Association of serum α-tocopherol with sex steroid hormones and interactions with smoking: implications for prostate cancer risk

Vitamin E may protect against prostate cancer, possibly only in smokers and, we hypothesize, through altered sex steroid hormones. A controlled trial in smokers showed that sex hormone levels were inversely associated with baseline serum alpha-tocopherol and decreased in response to vitamin E supplementation. The vitamin E-hormone relation is understudied in non-smokers. Serum sex steroid hormones and alpha-tocopherol were measured for 1,457 men in NHANES III. Multivariable-adjusted geometric mean hormone concentrations by alpha-tocopherol quintile were estimated. We observed lower mean testosterone, estradiol, and SHBG concentrations with increasing serum alpha-tocopherol (Q1 = 5.5 and Q5 = 4.6 ng/ml, p-trend = 0.0007; Q1 = 37.8 and Q5 = 33.1 pg/ml, p-trend = 0.02; Q1 = 38.8 and Q5 = 30.6 pg/ml, p-trend = 0.05, respectively). Interactions between serum alpha-tocopherol and exposure to cigarette smoke for total testosterone, total estradiol, and SHBG were found with the inverse relation observed only among smokers. Results from this nationally representative, cross-sectional study indicate an inverse association between serum alpha-tocopherol and circulating testosterone, estradiol, and SHBG, but only in men who smoked. Our findings support vitamin E selectively influencing sex hormones in smokers and afford possible mechanisms through which vitamin E may impact prostate cancer risk.