The Association Between Early Menarche and Gestational Diabetes: A Secondary Analysis

Annabel S. Alfonseca1*, Uzoamaka V. Eziri1*, Anmol K. Kaur1*, Taylor S. Mewhiney1*, and Grace L.Tieko1*

¹Geisinger Commonwealth School of Medicine, Scranton, PA 18509 *Master of Biomedical Sciences Program Correspondence: tmewhiney@som.geisinger.edu

Abstract

Over the last few decades, the prevalence of gestational diabetes mellitus (GDM) has increased. Yearly, 2–14% of pregnancies are affected by GDM. Early age of menarche, the first menstrual period, has been associated with an increased risk of GDM. Race/ethnicity, socioeconomic status, environmental stress, and genetics may contribute to this finding. Early menarche age ranges are neither definitive nor universal and are based on studied populations. For this investigation, early menarche was defined as ages 9 to 12. Little data has been collected regarding the long-term consequences associated with early age of menarche. With new knowledge of at-risk communities with predispositions to GDM, more standardized guidelines and preventive measures can be implemented to better manage the long-term consequences of gestational diabetes. This investigation utilized secondary data from the National Health and Nutrition Examination Surveys (NHANES) Reproductive Health Questionnaire to address the gap in knowledge of early onset of menarche and later development of GDM in women living in the United States. This may have significant public health implications, as maternal obesity rates are increasing and can result in pregnancy complications. We hypothesize that early age of menarche (ages 9 to 12) will be associated with a higher risk of developing GDM in the United States. Our analysis showed there was a significant association between age of menarche and diabetes diagnosis while pregnant in addition to age of gestational diabetes diagnosis and age when delivering a baby 9 pounds or greater. These results contradict previous findings in the literature and call for further investigation into the relationship between early menarche, GDM, and race/ethnicity.

Introduction

The American Diabetes Association defines gestational diabetes mellitus (GDM) as any degree of glucose intolerance during pregnancy regardless of insulin or diet modification and whether the condition persists after pregnancy (1). As of November 2020, there were a total 330,571,917 people living in the United States, (2) with women making up 50.6% of the population (3). From 2000 to 2010, the prevalence of GDM increased by 56% (4), and every year 2–14% of pregnancies are affected by gestational diabetes. Data suggests GDM appears to be more prevalent in African American, American Indian, and Hispanic/Latina American women (5). For the United States, the public health implications of this are significant, as maternal obesity rates are increasing and can result in negative long-term outcomes for both the mother and the fetus (6). In addition to GDM, maternal obesity also increases the risk for several pregnancy complications, including gestational hypertension, maternal hypertensive disease or pre-eclampsia, risk of emergency cesarean delivery, and prolonged delivery times (7). As a result of these various complications, the neonate has increased adiposity and is at risk for birth complications. Children of women with GDM have a greater prevalence of childhood obesity and glucose intolerance (8). Additionally, women with a history of GDM have long-term risks associated with development of Type 2 diabetes mellitus (9), hypertension (10), dyslipidemia (11), and cardiovascular disease (12). Menarche, the first menstrual period in a female, is another factor of women’s reproductive health that has been correlated with the development of diabetes (13). Menstruation is the monthly shedding of the functional layer of the uterus (13). The average age of menarche varies within different ethnic and racial groups. On average, Non-Hispanic Black and Mexican American women reached menarche earlier than other groups at 11.82 to 12.36 and 11.81 to 12.37 years, respectively, compared to the average age of 12.38 to 12.67 years (14). The definition of early age of menarche varies and is defined from ages 9 to 11.5 (15). This is explained by its relation to the distribution of the onset of menarche in studied populations (15). As a result, ranges of early menarche are neither definitive nor universal (15). According to an NIH study, less than 10% of young women in the United States experience their first period before 11 years (16). Some factors that may contribute to this early occurrence are nutrition, race/ethnicity, socioeconomic status, environmental stress, and genetics (17). Little data have been collected regarding the long-term consequences associated with early age of menarche. Research suggests that early age of menarche is associated with increased risk for Type 2 diabetes (18). The University of Queensland found that the age at which girls start menstruating could predict an increased risk of developing diabetes during pregnancy (19). Early menarche has been associated with both the development of Type 2 diabetes and GDM, but these associations are not well-studied (5). Due to the similarities in causative factors and the lack of research available, we aimed to investigate the correlation between the early onset of menarche and the later development of GDM in women living in the United States. We investigated these similarities using secondary data by utilizing secondary data from the National Health and Nutrition Examination Surveys (NHANES) Reproductive Health Questionnaire. Furthermore, identifying certain ethnic and racial groups associated with early menarche and GDM will reveal communities most at risk. With new knowledge about at-risk communities with a predisposition to GDM, standardized guidelines and preventative measures can be implemented to better manage the long-term consequences of gestational diabetes.

Methods

Participants Questionnaires were used to obtain data. The topics of interest, assessed using a combination of scaled and dichotomous questions, included reproductive health, history of pregnancy and menstruation, hormone therapy and a myriad of other reproductive conditions in relation to the subject. To ensure accuracy, certain populations were oversampled to gather a representative sample of the civilian and noninstitutionalized population of the United States (21). For the Reproductive Health Questionnaire, females aged 12 years and older were included in the final data set. Variables in relation to hysterectomy and pregnancy at the time of survey were excluded from the data for women aged 12 to 19 and over 44 years old for disclosure purposes. The sample size is representative of certain populations in the United States.

Procedures

NHANES Reproductive Data and NHANES Demographic Data sets for years 2013 to 2018 were downloaded via the statistical software, SAS (Statistical Analysis System). The data were then imported into Microsoft Excel to be filtered. Code 777 (refused to answer) and code 999 (don’t know), were removed from the data. Answer choices of participants who experienced menarche after the age of 12 were also excluded. Additionally, women who had not started menarche at the time of the questionnaire were also excluded. Answer responses from male participants were removed from the data. Filtered data was imported into statistical software, SPSS (Statistical Product and Service Solutions) to perform data analysis. In SPSS, the data of each year interval was merged into a single data file.

The following variables were analyzed from the NHANES Reproductive data: RHQ010, age of menarche; RHQ162, participant told they had diabetes while pregnant; RHQ163, participant age of gestational diabetes diagnosis; and RHQ173, age when delivered baby 9 pounds or more. The following variables were analyzed from questionnaire data: RIAGENDR, gender of participant; RIDRETH3, ethnicity of participants was set to a nominal measure. RHQ010, RHQ163, and RHQ173 were set to a scale measure, where RHQ162 was set to a nominal measure. When necessary, the code/value of each variable was labeled. Values that were missing or would confound the data analysis were entered via the missing tab. The data values that were specified as user-missing were flagged for special treatment and were excluded from most calculations. The NHANES Reproductive Health Questionnaire and Demographics Data from 2013 to 2018 was used. The target population was residents of the United States who ranged from 12 to 50 years of age. Inmates or individuals who were part of the United States Armed Forces were not questioned. The first method of data collection was at the Mobile Examination Center (MEC), where participants were interviewed by a trained MEC interviewer using questionnaires: ComputerAssisted Personal Interview (CAPI) Questionnaire and AudioComputer-Assisted Self-Interview (ACASI) Questionnaire. The second method of data collection was household interviews. For this method, a trained interviewer screened for eligible participants at their doorstep using the Screener Questionnaire (20). Next, the following questionnaires were used: Relationship Questionnaire, Family Questionnaire, Sample Person Questionnaire. Both the MEC and household interviews utilized electronic questionnaire forms to record the data electronically and sent to the central survey database system (20). Every year an average of 5,000 people of all ages are recruited and interviewed (4). NHANES uses a complex, multistage probability design to sample the population in four stages through a top-down approach. First, Primary Sampling Units (PSUs) are selected, which are counties or groups of counties in the United States. Then, segments within PSUs are selected that make up a block or groups of blocks that contain a cluster of households. From those segments, individual households are chosen, and finally individuals from those households are selected for the interviews (20).

Data analysis A cross tabulation was utilized to evaluate the categorical occurrence of gestational diabetes between the abovementioned ethnic groups in SPSS. An ANOVA test was used to compare the following factors: age of menarche between 9 and 12 compared to age of gestational diabetes diagnosis. A Pearson correlation was used to investigate the associations between age of menarche between 9 and 12 vs age of gestational diabetes diagnosis, and age when delivered baby 9 pounds or more in comparison to age of gestational diabetes. Data for age of menarche in relation to age of gestational diabetes diagnosis and age of menarche assessed against ethnicity was graphically depicted to understand the prevalence of early menarche and any association it had with the development of gestational diabetes between ethnic groups. Age of menarche when compared to age when participants delivered a baby weighing 9 pounds or more was not represented graphically to depict understanding but was represented with a bivariate correlation test. The potential relationship between age of menarche and GDM diagnosis was assessed using a Pearson correlation test. A cross tabulation was performed to evaluate the pattern among ethnicity and age of first menarche. Throughout the duration of 2013 to 2018, the occurrences of menarche between ages 9 and 12 per ethnicity were calculated as percentages. The percentages were imported into Prism to formulate a donut chart to graphically depict the prevalence of the different ratios to compare the data of ethnicity and age of menarche.

Results

Figure 1 represents the comparison of age of menarche and mean age of GDM diagnosis. Figure 2 shows the comparison between age of menarche and ethnicity. The results depicted are for years 2013 to 2018. In Figure 2A, 27% of the 309 women who had their first menstrual period at age 9; most of the demographic was white women. In Figure 2B, 31% of 525 women experienced their first menstrual period at age 10. For Figure 2C at age 11, 34% of 1,363 women, and Figure 2D 36% of 2,488 women who were 12 years of age also showed that white women were most of the overall total. As shown in all figures, the demographic with the highest percentage was white women. Black and Mexican American women follow with the second and third highest percentages, respectively.

Figure 1. A one-way analysis of variance, ANOVA showed that the relationship between age of menarche and whether there was a GDM diagnosis at pregnancy was significant at the 0.05 p-level, (F (3,271) = 3.099, p = 0.027).

Discussion

A one-way ANOVA test was conducted to compare the means of age of menarche and diabetes diagnosis and to determine whether there were any statistically significant differences between the means of the two variables. The null hypothesis of this test was there is no statistical significance between age of menarche and diabetes diagnosis while pregnant. After completing the ANOVA test, there is enough evidence to reject the null hypothesis. A p-value of 0.027 signifies the strength of the relationship between age of menarche and whether a diabetes diagnosis was given during pregnancy. This strengthens and emphasizes analyses that suggests that younger age at menarche is associated with higher risk of Type 2 diabetes (24). A Pearson correlation was computed to assess the relationship between age of menarche (RHQ010) and if the patient was told they had diabetes in pregnancy (yes/no) (RHQ162). The results of the Pearson correlation indicated a level of significance. There was a positive, but weak correlation between age of menarche and age of GDM diagnosis, (r = 0.042, n = 4,706, p = 0.022). Correlation is significant at the 0.05 level (2-tailed). The Pearson correlation of 0.042 is weak yet positive, so this suggests that there is a statistically significant correlation. Additionally, the p-value of 0.022 suggests significance and to reject the null hypothesis. This weak but positive correlation supports the hypothesis that as women experienced menarche at an earlier age, the more likely they were to develop GDM in pregnancy. This is due to the ANOVA test suggesting significance. Previous studies have observed an association between early age of menarche and increased risk of GDM (13). Race/ethnicity, socioeconomic status, environmental stress, and genetics may contribute to this association (17). However, the weak correlation may be due to the fact that survey data was utilized to perform this study. Participants enrolled in the study may not have answered accurately as some may not remember when they experienced menarche. Additionally, menarche is a taboo and sensitive subject in some cultures, which may influence how the women answered question RHQ010.

Another Pearson correlation was computed to assess the relationship between age told they had diabetes while pregnant (RHQ163) and age when the participant delivered a baby

Figure 2. Ethnic representation of ages of menarche for 2013-2018 NHANES Data. Age (A) 9, (B) 10, (C) 11, and (D) 12.

9 pounds or more (RHQ173). The results of the Pearson correlation indicated a level of significance. There was a positive, but weak correlation between age of menarche and age of GDM diagnosis, (r = 0.621, n = 76, p = <0.001). Correlation is significant at the 0.01 level (2-tailed). The Pearson correlation of 0.621 suggests a strong positive association between the age women were told they had diabetes while pregnant and the age when delivering a baby 9 pounds or more. The results were expected based on other studies. This also depicts the significant public health implications of pregnant women diagnosed with GDM. Previous studies have noted that the risk of developing GDM is 2 and 4 times higher among overweight and obese women, respectively, when compared to normalweight pregnant women (24). Maternal obesity rates can result in negative lifetime outcomes for both the mother and the fetus. Maternal obesity also increases the risk for a number of pregnancy complications like gestational hypertension, maternal hypertensive disease or pre-eclampsia, risk of emergency cesarean delivery, and prolonged delivery times (7). As a result of these various complications, the neonate is at risk for macrosomia or increased body fat. Additionally, early age of menarche and mean age of GDM diagnosis was also compared (Figure 1). The ANOVA statistical data showed that the relationship between age of menarche and whether there was a GDM diagnosis at pregnancy was significant at the 0.05 p-level, F (3,271) = 3.099, p = 0.027. The purpose of this comparison was to see if developing GDM diagnosis at a later age was associated with early age of menarche, as previous studies have shown that early age of menarche is linked to increased risk of GDM (26). The results shown in Figure 1 depict a significant positive correlation, suggesting that pregnant women who were diagnosed with GDM at a later age were likely to have experienced menarche at a younger age. This suggests that age at which GDM diagnosis occurred in pregnancy may be correlated with earlier age of menarche. These results were obtained from subjective survey data, which is a limitation. Future studies should examine and confirm this finding.

In Figure 2, early age of menarche (9–12) was compared to ethnicity for years 2013-2018. Results showed that a higher percentage of Non-Hispanic white women experienced early menarche for each age studied (9–12). This was followed by Non-Hispanic African American and Mexican American women. These results were not expected, as previous studies have shown that the age of menarche of non-Hispanic African American girls was significantly earlier than non-Hispanic white and Mexican American women (16). The limitations are also due to survey data being utilized. Future studies should focus on data that is collected in ways that minimizes bias and uncertainty. The main limitation of this study was the method of instrumentation. The data utilized in the analysis came from a survey database. The data collection relied entirely on self-reported information. The CDC employees screened all participants thoroughly to ensure eligibility in the study prior to providing them with the extensive survey. However, the process of selection is also based on subjective responses. From beginning to end, the method of instrumentation has the potential to introduce uncertainty through social desirability and recall bias. Social desirability is the inclination to present one's reality and experiences in a socially acceptable manner by embellishment or omission (22). Participants may alter the facts to portray themselves in a positive manner, either to appeal to the interviewer or to detract from revealing unfavorable details. Additionally, recall bias played a significant role in this analysis. Recall bias, also referred to as telescoping, is the phenomenon of misattributing occurrences to earlier or later dates (23). Mistakenly recalling an event as having happened more recently than it did is known as forward telescoping. Backward telescoping describes the opposite bias — erroneously remembering an event as having occurred earlier than it did (24). A participant’s skewed perception of time could lead to altered results when investigating monumental, age-based life changes, such as menarche. These limitations, while intractable, can be minimized by employing data collectors that reflect the ethnicities of the target population, instructing them to utilize neutral language, and have questions that assess different time in various ways, i.e., age in years, grade in school, or calendar year.

Conclusion

The results of our study warrant future research, which may include looking deeper into the participant demographics from the NHANES sample surveys and other questions. Other questions on the reproductive survey may also be included as a comparison to the questions that related to gestational diabetes, such as family history of gestational diabetes, family history of early menarche, and diagnosis of obesity. To further dive into this topic, a different survey could be added in addition to the NHANES to introduce variety and new perspective to the mix of data already incorporated. Our analysis suggests that younger age at menarche is associated with higher risk of Type 2 diabetes, and as women experience menarche early on, they are more likely to develop GDM in pregnancy. There is a strong positive association between age women were diagnosed with diabetes while pregnant and age when delivering a baby 9 pounds or more; along with a higher percentage of NonHispanic white women experienced early menarche for each age studied.

Appendix

NHANES variables: RHQ010, age of menarche RHQ162, participant told they had diabetes while pregnant RHQ163, participant age of gestational diabetes diagnosis RHQ173, age when delivered baby 9lbs or more RIAGENDR, gender of participant RIDRETH3, ethnicity of participants

Acknowledgments

We thank Brian J. Piper, PhD, MS, along with Elizabeth Kuchinski BS, MPH, and the teaching assistants Jonique Depina, MS, and Yasmin Mamani, MS, for their time and devotion to our paper and for providing us with the necessary guidelines needed.

Disclosures

There is no financial relationship between this paper’s authors and any health care related institutions mentioned.

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