Relationship between serum hormone concentrations, reproductive history, alcohol consumption and genetic polymorphisms in pre‐menopausal women

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Abstract
Reproductive characteristics, alcohol intake and polymorphisms in genes encoding sex‐steroid metabolizing enzymes might influence the risk of hormone‐related cancers by changing circulating concentrations of sex hormones. The relationship between these factors and serum concentrations of estradiol, progesterone, androstenedione, testosterone and DHEA was evaluated in a cross‐sectional study of 218 pre‐menopausal women from Kaiser Permanente Health Plan in Portland, Oregon. Risk factor information was obtained from questionnaires and hormone serum concentrations were determined by radioimmunoassays. Genotypes for CYP11A 5′UTR(tttta)n, CYP17 5′‐UTR −34 T>C, CYP19 IVS4(ttta)n, CYP1B1 (L432V and S453N) and COMT (V158M) were determined from genomic DNA samples. Increasing number of full‐term pregnancies was associated with a significant decrease in late‐follicular progesterone levels (p‐trend = 0.03). Increasing alcohol consumption was associated with higher estradiol levels averaged through the menstrual cycle (p‐trend = 0.009) and higher progesterone levels during luteal phase (p‐trend = 0.04). Androstenedione and testosterone levels were higher among light to moderate drinkers compared to non‐drinkers, although we only observe a significant trend with increasing levels of alcohol consumption for androstenedione. Women heterozygous or homozygous for the CYP1B1 L432V or the S453N polymorphisms had increased luteal estradiol levels (p‐value = 0.04 for L432V and 0.04 for S453N). None of the other factors evaluated was significantly associated with serum concentration of hormones. In conclusion, results from this cross‐sectional study of pre‐menopausal women provide support for an association between light to moderate alcohol intake and elevated levels of estrogen and androgen levels. Our data suggest that circulating levels of progesterone might be related to parity and alcohol consumption, however the biological plausibility of the observed associations is unclear. We found little support for an influence of the evaluated genetic polymorphisms in the steroid synthesis and metabolism pathway on serum hormone levels, except for a possible effect of the CYP1B1 L432V and S453N polymorphisms on serum estradiol levels.