Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study

Abstract

Background: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC).Methods: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E 2 ); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E 2 were calculated from absolute concentrations of T, E 2 , and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression.Results: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile ¼ 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E 2 , fE 2, and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR ¼ 3.14; 95% CI, 1.21-9.37), whereas E 2 and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre-or postmenopausal women.Conclusions: Our findings suggest for the first time that T and possibly E 2 may be involved in the etiology of ICC.Impact: The responsiveness of cervical tumors to hormone modulators is worth exploring. Cancer Epidemiol Biomarkers Prev; 20(12); 2532-40. Ó2011 AACR.

17β-Aminoestrogens induce guinea pig airway smooth muscle hyperresponsiveness through L-type Ca 2+ channels activation

“…Aminoestrol lacks the substituent alkyl-alcohol on the amino group, the change of -NH 2 in this molecule for the -OH in C17 of E 2 produces a drop of its estrogenic properties in vivo and in vitro models, and confers to this steroid an increase of selectivity for the ERb interaction [24]. In this regard, the role of estrogens on the ERa in human cervical cancer has been well documented [25] and therefore the main effect of aminoestrol on the ERb may diminish deleterious consequences on the reproductive system, representing an advantage to HRT.…”

Cancer in Transgender People: Evidence and Methodological Considerations

“…Although carcinogenicity of HPV infections is well established (21), the relationship between cervical cancer and testosterone is unclear. In premenopausal women, free, but not total, testosterone was associated with a greater risk of invasive cervical carcinoma, while among postmenopausal women, a positive association was observed for total, but not free, testosterone (92). How these observations apply to transmen is not known.…”

Increased 17ß-hydroxysteroid dehydrogenase type 1 levels in primary cervical cancer

“…The influence of estrogen levels in blood plasma on cervical carcinogenesis has also been evaluated in case-control studies [32,33]. The prolonged treatment of post-menopausal women with estradiol-progestin has been accompanied by an increased occurrence of cervical adenocarcinoma.…”

“…In a study of women with invasive cervical carcinoma and cervical intraepithelial neoplasia grade 3, Rinaldi et al in 2011 suggested a role for testosterone and possibly E2 in invasive cervical carcinoma [33].…”