Ovarian hormones and reproductive risk factors for breast cancer in premenopausal women: the Norwegian EBBA-I study

BACKGROUND: Ovarian hormones, parity and length of 'menarche-to-first birth' time interval are known risk factors for breast cancer, yet the associations between I 7$\beta$-estradiol, progesterone and these reproductive factors remain unclear. METHODS: A total of 204 women (25-35 years) who participated in the Norwegian EBBA-I study collected daily saliva samples for one complete menstrual cycle, and filled in a reproductive history questionnaire. Anthropometry was measured and saliva samples were analyzed for ovarian hormones. Associations between parity, the interval and ovarian hormones, and effects of hormone-related lifestyle factors were studied in linear regression models. RESULTS: Mean age was 30.7 years, and age of menarche 13.1 years. Parous women had on average 1.9 births, and age at first birth was 24.5 years. No association was observed between parity and ovarian steroids. In nulliparous women, higher waist circumference ($\ge$)77.75 cm) and longer oral contraceptive (OC) use ($\ge$)3 years) were associated with higher levels of I 7$\beta$-estradiol. Short (13.5 years) 'menarche-to-first birth' interval was associated with higher overall mean (P$_{trend}$ = 0.029), 47% higher maximum peak and 30% higher mid-cycle levels of I 7$\beta$-estradiol. We observed a 2.6% decrease in overall mean salivary I 7$\beta$-estradiol with each 1-year increase in the interval. CONCLUSIONS: Nulliparous women may be more susceptible to lifestyle factors, abdominal overweight and past OC use, influencing metabolic and hormonal profiles and thus breast cancer risk. Short time between 'menarche-to-first birth' is linked to higher ovarian hormone levels among regularly cycling women, suggesting that timing of first birth is related to fecundity.Human Evolutionary Biolog

17-beta-Estradiol in relation to age at menarche and adult obesity in premenopausal women

BACKGROUND: We hypothesize that premenopausal endogenous estradiol may be associated with age at menarche and adult overweight and obesity, potentially contributing to breast cancer risk. METHODS: We assessed age at menarche by questionnaire among 204 healthy Norwegian women, aged 25 – 35 years. Measures of body composition included body mass index (BMI, kg/m2), waist circumference (WC, cm), waist-to-hip ratio (WHR) and fat percentage dual energy X-ray absorptiometry, (DEXA). Daily salivary 17-b-estradiol (E2) concentrations were collected throughout one entire menstrual cycle and assessed by radioimmunoassay (RIA). Linear regression analyses and linear mixed models for repeated measures were used and potential confounding factors and effect modifiers were tested. RESULTS: Among women with an early age at menarche (12 years), the overall mean salivary E2 concentration increased by 3.7 pmol/l (95% confidence interval, 1.8 – 5.7 pmol/l) with each 9.8 cm (1 SD) increase in WC, which represents a 20.7% change in the mean for the total group. Among the same early maturers, a 1 SD (0.06) change in WHR was directly associated with a 24.0% change in mean E2 concentration for the total group. CONCLUSIONS: Our findings support the hypothesis that early age at menarche, together with adult overweight and obesity, result in high levels of 17-b-estradiol throughout the menstrual cycle.AnthropologyHuman Evolutionary Biolog