Check treatment options for dysmenorrhea
Executive Summary
Early research indicates that women with moderate to severe menstrual cramps might find relief in vaginal administration of sildenafil citrate (Viagra, Pfizer), a drug commonly used for erectile dysfunction.
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Primary dysmenorrhea, or painful menstruation, is the most common cause of pelvic pain in women; as many as 90% of adolescent girls and more than 50% of menstruating women worldwide report symptoms, with 10-20% of them describing their pain as severe and distressing.
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Nonsteroidal anti-inflammatory drugs (NSAIDs), which likely act by reducing uterine hypercontractility, offer effective treatment of primary dysmenorrhea. Combined oral contraceptives also are effective at easing menstrual cramping.
Primary dysmenorrhea, or painful menstruation, is the most common cause of pelvic pain in women; as many as 90% of adolescent girls and more than 50% of menstruating women worldwide report symptoms, with 10-20% of them describing their pain as severe and distressing.1-5
Early research indicates that women with moderate to severe menstrual cramps might find relief in vaginal administration of sildenafil citrate (Viagra, Pfizer., New York City), a drug commonly used for erectile dysfunction.6
Why look at what is commonly called "the little blue pill" for possible pain relief of severe menstrual cramps? Sildenafil citrate, which is a nitric oxide donor drug, might help with pelvic pain because it might augment relaxant effects of the drug on myometrial cells, reverse the vasoconstriction caused by prostaglandins, and improve uterine blood flow.7,8 Although nitric oxide donor drugs cause vasodilatation and successfully alleviate pain, the incidence of side effects, such as headaches, might be too high for routine clinical use with oral route, researchers note.
Rapid absorption and quick pain relief are of utmost importance in treating dysmenorrhea, says Richard Legro, MD, professor of obstetrics and gynecology and public health sciences at Penn State University's College of Medicine in Hershey, PA. Vaginal administration accomplishes both and avoids the first pass effect of drug administration, he notes.
Vaginal administration has been effective in other treatments, observes Legro. One example is bromocriptine given for the treatment of hyperprolactinemia; oral administration has been associated with nausea and orthostatic hypertension. Data indicates that when the drug has been given vaginally, it has ameliorated those side effects,9 he notes.
Check the details
To conduct the study, researchers developed a double-blind, randomized, controlled trial comparing vaginal preparation of sildenafil citrate (100 mg single dose) to a placebo in 62 patients with primary dysmenorrhea.
The primary outcome was total pain relief over four consecutive hours comparing sildenafil citrate to placebo. Secondary outcomes were pain relief as measured by the visual analog scale and uterine artery pulsatility index. Subjects included women ages 18 to 35 with moderate to severe symptoms. Of the 29 women screened for the study, 25 were randomized to receive sildenafil or the placebo drug.
Data indicates the sildenafil citrate group had better pain relief compared with the placebo group [mean standard deviation (SD): 11.9 (3.2) versus 6.4
(2.1), respectively; difference in means = 5.3; 95% confidence interval (CI): (2.9,7.6); P < 0.001)]. On the visual analog scale, sildenafil citrate provided better pain relief than placebo at each time point. At the two-hour point, the pulsatility index 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)].6
The research group has applied for research project grant (R01) funding from the National Institutes of Health to pursue further testing of the drug for primary dysmenorrhea treatment, says Legro.
"If future studies confirm these findings, sildenafil may become a treatment option for patients with primary dysmenorrhea," said Legro. "Since primary dysmenorrhea is a condition that most women suffer from and seek treatment for at some points in their lives, the quest for new medication is justified."
What's available now?
What causes menstrual cramping? Prostaglandin is produced in the uterus at the time of menstruation and can cause uterine contractions that are associated with menstrual cramping. Women who produce high levels of prostaglandin have more intense contractions and more severe cramping.
A systematic review of evidence indicates that nonsteroidal anti-inflammatory drugs (NSAIDs), which likely act by reducing uterine hypercontractility, offer effective treatment of primary dysmenorrhea. Unfortunately, not all women can use NSAIDs; gastrointestinal effects are not uncommon.10 Even in those women who are able to use NSAIDs, such drugs are not completely effective.11
For women who want an alternative to NSAIDs, birth control pills represent an effective option for treatment of painful menstrual cramps. Oral contraceptives prevent ovulation, which in turn reduces the amount of prostaglandin produced in the uterus. By doing so, birth control pills relieve menstrual cramping. According to Contraceptive Technology, the levonorgestrel intrauterine device (Mirena, Bayer HealthCare Pharmaceuticals, Wayne, NJ) also is an excellent choice for women with dysmenorrhea because menstrual blood loss and duration of bleeding are reduced.12
REFERENCES
- Davis AR, Westhoff CL. Primary dysmenorrhea in adolescent girls and treatment with oral contraceptives. J Pediatr Adolesc Gynecol 2001; 14:3-8.
- Durain D. Primary dysmenorrhea: assessment and management update. J Midwifery Womens Health 2004; 49:520-528.
- Ortiz MI, Rangel-Flores E, Carrillo-Alarcón LC, et al. Prevalence and impact of primary dysmenorrhea among Mexican high school students. Int J Gynaecol Obstet 2009; 107:240-243.
- Fedorowicz Z, Nasser M, Jagannath VA, et al. Beta-2-adrenoceptor agonists for dysmenorrhoea. Cochrane Database Syst Rev 2012; doi: 10.1002/14651858.CD008585.pub2.
- Ju H, Jones M, Mishra G. The prevalence and risk factors of dysmenorrhea. Epidemiol Rev 2014; 36(1):104-113.
- Dmitrovic R, Kunselman AR, Legro RS. Sildenafil citrate in the treatment of pain in primary dysmenorrhea: a randomized controlled trial. Hum Reprod 2013; 28(11):2,958-2,965.
- Facchinetti F, Sgarbi L, Piccinini F, et al. A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial. Gynecol Endocrinol 2002; 16:39-43.
- Moya RA, Moisa CF, Morales F, et al. Transdermal glyceryl trinitrate in the management of primary dysmenorrhea. Int J Gynaecol Obstet 2000; 69:113-118.
- Kletzky OA, Vermesh M. Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia. Fertil Steril 1989; 51(2):269-272.
- Dawood MY. Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol 2006; 108:428-441.
- Berkley K. Primary dysmenorrhea: an urgent mandate. Pain Clinical Updates 2013; available at http://bit.ly/1eSPFfg.
- Nelson AL, Baldwin SB. Menstrual disorders. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
