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The authors investigated the association between age at menarche and risk of type 2 diabetes mellitus (T2DM) among 101,415 women from the Nurses’ Health Study (NHS) aged 34–59 years (1980–2006) and 100,547 women from Nurses’ Health Study II (NHS II) aged 26–46 years (1991–2005). During 2,430,274 and 1,373,875 person-years of follow-up, respectively, 7,963 and 2,739 incident cases of T2DM were documented. Young age at menarche was associated with increased risk of T2DM after adjustment for potential confounders, including body figure at age 10 years and body mass index (BMI; weight (kg)/height (m)2) at age 18 years. Relative risks of T2DM across age-at-menarche categories (≤11, 12, 13, 14, and ≥15 years) were 1.18 (95% confidence interval (CI): 1.10, 1.27), 1.09 (95% CI: 1.02, 1.17), 1.00 (referent), 0.92 (95% CI: 0.83, 1.01), and 0.95 (95% CI: 0.84, 1.06), respectively, in the NHS (P for trend < 0.0001) and 1.40 (95% CI: 1.24, 1.57), 1.13 (95% CI: 1.00, 1.27), 1.00 (referent), 0.98 (95% CI: 0.82, 1.18), and 0.96 (95% CI: 0.78, 1.19), respectively, in NHS II (P for trend < 0.0001). Associations were substantially attenuated after additional control for updated time-varying BMI. These data suggest that early menarche is associated with increased risk of T2DM in adulthood. The association may be largely mediated through excessive adult adiposity. The association was stronger among younger women, supporting a role for sex hormones in younger onset of T2DM, in addition to BMI. [ABSTRACT FROM PUBLISHER]

This study examined prospectively the associations of waist circumference and waist: hip circumference ratio with risk of breast cancer. A total of 47,382 US registered nurses who reported their waist and hip circumferences in 1986 were followed up through May 1994 for identification of incident cases of breast cancer. During 333,097 person-years of follow-up, 1, 037 invasive breast cancers were diagnosed. In proportional hazards analyses, waist circumference was nonsignificantly related to risk of premenopausal breast cancer but was significantly associated with postmenopausal breast cancer after adjustment for established breast cancer risk factors (for the highest quintile of wast circumference vs. the lowest, relative risk (RR) = 1.34; 95% confidence interval (CI): 1.05, 1.72). When the analysis was limited to postmenopausal women who had never received hormone replacement therapy, a stronger positive association was found (RR = 1.88; 95% CI: 1.25, 2.85). After the data were further controlled for body mass index, the positive association was only slightly atenuated (RR = 1.83; 95% CI: 1.12, 2.99). Among past and current postmenopausal hormone users, no significant associations were found. Similar but slightly weaker associations were observed between waist: hip ratio and breast cancer risk. These data suggest that greater waist circumference increases risk of breast cancer, especially among postmenopausal women who are otherwise at lower risk because of never having used estrogen replacement hormones. Am J Epidemiol 1999; 150: 1316-24. [ABSTRACT FROM PUBLISHER]

To assess prospectively the relation between body mass index, weight gain, repeated intentional weight losses, and the risk of self-reported hypertension, the authors studied 46, 224 women who were participants in the Nurses Health Study II, who were free of hypertension in 1993, and who completed questions on intentional weight losses between 1989 and 1993. Women who reported they had intentionally lost ≥20 lbs (9 kg) ≥3 times were classified as severe weight cyclers. Women who had intentionally lost ≥10 lbs (4.5 kg) ≥3 times, but who did not meet the criteria for severe weight cycling, were classified as mild weight cyclers. Between 1993 and 1995, 1, 107 incident cases of diagnosed hypertension were reported. Body mass index and weight gain, but not weight cycler status, were independently associated with the development of hypertension. For each 10 Ib (4.5 kg) gain in weight between 1989 and 1993, the risk of hypertension increased 20% (odds ratio (OR) = 1.20, 95% confidence interval (Cl) 1.15, 1.24). After adjustment for body mass index and weight gain, the risks associated with mild weight cycling (OR = 1.15, 95% Cl 1.00, 1.33) and severe weight cycling (OR = 1.13, 95% Cl 0.79, 1.61) were small and not significant. Thus, the results of this study offer support for the current weight guidelines and provide further evidence of the health risks associated with excessive weight and weight gain. However, these data do not suggest an independent effect of weight cycling on risk of hypertension. Am J Epidemiol 1999; 150: 573-9. [ABSTRACT FROM PUBLISHER]

This study examined prospectively the associations of waist circumference and waist: hip circumference ratio with risk of breast cancer. A total of 47,382 US registered nurses who reported their waist and hip circumferences in 1986 were followed up through May 1994 for identification of incident cases of breast cancer. During 333,097 person-years of follow-up, 1, 037 invasive breast cancers were diagnosed. In proportional hazards analyses, waist circumference was nonsignificantly related to risk of premenopausal breast cancer but was significantly associated with postmenopausal breast cancer after adjustment for established breast cancer risk factors (for the highest quintile of wast circumference vs. the lowest, relative risk (RR) = 1.34; 95% confidence interval (CI): 1.05, 1.72). When the analysis was limited to postmenopausal women who had never received hormone replacement therapy, a stronger positive association was found (RR = 1.88; 95% CI: 1.25, 2.85). After the data were further controlled for body mass index, the positive association was only slightly atenuated (RR = 1.83; 95% CI: 1.12, 2.99). Among past and current postmenopausal hormone users, no significant associations were found. Similar but slightly weaker associations were observed between waist: hip ratio and breast cancer risk. These data suggest that greater waist circumference increases risk of breast cancer, especially among postmenopausal women who are otherwise at lower risk because of never having used estrogen replacement hormones. Am J Epidemiol 1999; 150: 1316-24. [ABSTRACT FROM PUBLISHER]

Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25–42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche >13 years compared with age ≤12 years was 0.66 (95% confidence interval (CI) 0.44–0.99). Short and long menstrual cycle lengths at ages 18–22 years were associated with reduced risk. Compared with menstrual cycle length 26–31 days, the multivariate relative risks (95% CIs) for more extreme cycle lengths were: <26 days, 0.50 (0.25–0.98); 32–39 days, 0.81 (0.51–1.28); and >39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18–0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18–0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer. Am J Epidemiol 1998; 147: 636–43. [ABSTRACT FROM AUTHOR]

The return of fertility for women who discontinue oral contraceptives takes longer as compared with women who discontinue other methods of contraception. It remains unclear, however, whether subsequent fertility differs according to duration or age at first use. The authors performed a nested case-control study within a cohort of 116,686 female registered nurses residing in 14 US states. Baseline information was reported on mailed questionnaires in 1989. Cases comprised 1,917 married nurses without previous pregnancy who were unable to become pregnant for at least 1 year and were subsequently diagnosed with primary ovulatory infertility. Controls comprised 44,521 married parous nurses with no history of infertility and no pregnancies lasting less than 6 months. After allowing for 2 years of suppressed fertility following discontinuation of oral contraceptive use and excluding women with signs of menstrual or hormonal disorder, the authors found that the multivariate relative risk for ovulatory causes of delayed fertility was 1.2 (95% confidence interval 0.7–1.9) for ever users. There was no statistically significant trend of increasing risk with increasing duration of use and younger age at first use. The fact that 88 percent of cases reported an eventual pregnancy by 1993 suggests that absolute fertility was not impaired. Am J Epidemiol 1997;146:258–65. [ABSTRACT FROM AUTHOR]

The associations between toenail levels of five trace elements and breast cancer risk were studied among a cohort of 62, 641 US women who provided toenail clippings and were free from diagnosed breast cancer in 1982. Among 433 cases of breast cancer identified during 4 years of follow-up and their matched controls, the odds ratios comparing the highest with the lowest quintiles and adjusted for established breast cancer risk factors were as follows: for arsenic, 1.12 (95% confidence interval (CI) 0.66–1.91); for copper, 0.91 (95% CI 0.59–1.42); for chromium, 0.96 (95% Cl 0.61–1.52); for iron, 0.89 (95% CI 0.56–1.40); and for zinc, 1.09 (95% CI 0.70–1.70). Among postmenopausal women, a marginally significant positive association was observed between toenail chromium levels and breast cancer risk (odds ratio = 1.71, 95% Cl 0.87–3.35) (p for trend = 0.07). However, the association between chromium and breast cancer risk was inverse among premenopausal women. Although data on the validity of toenail levels of certain of these elements are limited, these results do not provide evidence for an important effect of arsenic, copper, chromium, iron, or zinc on breast cancer risk. Am J Epidemiol 1996;144:653–60. [ABSTRACT FROM AUTHOR]