Early menarche may be associated with increased risk of cardiovascular disease. The aim of this study was to evaluate the relationship between age at menarche and metabolic syndrome (MetS) in Korean premenopausal women.
We used nationally representative data from the Korea National Health and Nutrition Examination Survey from 2013 to 2014, and 3,023 premenopausal women aged 20–55 years were our subjects. We defined early menarche as age at first menstrual period less than 12 years. Multivariable logistic regression analysis was used to evaluate the relationship between age at menarche and MetS after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables.
MetS was much more common in women aged 40–55 years than in women aged 20–39 years (4.1% vs. 15.1%). Compared with women who experienced menarche at age 12–15 years, the risk of MetS in the early menarche group was not higher in either age group, after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables (odds ratio [OR], 1.767; 95% confidence interval [CI], 0.718–4.351 in those aged 20–39 years; OR, 1.780; 95% CI, 0.775–4.085 in those aged 40–55 years). The risk of MetS in women with menarche at age ≥16 years was not higher than in women with menarche at age 12–15 years.
Early or late menarche was not associated with an increased risk of MetS in premenopausal Korean women. Even before menopause, current age has a major influence on the development of MetS.
Menarche is one of the most important markers of puberty [
Age at menarche in developed countries has decreased from 16.5 years in 1840 to 13.0 years in the 1960s, and has plateaued at approximately 12.5 years [
The metabolic syndrome (MetS) is a group of risk factors for type 2 diabetes and CVD, including hypertension, hyperglycemia, elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C), and central obesity, and is a major predictive variable for CVD. If the age at menarche is one of the factors that can identify the risk of MetS in adulthood, it can be used for early identification of those with risk factors for adult CVD and for prevention of CVD.
However, previous studies in Korean women have shown inconsistent results for the relationship between age at menarche and MetS, and studies mainly focused on postmenopausal women did not reflect recent changes in age at menarche. The aim of this study is to investigate the relationship between age at menarche and MetS in premenopausal women using data from KNHANES 2013–2014 and to determine whether age at menarche is an independent risk factor for MetS and CVD.
This study was conducted using data from KNHANES 2013–2014. The KNHANES is a cross-sectional and nationally representative survey that was designed to evaluate the health and nutritional status in the Korean population of all ages. All participants provided written informed consent, and the institutional review board of the Korea Centers for Disease Control and Prevention approved the study protocol (2013-07CON-03-4C, 2013-12EXP-03-5C). The KNHANES is based on complex, multistage stratified and clustered samples of the Korean population. We selected 3,023 participants among 3,219 premenopausal women aged 20 to 55 years who had complete information on marital status, household income, education level, smoking status, alcohol consumption, physical activity, number of pregnancies, use of oral contraceptives, duration of lactation, and duration of estrogen exposure.
Participants answered a self-reported questionnaire on their current age, socioeconomic variables (marital status, household income, education level), lifestyle variables (smoking status, alcohol consumption, physical activity), and reproductive variables (number of pregnancies, use of oral contraceptives, duration of lactation). Early menarche was defined as age at the first menstrual period less than 12 years, and late menarche was defined as age at the first menstrual period greater than or equal to 16 years [
Marital status was divided into two groups. Those who had a spouse or were living with a partner were classified as married, and all others were classified as unmarried. Household income was classified by quartiles based on monthly average family equivalent income: high, higher-middle, lower-middle, and lower. Education level was divided into two groups: high school graduate or less, and college graduate or more.
Smoking status was divided into three groups. (1) Non-smokers were defined as individuals who had never smoked or had smoked less than 100 cigarettes in their lifetime. (2) Past smokers were defined as individuals who had smoked more than 100 cigarettes in the past, but do not currently smoke. (3) Current smokers were defined as individuals who had smoked more than 100 cigarettes and continued to smoke at the time of questionnaire completion. Those who drank more than 5 glasses of alcohol per session and more frequently than twice a week were classified into the high risk drinking group according to the KNHANES recommendations. The physically active group was defined by walking for more than 30 minutes per session and more than five days a week.
The number of pregnancies was divided into two groups, based on pregnancies more than or equal to 3 times, including abortion; use of oral contraceptives was divided into two groups, based on oral contraceptive use for more than 1 month [
Physical examinations and blood tests were performed by the survey team to assess MetS. The body mass index (BMI) was calculated by dividing the measured weight by the square of the height. Plasma glucose, triglycerides, and HDL-C were measured using a Hitachi Automatic Analyzer 7600-210 (Hitachi, Tokyo, Japan) after an 8–12-hour overnight fast. MetS was defined according to International Diabetes Federation and National Heart, Lung, and Blood Institute/American Heart Association guidelines as any three or more of the following [
Statistical analysis was performed using sampling weights according to KNHANES guidelines. Because the prevalence of MetS increases as age increases, participants were divided into two groups based on age at the time of the survey: 20–39 years and 40–55 years. In order to compare the characteristics of participants according to age at menarche, continuous variables were reported as mean and standard deviation using analysis of variance, and categorical variables were reported as percentage using the chi-square test. Post-hoc testing using the Bonferroni method was performed to examine differences between the components of MetS in three groups according to the age at menarche. To investigate the independent relationship between age at menarche and MetS, we used multivariable logistic regression analysis. We examined the adjusted odds ratios (ORs) and 95% confidence intervals (CIs), controlling for current age, socioeconomic status, lifestyle variables, reproductive status, and duration of estrogen exposure. SAS ver. 9.2 (SAS Institute Inc., Cary, NC, USA) was used to perform all statistical analyses. P-values less than 0.05 were considered statistically significant.
The prevalence of MetS was 8.7% with menarche at <12 years, 8.3% with menarche at 12–15 years, and 15.3% with menarche at ≥16 years.
Age at menarche did not show a significant correlation with MetS after analysis of age at menarche as a continuous variable (data not shown).
We investigated the relationship between age at menarche and MetS in premenopausal Korean women aged 20–55 years using data from KNHANES 2013–2014. Women with early and late menarche did not have increased risk of MetS compared with those who had menarche at 12–15 years of age.
Previous studies have shown inconsistent results for the relationship between age at menarche and MetS. Consistent with our findings, a meta-analysis based on nine articles with prospective studies of both pre- and postmenopausal women showed no association between age at menarche and overall cardiovascular death [
In contrast to our findings, Lim et al. [
Age, a well-known risk factor for MetS, is also closely related to age at menarche. Mean current age was significantly different by about 6 years according to age at menarche in two previous Korean studies, in contrast to our findings [
The specific and direct underlying mechanisms involved in the association between age at menarche and MetS remain poorly understood, but it can be inferred that childhood obesity may trigger both early menarche and MetS in later life. Excess adipocytes increase the levels of the adrenal androgen dehydroepiandrosterone and estradiol and reduce the levels of sex hormone-binding globulin (SHBG) [
This study has several limitations. First, the cross-sectional design of this study prevents determination of the precise causal relationship, although age at menarche precedes MetS. Second, we could not identify a correlation between risk factors at the time of menarche, such as socioeconomic status, BMI, and sex hormone levels, which could contribute to the increase of MetS in adulthood in the early menarche group. Although we controlled a variety of predictable confounding variables, there may still be other confounders that affect MetS, such as genetic background, dietary patterns, and stressful living conditions. Third, there was a limit to measuring the precise duration of estrogen exposure. Therefore, further studies are required to confirm the relationship between duration of estrogen exposure, age at menarche, and MetS.
Despite these potential limitations, this study has several strengths. First, we used the data from KNHANES, a nationally representative survey, to confirm the relationship between age at menarche and MetS. Second, most previous studies on early menarche were conducted in postmenopausal women, but this study reflected the recent changes in age at menarche because our subjects were relatively young women aged 20–55 years before menopause. In particular, we included women born in the late 1980s, when the age at menarche decreased most rapidly in Korea. Finally, in order to reduce age-grouprelated cohort effects on the association between age at menarche and MetS, we performed analyses after dividing subjects into two groups based on age at the time of survey. Our study revealed that the older the women, the more recent the survey, and the younger the birth cohort, the greater the risk of MetS. In other words, individual aging, period influence, and birth cohort turnover may have simultaneously influenced the relationship between the age at menarche and MetS. In order to reflect both aging of individuals and change at a societal level, long-term prospective studies or age-period-cohort analysis of repeated cross-sectional surveys are needed.
In conclusion, early or late menarche was not associated with an increased risk of MetS in premenopausal Korean women. Even before menopause, current age has a major influence on the development of MetS.
No potential conflict of interest relevant to this article was reported.
Characteristics of premenopausal women stratified by age at menarche
Characteristic | Age at menarche (y) |
P-value | ||
---|---|---|---|---|
<12 (n=288) | 12–15 (n=2,321) | ≥16 (n=414) | ||
Age at the time of survey (y) | 30.98±0.60 | 37.09±0.23 | 43.96±0.60 | <0.001 |
Age at menarche (y) | 10.74±0.04 | 13.44±0.03 | 16.76±0.06 | <0.001 |
Height (cm) | 160.03±0.38 | 160.04±0.14 | 158.50±0.35 | <0.001 |
Weight (kg) | 59.00±0.70 | 57.64±0.21 | 57.36±0.50 | 0.122 |
Married | 51.3 (3.4) | 70.8 (1.2) | 78.2 (2.2) | <0.001 |
Household income | 0.683 | |||
Low | 8.3 (1.8) | 7.5 (0.7) | 9.9 (2.1) | |
Mid-low | 25.4 (3.0) | 25.4 (1.2) | 25.8 (2.6) | |
Mid-high | 30.4 (2.8) | 32.9 (1.2) | 34.0 (2.6) | |
High | 35.9 (3.1) | 34.2 (1.5) | 30.3 (2.9) | |
College graduate or more | 61.8 (3.3) | 48.3 (1.3) | 29.3 (2.3) | <0.001 |
Smoking status | 0.737 | |||
Never | 86.4 (2.3) | 88.7 (0.8) | 87.0 (1.7) | |
Past | 6.1 (1.5) | 4.9 (0.5) | 5.8 (1.3) | |
Current | 7.5 (1.7) | 6.4 (0.6) | 7.1 (1.3) | |
High-risk drinking | 10.1 (1.9) | 6.6 (0.6) | 8.2 (1.6) | 0.097 |
Physically active | 43.0 (3.2) | 37.7 (1.1) | 31.2 (2.4) | 0.009 |
No. of pregnancies ≥3 | 34.9 (4.2) | 54.1 (1.2) | 63.4 (2.4) | <0.001 |
History of oral contraceptive use | 11.8 (2.2) | 10.3 (0.7) | 12.6 (1.9) | 0.437 |
Duration of lactation | <0.001 | |||
Never | 57.9 (3.2) | 43.4 (1.2) | 34.4 (2.8) | |
<6 mo | 10.5 (1.8) | 11.7 (0.7) | 8.8 (1.5) | |
6–12 mo | 8.5 (1.8) | 10.4 (0.6) | 11.0 (1.6) | |
≥12 mo | 23.1 (2.9) | 34.5 (1.1) | 45.8 (2.8) |
Values are presented as mean±standard error or % (standard error). Differences between early menarche (or late menarche) and reference group were compared using analysis of variance for continuous variables and the chi-square test for percentage.
Components of metabolic syndrome in premenopausal women by age at menarche and age at the time of survey
Characteristic | Age at menarche (y) |
P-value | ||
---|---|---|---|---|
<12 | 12–15 | ≥16 | ||
20–39 y | ||||
Body mass index (kg/m2) | 23.00±0.27 |
21.86±0.12 |
21.28±0.36 |
<0.001 |
Waist circumference (cm) | 75.98±0.62 |
73.08±0.31 |
72.48±1.01 |
<0.001 |
HDL cholesterol (mg/dL) | 59.73±0.95 |
58.49±0.36 |
59.40±1.37 |
0.451 |
Fasting triglycerides (mg/dL) | 90.40±6.45 |
85.69±1.75 |
101.17±15.07 |
0.396 |
Fasting glucose (mg/dL) | 90.08±0.54 |
90.63±0.48 |
92.30±2.63 |
0.815 |
Systolic pressure (mm Hg) | 104.99±0.73 |
104.47±0.32 |
105.28±1.02 |
0.875 |
Diastolic pressure (mm Hg) | 69.67±0.75 |
69.46±0.29 |
68.38±0.82 |
0.401 |
40–55 y | ||||
Body mass index (kg/m2) | 24.24±0.55 |
23.42±0.12 |
23.13±0.18 |
0.274 |
Waist circumference (cm) | 79.43±1.59 |
77.09±0.33 |
76.15±0.50 |
0.204 |
HDL cholesterol (mg/dL) | 56.81±2.56 |
56.52±0.40 |
56.12±0.83 |
1.000 |
Fasting triglycerides (mg/dL) | 101.34±11.90 |
112.25±2.39 |
117.46±5.71 |
0.807 |
Fasting glucose (mg/dL) | 97.31±3.65 |
96.35±0.54 |
95.74±1.05 |
0.603 |
Systolic pressure (mm Hg) | 114.11±2.30 |
111.65±0.48 |
115.45±1.11 |
0.04 |
Diastolic pressure (mm Hg) | 76.20±1.81 |
73.92±0.34 |
75.78±0.76 |
0.05 |
Values are presented as mean±standard error. Differences between early menarche (or late menarche) and reference group were compared using analysis of variance after adjusting for current age of participants.
HDL, high-density lipoprotein.
The same symbols indicate non-significant differences between groups based on the Bonferroni test for analysis of variance.
Risk of metabolic syndrome according to age at menarche and age at the time of survey
Characteristic | Age at menarche (y) |
||
---|---|---|---|
<12 | 12–15 | ≥16 | |
20–39 y | |||
Model 1 | 1.922 (0.951–3.885) | 1.000 | 1.053 (0.317–3.500) |
Model 2 | 2.035 (1.011–4.094) | 1.000 | 0.931 (0.283–3.068) |
Model 3 | 1.767 (0.718–4.351) | 1.000 | 0.743 (0.171–3.219) |
Model 4 | 0.900 (0.228–3.560) | 1.000 | 1.375 (0.320–5.913) |
40–55 y | |||
Model 1 | 2.171 (0.988–4.772) | 1.000 | 1.094 (0.773–1.547) |
Model 2 | 2.346 (1.094–5.033) | 1.000 | 1.005 (0.696–1.452) |
Model 3 | 1.780 (0.775–4.085) | 1.000 | 0.981 (0.672–1.434) |
Model 4 | 1.211 (0.483–3.035) | 1.000 | 1.589 (0.682–3.703) |
Values are presented as odds ratio (95% confidence interval). Odds ratios for metabolic syndrome according to age at menarche; multivariable logistic regression was used. Model 1: adjusted for current age; model 2: adjusted for marital status, household income, education level, smoking status, alcohol consumption, and physical activity, in addition to model 1; model 3: adjusted for number of pregnancies, use of oral contraceptive, and duration of lactation, in addition to model 2; and model 4: adjusted for duration of estrogen exposure, in addition to model 3.
Age at menarche (y) |
|||
---|---|---|---|
<12 | 12–15 | ≥16 | |
Model 1 | 2.054 (1.204–3.504) | 1.000 | 1.109 (0.785–1.567) |
Model 2 | 2.194 (1.292–3.727) | 1.000 | 0.998 (0.695–1.432) |
Model 3 | 1.919 (1.020–3.608) | 1.000 | 0.975 (0.673–1.412) |
Values are presented as odds ratio (95% confidence interval). Odds ratios for metabolic syndrome according to the age at menarche; multivariable logistic regression was used. Model 1: adjusted for current age; model 2: adjusted for marital status, household income, education level, smoking status, alcohol consumption, and physical activity, in addition to model 1; and model 3: adjusted for number of pregnancies, use of oral contraceptive, and duration of lactation, in addition to model 2.