2656 Physical Activity during Pregnancy and Age at Menarche of the Daughter Lisa H. Colbert,1 Barry I. Graubard,2 Karin B. Michels,3,4,5 Walter C. Willett,3,6 and Michele R. Forman7 1Department of Kinesiology and Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, Wisconsin; 2Biostatistics Branch, National Cancer Institute, Bethesda, Maryland; 3Channing Laboratory, Department of Medicine, 4Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, and Harvard Medical School, Departments of 5Epidemiology and 6Nutrition, Harvard School of Public Health, Boston, Massachusetts; and 7Department of Epidemiology, M. D. Anderson Cancer Center, Houston, Texas Abstract In utero exposures have been proposed as possible for specific covariates including daughter’s childhood determinants of later disease risk. Given that a later body size, neither home nor occupational activity age at menarche is a breast cancer risk factor, and that alone were associated with age at menarche of the higher childhood physical activity has been associated daughter, but there was a direct association with P with a later menarcheal age, it is possible that a leisure-time physical activity ( trend < 0.001). Com- pregnant mother’s activity may also influence this pared with women inactive in their leisure-time, outcome. The purpose of this study was to determine women who were highly active had daughters with if a mother’s physical activity during pregnancy is menarche 1.1 (95% confidence interval, 0.3-1.9) months related to their daughter’s menarcheal age. Partici- later. Using a composite variable of both home and pants of the Nurses’ Health Study II reported their age leisure-time activity, daughters of women who were at menarche to the nearest year, whereas their mothers highly active at home and in their leisure-time had (n = 33,016) completed surveys regarding their health daughters with menarche 3.1 (95% confidence interval, and lifestyle habits during their pregnancy with their 0.4-5.9) months later than those who were highly daughters. Mothers reported their home, occupational, inactive in both. Physical activity during pregnancy and leisure-time physical activities, as well as the may be associated with a modest delay in menarcheal activity of their daughters at ages 5 to 10 years. Using age in offspring. (Cancer Epidemiol Biomarkers Prev multiple linear regression analysis with adjustment 2008;17(10):2656–62) Introduction Age at menarche, a well-known reproductive-related throughout life (11). Although initial hypotheses focused risk factor for breast cancer, is associated with an on cardiovascular-related diseases, Trichopoulos sug- f10% to 20% reduction in risk for each year of delay gested that in utero exposures might also be related to the in menses (1). Several studies have noted a later age at development of breast cancer, and that this relationship menarche in active girls when compared with their less might be due to alterations in estrogen exposure (12). active peers (2-4). This delay in menarche has been This hypothesis has been supported by epidemiologic suggested as one possible mechanism through which evidence demonstrating a higher breast cancer risk in physical activity may reduce the risk of breast cancer dizygotic twins, and a lower risk in daughters born to (5, 6). preeclamptic mothers (13). There is also a fairly Chronic diseases have been associated with earlier life consistent direct association between birthweight and exposures. Birthweight is linked to the development of breast cancer risk (14, 15). hypertension, insulin resistance, and cardiovascular Interestingly, age at menarche has been associated disease in adulthood (7-10). These relationships form with potential exposures in utero. Specifically, exposure the basis of what has been termed ‘‘fetal programming’’ to dichlorodiphenyldichloroethylene (16) and maternal of chronic disease, in which it has been hypothesized that cigarette smoking and tea drinking in pregnancy are interactions of fetal exposures and genotypes in utero can related to an earlier age at menarche (17). Bouts of alter the architecture and physiologic function of organs physical activity and exercise can result in numerous metabolic, hormonal, and physiologic changes in the body, dependent on the intensity, duration, and type of activity done; therefore, activity during pregnancy may change the milieu of the fetus. In particular, it is possible Received 3/1/08; revised 7/3/08; accepted 7/9/08. that the total estrogen or growth factor–related exposure Grant support: National Cancer Institute’s Intramural Research Program (M. Forman and B. Graubard), N02-RC-17027 (W. Willett and K. Michels), and PO 263 MQ 411027 of the fetus is altered with physical activity of the (W. Willett and K. Michels). pregnant mother, and that these changes could be related Requests for reprints: Lisa H. Colbert, Department of Kinesiology, University of to age at menarche in the daughter, and thus, her breast Wisconsin, 2000 Observatory Drive, Madison, WI 53706. Phone: 608-265-5946. E-mail: [email protected] cancer risk. In a cohort of nurses whose mothers reported Copyright D 2008 American Association for Cancer Research. physical activity in the index pregnancy, we therefore doi:10.1158/1055-9965.EPI-08-0194 hypothesized that daughters of mothers who were Cancer Epidemiol Biomarkers Prev 2008;17(10). October 2008 Downloaded from cebp.aacrjournals.org on September 28, 2021. © 2008 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention 2657 physically active will have a delayed age at menarche home. For occupational activity, mothers chose from compared with daughters of mothers who were less categories of not applicable/not working, mostly sitting physically active while pregnant. and standing, mostly walking with some sitting and standing, or mostly heavy labor with some walking and standing and little sitting. The leisure-time activity Materials and Methods question read ‘‘When you were pregnant with your nurse daughter, aside from housework and job-related Study Population. The study population consists of activities, which of the following best describes your participants in the Nurses’ Health Study II (NHS II) physical activity (e.g., walking and recreation).’’ An whose mothers were enrolled in the Nurses’ Mothers’ ordered categorical response with five options ranging Cohort Study. In 2001, members of the NHS I and NHS II from highly active to inactive, with cues (equivalent to who were free of cancer (other than nonmelanoma walking f3 or more miles every day, to no walking or skin cancer) and who had mothers who were still alive other regular exercise, respectively) was selected. A (n = 52,166), were sent surveys for their mothers to composite activity variable was created using the home complete concerning their pregnancy with the nurse and leisure questions to categorize women into five daughter. A total of 39,904 (76.5%) of the surveys were groups ranging from highly inactive to highly active as returned. The Institutional Review Board of the Brigham depicted in Table 1. Additionally, the mothers reported and Women’s Hospital approved this study. For ease of their nurse daughter’s overall physical activity at ages analysis, we have limited the current analytic data set to 3 to 5 and 5 to 10 years using a similarly ordered the women from NHS II, from which 35,830 surveys categorical response in which they compared them to were returned. The nurse daughters were born between other girls their age. 1946 and 1965. The mothers completed surveys regard- The mothers self-reported their usual body weight ing demographics, health, and lifestyle habits pertaining priortopregnancy,height,race,education,home to the pregnancy with their nurse daughters, as well as ownership, dates of their own and their daughter’s birth, early life events of the daughters. The women reported the sibship and birthweight of the daughter, approximate information from memory, sources such as baby books or weight gain during pregnancy, and smoking status birth certificates, or help from family members. Addi- during their pregnancy. On the 1989 NHS II question- tionally, some information was reported by the nurse naire, the nurses reported their age at menarche to the daughters on NHS II surveys (age at menarche, somato- nearest year and their body shape at ages 5 and 10 years grams at ages 5 and 10 years) and merged with the using somatograms (on a scale ranging from 1 to 9). We mother’s information. Of the 35,830 women who com- calculated a ‘‘growth velocity’’ measure and categorized pleted the survey, 88 identified that their daughters were the nurses by change in somatogram score between ages adopted, and 1,807 were missing adoption information, 5 and 10 years. Girls staying within one unit of their age 5 and thus were excluded from the study. Of the somatogram over the 5-year period were classified as remaining women, 804 were missing physical activity stable, and girls who increased or decreased two or more information and 115 of the daughters were missing their units on the 1 to 9 scale were considered as increasing or age at menarche for a final analytic sample of 33,016. decreasing body size, respectively. Assessment of Physical Activity, Age at Menarche, Statistical Analysis. Multiple linear regression was and Covariates. Physical activity during pregnancy was used to examine the association between physical activity queried using three separate questions for household, of the mothers during pregnancy and age at menarche occupational, and leisure-time activity. For both house- of the daughters. Because the age at menarche was hold and occupational activities, the questions began reported to the nearest year and the differences by level with ‘‘When you were pregnant with your nurse of physical activity were small, we multiplied the h- daughter, how would you classify your physical activity coefficients by 12to calculate the difference in age at patterns...’’ and ended with ‘‘...at home’’ or ‘‘...at work menarche in months.