NEWS & VIEWS those with only provoked pain (48% success compared with 60%). Despite these positive findings, nearly half (44%) of the women in the study did not receive any type of relief from their dyspareunia at 3 months. Although we cannot extrapolate these results to describe the whole population, medically intra ctable vulvodynia is the reality for some women. Surgery to remove a high-density area of nerve fibres in the vestibular tissues (vesibulectomy) might be considered for these patients. 9 With this in mind, Tommola et al. 10 sought to determine whether long-term pain among women who failed medical therapy and opted to receive surgical intervention was similar in those women who received successful medical management. This study stands out amongst similar studies that have reported the short-term efficacy or effectiveness of vestibulectomy because of its long followup period. The vestibulectomy cohort was followed for a median of 47 months and the cohort of women with severe vulvar vestibulitis receiving only medical management was followed for a median of 77 months. As expected, women who received the posterior vestibulectomy had higher baseline scores for dyspareunia. Regardless of their treatment decision, 89% of women in the study were satisfied with their treatment. Furthermore, years after surgery, the women who originally had the most severe phenotype of vulvar vestibulitis (and therefore required vestibulectomy) were as likely as the medically managed women to have reduced vulvar pain (66.7% in the surgery group compared with 78.1% in the medically managed group) and be sexually active (81.1% compared with 72.0%). However, a considerable proportion of women from both groups had pain problems with sex (42.9% compared with 33.3%) at the end of the follow-up period. These observational studies from clinical populations provide valuable, never-beforepublished evidence of the effectiveness of certain treatments for vulvodynia, which at its onset can seem quite daunting for the patient and practitioner. In addition to randomized clinical trials, improvement upon these studies includes multicentre enrolment to increase participation. Indeed, population-based studies could benefit from partnering with vulvodynia advocacy groups who can assist in recruitment. Larger cohorts with untreated control groups would enable subdivision of patients on the basis of differences in pain phenotypes and
to determine whether other factors such as comorbid pain conditions (for example, irritable bowel syndrome or fibromyalgia), which are common among these women, could account for the differences in existing pain after vulvodynia treatment. Whichever methods are used to improve future studies, or the interventions tested, a conversation across disciplines should be centred on our threshold for successful treatment of vulvodynia. Are we willing to conclude that dyspareunia among 40–50% of patients after treatment is as good as it gets? University of Minnesota, Division of Epidemiology and Community Health, School of Public Health, 1300 South 2nd Street, Suite 300, Minneapolis MN 55454, USA.
[email protected] Competing interests The author declares no competing interests. 1.
2.
ACOG Committee on Gynecologic Practice. ACOG committee opinion: number 345, October 2006: vulvodynia. Obstet. Gynecol. 108, 1049–1052 (2006). Bachmann, G. A. et al. Vulvodynia: a state‑of‑the-art consensus on definitions,
diagnosis and management. J. Reprod. Med. 51, 447–456 (2006). 3. Goetsch, M. F. et al. Histologic and receptor analysis of primary and secondary vestibulodynia and controls: a prospective study. Am. J. Obstet. Gynecol. 202, 614.e1–e8 (2010). 4. Reed, B. D. Vulvodynia: diagnosis and management. Am. Fam. Physician 73, 1231–1238 (2006). 5. Haefner, H. K. et al. The vulvodynia guideline. J. Low. Genit. Tract Dis. 9, 40–51 (2005). 6. Nguyen, R. H. et al. Comfort in discussing vulvar pain in social relationships among women with vulvodynia. J. Reprod. Med. 57, 109–114 (2012). 7. Pagano, R. & Wong, S. Use of amitriptyline cream in the management of entry dyspareunia due to provoked vestibulodynia. J. Low. Genit. Tract Dis. http://dx.doi.org/10.1097/ LGT.0b013e3182449bd6. 8. Marinoff, S. C. & Turner, M. L. Vulvar vestibulitis syndrome: an overview. Am. J. Obstet. Gynecol. 165, 1228–1238 (1991). 9. Kehoe, S. & Luesley, D. Vulvar vestibulitis treated by modified vestibulectomy. Int. J. Gynaecol. Obstet. 64, 147–152 (1999). 10. Tommola, P., Unkila-Kallio, L. & Paavonen, J. Long-term well-being after surgical or conservative treatment of severe vulvar vestibulitis. Acta Obstet. Gynecol. Scand. http://dx.doi.org/10.1111/ j.1600-04122012.01466.x.
SEXUAL MEDICINE
Why stop a good thing? Discontinuing PDE5 inhibitors Helen M. Conaglen and John V. Conaglen
Reasons why men discontinue a medication that successfully addresses their erectile dysfunction have been investigated often. A recent study adds few new reasons for discontinuation, but does report which medical conditions result in men discontinuing due to PDE5 inhibitors not being able to restore their erectile function. Conaglen, H. M. & Conaglen, J. V. Nat. Rev. Urol. 9, 483–485 (2012); published online 14 August 2012; doi:10.1038/nrurol.2012.165
Most studies investigating reasons for discontinuation of successful treatments for erectile dysfunction (ED) have been published relatively soon after each type of therapy has been introduced.1,2 As the majority of the studies arose from medical clinics for the treatment of men with ED, it is not surprising that the majority of reports have assessed the reasons for discontinuation from a medical rather than multidisciplinary perspective. In addition, the vast majority of papers about phospho diesterase type 5 (PDE5) inhibitor discontinuation have adopted quantitative approaches to determining the issues.3 Even in extensive reviews of the studies, the lack
NATURE REVIEWS | UROLOGY
of consensus as to why men stop taking their ED medication—despite successful treatment—is obvious.3 Since 1998, when sildenafil was first introduced, the list of reasons for dis continuation of PDE5 inhibitors given in the various studies has grown. Despite numerous reports, it remains unclear as to whether further interventions alongside the prescription of PDE5 inhibitors would ensure ongoing use of the medication when necessary and result in better outcomes for the man and his partner. Reasons for discontinuation categorized within past research and summarized in various reviews have included recovery of VOLUME 9 | SEPTEMBER 2012 | 483
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NEWS & VIEWS Practice points ■■ Involving partners in treatment decisionmaking improves outcomes for men with erectile dysfunction ■■ Educating couples helps to ensure the best use of PDE5 inhibitors ■■ Relationship issues are unlikely to be solved by PDE5 inhibitors alone, and a biopsychosocial approach is recommended
erectile function, cost, emotional factors, lack of efficacy, adverse effects, loss of sexual desire, lower International Index of Erectile Function (IIEF) scores at PDE5 inhibitor initiation, as well as the inconvenience and embarrassment when obtaining medications.3–6,8 However, even these reasons are disputed from paper to paper— some investigators state that adverse effects and lack of efficacy drive discontinuation,5,8 whereas others report that 79% of discontinuations are not treatment-related.6 In order to further elucidate these data, Carvalheira and colleagues7 have undertaken a careful study of 327 men presenting with ED at a private andrological outpatient clinic, investigating their use of PDE5 inhibitors over 3 years. Within the study they have assigned aetiology of ED categories to participants and can, therefore, report that men in their sample with arteriogenic, diabetic or iatrogenic ED were more likely than men with venogenic aetiologies to dis continue use of their PDE5 inhibitors. These findings are not surprising, and reporting the proportion of men in each group could be construed as useful for clinicians advising their patients. However, the sample is from a specialized clinic and, therefore, the data might not represent patient groups encountered elsewhere. The researchers also asked men to endorse their reasons for discontinuation based on a checklist, as several earlier studies have done, and conducted telephone interviews in which they asked two open-ended questions about reasons for abandonment of the medication. As it is not clear whether the quantitative checklist was completed online before or after the qualitative questions, it is possible that the checklist primed men with respect to answers to the later questions. Having set up the opportunity for a qualitative interview by telephone it is a pity that only two questions were addressed: ‘How did you take the inhibitor?’ and ‘What reasons led you to stop the medication?’. A more informative picture of each man’s context might have emerged with questions 484 | SEPTEMBER 2012 | VOLUME 9
about his relationship, partner’s interest and understanding of his difficulties and the attitudes of both parties to the medication, for example. Even so, the result was a comprehensive list of reasons why men abandon PDE5 inhibitors at various time points of their treatment, together with percentages of men discontinuing the medication for the different categories of ED. Most of the reasons for discontinuation reported by Carvalheira et al.7 have already been reported in the literature. However, although the paper has contributed few new reasons for discontinuation of PDE5 inhibitors, it has made a useful clinical contribution. The study has elaborated on the types of ED most likely to be associated with discontinuing the medication, and the stage of treatment at which men chose to abandon PDE5 inhibitor therapy. Noticeably fewer men who discontinued their medication stopped therapy after 1 year of treatment (18%) compared with 4–12 months (27%) or 1–3 months (56%). The authors also report that diabetics (73% dropout rate) and men with iatrogenic ED (65%) were more likely to discontinue treatment than men with venogenic ED (39%). These data suggest that the men for whom the prescribed treatment was less likely to be effective probably found this was so within 3 months and discontinued at that point; however, the authors did not report whether men with these conditions stopped therapy sooner rather than later in the study.
‘‘
A multidisciplinary approach to treating ED is often agreed to be ideal, but seldom found in practice
’’
The group has also shown that interviewing men following their medication discontinuation results in a broader range of reasons being noted than a checklist will quantify. Some of these reasons generate important therapeutic possibilities—for example, men who fear using PDE5 inhibitors because of concerns regarding cardiovascular safety would potentially benefit from educational intervention pointing out the positive effects of the drugs on heart tissue and the lack of evidence for their fears. Such education should really be part of the prescribing process. In addition, the recognition that ‘anxiety, negative emotions, fears and dysfunctional beliefs’ led to discontinuation point to another potential intervention to assist these men—such
issues are best dealt with in a supportive psychological manner addressing the men’s issues with sound psychotherapeutic advice. A multidisciplinary approach to treating ED is often agreed to be ideal, but seldom found in practice—even, it would seem, in private clinics. An interesting issue in studies of PDE5 inhibitor use or discontinuation is the discrepancy between the number of prescriptions written and the numbers filled.8 Carvalheira et al. 7 have reported that almost 3% of the men in their study professed embarrassment in obtaining the drug and almost 6% did not even try the drug once it was prescribed. One explanation for this discrepancy between prescription and compliance figures lies in the use of the medication for an activity that usually involves another person as well as the patient for whom it is prescribed. For this reason alone, it is surprising that there is still only one published study that has sought the perspective of the partners of men with ED in discussion of continuation or discontinuation of PDE5 medications.4 Interviewing partners can uncover reasons other than the patient’s own difficulties that hamper the use of the medication, such as vaginal dryness due to lack of oestrogen in a postmenopausal partner. Prescribing oestrogen in accordance with the North American Menopause Society’s position statement 9 can increase the female partner’s capacity to enjoy sexual experiences, which, in turn, potentially increases the likelihood that men will continue to engage in sexual activity and will, therefore, continue using their PDE5 inhibitors. Carvalheira’s study concurs with the benefit of having female partners present at a man’s ED consultation, but does not give any reasons why this might be helpful. Another comparison that might be made between the study investigating couples continuation 4 and Carvalheira and colleagues’ 7 paper regards the variation in rates of ongoing usage. In the couples study,4 71% of men continued using PDE5 inhibitors over 12–18 months, whereas only 45% of the Portuguese cohort studied by Carvalheira continued during the 36-month study period. As the authors themselves conclude, improved patient (and partner) education alongside prescribing might lead to fewer men discontinuing these drugs. The sample statements gathered in response to the qualitative questions demonstrate that a number of the men could have bene fitted from psychosexual intervention www.nature.com/nrurol
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NEWS & VIEWS helping them and their partner with their relationship. Whilst not explicitly stated by the authors, the implied conclusion is that taking a more biopsychosocial approach when treating men with ED and their partners would improve outcomes for all concerned. This conclusion has been stated before3 and the approach is mentioned in the discussion of the study,9 but is somewhat difficult in practice; perhaps the time has come to further investigate the ideal multi disciplinary treatment package for men with ED and their partners. Sexual Health Research Unit, Waikato Clinical School, University of Auckland, Peter Rothwell Academic Centre, Waikato Hospital, Pembroke Street, Private Bag 3200, Hamilton 3240, New Zealand (H. M. Conaglen, J. V. Conaglen). Correspondence to: H. M. Conaglen
[email protected]
Competing interests The authors declare no competing interests. 1.
2.
3.
4.
5.
Althof, S. E. et al. Why do so many people drop out from auto-injection therapy for impotence? J. Sex Marital Ther. 15, 121–129 (1989). Kramarsky-Binkhorst, S. Female partner perception of Small-Carrion implant. Urology 12, 545–548 (1978). Al-Shaiji, T. F. & Brock, G. B. Phosphodiesterase type 5 inhibitors for the management of erectile dysfunction: Preference and adherence to treatment. Curr. Pharm. Des. 15, 3486–3495 (2009). Conaglen, H. M. & Conaglen, J. V. Couples’ reasons for adherence to, or discontinuation of, PDE type 5 inhibitors for men with erectile dysfunction at 12 to 24-month follow-up after a 6-month free trial. J. Sex. Med. 9, 857–865 (2012). Giannitsas, K., Konstantinopoulos, A., Patsialis, C. & Perimenis, P. Preference for and adherence to oral phosphodiesterase‑5 inhibitors in the treatment of erectile dysfunction. Patient Prefer. Adherence 2, 149–155 (2008).
NATURE REVIEWS | UROLOGY
6.
Padma-Nathan, H., Eardley, I., Kloner, R. A., Laties, A. M. & Montorsi, F. A 4‑year update on the safety of sildenafil citrate (Viagra). Urology 60 (Suppl. 2), 67–90 (2002). 7. Carvalheira, A. A., Pereira, N. M., Maroco, J. & Forjaz, V. Dropout in the treatment of erectile dysfunction with PDE5: A study on predictors and a qualitative analysis of reasons for discontinuation. J. Sex. Med. doi:10.1111/j.1743-61092012.02787.x. 8. Sato, Y. et al. How long do patients with erectile dysfunction continue to use sildenafil citrate? Dropout rate from treatment course as outcome in real life. Int. J. Urol. 14, 339–342 (2007). 9. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy: 2007 position statement of The North American Menopause Society. Menopause 14 (3 Pt 1), 355–369 (2007). doi:10.1097/ gme.0b013e318051718c. 10. Althof, S. E. When an erection alone is not enough: Biopsychosocial obstacles to lovemaking. Int. J. Impot. Res. 14 (Suppl. 1), S99–S104 (2002).
VOLUME 9 | SEPTEMBER 2012 | 485 © 2012 Macmillan Publishers Limited. All rights reserved
