The evidence for an etiological relationship between oral contraceptive use and dysplastic change in cervical tissue

A case-control study of 112 patients with cervical intraepithelial neoplasia (CIN) and 131 control subjects was conducted. Estradiol receptor levels were determined in the total (cytosolic-nucleosolic) fraction of the neoplastic cervical specimens taken during the late proliferative phase of their cycle from 58 premenopausal patients who had been oral contraceptive (OC) users for at least 2 years and from 54 premenopausal women who had not been OC users. All specimens contained variable amount of estradiol receptor (from 7.6 to 53.0 fmol estradiol/mg protein and 7.2 to 29.3 fmol estradiol/mg protein in patients who were OC users and non-users, respectively). A significant correlation was found between estradiol receptor concentration and histological grading in both groups, likewise higher levels of estradiol receptor were observed in the low-grade CIN group tissue from patients who were OC users (p < 0.05). At the same time 17 beta-estradiol and progesterone levels were also determined in the serum of all women who had not used an OC for at least 12 months. The mean +/- SD estradiol serum levels in non-users of OC with CIN (0.189 +/- 0.08 ng/ml, follicular phase) were greater than the mean +/- SD (1.163 +/- 0.33 ng/ml, luteal phase) progesterone serum concentration. Serum estradiol levels were significantly higher (p < 0.05) in OC users, whereas progesterone levels were not (p > 0.05). OC users had an increased risk (odds ratio = 1.31, 95% CI 1.0-2.3) of cervical neoplasia.