Body fat, measured by BMI, was strongly associated with long cycles and irregular cycles (Figure 2). Women with high normal BMIs of 24–25 had twice the odds of long cycles compared with women with BMIs of 22–23, and the association grew stronger with each category of BMI. The odds of having a long cycle were five times higher among those with a BMI of 35 or higher (odds ratio [OR] = 5.4; 95% confidence interval [CI] = 2.1–13.7). Women in this heaviest group also showed increased odds of irregular cycles. There was a similar dose-response relation between BMI and odds of irregular cycles.
Age at menarche before age 12 was moderately associated with increased odds of short cycles and intermenstrual bleeding after adjusting for covariates (Figure 3). Having a late age of menarche (age 15 or older) was associated with almost three times the odds of long cycles and about a doubling in the odds of irregular cycles.
Cigarette smoking was associated with short cycles and with irregular cycles (Figure 4). The odds of having irregular cycles were 3.6 among women who smoked more than a pack a day compared with nonsmokers (95% CI = 1.7–8.0).
Self-reported history of Graves’ disease was associated with more than a four-fold increase in odds of long cycles (Table 2). Depression treated with medication was associated with about a doubling of intermenstrual bleeding, irregular cycles, and long cycles. History of diabetes was associated with increased odds of irregular and long cycles. We did not have enough cases to analyze diabetes by age of onset or more detailed data to distinguish between type 1 and type 2 diabetes. History of drug-treated high blood pressure, rheumatoid arthritis, stroke, goiter, and other thyroid disorders was not associated with menstrual cycle patterns.
Having irregular cycles was associated with increased odds of never having been pregnant (Table 3). Long or irregular cycles were each associated with more than twice the odds of infertility. Intermenstrual bleeding was also associated with increased odds of infertility. Long and irregular cycles were each associated with about a doubling in odds of fetal loss in the most recent pregnancy of women reporting a pregnancy within the past 5 years, after adjusting for current body mass, age, and smoking when the pregnancy ended.
Our data are consistent with studies reporting that mean menstrual cycle length shortens after age 20 and menstrual cycle variability decreases as women age up to the onset of the menopausal transition. 6,12,15
The literature suggests that risk of long or irregular cycles increases at both extremes of the weight distribution. 1,10,16,17 However, only limited information is available on the risk of long or irregular cycles among women with intermediate body size. Ours is one of the first studies to show such a clear dose-effect relation between BMI and long or irregular cycles. A cross-sectional study of 26,000 women in a weight-loss program also reported linear relations between weight (BMI not measured) and odds of long or irregular cycles. 18 A smaller, prospective study by Symons et al. 19 reported a J-shaped relation between body mass and cycle length (but not with irregular cycles). In both the Symons study and ours, odds of a long cycle increased in a stepwise manner at BMIs above 23. Our data also resemble the J-shaped relation reported by Symons et al., although the confidence interval for the elevated odds of long cycles among thin women did not exclude 1.0.
We found that onset of menses before age 13 was associated with short cycles and intermenstrual bleeding for women at age 21–40. Menarche at age 15 or later was associated with having long cycles and irregular cycles. In a study of women age 12–14 followed prospectively for 2 years, investigators reported a similar pattern; late age of menarche was associated with longer mean cycle length and increased menstrual cycle variability. 20 The relation between age of menarche and subsequent menstrual cycle characteristics among adult women could result from continued exposure to factors such as intense exercise. 16 Alternatively, the sensitivities of biological feedback systems and mechanisms controlling bleeding may be set before puberty and then affect both age at menarche and adult menstrual patterns.
Some studies have reported more frequent, short cycles among smokers 21 or heavy smokers, 22 although several studies did not find associations between smoking and cycle length. 23,24 Our data support an association, with even moderate smokers having increased odds of short cycles. Most previous studies (but not all) 24 have reported increased menstrual cycle variability among smokers, 21 particularly heavy smokers. 22,23 We found an association between heavy smoking and irregular cycles that was not apparent for lighter smokers (Figure 4).
There are only limited data on the menstrual characteristics of women with chronic diseases. Long cycles are commonly reported among women with Graves’ disease; short cycles are a less common complication. 25 Our data are consistent with these observations. However, because we did not ask women whether they had ever had a medical evaluation for a menstrual problem, we are unable to rule out detection bias as a possible explanation. It is possible that women who had unusual menstrual cycle patterns were simply more likely to have had a thyroid function test.
In our data, diabetes was associated with increased odds of long and irregular cycles after adjusting for BMI and other covariates, although the confidence intervals for these associations were wide. In a cross-sectional study such as ours, the direction of causality is ambiguous. A Danish study of menstrual cycle patterns among diabetic women reported a four-fold increase in having menarche at age 17 or later (primary amenorrhea) and increased risk of secondary amenorrhea (6 months or longer without a period), long cycles, and irregular cycles. 26 In addition, in the Nurses’ Health Study, women with long or irregular menstrual cycles had a doubling in risk of developing type 2 diabetes mellitus after adjusting for BMI. 27
In our data, drug-treated depression was associated with increased odds of intermenstrual bleeding, irregular cycles, and long cycles. These associations might be attributable to increased stress among depressed women, to depression itself, or to the medication treatment for depression. We did not have data to clarify this further.
The underlying biology and mechanisms affecting menstrual cycle characteristics has not been well described. Variation in length of the follicular phase is responsible for most of the variability in cycle length, and follicular phase length depends on a process of follicular maturation and selection of the primary follicle. Both are dependent on FSH from the pituitary and appropriate ovarian response. Short and long cycles are more likely to be anovulatory than cycles of 25–35 days. 1 Women with highly variable cycle lengths are also more likely to have anovulatory cycles. 8 Both heavy and light women are more likely to have anovulatory cycles than women of intermediate body weight. 1,8 It would also be of interest to pursue the role of insulin sensitivity in the association between BMI and cycle characteristics. Clinical insulin resistance and elevated androgen levels were associated with long cycles among Pima Indians, 29 and long and irregular cycles were associated with risk of developing type 2 diabetes in the Nurses Health Study. 27
These data have some important limitations. We restricted our analysis to women who had completed two questionnaires and met a strict set of reproductive criteria, which raises concerns about possible biases. We tried to evaluate this, first by comparing women who answered both questionnaires with those who only completed the exposure questionnaire. We found that the distribution of demographic characteristics such as age, education, BMI, or number of children (as reported on the husband’s enrollment questionnaire) were similar in both groups. About one-fifth of the women who otherwise met the age criteria for inclusion were taking oral contraceptives. Women on oral contraceptives do not menstruate and thus cannot provide information on menstrual characteristics. However, because oral contraceptives are often prescribed for women who are having menstrual irregularities, our data may underestimate the prevalence of long or irregular cycles in our population. Selection bias could also have resulted if women chose to participate both because they had menstrual problems or related reproductive outcomes such as infertility and because they experienced the exposures of interest. Because we evaluated many exposures, we think this is an unlikely source of systematic bias.
Several other design limitations deserve comment. Because this was a study of women living on farms, there is a possible problem with generalizing our study results to other populations of women. We did not have data on stress or physical activity, both of which are important risk factors for menstrual cycle irregularities. 1,2,10,28 Although we omitted from analysis women who were currently breast feeding, pregnant, or taking oral contraceptives, we could not identify women who had recently stopped breast feeding, taking oral contraceptives, or ended a pregnancy, and they may have had cycles that did not reflect their typical patterns. Our measures of thyroid disease, diabetes, and other chronic diseases were based on self-report. Finally, the data were cross-sectional so the associations we observed may not be causal.
Despite these limitations, this is one of the largest studies of menstrual function among adult women in the United States, and our findings suggest some important new avenues for research on factors that may perturb menstrual function.
This paper is also one of the few papers to evaluate the association of self-reported menstrual cycle characteristics with other adverse reproductive outcomes. Women with irregular cycles were less likely to have ever been pregnant. Except for short cycles, every one of our menstrual cycle parameters was associated with a history of infertility. A California study of urinary biomarkers and menstrual function reported that women with current anovulatory cycles were four times as likely to have had difficulty becoming pregnant in the past. 22 In our data, long cycles and irregular cycles were associated with increased odds of prior fetal loss. Although these relations should be further investigated in a prospective study, it is likely that exposures or risk factors that perturb normal menstruation also may increase a woman’s risk of other reproductive disorders.
This paper has demonstrated that menstrual patterns are influenced by a number of host and environmental characteristics. Importantly, these data suggest that even small increases in BMI have observable impacts on menstrual patterns. The increase in obesity in the United States and elsewhere increases the risk of reproductive problems as well as the risk of chronic disease. Menstrual cycle patterns result from biological systems that depend upon a woman’s hormonal status and that are sensitive to environmental influences. Therefore, factors that disrupt menstruation should be suspected of being capable of disrupting normal reproductive function. Identifying differences in women’s menstrual cycle characteristics, and understanding more about the determinants of those differences and their association to other reproductive outcomes, may yield important insights into women’s reproductive biology.
We thank Cheryl McDonnell for her help managing the Agricultural Health dataset and Pam Schwingl, Sheila Zahm, and Glinda Cooper for their helpful comments, which improved the manuscript.
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menstrual cycle; menstruation; obesity; smoking; thyroid diseases; depression
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