Sildenafil in women with sexual arousal disorder following spinal cord injury

Sexual Function Questionnaires.Table 2 shows

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Analyses were performed with SAS version 9.1.3 (SAS Institute Inc, Cary, North Carolina). One hundred women (Figure) of the 145 screened met eligibility requirements. Among the most frequent causes for exclusion were ineligible protocol criteria (ie, lack of acceptable and verifiable form of contraception, perimenopausal with irregular cycles or amenorrhea, non-SRI sexual dysfunction augmentation, switching antidepressant agent, other treatments for sexual dysfunction), and other miscellaneous reasons (partner issues, abnormal Papanicolaou test results, medical comorbidity, excessive alcohol use, or relationship or partner problems). Two eligible participants were withdrawn after they were screened but before they were randomized. One patient had a change in antidepressant dose made by her primary care physician.

Increased genital blood flow

The other patient withdrew due to her partner's serious injuries. The 2 nonrandomized and untreated women did not differ on any demographic characteristics from those who entered the trial and were not included in the analyses. A total of 98 women were randomly assigned to receive active sildenafil (n = 49) or placebo (n = 49). The mean (SD) age of the women was 36.7 (7.1) years. They had been taking antidepressant medication for 27.7 (34.6) months.

Safety Considerations

Distribution of prescribed antidepressants was comparable between groups. There were no statistically significant differences between baseline demographics in the assigned treatment groups (Table 1). Systematic review for any protocol deviations in patient enrollment was undertaken before unbinding. The 98 randomized women constituted the last-observation-carried-forward analysis. Seventy-six women (77.6%) completed the study: with 75.5% (37 of 49) in the placebo group and 79.6% (39 of 49) in the sildenafil group and constituted the completer population. the mean (SD) scores on the

secondary outcome measures from baseline to

• Psychological support can enhance the effectiveness of medical treatments.
• Female sexual health is complex and multifaceted.
• Sildenafil should not replace comprehensive sexual health assessments.
• Evidence supports combining medication with behavioral therapies.

study end for both treatment groups.

In comparing the baseline sexual function questionnaire domain scores with

1. How it works

Nine women in the placebo group and 4 in the sildenafil group discontinued prematurely for lack of efficacy. The other 6 in sildenafil and 3 in the placebo groups were lost to follow-up. No discontinuations for intolerable or serious adverse events were reported (Figure). As determined by the inclusion criteria, the prevalence of sexual problems was high and the mean (SD) number of problems reported was 3.0 (0.7) for the sildenafil group and 2.8 (0.7) the placebo group (P = .21), with 95.8% of women reporting more than 1 complaint. They reported disturbances in desire (87.8%), subjective arousal (80.6%), lubrication (79.6%), orgasm delay (98.7%), and other difficulties (23.6%), which included anorgasmia, lack of pleasure, and pain.

Exclusion Criteria

Prior to study entry, the women self-reported a mean (SD) of 6.0 (5.2) sexual attempts per month, of which 1.4 (2.0), or 29.6% (34.9%), were considered successful. There were no statistically significant differences between treatment groups in number or type of sexual problems or in number or percentage success of sexual attempts at baseline (Table 1). The difference from baseline to end point in the mean (SD) change in the Clinical Global Impression scale sexual function improvement by intent-to-treat last-observation-carried-forward analyses (ie, lower ordinal score) was 4.8 (0.7) to 2.8 (1.0) with a difference of 1.91 (95% CI, 1.57-2.26) for the sildenafil group vs 4.7 (0.9) to 3.6 (0.9) with a difference of 1.10 (95% CI, 0.75-1.46) for the placebo group, which showed a significant difference of 0.8 (95% CI, 0.6-1.0, P = .001) between groups (Table 2). To adjust for potential bias introduced by patients who prematurely discontinued, a more conservative intent-to-treat analysis assigning return-to-baseline values carried forward of those who did not complete the study showed a baseline-to-end point mean difference in the Clinical Global Impression scores of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil vs 0.9 (95% CI, 0.6-1.3) for women taking placebo and a significant 0.6 (95% CI, 0.3-0.8) mean change difference between groups (P = .03). Clinically, 73% of women taking placebo compared with 28% of women taking sildenafil reported no improvement with treatment (Clinical Global Impression score >3 was rated as no improvement). those at the end of the study, women in the

sildenafil group had a higher

Treatment Information

Responses of not applicable were entered as missing. To provide concurrent validity, we used the Arizona Sexual Experience and the University of New Mexico Sexual Function Inventory scales. Both are shorter and well-established instruments that have been validated in patients with psychiatric disorders. They weight sexual function domains equally with different wording and anchors at administration. The Arizona scale is a 5-item, patient-rated questionnaire that quantifies sexual drive, arousal (subjective excitement), lubrication (physiological excitement), ability to reach orgasm, and orgasm satisfaction using anchored 6-point scales from 1 (good function) to 6 (poor function) for each item with a total score ranging from 5 to 30 (higher scores indicate greater sexual dysfunction).28 The University of New Mexico scale29 is a 5-item, clinician-rated—for this study—questionnaire derived from and similar to the Arizona28 and the Massachusetts General Hospital-Sexual Function questionnaires.30 It uses anchored 6-point scales from 1 (good function) to 6 (poor function) for each item (desire, sexual arousal, ability to achieve lubrication, ability to achieve orgasm, and overall satisfaction) to quantify presence and changes in sexual dysfunction independent of disease state or medication (lower scores indicate better or improvement in sexual function).

Female neurogenic sexual dysfunction secondary to clitoral neuropathy

The 17-item Hamilton depression rating23 was administered at baseline and at weeks 2, 4, and 8 (or last visit) to monitor depression severity to ensure that the severity of depression had not changed to be more than 10 (relapse of major depression excluded study continuation). A second Hamilton anxiety rating24 occurred at week 8. The clinical assessment of each patient and medical record was used to confirm DSM-IV–defined major depressive disorder in remission, substance-induced sexual dysfunction, and any exclusionary diagnoses. Serum blood samples drawn at baseline and at study end, before 11 AM on days 1 to 10 of the menstrual period (follicular phase), were stored at −80°C until assayed and measured following prescribed procedures (eg, chemiluminescent enzyme immunoassay, microparticle enzyme immunoassay, radioimmunoassay) at the Reproductive Endocrine Reference Laboratory at Massachusetts General Hospital, Boston. Full analysis procedures with lower limits of detection reported for assays performed at the Massachusetts General Hospital General Clinical Research Center core laboratory using commercially available kits are published by the manufacturer and available on request.

Sexual Health in the Neurogenic Patient

Baseline demographics, safety, and tolerability evaluations were compared using descriptive statistics by χ2 and Fisher exact tests (when cell sizes were <5). Independent samples t tests compared baseline patient characteristics and Clinical Global Impression sexual function scores between the study groups at end point. The χ2 analyses were used to evaluate group differences in categorical measures. Analyses were based on intent-to-treat with the last-observation-carried-forward analyses performed on all variables and included data from all protocol-treated patients. All randomized patients received and took at least 1 dose of study trial medication, had at least 1 efficacy assessment, and were included regardless of protocol deviations or whether they completed the study. mean (SD) improvement (orgasm, P=.01)

• Sildenafil may improve blood flow, but effectiveness varies.
• The drug is not FDA-approved specifically for female use.
• Ongoing research aims to determine its safety for women.
• Lifestyle changes and therapy are often preferred first-line treatments.

than women taking placebo for all domains except for pain.

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The final analysis included women who completed the trial, but for the women who did not complete the trial, their baseline value was carried forward in separate analyses. The change in sexual functioning by Clinical Global Impression sexual function score and all other questionnaires from baseline to each patient's own end point were the dependent measures of efficacy. A repeated measures analysis of variance was used to determine differences between placebo and sildenafil in the change from baseline to end point for the measures of efficacy and depression severity (time × group interaction). In addition, exact nonparametric methods were applied to the efficacy measures to substantiate results that rely on distributional assumptions. Findings were also confirmed with analysis of covariance and Wilcoxon rank sum tests for primary analyses.

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All statistical tests were 2-sided, and all hypotheses were evaluated at the 5% significance level. The F test of the overall hypothesis test was first conducted before multiple comparisons analyses. Sample-size calculations were based on detecting a difference in full response rates at 8 weeks, assuming a response rate of 70% for sildenafil and 35% for placebo. Thus, a sample size of 82 evaluable patients (41 per group) was expected to detect a significant difference with 90% power for a type I error rate of α = .05 between sildenafil and placebo (2-sided). Assuming 20% attrition, 100 patients were planned to be randomized and 98 patients were entered.

Cite this article

The sample size determination assumed no interactions of treatment with site or antidepressant. The primary analysis was according to assignment at randomization. In addition to determination of this narrow measure of efficacy based on all randomized patients and imputing the worst rank scores for early exclusions due to protocol violations before and without taking the trial drug, there was a general efficacy analysis for all protocol-treated patients and all trial completers. Adjusted means (SDs) sildenafil syrup were determined and reported. Where applicable, 95% confidence intervals (CIs) are provided.