Michael Sand

Sexual Desire and the Female Sexual Function Index (FSFI): A Sexual Desire Cutpoint for Clinical Interpretation of the FSFI in Women with and without Hypoactive Sexual Desire Disorder

INTRODUCTION A validated cutpoint for the total Female Sexual Function Index scale score exists to classify women with and without sexual dysfunction. However, there is no sexual desire (SD) domain-specific cutpoint for assessing the presence of diminished desire in women with or without a sexual desire problem. AIMS This article defines and validates a specific cutpoint on the SD domain for differentiating women with and without hypoactive sexual desire disorder (HSDD). METHODS Eight datasets (618 women) were included in the development dataset. Four independent datasets (892 women) were used in the validation portion of the study. MAIN OUTCOME MEASURES Diagnosis of HSDD was clinician-derived. Receiver-operator characteristic (ROC) curves were used to develop the cutpoint, which was confirmed in the validation dataset. RESULTS The use of a diagnostic cutpoint for classifying women with SD scores of 5 or less on the SD domain as having HSDD and those with SD scores of 6 or more as not having HSDD maximized diagnostic sensitivity and specificity. In the development sample, the sensitivity and specificity for predicting HSDD (with or without other conditions) were 75% and 84%, respectively, and the corresponding sensitivity and specificity in the validation sample were 92% and 89%, respectively. CONCLUSIONS These analyses support the diagnostic accuracy of the SD domain for use in future observational studies and clinical trials of HSDD.

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions—Part I

INTRODUCTION A nomenclature is defined as a classification system for assigning names or terms in a scientific discipline. A nosology more specifically provides a scientific classification system for diseases or disorders. Historically, the nosologic system informing female sexual dysfunction (FSD) has been the system developed by the American Psychiatric Association in its Diagnostic and Statistical Manual of Mental Disorders (DSM-III through DSM-5). Experts have recognized limitations of its use in clinical practice, including concerns that the DSM-5 system does not adequately reflect the spectrum and presentation of FSD. AIM To review the central considerations and issues that underlie the development of a new evidence-based nomenclature that reliably and validly defines the categories of FSD and will effectively function in clinical and research settings, serve as a basis for International Classification of Diseases (ICD) codes, and provide regulatory guidance for interventions designed as FSD treatments. METHODS The International Society for the Study of Womens Sexual Health conducted a 2-day conference on nomenclature for FSD in December 2013. Key opinion leaders representing diverse areas of expertise discussed ideal characteristics, existing DSM definitions, and current and future ICD coding to develop consensus for this new nomenclature. MAIN OUTCOME MEASURE A comprehensive appreciation of the parameters and characteristics essential to a new FSD nomenclature and terminology that will serve as the principal nosology for the description and diagnosis of FSD. RESULTS A critical appraisal of the essential elements of a classification system for diagnosing FSD was accomplished. The applicability of DSM-5 FSD definitions was challenged; and the considerations for developing a new nomenclature were discussed, including comorbidities, clinical thresholds, alternative etiologies, and validity. CONCLUSION The essential elements for developing a valid, reliable, credible, and clinically applicable nosology for FSD were enumerated as a preamble to constructing the actual nosologic system (Part II).

High-intensity Erotic Visual Stimuli De-activate the Primary Visual Cortex in Women

INTRODUCTION The primary visual cortex, Brodmanns area (BA 17), plays a vital role in basic survival mechanisms in humans. In most neuro-imaging studies in which the volunteers have to watch pictures or movies, the primary visual cortex is similarly activated independent of the content of the pictures or movies. However, in case the volunteers perform demanding non-visual tasks, the primary visual cortex becomes de-activated, although the amount of incoming visual sensory information is the same. AIM Do low- and high-intensity erotic movies, compared to neutral movies, produce similar de-activation of the primary visual cortex? METHODS Brain activation/de-activation was studied by Positron Emission Tomography scanning of the brains of 12 healthy heterosexual premenopausal women, aged 18-47, who watched neutral, low- and high-intensity erotic film segments. MAIN OUTCOME MEASURES We measured differences in regional cerebral blood flow (rCBF) in the primary visual cortex during watching neutral, low-intensity erotic, and high-intensity erotic film segments. RESULTS Watching high-intensity erotic, but not low-intensity erotic movies, compared to neutral movies resulted in strong de-activation of the primary (BA 17) and adjoining parts of the secondary visual cortex. CONCLUSIONS The strong de-activation during watching high-intensity erotic film might represent compensation for the increased blood supply in the brain regions involved in sexual arousal, also because high-intensity erotic movies do not require precise scanning of the visual field, because the impact is clear to the observer.

Correlates of PDE5i Use among Subjects with Erectile Dysfunction in Two Population‐Based Surveys

INTRODUCTION Erectile dysfunction (ED) is thought to affect some 150 million men worldwide, but many men with ED symptoms do not seek treatment. Existing surveys suggest that men with severe ED and who report support from their partners are more likely to receive treatment than were others. Less is known, however, concerning the influence of sociomedical factors such as income and body composition on receipt of treatment. AIM The aim of this study was to determine the importance of socioeconomic status, comorbidities, and body composition on receipt of treatment for ED symptoms. METHODS We used data on 638 men enrolled in the Boston Area Community Health (BACH) survey reporting ED symptoms and/or treatment for ED as evidenced by phosphodiesterase type 5 inhibitor (PDE5i) use. Logistic regression was employed to assess the relative strength of association between receipt of treatment and socioeconomic factors, body mass index, and medical factors. A replication of these results was then provided via a parallel model using the 2004 follow-up of the Mens Attitudes to Life Events and Sexuality (MALES). MAIN OUTCOME MEASURE In BACH, ED was deemed present if a subject scored 16 points or fewer on the five-item International Index of Erectile Function or reported PDE5i use. In MALES, presence of ED was indicated by use of a validated single question querying ED severity. RESULTS Controlling for age, body composition and other factors, increased household income, availability of a sexual partner, and provider diagnosis of high blood pressure were positively associated with treatment seeking via the use of PDE5i therapy in BACH. Results on data available in MALES produced similar results for household income and partner availability. CONCLUSION These data provide evidence that financial disadvantage may present a barrier to treatment of ED, an increasingly important sentinel marker of the cardiovascular and overall health among aging men.

Female Assessment of Male Erectile Dysfunction Detection Scale (FAME): Development and Validation

INTRODUCTION Although erectile dysfunction (ED) affects both members of the couple, no tools exist for the detection of ED by the female partner. AIM The aim of this study was to develop a scale for the detection of ED, as assessed by the female partner. METHODS Development and validation of the Female Assessment of Male Erectile dysfunction detection scale (FAME) consisted of five stages: (i) two focus group discussions conducted among female partners of ED sufferers; (ii) item construction; (iii) initial content validation to document face validity and reduce number of items; (iv) final selection of items and investigation of concurrent validity and reliability, sensitivity and specificity of the scale in 83 Spanish-speaking couples; and (v) multicenter study conducted in a group of 106 English-speaking couples. Concurrent validity was assessed using Spearmans rho correlation coefficients between FAME and clinical diagnosis, the Sexual Health Inventory for Men (SHIM), and the erectile function domain of the International Index of Erectile Function (IIEF-EF). Reliability was tested using Cronbachs alpha, and sensitivity and specificity was investigated using clinical diagnosis as the gold standard criterion. MAIN OUTCOME MEASURES Validity, reliability, specificity, and sensitivity of the FAME scale when correlated with SHIM, IIEF-EF, and clinical diagnosis. RESULTS Qualitative analysis yielded 44 clues; 21 items demonstrated statistical significance as the best discriminating items using a t-test for independent samples. A final scale of six items was tested for validity, reliability, specificity, and sensitivity. FAME correlated significantly with clinical diagnosis (0.791, P < 0.001), the SHIM (0.788, P < 0.001), and the IIEF-EF (0.777, P < 0.001). Additional support for discriminant validity was obtained with receiver operating characteristics analysis. Cronbachs alpha was 0.941. Sensitivity was 96.1% and specificity 86.0%. CONCLUSIONS Accurate detection of ED in men by the female partner is possible. In this study, FAME demonstrated concurrent validity and very good reliability, as well as excellent sensitivity and specificity.

Commentary on “Critical Flaws in the FSFI and IIEF”

This invited commentary responds to recent criticisms of two validated and widely used sexual function questionnaires, the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF) (Forbes, Baillie, & Schniering, 2014). We take issue with the conceptual arguments presented, selective review of published literature on both instruments, and conclusions drawn from methodologically flawed findings from an Internet-based study in a nonrepresentative group of Australian men and women. Alternative perspectives on the IIEF and FSFI are presented.

A phase I, randomized, proof-of-clinical-mechanism study assessing the pharmacokinetics and pharmacodynamics of the oral PDE9A inhibitor BI 409306 in healthy male volunteers

Cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE) inhibitors are hypothesized to improve cognition in schizophrenia and Alzheimer disease by increasing cGMP levels in certain brain regions. This phase I, randomized, parallel‐group, double‐blind, placebo‐controlled study provides proof‐of‐mechanism evidence for BI 409306, a novel, oral PDE9A inhibitor.

Evaluation of the Sexual Desire Relationship Distress Scale (SDRDS) in Women with Hypoactive Sexual Desire Disorder

INTRODUCTION The Sexual Desire Relationship Distress Scale (SDRDS) was developed to address the need for a patient-reported outcome (PRO) measure of sexual distress associated with hypoactive sexual desire disorder (HSDD). The SDRDS is a 17-item PRO that includes items related to personal distress and distress related to relationship with partner. AIM The aim of this article was to evaluate the psychometric properties of the SDRDS among women with HSDD. METHODS Pre- and post-menopausal women with HSDD or with no sexual dysfunction completed the SDRDS, Sexual Activity Questions, Female Sexual Distress Scale-Revised (FSDS-R), and desire domain of the Female Sexual Function Index (FSFI) at baseline and 2 and 4 weeks later. MAIN OUTCOME MEASURES The main outcome measures of this article were item performance, internal consistency, test-retest reliability, construct validity, known groups validity, and responsiveness of the SDRDS. RESULTS Data from 260 women were analyzed: 101 in each of the pre- and post-menopausal HSDD groups and 29 in each of the pre- and post-menopausal control groups. No differences emerged between pre- and post-menopausal women. Least-squares mean (±standard errors [SE]) SDRDS score was higher in women with HSDD than in women with no sexual dysfunction (43.1 ± 0.9 vs. 6.1 ± 1.7; P < 0.0001), supporting known groups validity. Individual item scores correlated with total scores (r = 0.7-0.9; P < 0.0001). Internal consistency was high, with a Cronbachs alpha of 0.973 at baseline. Test-retest reliability was good, with an intraclass correlation coefficient of 0.89. SDRDS scores correlated strongly with other measures of sexual distress and sexual function including the FSDS-R and FSFI desire domain items. Preliminary analyses suggested that the SDRDS was sensitive to changes in clinical status. CONCLUSIONS The SDRDS provides a comprehensive and reliable assessment of distress due to decreased sexual desire in women with HSDD and may be a useful measure of treatment effects in clinical trials in women with this condition.

First‐in‐human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males

Aims The aim of the present study was to investigate the safety, tolerability, dose proportionality and relative bioavailability of tablet and oral solution formulations of BI 409306 in healthy male subjects, and to compare the safety and pharmacokinetics in subjects who were extensive metabolizers (EMs) or poor metabolizers (PMs) of cytochrome P450 (CYP)‐2C19. Methods The present randomized, double‐blind, placebo‐controlled, single‐centre study evaluated single rising doses of BI 409306 (0.5–500 mg) administered as a tablet or oral solution to EMs or PMs. Results Of 80 enrolled subjects (mean age 36.7 years), 79 (CYP2C19 EMs, 71; CYP2C19 PMs, eight) received treatment and completed the study. Adverse events (AEs) were mild to moderate in intensity. Overall, 17/71 (23.9%) EMs and 6/8 (75.0%) PMs experienced 28 and eight AEs, respectively, of which, 25 and seven AEs, respectively, were considered to be drug related. The most frequently reported AEs were nervous system and eye disorders; all occurred shortly (20–30 min) after administration and mostly resolved within 1–2 h. No serious AEs occurred. BI 409306 systemic absorption and elimination were rapid; peak plasma concentration (Cmax) was reached <1 h after drug administration, and the half‐life ranged from 0.99 h to 2.71 h. Both the tablet and oral solution resulted in similar exposures. In PMs, at dose levels of 10 mg and 100 mg, Cmax was 2.2–2.3‐fold higher, and the area under the plasma concentration–time curve over the time interval 0 extrapolated to infinity was 4.1–5.0‐fold higher compared with EMs. Conclusions In healthy male subjects, BI 409306 was generally safe and well tolerated, with rapid absorption and elimination. Systemic exposure was higher in CYP2C19 PMs than EMs at the same dose level.

Controversies in Sexual Medicine: Clinical and Basic Science Research in Sexual Medicine Must Rely, in Part, on Pharmaceutical Funding?

INTRODUCTION The conflict of interest in sexual medicine (SM) is a never-ending debate between scientists who consider possible and fruitful the partnership between science and the pharmaceutical industry (pharma) and others who are afraid that such a relationship might contaminate the veracity of scientific research. The aim of this Controversy is to appreciate opinions from both perspectives. METHODS Four scientists (three from academic or private practice and one employee of the industry) with expertise in the area of SM were asked to contribute with their opinions. MAIN OUTCOME MEASURE Expert opinion supported by the critical review of the currently available literature. RESULT Expert #1, who is Controversys section editor, and Expert #3 consider industry involvement in the field of SM problematic but potentially synergistic with the aim of science. On the other side, the Experts #2 and 4 argue that it is almost impossible to serve two masters. They believe that the pharma involved both in basic and applied research may jeopardize the independent evolution of the young SM. CONCLUSIONS After reading this Controversy, The Journal of Sexual Medicines readers should be able to judge by themselves the claims of the discussants and if the partnership between industry and SM is a risk or a potential benefit.