sildenafil-citrate and Dysmenorrhea

Although nonsteroidal antiinflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well-studied strategies. The goal of this review is to provide a background for treating menstrual pain when first-line options fail. Research on menstrual pain and failure of similar drugs in the antiplatelet category suggested potential mechanisms underlying nonsteroidal antiinflammatory drug resistance. Based on these mechanisms, alternative options may be helpful for refractory cases. This review also identifies key pathways in need of further study to optimize menstrual pain treatment.

Topics: Ablation Techniques; Anti-Inflammatory Agents, Non-Steroidal; Antidiuretic Hormone Receptor Antagonists; Aromatase Inhibitors; Calcium Channel Blockers; Complementary Therapies; Contraceptives, Oral, Hormonal; Denervation; Drug Resistance; Dysmenorrhea; Female; Gonadotropin-Releasing Hormone; Humans; Medication Adherence; Parasympatholytics; Pharmacogenomic Variants; Receptors, Oxytocin; Sildenafil Citrate; Uterus; Vasodilator Agents

Is a vaginal preparation of sildenafil citrate capable of alleviating acute menstrual pain in patients with primary dysmenorrhea (PD)?. A vaginal preparation of sildenafil citrate is capable of alleviating acute menstrual pain in patients with PD with no observed adverse effects.. Oral preparations of nitric oxide (NO) donor drugs augment relaxant effects of NO on myometrial cells, reverse the vasoconstriction caused by prostaglandins and successfully alleviate pain, but the incidence of side effects is too high for routine clinical use. Sildenafil citrate inhibits type 5-specific phosphodiesterase (PDE5), thus preventing the degradation of cyclic guanosine monophosphate (cGMP) in the muscle and augmenting the vasodilatory effects of NO. Therefore, by inhibiting PDE5, the tissue remains relaxed and more blood can circulate through. It has been used previously in a vaginal form with no observed side effects, and it enhances endometrial blood flow.. A double-blind, randomized, controlled trial comparing vaginal preparation of sildenafil citrate (100 mg single dose) to a placebo in 62 PD patients at the time of painful menstruation was conducted. The primary outcome was total pain relief over 4 consecutive hours (TOPAR4) comparing sildenafil citrate to placebo, where higher TOPAR4 scores represent better pain relief. Secondary outcomes were pain relief as measured by the visual analog scale (VAS) and uterine artery pulsatility index (PI). Subjects were recruited from December 2007 to January 2011. The trial was stopped due to closeout of the funding for the study.. Participants were women in good health, were aged 18-35 years and suffered from moderate to severe PD. They were randomized to either vaginal placebo or 100 mg vaginal sildenafil citrate in a 1:1 ratio using random permuted blocks having a block size of 4. At baseline and 1, 2, 3, and 4 h post-treatment, patients were asked to provide assessment of their degree of pain using two scales: (i) pain on the 5-level ordinal scale used for TOPAR4 calculation and (ii) pain level on the VAS. The study ended 4 h after treatment initiation.. Twenty-five subjects completed the study. Using the TOPAR4 score, the sildenafil citrate group had significantly better pain relief compared with the placebo group [mean (SD): 11.9 (3.2) versus 6.4 (2.1), respectively; difference in means = 5.3; 95% CI: (2.9,7.6); P < 0.001)]. On the VAS, sildenafil citrate provided better pain relief than placebo at each time point. At the 2-h time point, the PI was significantly lower in the sildenafil citrate group compared with the placebo group [mean (SD): 1.6 (0.6) versus 2.3 (0.5), respectively; difference in means = -0.7; 95% CI: (-1.2, -0.1); P = 0.01)].. Since we did not meet our sample size due to the loss of funding and could not confirm our primary hypothesis, larger studies of longer duration, likely multi-center, are needed to confirm the findings from this study.. A number of medications have been investigated to improve the treatment options for PD, but most have proven unsuccessful or to have an unfavorable risk/benefit ratio. Since PD is a condition that most women suffer from and seek treatment for at some point in their lives, our study offers hope that vaginal sildenafil citrate is a safe and effective option for patients who do not desire or are unresponsive to treatments now available on the market.. Funding for this study was provided by National Institutes of Health (NIH) grants RO3 TW007438 and K24 HD01476. The authors report no relevant conflicts of interest.. NCT00123162 (Clinical trials.gov).

Topics: Adolescent; Adult; Double-Blind Method; Dysmenorrhea; Female; Humans; Pain; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones