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.

Elevated prolactin levels among adult male sex offenders.

A sample of 528 successive admissions to the Phoenix Program, a voluntary inpatient treatment program for sex offenders, was studied in regards to serum prolactin levels. Serum prolactins were obtained as part of a battery of endocrine tests. A substantial number of patients had prolactin levels above the normal range, i.e., 21.0 microg/L. In this sample, fully 10.0% of the men showed elevated prolactin levels (the maximum being 41.0 microg/L), compared with an expected 2.5% according to laboratory norms. None of these individuals had clinical manifestations of prolactinoma. The significance of this increased rate of hyperprolactinemia in this sample of sexual offenders is unclear. There was a negative correlation with age and no correlation with other endocrine tests.

[Treatment of paraphilia and sexually aggressive impulsive behavior with the LHRH-agonist leuprolide acetate]. / Therapie mit dem LHRH-Agonisten Leuprorelinacetat bei Paraphilien und sexuell aggressiven Impulshandlungen.

Up to now there are no published results of therapy of paraphilia (Pedophilia, Sadism) and sexual aggressive impulsiveness with LHRH-(luteinizing hormone-releasing hormone) Agonists in the Germanspeaking countries. In this report we describe 11 patients which were treated with the LHRH-Agonist Leuprolide Acetate in a period of 12 months. The patients showed no tendency of sexual aggressive behaviour and reported an evident reduction of penile erection, ejaculation, masturbation, sexual deviant impulsiveness and fantasies. One patient died from suicide. In combination with other treatments LHRH-Agonists seem to be a very promising alternative to cyproterone acetate and its possible carcinogene effects.

Treatment of men with paraphilia with a long-acting analogue of gonadotropin-releasing hormone.

BACKGROUND: Men with deviant sexual behavior, or paraphilia, are usually treated with psychotherapy, antidepressant drugs, progestins, and antiandrogens, but these treatments are often ineffective. Selective inhibition of pituitary-gonadal function with a long-acting agonist analogue of gonadotropin-releasing hormone may abolish the deviant sexual behavior by reducing testosterone secretion. METHODS: In an uncontrolled observational study, we treated 30 men (mean age, 32 years) with severe long-standing paraphilia (25 with pedophilia and 5 with other types of abnormal behavior) with monthly injections of 3.75 mg of triptorelin and supportive psychotherapy for 8 to 42 months. The efficacy of therapy was evaluated monthly by the Intensity of Sexual Desire and Symptoms Scale and yearly by the Three Main Complaints questionnaire. RESULTS: All the men had a decrease in the number of deviant sexual fantasies and desires, from a mean (+/-SD) of 48+/-10 per week before therapy to zero during therapy (P<0.001), and a decrease in the number of incidents of abnormal sexual behavior (from 5+/-2 per month to zero, P<0.001) while receiving triptorelin. These effects were evident after 3 to 10 months of therapy (P<0.001) and persisted in all 24 men who continued therapy for at least 1 year. The men's mean serum testosterone concentration fell from 545+/-196 ng per deciliter (18.9+/-6.8 nmol per liter) before therapy to 23+/-14 ng per deciliter (0.8+/-0.5 nmol per liter, P<0.001) after 42 months of triptorelin. The main side effects were erectile failure, hot flashes, and decrease in bone mineral density in some men. CONCLUSIONS: Continuous administration of triptorelin, a long-acting agonist analogue of gonadotropin-releasing hormone, together with supportive psychotherapy, may be an effective treatment for men with severe paraphilia.

Medroxyprogesterone and paraphiles: do testosterone levels matter?

We examine the associations between pretreatment testosterone (TTS) levels and sociodemographic, clinical, and sexual behavioral characteristics. Two groups, low and normal pretreatment TTS, were treated with medroxyprogesterone acetate (MPA) and compared on clinical response (deviant and nondeviant sexual behaviors; recidivism) and length of time to return to pretreatment TTS after discontinuing MPA. Thirteen paraphilic men who were treated with MPA and had TTS levels monitored at approximately three-month intervals during and after MPA were followed naturalistically. The principal outcome measures pertained to TTS levels and data from a self-report psychosexual inventory, which quantified deviant and nondeviant sexual activities. Time to return to baseline TTS levels were analyzed with Kaplan-Meier survival analysis. Nonparametric methods were used to compare the two groups on other variables. Multiple regression was used to examine the contribution of combinations of variables to TTS outcome. Subjects with low pretreatment TTS received MPA for longer periods of time, and older subjects took longer to return to pretreatment TTS levels despite being treated for shorter periods of time. Although subjects with lower pretreatment TTS levels may be more sensitive to MPA's TTS-suppressive effects, the multiple regression analysis showed that age may be an important determinant of the time it take for TTS levels to return to pretreatment baseline. Sociodemographic, clinical, and self-reported measures of sexual behavior did not distinguish between low and normal TTS level groups. Only one relapse was detected. Further studies with larger samples are required to better understand the role of TTS monitoring of sex offenders treated with MPA, in order to justify its continued use as a measurement of treatment adequacy and to study its potential role as a predictor of treatment outcome.

Double-blind placebo crossover study of cyproterone acetate in the treatment of the paraphilias.

Cyproterone acetate is a powerful antiandrogen used in the treatment of the paraphilias for at least a decade. Studies have reported it effective in reducing the recidivism rates of sexual crimes perpetrated by men. It acts through competitive inhibition of the androgen receptors blocking the effects of testosterone and dihydrotestosterone. Systematic clinical study of its effectiveness and its clinical effects on sexual behavior is lacking, however. In the current study 19 paraphilic men who had also recidivated in a variety of sexual crimes were treated with cyproterone acetate and placebo in a double-blind crossover design. The use of active drug was associated with a significant reduction of some aspects of sexual behavior, particularly sexual fantasies. There were also significant effects on levels of circulating sex hormones and some effects on physiological measurements and self-reports of sexual arousal.

Effect of a long-lasting gonadotrophin hormone-releasing hormone agonist in six cases of severe male paraphilia.

Six men with severe paraphilia had been treated with depot gonadotrophin luteinizing releasing hormone analogue (GnRHa) (triptorelin 3.75 mg per month intramuscularly). In 5 cases, the treatment ended their deviant sexual behavior and markedly decreased their sexual fantasies and activities without further significant side effects than those related to hypoandrogenism. This clinical improvement was parallel to the gradual decrease of plasma testosterone level to castration values within the first month. The beneficial effect of this treatment had been maintained at follow-up varying from 7 months to 3 years. One patient interrupted the treatment at the end of the first year and relapsed within 10 weeks. GnRHa treatment, which leads to reversible castration, may constitute a promising treatment of paraphilic behavior and may favor the possibility of concurrent psychotherapy.

Low-dose oral medroxyprogesterone acetate in the management of the paraphilias.

BACKGROUND: There are no reports on the use of low-dose oral medroxyprogesterone acetate (MPA) in the treatment of the paraphilias. High-dose depot MPA treatment (500-800 mg i.m. weekly) has proven to control the behavioral manifestations of the paraphilias when testosterone levels decrease from pretreatment to prepubescent levels, but at the price of significant morbidity. METHOD: Oral MPA (60 mg/day for an average of 15.33 months) was given in an open nonblind trial to seven patients who met criteria for DSM-III-R paraphilias. Four of the subjects had shown inadequate improvement after 1 year of psychotherapy. RESULTS: Six subjects responded at 60 mg/day. Testosterone levels decreased by 50% to 75% (range, 100-400 ng/dL). No patient displayed significant side effects. All patients described significantly fewer paraphilic fantasies, and no patient reported engaging in paraphilic behaviors during oral MPA treatment. CONCLUSION: Double-blind placebo and phallometrically controlled tumescence studies need to be carried out to test the results of this study.

The management of a case of treatment-resistant paraphilia with a long-acting LHRH agonist.

A patient with multiple paraphilias who had been treated for several years with sex drive reducing agents (cyproterone acetate and medroxyprogesterone acetate) with little effect on sexual activity or fantasy was offered treatment with long-acting leuprolide acetate, on LHRH agonist. This produced a marked decrease in all reported sexual thoughts and activities with no significant side-effects.

Depo provera treatment for sex offending behavior: an evaluation of outcome.

Forty men, ages 16 to 78 years, with sex-offending behavior, were treated with combined medroxyprogesterone acetate (MPA), group therapy, and individual psychotherapy. Twenty-three are pedophiles; seven, rapists; and 10, exhibitionists. Five had sex-offending behavior that began after head trauma. The duration of MPA therapy, usual intramuscular dose 400 mg/wk, ranged from six months to 12 years, usually more than two years. These men were compared with a control group of 21 men who refused MPA therapy. They had similar types of sex-offending behavior and were treated with psychotherapy alone with follow-up for a period that ranged from two to 12 years. MPA-related side effects included excessive weight gain, malaise, migraine headaches, severe leg cramps, elevation of blood pressure, gastrointestinal complaints, gallbladder stones, and diabetes mellitus. Of the 40 individuals who took MPA, 10 are still on therapy. Eighteen percent reoffended while receiving MPA therapy; 35 percent reoffended after stopping MPA. In contrast, 58 percent of the control patients, who refused and never received MPA, reoffended. Patients defined as regressed were much more likely to reoffend off therapy than the patients defined as fixated. Other risk factors for reoffense include elevated baseline testosterone, previous head injury, never forming a marriage relationship, and alcohol and drug abuse. In spite of significant medical side effects, maintenance MPA offers benefit for the compulsive sex offender by reducing the reoffense rate.

[The clinico-biochemical characteristics of persons with paraphilias and a chromosome anomaly (47, XYY)]. / Kliniko-biokhimicheskie kharakteristiki lits s parafiliiami pri khromosomnoi anomalii (47, XYY).

The authors describe the results of a comprehensive examination of 5 persons with chromosomal aberration (47, XYY) manifesting the signs of deviation from normal sexual behavior. The examined were shown to have common dysontogenesis that manifested itself by retardation of the biological basis of sexuality, psychosexual formation together with retardation of the mental processes on the whole. Whatever variants of deviations from normal sexual behavior the common feature was predominance in the libido structure of sadistic aims, that contributed to the revealing of aggressive sexual behavior. Material changes were discovered by radioimmunoassay in the function of the hypothalamohypophyseal and gonadal system in persons with the "YY syndrome". The levels of prolactin and luteinizing hormone along with the LH/FSH ratio appeared significantly elevated. Disorders were also identified in the hypothalamohypophyseal and thyroid system. It is assumed that the discovered changes influence the serotoninergic mechanisms by which aggressive and pathological sexual behavior is formed in such persons.

[The level of sex hormones in men with a sexual behavior disorder in the form of exhibitionism]. / Uroven' polovykh gormonov u muzhchin s narusheniem seksual'nogo povedeniia v vide éksgibitsionizma.

The paper is concerned with the results of radioimmunological studies reflecting the importance of the function of the hypothalamohypophyseal-gonadal system in 29 men with the signs of organic brain lesions, against whom criminal proceedings were instituted because of exhibitionism. Among the examinees the subgroups with the hypothalamic and temporal syndromes were distinguished. The data obtained were compared to those in 25 mentally normal men and 17 examinees with residual organic brain lesions without sexual behavior abnormalities. The data derived have demonstrated the impairment of the function of the indicated system in the test subjects, associated with sexual behavior impairment in the form of exhibitionism which may form the biological basis for distortion of sexual self-consciousness.

Effect of large-dose progesterone on plasma levels of lipids, lipoproteins and apolipoproteins in males.

Eleven men with sexual deviation syndrome were hospitalized for treatment with medroxyprogesterone acetate (Depo-provera). Plasma total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apo A-I and LDL apo B were measured before and during Depo-provera treatment. Ten normolipidemic and one mildly hypertriglyceridemic patient with 117 +/- 17% ideal body weight were maintained on a regular hospital diet before and during the study. They received an average total dose of 1273 +/- 467 mg Depo-provera by im injections over a mean period of 17 +/- 6 days. In the whole group, Depo-provera significantly reduced the plasma total cholesterol by 12% (p less than 0.0005), triglycerides by 24% (p less than 0.005), LDL cholesterol by 13% (p less than 0.01), LDL apo B by 15% (p less than 0.05), and apo A-I by 7% (p less than 0.05). Total HDL cholesterol, HDL2 cholesterol and HDL3 cholesterol did not change significantly. Excluding from the data analysis a normolipidemic patient who had a significant weight loss during the study and the hypertriglyceridemic patient, the fall in apo A-I during Depo-provera treatment was no longer statistically significant. We conclude that short-term, pharmacological doses of progesterone significantly reduce plasma concentrations of cholesterol, triglycerides, LDL cholesterol, and LDL apo B in men.

Progesterone has no effect on serum thyroxine-binding globulin concentration in men.

To examine the possible effect of progesterone on circulating T4-binding globulin (TBG) in men, RIA measurements of plasma TBG and T4 levels were made before and after weekly administration of 500 mg medroxyprogesterone acetate, im, to men being treated for paraphilia (sexual deviation syndromes). No change in the mean pretreatment plasma TBG concentration was found after 7-29 days [21.5 +/- 1.2 (+/- SEM) to 22.0 +/- 0.9 microgram/ml; n = 14) or 381-415 days (23.0 +/- 2.5 to 23.1 +/- 2.5 micrograms/ml; n = 5) of medroxyprogesterone treatment. Similarly, the mean pretreatment plasma T4 concentration was unaltered by acute (9.7 +/- 0.6 to 9.7 +/- 0.4 microgram/dl; n = 14) or chronic (11.1 +/- 1.2 to 11.4 +/- 1.0 microgram/dl; n = 5) medroxyprogesterone therapy. We conclude that progestational agents alone do not modify circulating TBG or total T4 concentrations in men.

Physical, metabolic, and hormonal effects on men of long-term therapy with medroxyprogesterone acetate.

Twenty-three men were treated with injectable medroxyprogesterone acetate (MPA) for sex-offending behavior. The physical, hormonal, and metabolic effects were monitored. The patients had significant (P less than 0.001) weight gain and increases (P less than 0.0001) in systolic blood pressure independent of weight gain. MPA therapy decreased testosterone (P less than 0.0001), luteinizing hormone (P less than 0.005), and testicular size (P less than 0.001), but not follicle-stimulating hormone. MPA's suppression of total sperm count was not consistent, but MPA significantly reduced sperm motility (P less than 0.001) and percent normal morphology (P less than 0.005). Statistically insignificant increases in insulin response without changes in glucose tolerance occurred in all patients, but only one patient developed overt diabetes mellitus. Three men developed gallstones, but none had significant changes in liver function. Patients receiving high-dose MPA therapy should be carefully monitored for blood pressure changes, diabetes mellitus, and gallbladder dysfunction.

Is there hypothalamic-pituitary-gonadal dysfunction in paedophilia? A pilot study.

The hypothalamic - pituitary - gonadal axis was evaluated in men with paedophilia and non-paedophilic paraphilia, and in normal male controls, by infusion of 100 mcg. of synthetic luteinising hormone-releasing hormone (LHRH). There were no significant differences among groups in age, height, weight, testosterone, baseline luteinising hormone (LH) and follicle stimulating hormone (FSH), and FSH response to LHRH. However, there was a significant difference between the paedophilic group and the other two groups in the LH response to LHRH. The paedophiles responded with a marked elevation of LH, when compared with the non-paedophilic paraphiliacs and controls. These data indicate a hypothalamic - pituitary - gonadal dysfunction in paedophiles.

[Serum testosterone determination in the antiandrogen therapy of sexual deviations with cyproterone acetate (preliminary report of experiences)]. / Serumtestosteronbestimmung während der antiandrogenen Therapie von Sexualdeviationen mit Zyproteronazetat.

Total testosterone concentrations in the serum of patients treated with antiandrogens were measured by means of an industrially produced radioimmunological testosterone assay kit (VEB Sächsisches Serumwerk Dresden). Antiandrogen therapy using cyproterone acetate (Androcur) leads to a reduction in serum testosterone concentration which is significant at the p less than 0.01 level. The data suggest that testosterone concentrations vary inversely with increasing Androcur dosage; they are around 7 nmol/l at the doses conventionally administered. The testosterone concentrations obtained under depot-Androcur treatment suggest that intervals between injections should be less than 10 days.