Michael L. Krychman

For many, sleep and sex are crucial for physical, emotional, and mental well-being. Poor sleep quality is linked to a myriad of ailments from coronary artery disease to major depressive disorder. Likewise, a decrease in the frequency of sexual activity is associated with a decrease in self-rated health status. Kleine-Levin syndrome (KLS) is a rare sleep disorder that provides a unique lens to examine the intricate interplay between sleep and sex as it is one of the few sleep disorders defined by concomitant sexual dysfunction. This study reviews the literature on links between sleep disorders and sexuality with a focus on women's health followed by a case study of unusual patient with KLS with persistent genital arousal disorder. Literature searches were conducted for English language publications, including foreign language publications with English abstracts with ninety-five articles reviewed. The literature review is followed by a case report. We review the known literature linking sleep and women's sexual health with a focus on insomnia, circadian rhythm sleep disorder, obstructive sleep apnea, restless leg syndrome, sexsomnia, and KLS. We then present a case of KLS-associated persistent genital arousal disorder, which was amenable to treatment with a multimodal approach aimed at symptomatic relief with intravaginal diazepam suppositories, topical clitoral lidocaine, and duloxetine. This case highlights that hypersexuality and persistent arousal cannot effectively be treated in isolation but rather must be contextualized within a patient's broader medical history and diagnoses. Specifically, sleep quality and potential sleep disorders should be assessed for those presenting with sexual health complaints (and vice versa). Zwerling B, Keymeulen S, Krychman ML. Sleep and Sex: A Review of the Interrelationship of Sleep and Sexuality Disorders in the Female Population, Through the Lens of Sleeping Beauty Syndrome. Sex Med Rev 2020;XX:XXX-XXX.

Vaginal dilators are often prescribed to facilitate an adaptive brain-body connection to decrease anxiety and pain that can be experienced in anticipation of sexual intercourse among populations of women with sexual pain syndromes. Postmenopausal women, cancer survivors, and women with a wide variety of pelvic floor disorders who experience genito-pelvic pain/penetration disorder (GPPPD) are often advised to incorporate vaginal dilators into their pelvic floor rehabilitation program and treatment regimens to enable penetrative intercourse with less pain. However, little is known about the behaviors of dilator users, what treatment protocols are most effective, how patients are currently using their dilators, and how effective are clinicians in helping their patients achieve success with their dilation therapy. A recent PubMed literature search was performed using the key words vaginal dilator, vaginal dilator therapy, sexual quality of life, vaginal stenosis, vaginal dilation, vaginismus. A total of 29 English articles were reviewed and summarized. Articles were excluded for the following reasons: not in English and unrelated to dilator therapy. This article will summarize the current research on vaginal dilators and discuss needs for future research to maximize patients' compliance and success with this treatment. Much of the summary data regarding user behavior will come from the early survey data with Milli, a novel, patient-controlled electronic dilator that slowly expands 1 mm at a time from its smallest diameter, 15 mm to a maximum diameter of 40 mm. Milli is currently being used by more than 1,000 women, and 3-month follow-up data were recorded on 335 of those patients. Dilators exist in multiple forms (plastic, latex, and medical grade material), may come individually or in sets, and many have special features such as vibration or the ability to be heated or cooled before use. Little is known about patients' use of dilators and the Milli's 3-month survey serves as an insight to patient dilator behavior. The most common medical goals for patients undergoing dilation treatment were return to penetrative intercourse and pain reduction during coitus. Patients were dilated on average 2.72 days/week; 56.8% of patients had suffered from sexual pain for 2 or more years and 36.3% had previously used static dilators. More than 70% of Milli users purchased Milli and are using Milli without the direct guidance of a clinician. The most common emotions patients used to describe their treatment were not only "anxious," "frustrated," but also "empowered" and "optimistic." The most common dilatory session duration was 6-10 minutes, mostly in the evening/bedtime (68.3%), located in the bedroom (96.8%). Adjunctive treatment included the following: vaginal moisturizers, local estrogen products, coital lubricants, and genital pelvic floor physical therapy. During the dilation sessions, women most often watched TV/videos, practiced mindfulness, or listened to soothing music. Factors that showed trends toward improved patient outcomes were length of dilation treatment (greater than 3 months) and use of meditation and soothing music. Factors not associated with improvement trends were as follows: when/where patients dilated and patient demographics including age, race, or religious preferences. Patients who purchase dilators have often suffered with their condition for a long time and had difficulty finding a competent health-care clinician well versed in sexual pain syndromes that can help them. When patients did find a clinician, there were no clinically proven standardized protocols or formalized guidelines to give to patients about how to best use their dilators. Larger long-term interventions investigating a standardized dilation protocol are planned in future studies to better elucidate the effective and optimal dilation treatment plans. Liu M, Juravic M, Mazza G, et al. Vaginal Dilators: Issues and Answers. Sex Med Rev 2020;XX:XXX-XXX.

Objective: This subanalysis of the VIVEVE I trial aimed to evaluate the impact of cryogen-cooled monopolar radiofrequency (CMRF) therapy, for the treatment of vaginal laxity, on the domains of sexual function included in the Female Sexual Function Index (FSFI). Materials and Methods: The VIVEVE I clinical trial was prospective, randomized, single-blind, and Sham-controlled. Nine clinical study centers in Canada, Italy, Spain, and Japan were included. This subanalysis included premenopausal women with self-reported vaginal laxity who had ≥1 term vaginal delivery and a baseline FSFI total score ≤26.5, indicating sexual dysfunction. Enrolled subjects were randomized (2:1) to receive CMRF therapy [Active (90 J/cm ² ) vs. Sham (≤1 J/cm ² )] delivered to the vaginal tissue. Independent analyses were conducted for each FSFI domain to evaluate both the mean change, as well as the clinically important change for Active- versus Sham-treated subjects at 6 months post-intervention. Results: Subjects randomized to Active treatment ( n = 73) had greater improvement than Sham subjects ( n = 35) on all FSFI domains of sexual function at 6 months postintervention. The analysis of covariance change from baseline analyses showed statistically significant improvements, in favor of Active treatment, for sexual arousal ( p = 0.004), lubrication ( p = 0.04), and orgasm ( p = 0.007). In addition, Active treatment was associated with clinically important and statistically significant improvements in sexual desire [Odds ratio (OR) = 3.01 (1.11–8.17)], arousal [OR = 2.73 (1.06–7.04)], and orgasm [OR = 2.58 (1.08–6.18)]. Conclusions: This subanalysis showed CMRF therapy is associated with statistically significant and clinically important improvements in sexual function in women with vaginal laxity. These findings provide the first randomized, placebo-controlled energy-based device evidence for functional improvements associated with a nonsurgical modality for a highly prevalent and undertreated condition.

Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. The Female Sexual Function Index (FSFI) is a validated self-report questionnaire comprising 6 domains of sexual functioning: desire, arousal, lubrication, orgasm, satisfaction, and pain. This post hoc analysis evaluated the effect of flibanserin treatment across the 6 FSFI domains. Patient-level data were pooled from three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg once daily (qhs) in premenopausal women with HSDD. Between group differences in change from baseline to week 24 (last observation carried forward [LOCF]) on FSFI domain and total scores were evaluated using analysis of covariance. This analysis included 2368 women (flibanserin, n=1165; placebo, n=1204) who had at least one on-treatment efficacy assessment. The least-squares mean differences (standard error of the mean) in change scores from baseline to week 24 (LOCF) for flibanserin versus placebo were 0.3 (0.1) for the FSFI desire domain, 0.4 (0.1) for the arousal domain, 0.3 (0.1) for the lubrication domain, 0.3 (0.1) for the orgasm domain, 0.3 (0.1) for the satisfaction domain, 0.2 (0.1) for the pain domain, and 1.9 (0.3) for the total score; all P less than 0.0001 except P less than 0.01 for pain. Treatment with flibanserin produced significant improvement not only in the FSFI desire domain (a key outcome in clinical trials of HSDD) but also across the other domains of sexual function assessed by the FSFI.

Introduction: Postmenopausal women's knowledge about vulvar and vaginal atrophy (VVA) and available treatment options has historically been inadequate. Recent direct-to-consumer marketing and educational efforts would have been expected to increase awareness and treatment options. Aim: To compare results of the Women's EMPOWER survey with other available VVA surveys to assess progress in women's understanding and approaches to treatment of VVA. Methods: The Women's EMPOWER survey, an internet-based survey of US women with VVA symptoms, assessed women's awareness of VVA and their behaviors and attitudes associated with symptom treatment. Main Outcome Measures: These survey results were compared with previously published results of the Revealing Vaginal Effects at Mid-Life (REVEAL), Women's Voices in Menopause (WVM), Vaginal Health: Insight, Views, & Attitudes (VIVA), Clarifying Vaginal Atrophy's Impact on Sex and Relationship (CLOSER), and Real Women's Views of Treatment Options for Menopausal Vaginal Changes (REVIVE) surveys. Results: Results of the Women's EMPOWER survey were consistent with those of past VVA surveys and showed that postmenopausal women generally failed to recognize VVA and its chronic, progressive process and that they were reluctant to discuss vaginal or sexual symptoms with their health care professionals (HCPs). However, women indicated a strong desire for accurate medical information about VVA from their health care professionals and a willingness to learn if HCPs would initiate the conversation. Most women believed that vaginal symptoms are a normal part of aging and they just need to cope with the symptoms. In the United States, women were most concerned with safety-related issues, including increased risk of breast cancer, side effects, and systemic absorption. Conclusion: The Women's EMPOWER survey demonstrates and reinforces that even with multimedia marketing and educational strategies in the years after other major VVA surveys, minimal progress has been made toward increasing women's awareness of, knowledge about, or understanding of VVA. Based on these data, a focus on initiating discussions and education with postmenopausal women so that they better comprehend VVA as a chronic progressive medical condition (not just aging), the symptoms associated with VVA, and the benefit-risk profile regarding treatment options is warranted.

Introduction: Vaginal laxity is a highly prevalent and undertreated medical condition. Aim: To evaluate the efficacy and safety of surface-cooled, monopolar radiofrequency (RFc) therapy for the treatment of vaginal laxity in the VIVEVE I trial. Methods: The VIVEVE I trial was a prospective, randomized, single-blinded, and sham-controlled study. Nine study centers in Canada, Italy, Spain, and Japan participated. Women presenting with vaginal laxity were screened and informed consent was obtained. Major study inclusion criteria were premenopausal status, age at least 18 years, at least one full-term vaginal delivery, and normal genito-pelvic examination results. Enrolled subjects were randomized (2:1) to receive RFc therapy (Active [90 J/cm2] vs Sham [1 J/cm2], respectively) delivered to the vaginal tissue. Main Outcome Measures: The primary efficacy outcome was the proportion of randomized subjects reporting “no vaginal laxity” (Active vs Sham) at 6 months postintervention, which was assessed using the Vaginal Laxity Questionnaire. Treatment-emergent adverse events were evaluated in all treated subjects. Secondary efficacy end points included change on the Female Sexual Function Index (FSFI) and the revised Female Sexual Distress Scale (FSDS-R). Results: No vaginal laxity was achieved by 43.5% and 19.6% (P = .002) in the Active and Sham groups, respectively. Differences in FSFI and FSDS-R total scores (Active vs Sham) were 1.8 (P = .031) and −2.42 (P = .056), respectively, in favor of Active treatment. Treatment-emergent adverse events were reported by 11.1% and 12.3% of subjects in the Active and Sham arms, respectively. Conclusion: The VIVEVE I trial is the first randomized, controlled, blinded, clinical study of RFc for the treatment of vaginal laxity. A single treatment of RFc therapy was found to be safe and associated with both improved vaginal laxity and improved sexual function. The results from this trial support the use of a novel non-surgical therapy for vaginal laxity, a prevalent and undertreated condition.