Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]

INTRODUCTION: Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue. Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed. METHODS: A total of 205 women (age range 49–65 years) with Wolfe P2 or DY mammographic breast patterns were randomly assigned to receive either a red clover-derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein) or placebo. Change in mammographic breast density, serum oestradiol, FSH, LH, menopausal symptoms and lymphocyte tyrosine kinase activity from baseline to 12 months were assessed. RESULTS: A total of 177 women completed the trial. Mammographic breast density decreased in both groups but the difference between the treatment and placebo was not statistically significant. There was a significant interaction between treatment group and oestrogen receptor (ESR1) PvuII polymorphism for the change in estimated percentage breast density (mean ± standard deviation): TT isoflavone 1.4 ± 12.3% and TT placebo -9.6 ± 14.2%; CT isoflavone -5.2 ± 12.0% and CT placebo -2.8 ± 10.3%; and CC isoflavone -3.4 ± 9.7% and CC placebo -1.1 ± 9.5%. There were no statistically significant treatment effects on oestradiol, FSH, or LH (assessed only in postmenopausal women), or on lymphocyte tyrosine kinase activity. Baseline levels of menopausal symptoms were low, and there were no statistically significant treatment effects on frequency of hot flushes or other menopausal symptoms. CONCLUSION: In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density, the isoflavone supplement did not increase mammographic breast density in this population of women. Furthermore, there were no effects on oestradiol, gonadotrophins, lymphocyte tyrosine kinase activity, or menopausal symptoms

Higher Dihydrotestosterone Is Associated with the Incidence of Lung Cancer in Older Men

© 2017, Springer Science+Business Media New York. Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06–1.60; p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08–1.54; p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms