Abstract: We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis). Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation. Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect. Primary outcome: recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated. Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone. Secondary outcomes:The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes. We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending. The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained. It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.

Plain-language summary: We found seven randomised trials involving 138 participants, which provided data on 123. All were male, aged between 16 and 68 years. Offending ranged from very serious (e.g., rape) to minor criminality (e.g., exhibitionism). Comparators included placebo (five studies), psychological treatment (one study), and a combination of psychological and pharmacological treatment (one study). Five studies took place in the community and two in a secure hospital. Duration varied between three and 13 months. Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA). In two of these studies, MPA was given alongside a psychological therapy (assertiveness training or imaginal desensitisation). The seventh study assessed the effectiveness of two antipsychotics (benperidol and chlorpromazine) versus placebo. Meta-analysis was not possible due to heterogeneity of interventions, comparator groups, study designs, and other issues. Two studies reported reoffending rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reoffending at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of reoffending amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm (n = 5) dropped out immediately, despite treatment being court mandated. Two studies did not report reoffending rates as they both took place in a secure psychiatric facility from which none were discharged. Three community studies did not formally report reoffending at all, focusing largely on 'abnormal sexual activity'. Secondary outcomes: Studies reported a variety of secondary outcomes. Results suggested that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself. Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and anxiety. One study measured anxiety formally; one study measured anger/aggression. Adverse events: Six studies provided information on adverse events and none tested the effects of testosterone-suppressing drugs beyond six to eight months. The most severe were reported in a trial of antipsychotic medication. Reported side effects in two trials of oral MPA and CPA included considerable weight gain. Side effects of intramuscular MPA led to discontinuation in some participants. Important increases in depression and excess salivation were reported in one trial of oral MPA. No deaths and no suicide attempts were reported in any study. We conclude that these seven trials (published more than 20 years ago), examining only a limited number of drugs, provide a poor evidence base to guide practice. Not only were the trials small, they were of short duration, included varied participants, and none trialled the newer drugs currently in use, particularly SSRIs or GnRH analogues. The results of this review, therefore, do not allow firm conclusions to be drawn regarding pharmacological interventions as an effective intervention for reducing sexual offending. New studies are needed that address these deficits. Data should also be collected on the characteristics of those who refuse, drop out, and complete treatment. Overall, the quality of the evidence was poor. We had concerns about: number of participants leaving studies, blinding of those who measured outcomes, ways in which investigators concealed allocation of treatment to those delivering it, and reporting of our primary outcome: reoffending.