Increased serum levels of nitric oxide metabolites among users: a possible role in progestin-induced bleeding

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Abstract
BACKGROUND: Nitric oxide (NO) is a potent angiogenic and vasodilator factor that could be involved in progestin-induced bleeding. This study aimed to assess possible changes in the serum levels of NO metabolites in progestin-only contraceptive users and to identify any correlation between some of their clinical characteristics and NO metabolite levels. METHODS: This cross-sectional study included 37 contraceptive users; a single 5 ml venous blood was collected at different periods of contraceptive use. Women were divided into users with acceptable menstrual bleeding (n=13) and those having abnormal bleeding patterns (n=24). The controls are 13 age-matched healthy women; they were fertile, had regular menstruation and did not use any contraceptive method in the previous 3 months. NO was determined by the evaluation of its oxidation products (nitrites and nitrates) where the nitrates were reduced to nitrites with cadmium filings; total serum concentrations of nitrites were measured by using the Griess reaction. RESULTS: The mean serum levels of NO metabolites were significantly higher in the contraceptive users than in the controls (mean±SE) 34.9±11.3 versus 6.1±1.5 μmol/l (PPPPP<0.05). CONCLUSION: The significantly increased serum levels of NO metabolites among contraceptive users may primarily reflect an increase in its endometrial production, possibly secondary to its increased liberation by systemic vascular endothelium.This may result in enhanced endometrial angiogenesis and vascular dilatation which can induce and perpetuate abnormal excessive/prolonged uterine bleeding.