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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 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.

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.

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.

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.

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.

Background and aims There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case–control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire – Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery–Åsberg Depression Rating Scale – Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.

The objectives of this study are to compare the two definitions of female sexual dysfunction, namely dysfunction per se (A category) and personal distress caused by dysfunction (B category), and to gauge their associations with some sociodemographic aspects and level of sexual well-being. The subjects were a nationally representative sample of sexually active Swedish women (n: 1056) aged 18-65 y, who participated in a combined structured interview/questionnaire investigation. The functions analysed were: self-reported sexual desire, interest, lubrication, orgasm, genital pain and vaginism, which were subclassified for the A and B categories into no, mild (sporadically occurring) and manifest dysfunction. Sexual well-being was reported along a six-grade scale ranging from very satisfied to very dissatisfied. The sociodemographic items registered were: education, occupation, financial situation, social group, immigrant status, location of domicile and church-going. Aggregated mild and manifest dysfunction per se of sexual interest, orgasm and vaginal lubrication were reported by about 60-90%. More than one-third had dyspareunia, but few reported vaginism. Mild dysfunctions were clearly more common than manifest dysfunctions. Not fully 45% of those with manifest low interest and orgasm perceived these dysfunctions as manifestly distressing, while in 60-70% lubricational insufficiency of dyspareunia led to manifest distress. Age and the included sociodemographic variables had marginal or no influence on sexual functions. A four-factor sexual function pattern was identified, closely linking A and B categories in a pairwise manner. Three factors, labelled sexual desire, orgasm and genital function were powerful classifiers (discriminant analysis) of level of sexual well-being. Hence, it is a matter of taste whether to use the A or the B category. Together, they can explain the gross level of satisfaction with sexual life to an adequate extent.

Immobilized metal affinity chromatography (IMAC) purification of secreted histidine-tagged proteins in eukaryotic cell culture supernatants is often problematic. Incompatibility with the cell culture media appears as stripping of the immobilized metal ions required for binding of target proteins. The stripping effect is aggravated by low target protein concentrations and hence large sample volumes.