Primary dysmenorrhea (PD) is the most common cause of pelvic pain in women, estimated to affect up to 90% of the female population. The etiology is poorly understood and treatment options are limited. The medications that are usually prescribed in this condition are drugs that block prostaglandin production (which have the disadvantage of possible serious side-effects), and oral contraceptives (not effective in all patients with PD, because in certain women cyclic regimen of hormones and withdrawal bleeding allows the production of prostaglandins, and pain persists). The specific aim of this proposal is to explore different treatment options in patients who suffer from PD. We propose to conduct two separate trials, to determine the efficacy of continuous contraceptive regimen for chronic relief, and sildenafil citrate for acute relief, in the treatment of PD. The first trial is a double blind randomized controlled trial comparing continuous combined low-dose oral contraceptive regimen to the traditional 21/7 regimen for the period of 6 months in PD patients. The second trial is also a double blind randomized controlled trial that uses a single dose of vaginal sildenafil citrate 100 mg compared to a single dose of placebo over a 4-hour period in patients with PD. We have received an IND with the FDA for this trial. We hypothesize that both of our treatment options will have a reduction in PD, as determined by validated instruments, that is significant compared to the reference group. Continuous oral contraceptive regimen reduces the extent and duration of menstrual and premenstrual symptoms, but it has never before been studied as a primary treatment of PD. Recent studies show its superiority to traditional regimen in the treatment of endometriosis, the leading cause of secondary dysmenorrhea. In the second trial, we plan to utilize the vasodilatative properties of sildenafil citrate to reverse ischemia of the uterine muscle caused by excess prostaglandin production, as ischemia is thought to cause the pain. To date sildenafil citrate has not been studied in the treatment of PD. This research will be done primarily in Croatia, at University Hospital Sveti Dun, in collaboration with Richard S. Legro, as an extension of NIH grant #RO1HD43332-01. Since primary dysmenorrhea is such a common and debilitating condition, finding two new treatment options that can offer safe and substantial pain relief would have great impact on future research in this area, eventually helping millions of women worldwide. [unreadable] [unreadable] [unreadable]