Effect of Gonadotropin-Releasing Hormone Antagonist on Risk of Committing Child Sexual Abuse in Men With Pedophilic Disorder

Abstract

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 MEASURESThe 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 eff...

Risk Factors for Sexual Offending in Self-Referred Men With Pedophilic Disorder: A Swedish Case-Control Study

“…This case-control study was part of the research project Pedophilia at Risk-Investigations of Treatment and Biomarkers (PRIOTAB), conducted from March 2016 to April 2019 at the Karolinska University Hospital in Stockholm, Sweden. PRIOTAB included clinical interviews, psychological testing and selfreports, neuroimaging, blood sampling and enrollment in a double-blind, randomized controlled efficacy trial (RCT) of the testosterone-suppressing medication degarelix (Landgren et al, 2020). Individuals calling PrevenTell 1 , a national telephone helpline addressing unwanted sexuality were screened for PD and invited to participate.…”

“…Hence, the composite risk score is based on self-, expert-completed and behavioral measures and potentially treatment sensitive since all five included domains could capture change over time. The five-domain score was used as the primary outcome measure in the PRIOTAB RCT (Landgren et al, 2020). Here we report both the five-domain score and a four-domain score (range 0-12) excluding pedophilic attraction; part of the inclusion criteria for PRIOTAB but also the grouping criterion for the present case-control study.…”

“…Future studies should investigate prospectively the ability of the measures tested here to predict sexual offending, preferably by looking at risk behaviors and situations, self-reports of child sexual offending, and suspicions/arrests for suspected sexual offenses including CSAM crime (Långström et al, 2013). Also, the malleability of these dynamic risk factors or potential treatment effect mediators should be investigated, as attempted in the recently published results of the PRIOTAB RCT of degarelix (Landgren et al, 2020).…”

Neuropilin‐1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction

“…Children experiencing early puberty are indeed at risk for sexual abuse or early sexual debut (Golub et al , ). Interestingly, human imaging studies have recently shown that the treatment of individuals with kisspeptin, a peptide known to activate the release of GnRH, both enhances responses to sexual stimuli and reduces sexual aversion (Comninos et al , , ) and that treatment with a GnRH antagonist diminishes the risk of sexual offense in men with pedophilic disorder (Landgren et al , ). In addition to evoking behavioral disorders, the early maturation of the HPG axis in juvenile females may also alter the expression of chemical signals known to block sexual approaches by males in mice (Ferrero et al , ) and sexual arousal in men (Gelstein et al , ).…”

Commentary on guidelines for the pharmacological treatment of paraphilic disorders

“…6, 409-411 https://doi.org/10.1080/15622975.2020 gonadotropin-releasing hormone analogue, together with supportive psychotherapy followed for up to 15 years; as long as patients continued with pharmacological treatment, no recidivism was detected. Recently (Landgren et al 2020) reported on a randomised clinical trial of dagarelix, a gonadotropin-releasing hormone antagonist that reduces testosterone. This was found to reduce the risk score of committing sexual abuse in men with paedophilic disorder 2 weeks after the initial injection.…”