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Endogenous sex steroids in premenopausal women and risk of breast cancer: the ORDET cohort

Eva S Schernhammer123*, Francesca Sperati4, Pedram Razavi5, Claudia Agnoli6, Sabina Sieri6, Franco Berrino7, Vittorio Krogh6, Carlo Alberto Abbagnato8, Sara Grioni6, Giovanni Blandino49, Holger J Schunemann9 and Paola Muti102*

Author Affiliations

1 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Longwood Avenue, Boston, MA 02115, USA

2 Department of Epidemiology, Harvard School of Public Health, Huntington Avenue, Boston, MA 02115, USA

3 ACR-ITR & LBI-ACR VIEnna, Kundratstrasse, 1100 Wien, Austria, EU

4 Istituto Nazionale Tumori Regina Elena IRCCS, Via Elio Chianesi, 00144 Roma, Italy, EU

5 Department of Preventive Medicine, University of Southern California, N Soto Street, Los Angeles, CA 90089, USA

6 Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian, 20133 Milan, Italy, EU

7 Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian, 20133 Milan, Italy, EU

8 Centro Medico Diagnostico Emilia, Via Sorbelli, 40124 Bolgna, Italy, EU

9 Department of Clinical Epidemiology and Biostatistics, McMaster University, Main Street West Hamilton, ON L8S 4K1, Canada

10 Department of Oncology, McMaster University, Main Street West Hamilton, ON L8S 4K1, Canada

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Breast Cancer Research 2013, 15:R46  doi:10.1186/bcr3438

Published: 18 June 2013



Previous studies showed that higher testosterone levels are associated with greater risk of breast cancer in premenopausal women, but the literature is scant and inconsistent.


In a prospective nested case-control study of 104 premenopausal women with incident breast cancer and 225 matched controls, all characterized by regular menstrual cycles throughout their lifetime, we measured the concentration of estradiol, total and free testosterone (FT), progesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in blood samples collected on days 20 through 24 of their cycles.


In logistic regression models, the multivariate odds ratios (ORs) of invasive breast cancer for women in the highest tertile of circulating FT compared with the lowest was 2.43 (95% confidence interval (95% CI), 1.15 to 5.10; Ptrend = 0.03), whereas for total testosterone, the association had the same direction but was not statistically significant (OR, 1.27; 95% CI, 0.62 to 2.61; Ptrend = 0.51). Endogenous progesterone was not statistically associated with breast cancer (OR, 1.16; 95% CI, 0.60 to 2.27; Ptrend = 0.75), nor were the other considered hormones.


Consistent with previous prospective studies in premenopausal women and our own earlier investigation, we observed that higher levels of FT are positively associated with breast cancer risk in women with regular menstrual cycles throughout their lifetimes. No evidence of risk was found associated with the other endogenous sex steroids.

sex steroids; estrogens; androgens; premenopausal; breast cancer