Structural brain differences related to compulsive sexual behavior disorder.

Background and aims: Compulsive sexual behavior disorder (CSBD) has been included as an impulse control disorder in the International Classification of Diseases (ICD-11). However, the neurobiological mechanisms underlying CSBD remain largely unknown, and given previous indications of addiction-like mechanisms at play, the aim of the present study was to investigate if CSBD is associated with structural brain differences in regions involved in reward processing. Methods: We analyzed structural MRI data of 22 male CSBD patients (mean = 38.7 years, SD = 11.7) and 20 matched healthy controls (HC; mean = 37.6 years, SD = 8.5). Main outcome measures were regional cortical thickness and surface area. We also tested for case-control differences in subcortical structures and the effects of demographic and clinical variables, such as CSBD symptom severity, on neuroimaging outcomes. Moreover, we explored case-control differences in regions outside our hypothesis including white matter. Results: CSBD patients had significantly lower cortical surface area in right posterior cingulate cortex than HC. We found negative correlations between right posterior cingulate area and CSBD symptoms scores. There were no group differences in subcortical volume. Conclusions: Our findings suggest that CSBD is associated with structural brain differences, which contributes to a better understanding of CSBD and encourages further clarifications of the neurobiological mechanisms underlying the disorder.

Effects of internet-delivered cognitive behavioral therapy on use of child sexual abuse material: A randomized placebo-controlled trial on the Darknet.

Introduction: The use of child sexual abuse material (CSAM) is an international public health and child protection challenge. Objective: To investigate whether Prevent It, a therapist-supported, internet-delivered, eight-week, cognitive behavioral therapy, reduces CSAM viewing among users. Methods: We conducted a global online single-blind (participants), parallel-group, superiority, randomized, psychological placebo-controlled trial with a one-month follow-up, 2019-2021 (ISRCTN76841676). We recruited anonymous participants, mainly from Darknet forums. Inclusion criteria: age 18+ years, past week CSAM use, and sufficient English language skills; exclusion criteria: severe psychiatric illness or non-serious intent to participate. The main outcome was change in self-reported, weekly viewing time from pre- to post-treatment, according to the Sexual Child Molestation Risk Assessment+. Results: A total of 160 participants (157 male, 2 non-binary, and 1 not reporting gender) from all world regions (age intervals [%]: 18-29 [49]; 30-39 [30]; 40-49 [15]; 50-59 [6]) were randomized (1:1) to Prevent It (N = 80) or Placebo (N = 80). Between-group, intention-to-treat analyses suggested a significantly larger decrease in viewing time in Prevent It participants vs. controls pre- to post-treatment (Prevent It: N = 76, Placebo: N = 78, estimate -0.25, 95 % CI, -0.46 to -0.04, p = .017, Cohen's d 0.18). Negative side effects from treatment were fewer in Prevent It compared to control participants and neither group reported severe adverse events. Conclusion: We provide initial support for the feasibility, efficacy, and safety of Prevent It to reduce CSAM viewing among motivated users. Further research is needed to validate these findings.

Neural and behavioral correlates of sexual stimuli anticipation point to addiction-like mechanisms in compulsive sexual behavior disorder.

Background and aims: Compulsive sexual behavior disorder (CSBD) is characterized by persistent patterns of failure to control sexual impulses resulting in repetitive sexual behavior, pursued despite adverse consequences. Despite previous indications of addiction-like mechanisms and the recent impulse-control disorder classification in the International Classification of Diseases (ICD-11), the neurobiological processes underlying CSBD are unknown. Methods: We designed and applied a behavioral paradigm aimed at disentangling processes related to anticipation and viewing of erotic stimuli. In 22 male CSBD patients (age: M = 38.7, SD = 11.7) and 20 healthy male controls (HC, age: M = 37.6, SD = 8.5), we measured behavioral responses and neural activity during functional magnetic resonance imaging (fMRI). The main outcomes were response time differences between erotic and non-erotic trials and ventral striatum (VS) activity during anticipation of visual stimuli. We related these outcomes with each other, to CSBD diagnosis, and symptom severity. Results: We found robust case-control differences on behavioral level, where CSBD patients showed larger response time differences between erotic and non-erotic trials than HC. The task induced reliable main activations within each group. While we did not observe significant group differences in VS activity, VS activity during anticipation correlated with response time differences and self-ratings for anticipation of erotic stimuli. Discussion and Conclusions: Our results support the validity and applicability of the developed task and suggest that CSBD is associated with altered behavioral correlates of anticipation, which were associated with ventral striatum activity during anticipation of erotic stimuli. This supports the idea that addiction-like mechanisms play a role in CSBD.

HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder.

BACKGROUND: Hypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration. METHODS: This study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage. GENETICS: ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups. RESULTS: Quality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge - the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05). CONCLUSION: EA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.

High Plasma Oxytocin Levels in Men With Hypersexual Disorder.

CONTEXT: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior. OBJECTIVE: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol. DESIGN: Longitudinal. SETTING: ANOVA clinic (Karolinska University Hospital). PATIENTS OR OTHER PARTICIPANTS: 64 males with HD and 38 age-matched healthy volunteers. MAIN OUTCOME MEASURES: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms. INTERVENTIONS: A patient subgroup (n = 30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured. RESULTS: Hypersexual men (n = 64) exhibited significantly higher oxytocin plasma levels (mean ±â€…SD: 31.0 ±â€…9.9 pM) compared with healthy volunteers (16.9 ±â€…3.9 pM; P < 0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n = 30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5 ±â€…10.1 pM) to posttreatment (20.2 ±â€…8.0 pM; P < 0.001). CONCLUSIONS: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.

A randomised controlled trial of fluoxetine versus naltrexone in compulsive sexual behaviour disorder: presentation of the study protocol.

BACKGROUND: Compulsive sexual behaviour disorder is a new disorder in the International Classification of Diseases (ICD-11), and is associated with negative consequences in different areas of life. Evidence for pharmacological treatment of compulsive sexual behaviour disorder is weak and treatment options are limited. This proposed study will be the largest and the first randomised controlled trial comparing the efficacy and tolerability of two active drugs in compulsive sexual behaviour disorder. METHODS AND ANALYSIS: Eighty adult participants with compulsive sexual behaviour disorder according to ICD-11 will be randomised to receive either naltrexone 25-50 mg or fluoxetine 20-40 mg for 8 weeks, followed by 6 weeks without treatment. The study will be conducted in a subspecialised outpatient sexual medicine unit at Karolinska University Hospital, Stockholm, Sweden. The study is financed by grants and entirely independent of the manufacturers.Exclusion criteria include severe psychiatric or psychical illness, changes to concurrent medication and non-compatible factors contraindicating the use of either drug. The primary outcome measure is the Hypersexual Disorder: Current Assessment Scale (HD: CAS), and tolerability will be assessed by the Udvalg for Kliniske Undersogelser side effect rating scale (UKU), drug accountability, adherence to treatment and drop-out rate. Participants will complete questionnaires at regular intervals, with the main endpoint for efficacy after 8 weeks (end of treatment) and after 14 weeks (follow-up). Blood chemistry will be repeatedly collected as a safety precaution and for research purposes. The results will be analysed using an appropriate analysis of variance model or a mixed model, depending on the distribution of HD: CAS and the extent of missing data. ETHICS AND DISSEMINATION: The Swedish Ethical Review Authority and the Swedish Medical Products Agency have approved the study on 27 May 2020 and 4 June 2020, respectively (ref. no. 2020-02069 and ref. no. 5.1-2020-48282). Findings will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: 2019-004255-36.

HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes.

DNA methylation shifts in Hypothalamic-pituitary-adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

Frequency of Pornography Use and Sexual Health Outcomes in Sweden: Analysis of a National Probability Survey.

BACKGROUND: Little is known about pornography use and its relationship with sexual health outcomes in the general population. AIM: To assess frequency of pornography use and the association of sexual health outcomes with frequent pornography use in Sweden. METHODS: Cross-sectional analysis of 14,135 participants (6,169 men and 7,966 women) aged 16-84 years in a Swedish nationally representative survey from 2017. We used logistic regression to assess the association of sexual health outcomes with use of pornography ≥3 times/wk. OUTCOMES: Frequency of pornography use (never; less than once/mo to 3 times/mo; 1-2 times/wk; 3-5 times/wk; and daily or almost daily) and sexual health outcomes (eg, sexual satisfaction and sexual health problems). RESULTS: In total, 68.7% of men and 27.0% of women used pornography. Among men aged 16-24 years, 17.2% used pornography daily or almost daily, 24.7% used pornography 3-5 d/wk and 23.7% used pornography 1-2 d/wk. Among women aged 16-24 years, the proportions were 1.2% for daily or almost daily, 3.1% for 3-5 times/wk, and 8.6% for 1-2 times/wk. Frequency of pornography use decreased with age among both men and women. While 22.6% of all men and 15.4% of all women reported that their or a sex partner's pornography use predominantly had positive effects on their sex life, 4.7% of men and 4.0% of women reported that the effects were predominantly negative. Variables indicating sexual dissatisfaction and sexual health problems were associated with use of pornography ≥3 times/wk: for example, dissatisfaction with sex life (age-adjusted odds ratio [aOR]: men 2.90 [95% CI 2.40-3.51]; women 1.85 [95% CI 1.09-3.16]), not having sex in the preferred way (aOR: men 2.48 [95% CI 1.92-3.20]; women 3.59 [95% CI 2.00-6.42]) and erection problems (aOR: men 2.18 [95% CI 1.73-2.76]). CLINICAL IMPLICATIONS: While frequent pornography use is common, potential effects on sexual health outcomes are likely to differ between individuals. STRENGTH & LIMITATIONS: We used a large and recent nationally representative survey with detailed information regarding frequency of pornography use. The temporality of associations of sexual health variables with frequency of pornography use could not be assessed. CONCLUSION: In this analysis of a nationally representative survey in Sweden, we found that frequent pornography use was common among young men; that reporting predominantly positive effects of pornography use on the sex life was more common than reporting predominantly negative effects; and that sexual dissatisfaction and sexual health problems were associated with using pornography ≥3 times/wk. Malki K, Rahm C, Öberg KG, et al. Frequency of Pornography Use and Sexual Health Outcomes in Sweden: Analysis of a National Probability Survey. J Sex Med 2021;18:1735-1751.

Impulsivity in Compulsive Sexual Behavior Disorder and Pedophilic Disorder.

BACKGROUND AND AIMS: Impulsivity is regarded as a risk factor for sexual crime reoffending, and a suggested core feature in Compulsive Sexual Behavior Disorder. The aim of this study was to explore clinical (e.g. neurodevelopmental disorders), behavioral and neurocognitive dimensions of impulsivity in disorders of problematic sexuality, and the possible correlation between sexual compulsivity and impulsivity. METHODS: Men with Compulsive Sexual Behavior Disorder (n = 20), and Pedophilic Disorder (n = 55), enrolled in two separate drug trials in a specialized Swedish sexual medicine outpatient clinic, as well as healthy male controls (n = 57) were assessed with the Hypersexual Behavior Inventory (HBI) for sexual compulsivity, and with the Barratt Impulsiveness Scale (BIS) and Connors' Continuous Performance Test-II (CPT-II) for impulsivity. Psychiatric comorbidity information was extracted from interviews and patient case files. RESULTS: Approximately a quarter of the clinical groups had Attention-Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder. Both clinical groups reported more compulsive sexuality (r = 0.73-0.75) and attentional impulsivity (r = 0.36-0.38) than controls (P < 0.05). Based on results on univariate correlation analysis, BIS attentional score, ADHD, and Commissions T-score from CPT-II were entered in a multiple linear regression model, which accounted for 15% of the variance in HBI score (P < 0.0001). BIS attentional score was the only independent positive predictor of HBI (P = 0.001). DISCUSSION: Self-rated attentional impulsivity is an important associated factor of compulsive sexuality, even after controlling for ADHD. Psychiatric comorbidity and compulsive sexuality are common in Pedophilic Disorder. CONCLUSION: Neurodevelopmental disorders and attentional impulsivity - including suitable interventions - should be further investigated in both disorders.

Reaching Men and Women at Risk of Committing Sexual Offences - Findings From the National Swedish Telephone Helpline PrevenTell.

BACKGROUND: In 2012 the Swedish Helpline project PrevenTell, targeting men and women with self-identified out-of-control and paraphilic sexual behavior, was launched by ANOVA, Karolinska University Hospital. The overall purpose was to reach the target group and via a telephone-contact encourage further on-site assessment and treatment. AIM: To describe men and women contacting PrevenTell during the first 7 years by delineate sexuality-related risk-factors for sexual violence, gender differences, and age- and gender-preferences when reporting a pedophilic interest. METHOD: A 52-item semi-structured telephone interview was conducted by experts in sexual medicine with individuals who contacted the helpline. The interview covered sociodemographic characteristics, problematic sexual behavior(s), and mental health and based on the information reported, interventions included recommending an appointment at ANOVA, supporting other appropriate healthcare, or motivation of individuals still ambivalent to treatment. RESULTS: Data collection took place between March 2012 and October 2019. A total of 1573 respondents in the main target group (1454 men and 119 women) gave informed consent for participation. Compulsive sexual behavior was reported by 69% of respondents and 56% described at least one paraphilic interest. The prevalence of concomitant compulsive sexual behavior and a paraphilic interest was high, varying between 65% and 83%. Significant gender differences were found in socioeconomic and mental health variables, in which women showed fewer positive and stable life factors compared to men. A sexual preference for minors was reported by 24% of respondents. In this group, 63% reported use of child sexual exploitation material and 15% committed child sexual abuse. Respondents were offered anonymity, however 55% disclosed their identity and were enrolled for further assessment and treatment at ANOVA. CLINICAL IMPLICATIONS: The result of this study is of substantial relevance when developing secondary preventive initiatives targeting sexual violence in the community. STRENGTHS AND LIMITATIONS: This is the first study to present data from a national helpline targeting both men and women with a wide range of self-identified problematic sexual behaviors. Limitations include the lack of diagnostic confirmation on-site, hence, presented data provides only an indication of clinical conditions. Furthermore, the main objective of the interview was to motivate participants to seek further treatment, sometimes necessary to prioritize this over adherence to the semi-structured questionnaire, explaining the relatively high absence rate in some variables. CONCLUSION: Men and women at risk of committing sexual crimes can be reached through a national helpline service and motivated to undergo further assessment and treatment. Adebahr R, Söderström EZ, Arver S, et al. Reaching Men and Women at Risk of Committing Sexual Offences - Findings From the National Swedish Telephone Helpline PrevenTell. J Sex Med 2021;18:1571-1581.

Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men: A Pilot Study.

BACKGROUND: Hypersexual disorder (HD) is a condition in which the individual experiences loss of control over engagement in sexual behaviors, leading to negative effects on various areas of life. Paraphilias often present concomitantly with HD, and although cognitive behavioral therapy (CBT) has been proven to reduce engagement in hypersexual behavior, no studies have investigated the effects of Internet-administered CBT (ICBT) on HD, with or without paraphilia(s) or paraphilic disorder(s). AIM: To investigate the effects of Internet-administered CBT on HD, with or without paraphilia(s) or paraphilic disorder(s). METHODS: Male participants (n = 36) evaluated positive according to the proposed diagnostic HD criteria, with or without paraphilia(s) or paraphilic disorder(s), received 12 weeks of ICBT. Measures were administered weekly over the treatment period, with an additional follow-up measurement 3 months after completion of treatment. An assessment interview was performed 2 weeks after treatment. OUTCOMES: The primary outcome was the Hypersexual Behavior Inventory (HBI-19), and secondary outcomes were the Hypersexual Disorder: Current Assessment Scale (HD:CAS), the Sexual Compulsivity Scale (SCS), as well as a tentative composite of 6 Severity Self-rating Measures, for Paraphilic Disorders and depression (Montgomery-Åsberg Depression Rating Scale [MADRS-S]), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure [CORE-OM]), and treatment satisfaction (CSQ-8). RESULTS: Large, significant decreases in HD symptoms and sexual compulsivity were found, as well as moderate improvements in psychiatric well-being and paraphilic symptoms. These effects remained stable 3 months after treatment. CLINICAL IMPLICATIONS: ICBT can ameliorate HD symptoms, psychiatric distress, and paraphilic symptoms, which suggests that the ICBT for HD, with or without paraphilia(s) or paraphilic disorder(s), may constitute a valuable addition of treatment options in clinical settings. STRENGTHS AND LIMITATIONS: This is the first study evaluating the efficacy of ICBT on a sample of men suffering from HD. In addition, a proportion of the sample reported concomitant paraphilic interests and disorders, thus mirroring an everyday clinical practice in the field of sexual medicine. No control group was assigned, and some of the outcome measures are still to be validated. The long-term effects of ICBT and its efficacy in hypersexual women are unknown. CONCLUSIONS: This study gives support for ICBT as an effective treatment option for HD. Future evaluations of the treatment program should include women and larger samples in randomized controlled procedures and investigate the long-term effects. Hallberg J, Kaldo V, Arver S, et al. Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men: A Pilot Study. J Sex Med 2020;17:2039-2054.

Naltrexone in Compulsive Sexual Behavior Disorder: A Feasibility Study of Twenty Men.

BACKGROUND: Compulsive sexual behavior disorder (CSBD) is a common disorder affecting different areas of life, although studies focusing on pharmacological treatment are sparse. AIM: To investigate whether the opioid receptor antagonist naltrexone is feasible and tolerable and can provide symptom reduction in CSBD. METHODS: Twenty men aged 27-60 years (mean = 38.8 years, standard deviation = 10.3) with CSBD seeking treatment in an outpatient nonforensic clinic received four weeks of naltrexone 25-50 mg. Measurements were made before, during, and four weeks after treatment. OUTCOMES: The self-assessment Hypersexual Disorder: Current Assessment Scale (HD: CAS) score was the primary outcome measure, and secondary outcomes were the Hypersexual Behavior Inventory (HBI) score, reported adverse effects, adherence to treatment, and dropouts. RESULTS: There was significant decrease on both HD: CAS and HBI scores during treatment with naltrexone. Even though some of the effects remained after treatment, the increased scores on HD: CAS indicated worsening of CSBD symptoms. The most reported side effects were fatigue (55%), nausea (30%), vertigo (30%), and abdominal pain (30%). However, there were no serious adverse effects leading to discontinuation of naltrexone. CLINICAL IMPLICATIONS: Despite side effects being common, naltrexone seems to be feasible in the treatment of CSBD. STRENGTHS & LIMITATIONS: Being the first nonforensic prospective trial on naltrexone in CSBD, this study provides novel insights on a pharmacological intervention. However, owing to the small sample size and the lack of a control group, conclusions of effectiveness should be interpreted with caution. CONCLUSION: Naltrexone is feasible and tolerable and may reduce symptoms of CSBD; nevertheless, future studies should ensure a randomized controlled procedure to evaluate possible effectiveness. Savard J, Öberg KG, Chatzittofis A, et al. Naltrexone in Compulsive Sexual Behavior Disorder: A Feasibility Study of Twenty Men. J Sex Med 2020;17:1544-1552.

Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder.

INTRODUCTION: Hypersexual disorder as suggested to be included in the Diagnostic and Statistical Manual of Mental Disorders-5 integrates aspects of sexual desire deregulation, impulsivity, and compulsivity. However, it is unknown how it affects gonadal activity and the function of the hypothalamus-pituitary-gonadal (HPG) axis. AIM: The aim of this study was to investigate testosterone and luteinizing hormone (LH) levels in hypersexual men compared with healthy controls. Furthermore, we investigated associations between epigenetic markers and hormone levels. METHODS: Basal morning plasma levels of testosterone, LH, and sex hormone-binding globulin (SHBG) were assessed in 67 hypersexual men (mean age: 39.2 years) compared with 39 age-matched healthy controls (mean age: 37.5 years). The Sexual Compulsivity Scale and the Hypersexual Disorder: Current Assessment Scale were used for assessing hypersexual behavior, the Montgomery-Åsberg Depression Scale-self rating was used for depression severity, and the Childhood Trauma Questionnaire (CTQ) was used for assessing history of childhood adversity. The genome-wide methylation pattern of more than 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. CpG sites located within 2,000 bp of the transcriptional start site of hypothalamus pituitary adrenal (HPA) and HPG axis-coupled genes were included. MAIN OUTCOME MEASURES: Testosterone and LH plasma levels in association with clinical rating and a secondary outcome was the epigenetic profile of HPA and HPG axis-coupled CpG sites with testosterone and LH levels. RESULTS: LH plasma levels were significantly higher in patients with hypersexual disorder than in healthy volunteers. No significant differences in plasma testosterone, follicle stimulating hormone, prolactin, and SHBG levels were found between the groups. There were no significant associations between DNA methylation of HPA and HPG axis-coupled genes and plasma testosterone or LH levels after multiple testing corrections. CONCLUSIONS: Subtle dysregulation of the HPG axis, with increased LH plasma levels but no difference in testosterone levels may be present in hypersexual men. Chatzittofis A, Boström AE, Öberg KG, et al. Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder. Sex Med 2020;8:243-250.

Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes.

Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification 'Compulsive Sexual Behavior Disorder' is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD - cg18222192 (MIR708)(p < 10E-05,pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.

Vibrator-Assisted Start-Stop Exercises Improve Premature Ejaculation Symptoms: A Randomized Controlled Trial.

Premature ejaculation (PE) is associated with decreased quality of life, lower confidence and self-esteem, and higher levels of depression, anxiety, and interpersonal difficulties. Here we investigated the effectiveness of vibrator-assisted start-stop exercises for treatment of PE, and whether the treatment effect could be enhanced by an additional psychobehavioral intervention. Fifty participants with a mean age of 41.7 years were included and randomized into two treatment groups and a waiting list control group. Participants were instructed to perform start-stop exercises while stimulating the penis with a purpose-made vibrator, 3 times a week for 6 weeks. Additionally, participants in one of the treatment groups received additional psychoeducation and performed mindfulness meditation-based body scan exercises three times a week. Data were gathered through online questionnaires before and after treatment, as well as 3 and 6 months after treatment. The interventions reduced PE symptoms with large effect sizes (partial η2 = .20 across the three groups, d [95% CI] = 1.05 [.27, 1.82] and 1.07 [.32, 1.82] for treatment groups compared to waiting list control group). The additional psychobehavioral intervention did not further reduce PE symptoms, but did decrease PE-associated negative symptoms such as levels of sexual distress, anxiety, and depression. No side effects were reported. Vibrator-assisted start-stop exercises can be offered as an adequate treatment option for PE.

A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men.

BACKGROUND: Hypersexual disorder (HD) is defined as a condition in which the individual loses control over engagement in sexual behaviors, leading to distress and negative effects on key life areas. Cognitive behavioral therapy (CBT) has been proven to reduce symptoms of hypersexual behavior; however, no randomized controlled study of CBT interventions for HD has been reported previously. AIM: To investigate the efficacy of group-administered CBT for HD. METHODS: Male participants (n = 137) diagnosed with HD, were randomized between 7 weeks of group-administered CBT (n = 70) and a waitlist control receiving the intervention after 8 weeks (n = 67). Measurements were administered at pre-, mid-, and posttreatment, with follow-up after 3 and 6 months. OUTCOMES: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD:CAS), and secondary outcomes were the Sexual Compulsivity Scale (SCS) and measures of depression (Montgomery-Åsberg Depression Rating Scale (MADRS-S), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), and treatment satisfaction (CSQ-8). RESULTS: A significantly greater decrease in HD symptoms and sexual compulsivity, as well as significantly greater improvements in psychiatric well-being, were found for the treatment condition compared with the waitlist. These effects remained stable at 3 and 6 months after treatment. CLINICAL IMPLICATIONS: CBT can ameliorate HD symptoms and psychiatric distress, suggesting that the CBT program may serve as a first-line treatment in clinical settings. STRENGTHS & LIMITATIONS: This is the first randomized controlled study evaluating the efficacy of a CBT program in a rather large sample of HD-specific diagnosed men. The long-term treatment effects are vague due to the low response rate on follow-up measurements, and the efficacy of this program for hypersexual women remains unknown. CONCLUSION: This study supports the efficacy of a group-administered CBT program as a treatment option for HD; however, future studies should include women, comprise dismantling analysis of the constituting interventions, and evaluate other treatment formats, for example, administration via the Internet. Hallberg J, Kaldo V, Arver S, et al. A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men. J Sex Med 2019;16:733-745.

A Randomized, Waiting-List-Controlled Study Shows That Brief, Mindfulness-Based Psychological Interventions Are Effective for Treatment of Women's Low Sexual Desire.

We evaluated two treatment conditions for low sexual desire in women: one where participants were administered a mindfulness-based treatment protocol and another with exercises focusing on scheduled sex and motivations for sex in addition to the aforementioned protocol. Seventy women (Mage 39.2, SD = 9.8) with complaints of low sexual desire were randomly allocated to one of these treatment conditions or a waiting-list condition. Participants attended four individual sessions and completed homework exercises. Questionnaire data were collected before and after treatment and at follow-ups three and six months later. Primary outcomes were the Female Sexual Function Index (FSFI) desire subdomain and the Sexual Interest and Desire Inventory-Female (SIDI-F). Secondary outcomes were the Female Sexual Distress Scale-Revised (FSDS-R), the Revised Dyadic Adjustment Scale (RDAS), the Perceived Relationship Quality Components Inventory (PRQC), and the Brief Symptom Inventory-18 (BSI-18). Women in both treatment conditions reported significantly higher sexual desire (FSFI desire d = 0.75 to 1.06) immediately following treatment, compared to the waiting list. Improvements were sustained at follow-up, accompanied by improvements in some secondary outcomes. We found no significant differences between the treatment conditions in terms of treatment effectiveness. Our study adds to the literature suggesting that mindfulness-based treatments are suitable options for treating low sexual desire in women.

Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self-Identified Hypersexual Behavior.

INTRODUCTION: The Hypersexual Disorder Screening Inventory (HDSI) was developed by the American Psychiatric Association for clinical screening of hypersexual disorder (HD). AIMS: To examine the distribution of the proposed diagnostic entity HD according to the HDSI in a sample of men and women seeking help for problematic hypersexuality and evaluate some psychometric properties. METHODS: Data on sociodemographics, the HDSI, the Sexual Compulsivity Scale (SCS), and the Cognitive and Behavioral Outcomes of Sexual Behavior were collected online from 16 women and 64 men who self-identified as hypersexual. Respondents were recruited by advertisements offering psychological treatment for hypersexual behavior. MAIN OUTCOME MEASURES: The HDSI, covering the proposed criteria for HD. RESULTS: Of the entire sample, 50% fulfilled the criteria for HD. Compared with men, women scored higher on the HDSI, engaged more often in risky sexual behavior, and worried more about physical injuries and pain. Men primarily used pornography, whereas women had sexual encounters. The HD group reported a larger number of sexual specifiers, higher scores on the SCS, more negative effects of sexual behavior, and more concerns about consequences compared with the non-HD group. Sociodemographics had no influence on HD. The HDSI's core diagnostic criteria showed high internal reliability for men (α = 0.80) and women (α = 0.81). A moderate correlation between the HDSI and the SCS was found (0.51). The vast majority of the entire sample (76 of 80, 95%) fulfilled the criteria for sexual compulsivity according to the SCS. CONCLUSION: The HDSI could be used as a screening tool for HD, although further explorations of the empirical implications regarding criteria are needed, as are refinements of cutoff scores and specific sexual behaviors. Hypersexual problematic behavior causes distress and impairment and, although not included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, HD should be endorsed as a diagnosis to develop evidence-based treatment and future studies on its etiology. Öberg KG, Hallberg J, Kaldo V, et al. Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self-Identified Hypersexual Behavior. Sex Med 2017;5:e229-e236.

A Cognitive-Behavioral Therapy Group Intervention for Hypersexual Disorder: A Feasibility Study.

BACKGROUND: The proposed criteria of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition for hypersexual disorder (HD) included symptoms reported by patients seeking help for excessive and out-of-control non-paraphilic sexual behavior, including sexual behaviors in response to dysphoric mood states, impulsivity, and risk taking. Although no prior studies of cognitive-behavioral therapy (CBT) for the treatment of HD have been performed, CBT has been found effective for dysphoric mood states and impulsivity. AIM: To investigate the feasibility of a CBT manual developed for HD explored through symptom decrease, treatment attendance, and clients' treatment satisfaction. METHODS: Ten men with a diagnosis of HD took part in the CBT group program. Measurements were taken before, during, and at the end of treatment and 3 and 6 months after treatment. OUTCOMES: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD:CAS) score that measured the severity of problematic hypersexual symptoms and secondary outcomes were the Hypersexual Disorder Screening Inventory (HDSI) score, the proportion of attended sessions, and the Client Satisfaction Questionnaire (CSQ-8) score. RESULTS: Main results were significant decreases of HD symptoms from before to after treatment on HD:CAS and HDSI scores and a decrease in the number of problematic sexual behaviors during the course of therapy. A high attendance rate of 93% and a high treatment satisfaction score on CSQ-8 also were found. CLINICAL IMPLICATIONS: The CBT program seemed to ameliorate the symptoms of HD and therefore might be a feasible treatment option. STRENGTHS AND LIMITATIONS: This study provides data from a CBT program for the treatment of the specific proposed criteria of HD. Because of the small sample and lack of a control group, the results can be considered only preliminary. CONCLUSION: Although participants reported decreased HD symptoms after attending the CBT program, future studies should evaluate the treatment program with a larger sample and a randomized controlled procedure to ensure treatment effectiveness. Hallberg J, Kaldo V, Arver S, et al. A Cognitive-Behavioral Therapy Group Intervention for Hypersexual Disorder: A Feasibility Study. J Sex Med 2017;14:950-958.