Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature.

High-risk human papillomaviruses (HPVs) are involved in the etiopathogenesis of cervical intraepithelial neoplasia (CIN) and cervical cancer. After taking HPV into account, smoking habit appears to be the most significant environmental risk factor, and the risk of this malignancy increases significantly with intensity and duration of smoking. Women with human immunodeficiency virus (HIV) infection experience a higher incidence of CIN and invasive cervical cancer. Among HIV+ women, the highly active antiretroviral therapy increases the regression rate of CIN, but the majority of these lesions do not regress to normal. As far as oral contraceptives (OCs), a systematic review of 28 studies found that, compared with never pill users, the relative risk (RR) of cervical cancer increased with increasing duration of OC use. The results were similar for squamous cell carcinoma and adenocarcinoma, and the RRs decreased after pill discontinuation. However, by weighing risks and benefits, the World Health Organization does not recommend any change in OC practice. There is no correlation between hormone replacement therapy and cervical cancer. Experimental data have shown that estradiol and progesterone can modulate the host immune response to HPV16. Prophylactic vaccination in conjunction with cervical screening is the best prevention strategy for cervical cancer.

Effects of the new generation selective estrogen receptor modulator EM-652 and oral administration of estradiol valerate on circulating, brain, and adrenal beta-endorphin and allopregnanolone levels in intact fertile and ovariectomized rats.

OBJECTIVE: To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral beta-endorphin (beta-EP) and allopregnanolone levels in fertile and ovariectomized rats. DESIGN: Prospective study. SETTING: Animal laboratory in an academic research environment. ANIMALS: Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days. INTERVENTION(S): beta-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured. MAIN OUTCOME MEASURE(S): beta-Endorphin and allopregnanolone levels. RESULT(S): In ovariectomized rats, administration of EV or EM-652 reverses changes in beta-EP and allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in beta-EP and allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum. CONCLUSIONS: In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects.