Unknown

Dataset Information

0

Postmenopausal Androgen Metabolism and Endometrial Cancer Risk in the Women's Health Initiative Observational Study.


ABSTRACT: Background:After menopause, several androgens continue to be produced primarily by the adrenal glands; these can be converted into estrogens via aromatization or into androgen metabolites. It is unclear if androgens are associated with endometrial cancer risk independently of their being precursors to estrogens or if alternative metabolic pathways influence risk. Methods:We measured prediagnostic serum concentrations of 12 androgens and their metabolites using highly sensitive liquid chromatography-tandem mass spectrometry assays in a nested case-control study of postmenopausal women from the Women's Health Initiative Observational Study (313 endometrial cancer case subjects, 354 matched control subjects). Estrogens were previously assayed. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for endometrial cancer with adjustment for confounders. Results:Compared to the lowest concentrations, the highest levels of adrenal androgens were associated with increased endometrial cancer risk: dehydroepiandrosterone (5th vs 1st quintile: OR = 1.85, 95% CI = 1.06 to 3.25), androstenedione (OR = 2.36, 95% CI = 1.34 to 4.16), and testosterone (OR = 1.91, 95% CI = 1.12 to 3.24). Downstream androgen metabolites were not associated with endometrial cancer. Although increased risks for the parent androgens were still suggested after adjustment for unconjugated estradiol, the associations attenuated, and with the exception of androstenedione, were no longer statistically significant. We also evaluated ratios of estrogens relative to their androgenic precursors; both higher unconjugated estrone:androstenedione and higher unconjugated estradiol:testosterone were associated with increased endometrial cancer risk. Conclusions:We identified increased risks for endometrial cancer with the highest levels of adrenal androgens and high levels of estrogens relative to these androgens. As adrenal androgens can be aromatized to estrogens, this suggests androgens likely influence endometrial carcinogenesis via estrogen metabolism.

SUBMITTER: Michels KA 

PROVIDER: S-EPMC6620792 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Postmenopausal Androgen Metabolism and Endometrial Cancer Risk in the Women's Health Initiative Observational Study.

Michels Kara A KA   Brinton Louise A LA   Wentzensen Nicolas N   Pan Kathy K   Chen Chu C   Anderson Garnet L GL   Pfeiffer Ruth M RM   Xu Xia X   Rohan Thomas E TE   Trabert Britton B  

JNCI cancer spectrum 20190425 3


<h4>Background</h4>After menopause, several androgens continue to be produced primarily by the adrenal glands; these can be converted into estrogens via aromatization or into androgen metabolites. It is unclear if androgens are associated with endometrial cancer risk independently of their being precursors to estrogens or if alternative metabolic pathways influence risk.<h4>Methods</h4>We measured prediagnostic serum concentrations of 12 androgens and their metabolites using highly sensitive liq  ...[more]

Similar Datasets

| S-EPMC8755590 | biostudies-literature
| S-EPMC6660427 | biostudies-literature
| S-EPMC4873440 | biostudies-literature
| S-EPMC5625673 | biostudies-literature
| S-EPMC4929241 | biostudies-other
| S-EPMC4761296 | biostudies-literature
| S-EPMC3218630 | biostudies-literature
| S-EPMC4050510 | biostudies-other
| S-EPMC5808032 | biostudies-literature
| S-EPMC8971010 | biostudies-literature