Increased serum levels of nitric oxide metabolites among users of levonorgestrel-releasing implants [corrected] a possible role in progestin-induced bleeding.
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) [corrected] and to identify any correlation between some of their clinical characteristics and NO metabolite levels.


METHODS
This cross-sectional study included 37 LNG-implants [corrected] users; a single 5 ml venous blood was collected at different periods of [corrected] use. Women were divided into users with acceptable menstrual bleeding (n 5 13) [corrected] and those having abnormal bleeding patterns (n 5 24) [corrected] 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 [corrected] users than in the controls (mean+/-SE) 34.9+/-11.3 versus 6.1+/-1.5 mumol/l (P<0.001) [corrected] The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users with abnormal bleeding patterns than in those with normal bleeding patterns (mean+/-SE) 41.3+/-7.4 versus 23.2+/-5.8 mumol/l (P<0.001) [corrected] 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).


CONCLUSIONS
The significantly increased serum levels of NO metabolites among LNG-implants [corrected] 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.
Shaamash
A H
AH
Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Egypt. shamaamashayman@yahoo.com
Zakhari
M M
MM
D000328:Adult; D016022:Case-Control Studies; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D004717:Endometrium / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects / Q000494:pharmacology*; D008597:Menstrual Cycle / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D014592:Uterine Hemorrhage / Q000139:chemically induced; D014664:Vasodilation / Q000187:drug effects
D003280:Contraceptives, Oral, Synthetic; D009569:Nitric Oxide; D016912:Levonorgestrel