Maternal Steroid Hormone Levels in Early Pregnancy and Autism in the Offspring: A Population-Based, Nested Case-Control Study.

BACKGROUND: A role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting. METHODS: Here, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean = 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n = 118 autism with ID, n = 249 autism without ID, n = 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child's sex and maternal health, demographic, and socioeconomic factors. RESULTS: We observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean = 1.66; 95% CI, 1.24-2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean = 0.55; 95% CI, 0.36-0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean = 1.49; 95% CI, 1.11-1.99). We observed no evidence for interaction with sex of the child. CONCLUSIONS: These findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism.

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.

Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology.

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

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.

Pharmacological Treatment for Pedophilic Disorder and Compulsive Sexual Behavior Disorder: A Review.

Guidelines for the pharmacological treatment of paraphilic disorders have historically been based on data from forensic settings and on risk levels for sexual crime. However, emerging treatment options are being evaluated for individuals experiencing distress because of their sexual urges and preferences, targeting both paraphilic disorders such as pedophilic disorder (PeD) and the new diagnosis of compulsive sexual behavior disorder (CSBD) included in the International Classification of Diseases, 11th Revision (ICD-11). As in other mental disorders, this may enable individualized pharmacological treatment plans, taking into account components of sexuality (e.g. high libido, compulsivity, anxiety-driven/sex as coping), medical and psychiatric comorbidity, adverse effects and patient preferences. In order to expand on previous reviews, we conducted a literature search focusing on randomized controlled trials of pharmacological treatment for persons likely to have PeD or CSBD. Our search was not restricted to studies involving forensic or criminal samples. Twelve studies conducted between 1974 and 2021 were identified regardless of setting (outpatient or inpatient), with only one study conducted during the last decade. Of a total of 213 participants included in these studies, 122 (57%) were likely to have PeD, 34 (16%) were likely to have a CSBD, and the remainder had unspecified paraphilias (40, 21%) or sexual offense (17, 8%) as the treatment indication. The diagnostic procedure for PeD and/or CSBD, as well as comorbid psychiatric symptoms, has been described in seven studies. The studies provide some empirical evidence that testosterone-lowering drugs reduce sexual activity for patients with PeD or CSBD, but the body of evidence is meager. There is a need for studies using larger samples, specific criteria for inclusion, longer follow-up periods, and standardized outcome measures with adherence to international reporting guidelines.

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.

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.

Recommendations on the diagnosis, treatment and monitoring of testosterone deficiency in men.

The relative proportional increase of the elderly population within many countries will become one of the most significant social transformations of the twenty-first century and, for the first time in history, persons aged 65 or above outnumbered children under five years of age globally. One in four persons living in Europe and Northern America will be aged 65 or over. One of the goals of ISSAM is to raise awareness of the special health needs of older men. Since a significant number of aging men will eventually become testosterone deficient, the Hypogonadism panel of ISSAM updates its guidelines.

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.

Sperm quality in transgender women before or after gender affirming hormone therapy-A prospective cohort study.

BACKGROUND: Due to recent changes in the legal framework, access to fertility preservation (FP) for transgender individuals has opened up in several countries. In Sweden and the Nordic countries, fertility preservation for medical reasons is fully reimbursed as part of the established tax-funded healthcare services. As this issue is relatively new, procedures for FP have seldom been reported in the transgender patient population. The very limited literature has indicated that transgender women may have poorer sperm quality than cisgender men when assessing samples aimed at semen banking. OBJECTIVES: To assess sperm quality parameters of semen samples provided for FP by transgender women before or after gender affirming hormone therapy (GAHT), and to compare sperm quality with a reference population of unscreened men defined by the World Health Organization (WHO). Additionally, we aimed to describe referral patterns over calendar time and estimate time from referral to semen cryopreservation. MATERIAL AND METHODS: Prospective cohort study of 212 transgender women referred for FP to the Reproductive Medicine Clinic of Karolinska University Hospital, Sweden, between 2013 and 2018. Among 177 individuals that provided semen samples for cryopreservation, 16 had previously received GAHT. RESULTS: Individuals with previous GAHT presented with significantly lower total sperm count than individuals without GAHT (p = 0.002). However, higher proportions of sperm abnormalities were also noted among individuals who had not undergone previous GAHT, compared to the WHO reference population (p < 0.001). Referrals of transgender women for FP increased over time. The median time from referral to semen cryopreservation was 27 days. CONCLUSIONS: A high occurrence of sperm abnormalities was found in transgender women, especially among individuals who had previously received GAHT. The results underline the importance of thoroughly discussing parenthood options and FP with patients early after diagnosis and referring the patients for semen banking preferably before starting GAHT.

Androgen receptor polymorphism, testosterone levels, and prognosis in patients with acute myocardial infarction.

Aims: Low testosterone has been associated with cardiovascular disease in men but with contradictory findings. Testosterone bind to the androgen receptor and polymorphisms of the receptor gene such as CAG repeat length may affect transcriptional activity, possibly mitigating testosterone effects. The aims were to study the CAG repeat length and testosterone levels at four time points following a myocardial infarction (MI) and to analyse possible relationships between CAG repeat length and cardiovascular prognosis. Methods and results: Male patients admitted for acute MI (n = 122) from the Glucose in Acute Myocardial Infarction study were included. Blood samples were drawn at four time points (day after admission, at discharge, and at 3 and 12 months post-infarction) for assessment of testosterone levels. Patients were followed for a median of 11.6 years. Cox regression analyses were performed for CAG repeat length by one unit increment and by > vs. ≤median for cardiovascular events and all-cause mortality. Median CAG repeat length was 20. There was no difference in testosterone levels at each time point when dividing the cohort into ≤ vs. >CAG repeat median (=20). There was no association between CAG repeat length either as a continuous or categorical variable in unadjusted and age-adjusted Cox analyses for cardiovascular events. While CAG >20 was associated with all-cause mortality in unadjusted analyses (hazard ratio 2.19, 95% confidence interval 1.13-4.22; P = 0.02), it did not remain significant following adjustment for age. Conclusion: CAG repeat length was not associated with testosterone levels or prognosis in men with acute MI.

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.

Effect of Gonadotropin-Releasing Hormone Antagonist on Risk of Committing Child Sexual Abuse in Men With Pedophilic Disorder: A Randomized Clinical Trial.

Importance: Evidence-based treatments from randomized clinical trials for pedophilic disorder are lacking. Objective: To determine whether a gonadotropin-releasing hormone antagonist reduces dynamic risk factors for committing child sexual abuse. Design, Setting, and Participants: This academically initiated, double-blind, placebo-controlled, parallel-group, phase 2 randomized clinical trial was conducted at the ANOVA center in Stockholm, Sweden, from March 1, 2016, to April 30, 2019. Individuals who contacted PrevenTell, the national telephone helpline for unwanted sexuality, were recruited. Eligible participants were men seeking help aged 18 to 66 years with a pedophilic disorder diagnosis and no contraindications to the intervention. The primary end point was assessed by intent-to-treat analysis. Interventions: Randomization to receive either 2 subcutaneous injections of 120 mg of degarelix acetate or equal volume of placebo. Main Outcomes and Measures: The primary end point was the mean change between baseline and 2 weeks in the composite risk score of 5 domains of child sexual abuse ranging from 0 to 15 points; each domain could be rated from 0 to 3 points. Secondary end points included efficacy at 2 and 10 weeks as measured by the composite score, each risk domain, quality of life, self-reported effects, and adverse events. Results: A total of 52 male participants (mean [SD] age, 36 [12] years) were randomized to receive either degarelix (n = 25; with 1 withdrawal) or placebo (n = 26). At 2 weeks, the composite risk score decreased from 7.4 to 4.4 for participants in the degarelix group and from 7.8 to 6.6 for the placebo group, a mean between-group difference of -1.8 (95% CI, -3.2 to -0.5; P = .01). A decrease was seen in the composite score at 10 weeks (-2.2 [95% CI, -3.6 to -0.7]) as well as in the domains of pedophilic disorder (2 weeks: -0.7 [95% CI, -1.4 to 0.0]; 10 weeks: -1.1 [95% CI, -1.8 to -0.4]) and sexual preoccupation (2 weeks: -0.7 [95% CI, -1.2 to -0.3]; 10 weeks: -0.8 [95% CI, -1.3 to -0.3]) in the degarelix group compared with the placebo group. No difference was seen for the domains of self-rated risk (2 weeks: -0.4 [95% CI, -0.9 to 0.1]; 10 weeks: -0.5 [95% CI, -1 to 0.0]), low empathy (2 weeks: 0.2 [95% CI, -0.3 to 0.6]; 10 weeks: 0.2 [95% CI, -0.2 to 0.6]), and impaired self-regulation (2 weeks: -0.0 [95% CI, -0.7 to 0.6]; 10 weeks: 0.1 [95% CI, -0.5 to 0.8]), or quality of life (EuroQol 5 Dimensions questionnaire index score, 2 weeks: 0.06 [95% CI, -0.00 to 0.12], and 10 weeks: 0.04; 95% CI, -0.02 to 0.10; EuroQol visual analog scale, 2 weeks: 0.6 [95% CI, -9.7 to 10.9], and 10 weeks: 4.2 [95% CI, -6.0 to 14.4]). Two hospitalizations occurred from increased suicidal ideation, and more injection site reactions (degarelix: 22 of 25 [88%]; placebo: 1 of 26 [4%]) and hepatobiliary enzyme level elevations were reported by participants who received degarelix (degarelix: 11 of 25 [44%]; placebo: 2 of 26 [8%]). Among the 26 participants randomized to receive degarelix, 20 (77%) experienced positive effects (eg, improved attitude or behavior) on sexuality and 23 (89%) reported adverse effects on the body. Conclusion and Relevance: This trial found that degarelix reduced the risk score for committing child sexual abuse in men with pedophilic disorder 2 weeks after initial injection, suggesting use of the drug as a rapid-onset treatment option. Further studies are warranted into the effects and long-term adverse effects of hormone deficiency. Trial Registration: EU Clinical Trials Register Identifier: 2014-000647-32.

Placebo Responses Among Men With Erectile Dysfunction Enrolled in Phosphodiesterase 5 Inhibitor Trials: A Systematic Review and Meta-analysis.

Importance: Placebo responses in the treatment of erectile dysfunction (ED) are poorly described in the literature to date. Objective: To quantify the association of placebo with ED outcomes among men enrolled in placebo-controlled, phosphodiesterase 5 inhibitor (PDE5I) trials. Data Sources: For this systematic review and meta-analysis, a database search was conducted to identify double-blind, placebo-controlled studies using PDE5Is for the treatment of ED published from January 1, 1998, to December 31, 2018, within MEDLINE, Embase, Cochrane Library, and Web of Science. Only articles published in the English language were included. Study Selection: Double-blind, placebo-controlled randomized clinical trials of PDE5Is for ED were included. Studies were excluded if they did not provide distribution measures for statistical analysis. Study selection review assessments were conducted by 2 independent investigators. A total of 2215 studies were identified from the database search, and after review, 63 studies that included 12 564 men were analyzed. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Data were extracted from published reports by 2 independent reviewers. Quality assessment was performed using the Jadad scale. Data were pooled using a random-effects model. Main Outcomes and Measures: The main outcome was improvement in the erectile function domain of the International Index of Erectile Function questionnaire in the placebo arm of the included studies. Effect size was reported as bias-corrected standardized mean difference (Hedges g). The hypothesis was formulated before data extraction. Results: A total of 63 studies that included 12 564 men (mean [SD] age, 55 [7] years; age range, 36-68 years) were included. Erectile function was significantly improved among participants in the placebo arm, with a small to moderate effect size (Hedges g [SE], 0.35 [0.03]; P < .001). Placebo effect size was larger among participants with ED associated with posttraumatic stress disorder (Hedges g [SE], 0.78 [0.32]; P = .02) compared with the overall analysis. No significant difference was found between placebo and PDE5Is for ED after prostate surgery or radiotherapy (Hedges g [SE], 0.30 [0.17]; P = .08). Conclusions and Relevance: In this study, placebo was associated with improvement of ED, especially among men with ED-related posttraumatic stress disorder. No difference was found between placebo and PDE5I among men treated for ED after prostate surgery.

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.