Prostaglandin production in human endometrium following continuous exposure to low-dose levonorgestrel released from a vaginal ring.

ABSTRACT

PIP: Reverse phase high-performance liquid chromatography was used to analyze arachidonic acid metabolites produced by human endometrial cell cultures before and after long-term exposure to 20 mg/day of levonorgestrel released from a released from a vaginal ring. Biopsy specimens were obtained on day 24 of a control menstrual cycle and again 84 days after insertion of the vaginal ring. Significant changes resulting from levonorgestrel exposure were recorded in only 2 of the 14 products of synthesis resolved--6-keto-prostaglandin F 1-alpha at 24 hours and epoxide at 48 hours. There were dose-dependent decreases in all cyclo-oxygenase products and an increase in epoxygenase enzyme levels. Hydroxyeicosatetraenoic acid (HETES) production, on the other hand, was strongly associated with estradiol and thus appears to be under estrogenic control. Intermenstrual bleeding during the study period was correlated with the proportion of epoxide and HETES products in vitro. Investigation of the role of the epoxygenase metabolite identified in this study in the regulation of uterine vasculature is urged.