Human Reproduction 2005 20(4):1117; doi:10.1093/humrep/deh761
Increased serum levels of nitric oxide metabolites among users: a possible role in progestin-induced bleeding
Hum. Reprod., 20, 302–306, 2005
The title and abstract of the above paper have been corrected to read as follows:
Increased serum levels of nitric oxide metabolites among users of levonorgestrel-releasing implants: a possible role in progestin-induced bleeding
A.H.Shaamash1,3 and M.M.Zakhari2
Departments of 1Obstetrics and Gynecology and 2Biochemistry, Faculty of Medicine, Assiut University, Egypt. 3To whom correspondence should be addressed. E-mail: shamaashayman@yahoo.com
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 users of levonorgestrel-releasing implants (LNG-implants) and to identify any correlation between some of their clinical characteristics and NO metabolite levels. METHODS: This cross-sectional study included 37 LNG-implants users; a single 5ml venous blood was collected at different periods of use. Women were divided into users with acceptable menstrual bleeding (n 5 13) and those having abnormal bleeding patterns (n 5 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 LNG-implants users than in the controls (mean±SE) 34.9±11.3 versus 6.1±1.5 µmol/l (P<0.001). The mean serum levels of NO metabolites were significantly higher in the LNG-implants users with abnormal bleeding patterns than in those with normal bleeding patterns (mean±SE) 41.3±7.4 versus 23.2±5.8 µmol/l (P<0.001). There was a positive correlation between NO levels and both prolonged spotting and heavy/prolonged bleeding days (P<0.001 and P<0.01, respectively) and negative correlation between NO levels with the duration of use and length of the menstrual cycle (P<0.05). CONCLUSION: The significantly increased serum levels of NO metabolites among LNG-implants 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.
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