Leonard R. Derogatis

Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: Results from the INTIMATE NM1 Study

Objective: To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause. Design: A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 &mgr;g/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24). Results: A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels ≤160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels ≤160 nmol/L, mean change of 2.1 ± 0.28 versus 0.5 ± 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 ± 0.26 versus 0.5 ± 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated. Conclusions: Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder.

The derogatis interview for sexual functioning (DISF/DISF-SR): An introductory report

The current report describes a program of research designed to demonstrate the psychometric characteristics and validity of the Derogatis Interview for Sexual Functioning (DISF/DISF-SR), a set of brief, gender-keyed, multidimensional outcome measures designed to measure quality of sexual functioning. The primary goals of the development of the DISF/DISF-SR are outlined within the context of the principal measurement parameters involved in human sexual functioning. The development and rationale for both interview (DISF) and matching self-report (DISF-SR) versions of the instrument are presented, as is the rationale for developing distinct male and female forms. The studies described evaluate the reliabilities of both modalities of the DISF/DISF-SR and demonstrate confirmation for the hypothesized internal structure of the test. Research is provided that demonstrates dimensional uniqueness in subtest-total score relationships, and several studies are reviewed that show high discriminative validity for the DISF/DISF-SR in medical and community cohorts. The initial norms for the DISF/DISF-SR are also reviewed and described.

Validated Instruments for Assessing Female Sexual Function

In this article, we review five instruments for assessing female sexual dysfunction (FSD): the Brief Index of Sexual Functioning for Women (BISF-W; Taylor, Rosen, & Leiblum, 1994), the Changes in Sexual Functioning Questionnaire (CSFQ; Clayton, McGarvy, & Clavet, 1997), the Derogatis Interview for Sexual Functioning (DISF/DISFSR; Derogatis, 1997), the Female Sexual Function Index (FSFI; Rosen et al., 2000), and the Golombok Rust Inventory of Sexual Satisfaction (GRISS; Rust & Golombok, 1986). The purpose of this article is to highlight the psychometric properties of these questionnaires in an effort to assist researchers in selecting effective measurement tools for FSD.

Sexual Function, Dysfunction, and Sexual Distress in a Prospective, Population‐Based Sample of Mid‐Aged, Australian‐Born Women

INTRODUCTION Previous, population-based studies investigating the risk factors for sexual distress have not drawn on longitudinal data. AIMS Determine the prevalence of sexual distress and dysfunction, explore factors associated with/predictive of sexual distress, and describe changes in sexual function over a decade in a population-based sample of mid-aged women. METHODS Eleven-year prospective study of Australian-born women, aged 45-55 years, and menstruating at baseline. Short Personal Experiences Questionnaire (SPEQ) was completed in years 1 to 8 and 11 of follow-up. Female Sexual Distress Scale (FSDS) was completed in the 11th year of follow-up. MAIN OUTCOME MEASURES Validated outcome measures were the SPEQ (total sex score <or=7 indicates low sexual function) and FSDS (score >or=15 indicates sexual distress). RESULTS Two hundred fifty-seven women were interviewed in the 11th year of follow-up. All domains of sexual function declined significantly in the decade studied. Women using hormone therapy in year 11 had significantly greater responsivity and higher frequency of sexual activities than nonusers. Two hundred four women completed both the FSDS and SPEQ questionnaires. One hundred sixty-six (81%) women had an SPEQ score <or=7 of whom 34 (17% of the total sample) had an FSDS score >or=15, and were classified as having female sexual dysfunction. The multiple logistic regression analysis found that female sexual distress was concurrently associated with higher depression scores (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.10, 1.56) and more negative feelings for partner (OR 0.49, 95% CI 0.32, 0.76) and predicted by prior negative feelings for partner (OR 0.31, 95% CI 0.14, 0.70), and a greater decline in total sex score (OR 0.77, 95% CI 0.59, 0.99). CONCLUSIONS By the end of the sixth decade, women have low levels of sexual function. Hormone therapy may help these women maintain sexual function. A minority of these mostly postmenopausal women are significantly distressed about low sexual function. Sexual distress is associated with depression and relationship factors.

Efficacy of Flibanserin in Women with Hypoactive Sexual Desire Disorder: Results from the BEGONIA Trial

INTRODUCTION Hypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty. AIM The aim of this study was to assess the efficacy and safety of the 5-HT1A agonist/5-HT2A antagonist flibanserin in premenopausal women with HSDD. METHODS This was a randomized, placebo-controlled trial in which premenopausal women with HSDD (mean age: 36.6 years) were treated with flibanserin 100 mg once daily at bedtime (qhs) (n = 542) or placebo (n = 545) for 24 weeks. MAIN OUTCOME MEASURES Coprimary end points were the change from baseline to study end in Female Sexual Function Index (FSFI) desire domain score and in number of satisfying sexual events (SSE) over 28 days. Secondary end points included the change from baseline in FSFI total score, Female Sexual Distress Scale-Revised (FSDS-R) total score, and FSDS-R Item 13 score. RESULTS Compared with placebo, flibanserin led to increases in mean (standard deviation) SSE of 2.5 (4.6) vs. 1.5 (4.5), mean (standard error [SE]) FSFI desire domain score of 1.0 (0.1) vs. 0.7 (0.1), and mean (SE) FSFI total score of 5.3 (0.3) vs. 3.5 (0.3); and decreases in mean (SE) FSDS-R Item 13 score of -1.0 (0.1) vs. -0.7 (0.1) and mean (SE) FSDS-R total score of -9.4 (0.6) vs. -6.1 (0.6); all P ≤ 0.0001. The most frequently reported adverse events in the flibanserin group were somnolence, dizziness, and nausea, with adverse events leading to discontinuation in 9.6% of women receiving flibanserin vs. 3.7% on placebo. CONCLUSION In premenopausal women with HSDD, flibanserin 100 mg qhs resulted in significant improvements in the number of SSE and sexual desire (FSFI desire domain score) vs. placebo. Flibanserin was associated with significant reductions in distress associated with sexual dysfunction (FSDS-R total score) and distress associated with low sexual desire (FSDS-R Item 13) vs. placebo. There were no significant safety concerns associated with the use of flibanserin for 24 weeks.

Validation of the Profile of Female Sexual Function (PFSF) in Surgically and Naturally Menopausal Women

The Profile of Female Sexual Function (PFSF) is a patient-based instrument for the measuring of loss of sexual function in menopausal women with low libido (hypoactive female sexual desire disorder). The instrument, which contains 37 items in seven domains (sexual desire, arousal, orgasm, sexual pleasure, sexual concerns, sexual responsiveness, and sexual self-image) and a single-item measure of overall satisfaction with sexuality, has been extensively developed and initially validated in over 500 oophorectomized women with low libido in North America, Europe, and Australia. Initial validation results showed the PFSF is capable of discriminating these patients from age-matched controls and produced consistent responses and sensitivity across geographies. The objective of this nonrandomized, parallel-group study was to examine the psychometric properties of the final PFSF in an independent group of surgically menopausal women with low libido and to extend validation to naturally menopausal women with low libido. Participants from 16 study centers in North America included surgically (n = 59) and naturally (n = 88) menopausal women with low libido and their age-matched control subjects, both premenopausal (n = 57) and naturally menopausal (n = 47), who reported no problems with libido. Subjects completed the PFSF at baseline and again 4 weeks later. Adjusted mean scores for each of the seven domains were statistically significantly lower (P < 0.0001) in surgically menopausal women with low libido compared with age-matched control women, and in naturally menopausal women with low libido compared with naturally menopausal control women, demonstrating excellent discriminant validity. Test-retest reliability ranged from 0.57 to 0.91 for the seven domain scores, whereas internal-consistency reliability ranged from 0.74 to 0.95. Results of this research support the conclusion that the PFSF is a valid and reliable instrument for measurement of loss of sexual function in both naturally and surgically menopausal women with low libido.

Effect of Testosterone Replacement on Response to Sildenafil Citrate in Men With Erectile Dysfunction: A Parallel, Randomized Trial

BACKGROUND Erectile dysfunction and low testosterone levels frequently occur together. OBJECTIVE To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels. DESIGN Randomized, double-blind, parallel, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00512707) SETTING Outpatient academic research center. PARTICIPANTS Men aged 40 to 70 years with scores of 25 or less for the erectile function domain (EFD) of the International Index of Erectile Function, total testosterone levels less than 11.45 nmol/L (<330 ng/dL), or free testosterone levels less than 173.35 pmol/L (<50 pg/mL). INTERVENTION Sildenafil dose was optimized, and 140 participants were then randomly assigned to 14 weeks of daily transdermal gel that contained 10-g testosterone for 70 participants and placebo for the remaining 70 participants. All participants were included in the primary analysis, although 10 in the testosterone group and 12 in the placebo group did not complete the study. RESULTS At baseline, the 2 groups had similar EFD scores. Administration of sildenafil alone was associated with a substantial increase in EFD score (mean, 7.7 [95% CI, 6.5 to 8.8]), but change in EFD score after randomization did not differ between the groups (difference, 2.2 [CI, -0.8 to 5.1]; P = 0.150). The findings were similar for other domains of sexual function in younger men, more obese men, and men with lower baseline testosterone levels or an inadequate response to sildenafil alone. Frequency of adverse events was similar for testosterone and placebo groups. LIMITATION Whether testosterone could improve erectile function without sildenafil was not studied. CONCLUSION Sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with erectile dysfunction and low testosterone levels. PRIMARY FUNDING SOURCE National Institute of Child Health and Human Development.

Profile of Female Sexual Function: A patient-based, international, psychometric instrument for the assessment of hypoactive sexual desire in oophorectomized women

Objective:The purpose of this study was to develop a self-administered, patient-based questionnaire to assess loss of sexual desire and associated symptoms in postmenopausal women with hypoactive sexual desire disorder (HSDD) experiencing distress. Design:Preliminary items and domains of sexual function were identified through individual and focus group interviews with postmenopausal women in the United States and Europe. A subset of items was selected for translation and further analysis. Cognitive interviews were conducted with women with HSDD and non-HSDD women in eight countries to ensure items would have the same meaning in seven languages. The resulting instrument was tested in 325 oophorectomized women with HSDD and 255 age-matched nonoophorectomized control women in the United States, Canada, Europe, and Australia. Results:Psychometric item reduction analyses resulted in 37 items organized into seven domains characterizing female sexual function in postmenopausal women with HSDD. Excellent reliability and validity of the domains of the Profile of Female Sexual Function (PFSF) were observed in all geographic areas tested. Statistically significant differences between oophorectomized women with low libido and control women were found for all domains and all geographic areas. Conclusions:The PFSF is a new instrument specifically designed for measurement of sexual desire in oophorectomized women with low libido. Robust psychometric properties have been established in a large number of geographic regions and languages, making it useful for assessing therapeutic change in multinational clinical trials.

Development and validation of a new screening tool for hypoactive sexual desire disorder: The Brief Profile of Female Sexual Function© (B-PFSF©)

Aim. To develop a screening tool to allow a postmenopausal woman to determine whether to seek evaluation for hypoactive sexual desire disorder (HSDD). Methods. The Brief Profile of Female Sexual Function© (B-PFSF©) was developed using items from the Profile of Female Sexual Function© (PFSF©) and the Personal Distress Scale© (PDS©). Logistic regression analysis was used to select items best able to discriminate between women with HSDD (n = 743) and controls (n = 226) and a screening cut-off score was identified. Cross-validation analyses were conducted using PFSF and PDS responses from an independent group of 147 HSDD women and 104 controls. Forty cognitive interviews were additionally conducted to assess validity of the final tool. Results. A seven-item instrument was found to provide good discrimination between postmenopausal women with HSDD and controls and to be a reliable and valid tool. Ninety-six percent of women with HSDD and 97% of control women in the independent validation were classified correctly using the identified cut-off score. In the cognitive interviews, all women stated that the questionnaire was easy to complete and covered relevant aspects of sexual function. Conclusion. The Brief Profile of Female Sexual Function (B-PFSF) is psychometrically valid and appropriate for use as a self-administered screening tool.

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial

Aim: Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women. Methods: Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm. Results: Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), −11.1 versus −6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache. Conclusion: In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719).