A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial

Abstract

Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice forits treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO).The aim of the present studywas to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severeprimary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first daysof menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24h transdermal GTN for the first 3days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on thefirst day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable.Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 ±17.9; DCF, -18.9 ± 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher thanthose for DFC (after one hour: GTN, -12.8 ± 17.9; DFC, -18.9 ± 16.6 and after two hours: GTN, -23.7 ± 20.5; DFC, -59.7 ± 17.9, p = 0.0001). Low back pain was also relievedby both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache - attributed to its use - became intolerable. These findings indicate that GTNhas a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.