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

Abstract

Background: Ovarian hormones, parity and length of 'menarche-to-first birth' time interval are known risk factors for breast cancer, yet the associations between 17β-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 (≥ 77.75 cm) and longer oral contraceptive (OC) use (≥ 3 years) were associated with higher levels of 17β-estradiol. Short (<10 years) versus long (>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 17β-estradiol. We observed a 2.6% decrease in overall mean salivary 17β-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.

Figure 1

Daily salivary 17β-estradiol concentrations (geometric means) in mid-menstrual cycle for women categorized by (A) number of children; nulliparous (n= 99), 1–2 children (n= 74), 3–5 children (n= 17), (B) BMI; nulliparous and BMI <25 kg/m² (n= 70), nulliparous and BMI ≥25 kg/m² (n= 29), parous and BMI <25 kg/m² (n= 54), parous and BMI ≥25 kg/m² (n= 37), (C) WC (median split); nulliparous and waist circumference <77.75 cm (n= 61), nulliparous and waist circumference ≥77.75 cm (n= 38), parous and waist circumference <77.75 cm (n= 36), parous and waist circumference ≥77.75 cm (n= 55), (D) OC use (median split); nulliparous and OC <3 years total use (n= 55), nulliparous and OC ≥3 years total use (n= 44), parous and OC <3 years total use (n= 39), parous and OC ≥3 years total use (n= 52).

Figure 2

Daily salivary 17β-estradiol concentrations (geometric means) in mid-menstrual cycle for women categorized by tertiles of interval length from menarche to age at first full term birth. Lower tertile; interval <10 years (n= 26). Middle tertile; interval 10–13.5 years (n= 32). Upper tertile; interval >13.5 years (n= 33).