developed irregular menstruation caused by low SHBG level and high testosterone, FAI, and insulin levels. An increase in the BMI resulted to changes (either decrease or increase) in the value of SHBG (− 0.44), testosterone (+ 0.17), FAI (+ 0.42), and insulin (+ 0.54) [22].
The univariate regression analysis revealed that smoking was correlated with irregular menstruation; however, this association was not found in the multivariable regression analysis. To determine the effect of smoking on menstrual cycle irregularity, we categorized the smoking-related factors into the following: lifetime smoking status, secondhand smoking, cigarettes per day, age at smoking initiation, and pack-year. The results of the univariate logistic regression analysis revealed a statistically significant association between smoking status and irregular menstruation. Specifically, the current smokers had 1.4 times higher prevalence of menstrual cycle irregularity than non-smokers. However, the multivariable logistic regression analysis did not show a statistically significant difference in the prevalence of menstrual cycle irregularity between non-smokers and current smokers. This difference may be explained by multicollinearity because various factors, such as perceived stress, obesity, and alcohol consumption, were correlated with smoking.
The univariate analysis also revealed an association between menopause and smoking, although a dose–response relationship with regard to the pack-year was not observed. Participants who smoked at younger and older age had a tendency to develop early menopause. A previous study conducted among 14,889 women who were 18–23 years old in Austria indicated that ex-smokers had 1.2 times higher risk of developing irregular menstruation than non-smokers. For current smokers, the higher the number of smoked cigarettes, the higher the risk to develop irregular menstruation [33]. The findings of several previous studies also supported the association between smoking and early menopause. For example, one study involving 543 participants showed that current smokers were 0.8 years younger than non-smokers; however, no statistically significant difference was observed in regard to secondhand smoking between ex-smokers and current smokers [34]. Additionally, another previous study conducted among women aged 45–55 years old in Massachusetts demonstrated that smokers experienced menopause was 1.8 years earlier than non-smokers [35].
Additionally, a study based on the US National Health and Nutrition Examination Survey III demonstrated that smoking elevated the risk of developing early menopause among 5029 women who were older than 25 years old [36]. A systematic review of 96 articles based on 109 studies reported a association between smoking and early menopause, although a clear association between the quantities of cigarettes smoked or smoking period was not observed [21]. Moreover, one study also analyzed the relationship between prenatal and childhood household smoke exposure or adult active smoking and early natural menopause. The results showed current smokers who had been smoking period for > 26 years or > 10 cigarettes/day had higher risk of developing early natural menopause than the other current smokers [37].
The association between smoking and menopause may be attributed to the development of a hypoestrogenic state that is induced by smoking. A study conducted from 1977 to 1984 among 5000 women who were 34 years old or above showed that smokers had 19% lower level of estradiol based on urine test than non-smokers after menopause [38]. Furthermore, a study that involved 603 premenopausal women demonstrated that current smokers had lower total estrogen metabolite (EM) levels than non-smokers. These participants were shown to have significantly lower levels of parent estrogens, such as estradiol, 1-methoxyestradiol (a metabolite of the 2-hydroxylation pathway), estriol (an EM of the 16-hydroxylation pathway), and 16-epiestriol [39]. Moreover, one study conducted from 1982 to 1984 among 350 women aged 45–69 years revealed that smokers use 1.46 times more hormonal replacement therapy (HRT) than non-smokers (OR = 1.46, p = 0.005). On the other hand, the use of HRT was not statistically significant among ex-smokers. HRT is used when the estrogen level becomes low. Therefore, the increase use of HRT among smokers than non-smokers indicated that smoking induces hypoestrogenic state [40]. Another mechanism through which smoking induces hypoestrogenic state involves the increase in the level of HPA axis hormones, including adrenocorticotropic hormone, cortisol, and dehydroepiandrosterone, such as during stress [41].
The association between alcohol consumption and menstrual cycle irregularity was not found to be statistically significant. However, when we considered the behavioral patterns such as smoking status, obesity level, and alcohol consumption, these negative behaviors were significantly associated with the increased prevalence of menstrual cycle irregularity. While, smoking was inversely related to obesity, alcohol consumption could result in increasing the prevalence of obesity. Therefore, it may be plausible to consider the integration of behaviors when investigating menstrual cycle irregularity.
Menarche age was not significantly different between women who attained menopause before or after the age of 50 years. Some debates still exist on the relationship between menarche and menopausal ages. Women who began their menstruation at the age of 11 years or younger have an 80% higher chance of having menopause at the age of 40 years than those who started menstruating at the age of 13 years. Additionally, the risk of having menopause at the age of 40–44 years was approximately 30% [42]. However, our study indicated that premature menopause may be caused by acquired and environmental factors, rather than the menarche age. Hence, further research on this topic would be necessary [43, 44].
Our study has several limitations to consider when interpreting the results. First, because our study used cross-sectional data, causal relationships could not be determined. Second, most data on the participants’ characteristics were collected through self-reported questionnaires, except for BMI. Third, when assessing the factors affecting menopause, we could not consider other factors, except for smoking, because information regarding the participants’ at the time of their menopausal age was not available.