We investigated the role of androgens in premenopausal breast cancer by comparing serum testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulfate, progesterone, sex-hormone-binding globulin-binding capacity, and urinary testosterone and androstanediol in 63 women with breast adenocarcinoma and 70 healthy controls of similar age. With variables dichotomized at the 75th percentile, the age-adjusted relative risk was 3.4 (95% confidence interval, 1.6–7.3) for high versus low levels of serum testosterone, 2.1 (0.9–4.8) for urinary testosterone, and 2.5 (1.1–5.9) for serum dihydrotestosterone. We observed no differences in other hormones. The strength of the associations changed markedly with increasing time to the onset of the next menses. The risk for testosterone and dihydrotestosterone, which was negligible in women with onset within 5 days of sampling, increased progressively to nearly 10-fold higher than in unstratified data in women with onset 10 days or more after sampling. This study provides arguments in favor of a role for increased androgenic activity in premenopausal breast cancer. It also suggests that unknown factors related to cycle length may be important in modulating the strength of the association with testosterone. The results are discussed also in reference to possible biases and inadequacies in study design.

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This project was supported primarily by Research Grant 86/02609/44 Progetto Finalizzato Oncologia, from the Italian National Research Council (CNR); Dr. Toniolo received financial support from Research Grants CA13343 and CA16087 from the National Cancer Institute and Research Grant ES00260 from the National Institute of Environmental Health Sciences.

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