Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review.

Sexual delinquency is a global problem where those with paraphilic disorders, such as paedophiles, are more likely to commit and reoffend. Androgen deprivation therapy (ADT) has been suggested as a solution. The objective of this narrative review is to present current information on its risks, benefits and limitations as a treatment for paraphilias. The importance of testosterone in sexual function, the effect of its deficiency by age or by pharmacological treatment (anti-androgens, GnRH agonists and GnRH antagonists) and the effect of testosterone replacement therapy will be reviewed. The relationship between androgens, brain, sexual behaviour and pathophysiology of paraphilic disorders will also be explored. ADT reduces sexual urges, but has adverse effects and, because its reversible nature, it does not ensure less recidivism. Likewise, the research quality of ADT drugs is limited and not enough to support their use. Child sex offenders, and not paraphilic subjects who have not committed assaults, show signs of elevated prenatal exposure to androgens and a higher methylation state of the androgen receptor gene. Sexual behaviour is regulated by subcortical (hypothalamus, brainstem and spinal cord) and cortical structures of the brain, in addition to brain circuits (dopaminergic, serotonergic). Those with paraphilic disorders show abnormalities at these levels that could relate to the risk of sexual offences. In conclusion, androgens represent a significant part of the pathophysiology of paraphilias and therefore, ADT seems promising. Nonetheless, more studies are needed to make definite conclusions about the efficacy of long-term ADT in paraphilic patients.

Androgen Deprivation Therapy in Pedophilic Disorder: Exploring the Physical, Psychological, and Sexual Effects From a Patient's Perspective.

BACKGROUND: The use of androgen deprivation therapy (ADT) shows promising results in the treatment of paraphilic disorders. Although the side effects of ADT can be intrusive, there is no research into the experiences of patients with pedophilic disorder themselves. AIM: This research aims to explore the psychological, physical, and sexual experiences of ADT from the perspective of sex offenders diagnosed with pedophilic disorder. METHODS: Twelve semistructured in-depth interviews with male adults diagnosed with pedophilic disorder were conducted using a phenomenological approach. Six of the 12 respondents were on luteinizing hormone-releasing hormone agonists and the remaining on anti-androgens. Half of each group were inpatients, and the other half outpatients. The respondents were recruited in collaboration with one psychiatric hospital. The data were analyzed with help of a qualitative software application NVivo. OUTCOMES: The respondents described experiences on the use of ADT on a physical, psychological, and sexual level. RESULTS: The most prominent physical side effects mentioned were bone loss, weight gain, and breast formation. The respondents generally described a positive influence of the medication on their well-being. They felt more relaxed and experienced a reduction in frequency and intensity of sexual fantasies, anger, and aggressive feelings in general. In addition, all the respondents noticed a lower frequency of sexual contact and masturbation. Most of the participants experienced the use of ADT as a mandatory decision made by the treating psychiatrist. CLINICAL IMPLICATIONS: This study recommends informing patients and their loved ones on the potential side effects of ADT. Furthermore, training forensic counselors on potential side effects of ADT and methods to alleviate them can promote the dissemination of information and will encourage the informed consent procedure. STRENGTHS & LIMITATIONS: This is the first qualitative study about the experiences of ADT in men diagnosed with pedophilic disorder in Belgium. Future studies should include more than one treatment center. CONCLUSION: The majority of the participants had a positive attitude towards ADT in general. Boons L, Jeandarme I, Vervaeke G. Androgen Deprivation Therapy in Pedophilic Disorder: Exploring the Physical, Psychological, and Sexual Effects From a Patient's Perspective. J Sex Med 2021;18:353-362.

The pharmacologic treatment of problematic sexual interests, paraphilic disorders, and sexual preoccupation in adult men who have committed a sexual offence.

This paper provides an international perspective on the use of medications to treat problematic sexual interests, paraphilic disorders, and sexual preoccupation in men who have committed a sexual offence. Experts from Canada, the Czech Republic (CR), Russia, the United Kingdom, and the United States met in Prague, CR in May 2017 to review and compare their treatment approaches. This report is a summary of their discussions, including empirical data from CR and Russia which have not previously been published in the English language. All participants agreed that continuing international collaboration would be very useful for the development of ethical international prescribing guidelines, as well as pooling data from studies on the efficacy and utility of pharmacological and other biological treatments for people who have committed sexual offences.

Treatment of Paraphilic Disorders in Sexual Offenders or Men With a Risk of Sexual Offending With Luteinizing Hormone-Releasing Hormone Agonists: An Updated Systematic Review.

BACKGROUND: Different pharmacologic agents are used in the treatment of paraphilic disorders in sexual offenders or men with a risk of sexual offending, with luteinizing hormone-releasing hormone (LHRH) agonists being the agents introduced more recently to treatment regimens. AIM: To summarize the relevant literature concerning LHRH agonist treatment of paraphilic disorders in sexual offenders and update the previously published systematic review by Briken et al (J Clin Psychiatry 2003;64:890-897). METHODS: The PubMed and Google Scholar databases were searched for literature published from January 2003 through October 2017 using the following key words: LHRH agonists, GnRH agonists, antiandrogens AND paraphilia, pedophilia, sex offenders. OUTCOMES: Evaluation of the effectiveness and side effects of LHRH agonist treatment of paraphilic disorders in sexual offenders. RESULTS: After screening for duplicates and applying specific selection criteria, the search yielded 24 eligible studies reporting on a sample of 256 patients. There is increasing evidence that LHRH agonists are more effective than steroidal antiandrogens in lowering paraphilic sexual thoughts and behaviors. Current research also is based on methods that might be less susceptible to faking (eg, eye-tracking, brain imaging, and viewing-time measures). Side effects occurring most frequently are fatigue, hot flashes, depressive mood, weight gain, high blood pressure, diabetes, gynecomastia, loss of erectile function, and loss of bone mineral density. CLINICAL IMPLICATIONS: Although LHRH agonists seem to be the most effective drugs in the treatment of paraphilic fantasies and behaviors, they should be reserved for patients with a paraphilic disorder and the highest risk of sexual offending because of their extensive side effects. STRENGTHS AND LIMITATIONS: This systematic review considers all types of research on LHRH agonist treatment in patients with paraphilic disorders, thereby providing a complete overview of the current state of research. However, most studies are case reports or observational studies and randomized controlled clinical trials have not been conducted or published. CONCLUSIONS: LHRH agonists are a useful treatment when combined with psychotherapy in patients with a paraphilic disorder and the highest risk of sexual offending. However, throughout treatment, close monitoring of side effects is needed and ethical concerns must always be kept in mind. Turner D, Briken P. Treatment of Paraphilic Disorders in Sexual Offenders or Men With a Risk of Sexual Offending With Luteinizing Hormone-Releasing Hormone Agonists: An Updated Systematic Review. J Sex Med 2018;15:77-93.

[Urolithiasis in the Long-Term GnRH Agonist Treatment of Patients with Paraphilia: 3 Case Studies]. / Urolithiasis bei der Langzeitherapie mit GnRH-Agonisten bei Paraphilien ­ 3 Fallberichte.

The outpatient forensic aftercare department of the Charité Berlin treated 32 paraphilic sex offenders with GnRH analogues within the past 5 years. Out of those patients, three men suffered from urolithiasis and were in need of treatment. All 3 patients had previously developed osteopenia/osteoporosis while on antiandrogen treatment.This article describes these 3 cases and suggests an intense consideration of the possible occurrence of urolithiasis in sex offenders on antiandrogen treatment.

The Biological Treatment of Paraphilic Disorders: an Updated Review.

Paraphilic disorders are characterized by atypical sexual interests, fantasies, and behaviors that are subjectively distressing to patients or pose a risk of harm to others. By their very nature, some paraphilic disorders may predispose an individual to commit sexual offenses. The biological treatment of paraphilic disorders, then, is of paramount importance for psychiatry and society at large. Three categories of pharmacologic agents commonly used to treat paraphilic disorders are selective serotonin reuptake inhibitors, synthetic steroidal analogs, and gonadotropin-releasing hormone analogs. Each medication uses a different mechanism of action and has different effects on the physiological and psychological features of paraphilic disorders. In general, these medications have limited high-quality research to support their use. Despite this, some authors have proposed treatment algorithms for individuals with paraphilic disorders of varying severity. These guidelines offer clinicians potentially useful, rational approaches to assessing treatment need in individuals with paraphilic disorders. Recent neuroimaging research suggests that functional magnetic resonance imaging may offer further promise in effectively assessing paraphilic disorders to help direct treatment options.

Pharmacologic treatment of paraphilias.

The treatment of paraphilias remains a challenge in the mental health field. Combined pharmacologic and psychotherapeutic treatment is associated with better efficacy. The gold standard treatment of severe paraphilias in adult males is antiandrogen treatment with cognitive behavioral therapy. Selective serotonin reuptake inhibitors have been used in mild types of paraphilia and in cases of sexual compulsions and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe paraphilic subjects committing sexual offenses. In particular, gonadotropin-releasing hormone analogs have shown high efficacy working in a similar way to physical castration but being reversible at any time. Treatment recommendations, side effects, and contraindications are discussed.

Pharmacologic treatment of sex offenders with paraphilic disorder.

Sexual offending is both a social and a public health issue. Evidence demonstrates that a combination of pharmacological and psychotherapeutic approaches may reduce or even eliminate deviant sexual behavior in sex offenders with paraphilic disorders. In this article, we will review pharmacological treatment options for sex offenders with paraphilias. Both serotonin selective reuptake inhibitors (SSRIs) and antiandrogen treatments have been used with reported success in decreasing recidivism. SSRIs have been used in mild types of paraphilias and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe sex offenders with paraphilic disorders in order to reduce victimization. Combined pharmacological and psychotherapeutic treatment is associated with better efficacy. Imaging studies may improve the knowledge of paraphilic disorders and the mechanisms of action of current treatments. In spite of existing evidence, there is a need for independent, large-scale and good quality studies assessing the long-term efficacy and tolerance of treatments.

Prescription of testosterone-lowering medications for sex offender treatment in German forensic-psychiatric institutions.

INTRODUCTION: Different clinical guidelines suggest using testosterone-lowering medications (TLM) in sex offender treatment in addition to psychotherapy. Within Germany, there are two officially approved agents. So far, no current data exist about the routine use of TLM in a clinical context. AIM: The present observational study evaluates the frequency of the prescription of TLM and other medications in sex offender treatment in German forensic-psychiatric institutions. Experts are asked about the observed effects and side effects of TLM. METHOD: The heads of all 69 German forensic-psychiatric hospitals and outpatient clinics were asked to fill out a questionnaire assessing offender characteristics and treatment methods in use. MAIN OUTCOME MEASURES: Main outcome measures were the number of patients being treated with TLM and other pharmacological agents for reducing sexual drive. Further effects and side effects of the agents were evaluated. RESULTS: Thirty-two participating institutions reported on 3,963 patients, 611 of them being sex offenders (15.4%). Most sex offenders had been convicted for child sexual abuse (39.8%) or a sexual assault/rape (37.6%). Almost all sex offenders were treated psychotherapeutically and 37% were receiving an additional pharmacological treatment. Of all the sex offenders, 15.7% were treated with TLM; 10.6% were treated with a gonadotropin-releasing hormone agonist; and 5.1% were treated with cyproterone acetate. Of these, 26.0-75.4% showed improvements in such outcomes as reduction of frequency and/or intensity of sexual thoughts. The remaining 21.3% of sex offenders who received a pharmacological agent were treated with selective serotonin reuptake inhibitors (11.5%) or antipsychotic medications (9.8%). CONCLUSIONS: TLM are a frequently used addition to psychotherapy in sex offenders. In light of the lack of controlled clinical trials and the many side effects, benefits and risks should always be thoroughly assessed.

Pharmacological treatment of paraphilias.

BACKGROUND: The psychiatrist's main role is to provide care to the paraphilic patient and to reduce personal distress. However, in cases of paraphilia associated with sexual offences, reducing paraphilic behavior is critical in an approach to preventing sexual violence and reducing victimization. This review will focus on this specific population. METHOD: We discuss the recently published recommendations for the treatment of paraphilias of the World Federation of Societies of Biological Psychiatry which were based on a review of the available literature about pharmacological treatment of paraphilias (1970-2010). RESULTS AND CONCLUSION: Antiandrogens, and mostly GnRH analogues, significantly reduce the intensity and frequency of deviant sexual arousal and behavior, although informed consent is necessary in all cases. GnRH analogue treatment constitutes the most promising treatment for sex offenders at high risk of sexual violence, such as pedophiles or serial rapists. SSRIs remain an interesting option in adolescents, in patients with depressive or OCD disorders, or in mild paraphilias such as exhibitionism. Pharmacological interventions should be part of a more comprehensive treatment plan including psychotherapy and, in most cases, behavior therapy.

Current concepts in the pharmacotherapy of paraphilias.

Concerns about paraphilia and its treatment have grown in the past few years. Although the aetiology of paraphilia disorder is still not completely understood, pharmacological treatments have been proposed for this disorder. Paraphilias are a major burden for patients and society; nevertheless, only a few individuals with paraphilias voluntarily seek treatment. Antidepressants have been used in the treatment of certain types of mild (e.g. exhibitionism) and juvenile paraphilias. Antilibidinal hormonal treatments, such as steroidal antiandrogens and gonadotrophin-releasing hormone (GnRH) analogues, have also been studied and they seem to be effective in paraphilic disorders, although caution should be taken in the prescription of these treatments in order to avoid or minimize adverse effects and the risk of victimization. The combination of psychotherapy and pharmacological therapy is associated with better efficacy compared with either treatment as monotherapy. Paraphilia is a chronic disorder and a minimal duration of treatment of 3-5 years is highly recommended for severe paraphilia with a high risk of sexual violence. In conclusion, this review of the literature provides suggestive evidence that paraphilias are well characterized disorders marked by pathological dimensions. Although further research is necessary to confirm treatment efficacy and to improve our knowledge of long-term tolerance, available data on the use of selective serotonin reuptake inhibitors, steroidal antiandrogens and GnRH analogues strongly suggest the efficacy of these treatments for paraphilic disorders.

[Antiandrogenic pharmacotherapy of sexual offenders and home leave steps in the forensic psychiatric hospital Berlin]. / Antiandrogene Therapie und Lockerungen bei Sexualstraftätern im Massregelvollzug Berlin.

OBJECTIVE: Evaluation of the relationship between antiandrogenic therapy of sexual offenders and home leave steps in a forensic psychiatric hospital. METHODS: Retrospective evaluation of all sexual offenders (n = 79) who were treated in the forensic psychiatric hospital Berlin between the 1.1.1998 and the 1.1.2005. RESULTS: There is an increase in the number of patients treated with antiandrogenic medication during the observed time period. Patients under this kind of pharmacotherapy receive higher grades of home leave steps. CONCLUSIONS: As possible reasons for the observed changes we discuss the contemporaneous implementation of a new pharmacotherapeutic treatment option (LHRH-agonists) and an aggravation of the German criminal law for sexual offenders.

Drug treatment of paraphilic and nonparaphilic sexual disorders.

BACKGROUND: Paraphilias are characterized by recurrent, intense, sexually arousing fantasies, urges, or behaviors, over a period of > or =6 months, generally involving nonhuman objects, suffering or humiliation of oneself or one's partner, or children or other nonconsenting persons. These fantasies, urges, and behaviors produce clinically significant distress or impairments in social, occupational, and other important areas of functioning. OBJECTIVE: The goal of this article was to provide an in-depth review of the clinical pharmacology of the main antiandrogens (cyproterone acetate, medroxyprogesterone acetate [MPA], and the luteinizing hormone-releasing hormone [LHRH] agonists) used in the treatment of the paraphilias, as well as a discussion of the relevant clinical case reports, case series, and controlled trials. Treatment recommendations are also provided. METHODS: Relevant publications were identified through a search of the English-language literature indexed on MEDLINE/PubMed (1966-September 2008) using the search terms paraphilia, sex offender, hypersexuality, sexual behaviors, fetish, transvestic fetishism, sexual addiction, sexual compulsivism, selective serotonin reuptake inhibitors, tricyclic antidepressants, antiandrogens, cyproterone acetate, medroxyprogesterone acetate, LHRH agonists, and estrogens. Additional publications were identified from the bibliographies of retrieved publications. RESULTS: In vitro and in vivo (animal) studies have revealed that serotonin and prolactin inhibit sexual arousal, while norepinephrine (via alpha(1)-adrenoceptor activation), dopamine, acetylcholine (via muscarinic receptor activation), enkephalins, oxytocin, gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, testosterone/dihydrotestosterone, and estrogen/progesterone stimulate it. Most of the currently used pharmacologic treatments of the paraphilias have serotonin and testosterone/dihydrotestosterone as their targets. Cognitive-behavioral psychotherapy should be initiated in all offenders. In those at the highest risk of reoffending, psychotherapy should be initiated at the same time as drug therapy because their combination is associated with better results compared with either as monotherapy (especially in pedophiles). In offenders committing non-"hands-on" or violent paraphilias and those at low risk of reoffending, serotoninergic monotherapies (selective serotonin reuptake inhibitors [SSRIs] or tricyclic antidepressants) are reasonable choices (SSRIs are preferred). In other offenders, initial dual combination therapy (serotoninergic plus antiandrogenic) is recommended. Progestogens should be used before LHRH agonists or estrogens. Cyproterone acetate and MPA are preferred as oral and IM progestogens, respectively. Failure of dual combination serotoninergic/ progestogen therapy should prompt a change in one or both of the components (eg, SSRI to tricyclic antidepressants or vice versa, or cyproterone acetate to MPA or vice versa) or the addition or substitution of an LHRH agonist (leuprolide or triptorelin) for the progestogen. Estrogens are second- or third-line agents. Rarely, triple combination therapy is necessary (serotoninergic plus LHRH agonist or progestogen plus estrogen). It appears that recidivism rates are reduced by the use of psychotherapy alone, drug therapy alone, and more so by their combination. CONCLUSIONS: Although some progress has been made in the therapy of paraphilic and nonparaphilic sexual disorders, much work remains to be done. The development of more specific, more effective, and better-tolerated medications for these disorders should be recognized as a program worthy of greater support from government and pharmaceutical industry sources. Clinical studies performed to date have largely been of poor design, making the recommendations provided in this review tentative at best.

Pharmacology of sexually compulsive behavior.

In a meta-analysis on controlled outcomes evaluations of 22,000 sex offenders, Losel and Schmucker found 80 comparisons between treatment and control groups. The recidivism rate averaged 19% in treated groups, and 27% in controls. Most other reviews reported a lower rate of sexual recidivism in treated sexual offenders. Of 2039 citations in this study (including literature in five languages), 60 studies held independent comparisons. Problematic issues included the control groups; various hormonal, surgical, cognitive behavioral, and psychotherapeutic treatments; and sample sizes. In the 80 studies compared after the year 2000, 32% were reported after 2000, 45% originated in the United States, 45% were reported in journals, and 36% were unpublished. Treatment characteristics showed a significant lack of pharmacologic treatment (7.5%), whereas use cognitive and classical behavioral therapy was 64%. In 68% of the studies, no information was available on the integrity of the treatment implementation; 36% of the treatment settings were outpatient only, 31% were prison settings, and 12% were mixed settings (prison, hospital, and outpatient). Integrating research interpretations is complicated by the heterogeneity of sex offenders, with only 56% being adult men and 17.5% adolescents. Offense types reported included 74% child molestation, 48% incest, and 30% exhibitionism. Pedophilia was not singled out. Follow-up periods varied from 12 months to greater than 84 months. The definition of recidivism ran the gamut from arrest (24%), conviction (30%), charges (19%), and no indication (16%). Results were difficult to interpret because of the methodological problems with this type of study. Overall, a positive outcome was noted with sex offender treatment. Cognitive-behavioral and hormonal treatment were the most promising. Voluntary treatment led to a slightly better outcome than mandatory participation. When accounting for a low base rate of sexual recidivism, the reduction was 37%, which included psychological and medical modes of treatment. Which treatments will reduce recidivism rates in sex offenders is extremely difficult to conclude. Some treatment effects are determined from small studies; however, recidivism rates may be based on different criteria. Larger studies tend to be published more frequently than small studies, negative results may be less likely to be reported in published studies, and differences in mandatory versus voluntary treatment may occur. Clearly more high-quality outcome studies are needed to determine which treatments work best for which individuals. One size is unlikely to fit all. However, pharmacologic intervention, although not always the perfect choice, has improved and will continue to advance the treatment of paraphilic, nonparaphilic, and compulsive sexual behaviors.

Pharmacological management of inappropriate sexual behaviours: a review of its evidence, rationale and scope in relation to men with intellectual disabilities.

BACKGROUND: The management of inappropriate sexual behaviours (ISB) including sexual offending is difficult, especially when the person treated has intellectual disabilities (ID). Psychological therapies are the accepted first line of treatment. Pharmacological treatments have also been advocated, particularly for people who have committed serious sexual offences. There is limited information on available drugs and evidence of their efficacy in the treatment of ISBs, in particular for people with ID. METHODS: A literature search of electronic databases was undertaken. Pharmaceutical companies were contacted for unpublished information. Trials that included people with ID were systematically reviewed for the benefits and outcome in that population. RESULTS: Androgen depleting drugs (cyproterone acetate, medroxyprogesterone acetate and luteinising hormone releasing hormone agonists) and psychotropic drugs (serotonin specific reuptake inhibitors and antipsychotics) are the two major categories of medications used in the treatment of ISBs. The majority of studies identified were open trials and most relied on self-report measures. Trials that included people with ID were few in number. Most trials indicated beneficial effects including reduction in sexually deviant fantasies and behaviours. CONCLUSION: The quality of evidence base for the use of pharmacological agents in the treatment of ISBs is inadequate to justify their use in routine clinical practice. If used, they should only be a part of a comprehensive treatment programme and closely monitored. In addition, there are several clinical, ethical and legal issues to be addressed before considering pharmacological treatment of ISBs in people with ID.

Side effects of pharmacotherapy on bone with long-acting gonadorelin agonist triptorelin for paraphilia.

INTRODUCTION: There have been limited research studies concerning the use of libido inhibitors for the treatment of patients with a paraphilia. Observational studies suggest that agents that lower testosterone are an effective treatment for paraphilia. AIM: We report a case of hormonal treatment of paraphilia that was associated with side effects. METHOD: A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. RESULTS: The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. CONCLUSION: We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regime needs to be revised.

[Drug-therapy with sexual offenders]. / Pharmakotherapie bei Sexualstraftätern.

Sexual offenders are a heterogeneous group of offenders with different personality structures and different patterns of crime. As a consequence, difficulties arise with the definition of sexually deviant or offending behaviour, which depends on period of time and culture. After presenting the actual definition of sexual offences, their frequency is shown by means of German epidemiological data. The problem of the assumed relationship between paraphilia and sexual offending behaviour is called into question. After the description of the central neurobiological and endocrinological mechanisms, the established pharmacological treatment strategies (Selective Serotonine Reuptake Inhibitors, Antiadrogenes, LHRH (Luteotropic Hormone Releasing Hormone)-Agonists) are presented. Finally, the step-wise algorithm for the therapy of sexual according to Bradford is presented.