A gonadotropin releasing hormone (GnRH) analog may be more effective than the antiandrogen medroxyprogesterone(Drug information on medroxyprogesterone) (Depo-Provera) for "chemical castration" treatment of paraphilia, according to a study recently published in The New England Journal of Medicine.
Israeli researchers Ariel Rösler, M.D., of the Hebrew University Medical Center, Jerusalem, and Eliezer Witztum, M.D., Ben Gurion University of the Negev, Beer-Sheva, reported using triptorelin(Drug information on triptorelin) (Decapeptyl-CR) to reduce the number of deviant sexual fantasies, desires and incidents of abnormal sexual behaviors in 30 men with severe, long-standing paraphilia (Rösler and Witztum, 1998).
Although their study did not directly compare agents, the researchers attributed the effectiveness of the GnRH analog to a more complete inhibition of testosterone secretion and action than is associated with medroxyprogesterone. The mean serum testosterone level in the study population was reduced from 545 196 ng per deciliter before therapy to 23 14 ng after 42 months of monthly injections of 3.75 mg triptorelin. In men who interrupted or discontinued treatment, serum testosterone returned to baseline within two months.
Nine of the 30 men had previously received the antiandrogen cyproterone(Drug information on cyproterone) (not available in the United States) without achieving adequate behavioral control, and this treatment had been stopped at least 12 months before the triptorelin trial. Seven of the men had received a serotonergic agent, either fluvoxamine(Drug information on fluvoxamine) (Luvox) or fluoxetine(Drug information on fluoxetine) (Prozac) without adequate improvement, and these were discontinued two months before the current trial.
The men received supportive psychotherapy along with the triptorelin in an unblinded, observational study design without placebo control. Placebo was not utilized in the study because of the potential for the men to continue to offend without active medication. Two of three men who stopped taking the triptorelin due to side effects and were then treated with cyproterone did lose control of their paraphilia and were subsequently prosecuted and imprisoned for sex crimes. Two other men interrupted their triptorelin regimen for six months and 12 months in order to regain their fertility and capacity to father children within their marriages and also experienced resumption of paraphilia symptoms.
Triptorelin, unavailable in the United States, is similar to the long-acting GnRH analogs leuprolide (Lupron) and goserelin(Drug information on goserelin) (Zoladex), which are approved by the U.S. Food and Drug Administration for such indications as prostatic cancer, central precocious puberty and endometriosis. The administration of a GnRH analog initially stimulates gonadal steroid production, but continuous use exerts "negative feedback," suppressing ovarian and testicular steroidogenesis.
During the course of triptorelin treatment in this study, all 30 men demonstrated reduction in all paraphilia measures on the Three Main Complaints Questionnaire (Battle et al., 1996) and the Intensity of Sexual Desire and Symptoms Scale (Bancroft et al., 1974). The first instrument, administered at the beginning and end of the first year of therapy, is a 13-point scale rating the severity of the three problems ascertained in psychiatric evaluation to most affect the subject. The symptoms scale was administered at least twice before therapy and monthly during therapy to assess sexual interest and desire, sexual activity and sexual fantasies.
The investigators reported that "all 30 men stated that their sexual desire had decreased considerably and that their sexual behavior had become easily controllable." These self-assessments were given credence by the investigators for not only being consistent with other measures, but because the subjects were voluntary participants who were not required to initiate or continue the treatment study as a condition for leaving jail or avoiding prosecution.
"Deviant sexual fantasies and urges disappeared completely, and the frequency of masturbation was markedly reduced," the investigators noted. "The mean number of self-reported incidents of abnormal sexual behavior decreased from 5 2 per month (range, 2 to 8) before triptorelin therapy to zero during therapy."
Although 25 of the 30 subjects had been active pedophiles, there were no sexual offenses committed against a child during therapy. Nor was there, according to reports by the men, their relatives or probation officers, any resumption of exhibitionism, voyeurism or frotteurism during the treatment period "once the maximal [drug] effects were achieved," which occurred in a period of three to 10 months.
The principal drug side effects experienced by these men were the reduction in normal sexuality along with abnormal sexual behavior, hot flashes and decreased bone mineral density in the lumbar spine. The investigators suggested that the latter might be mitigated by concomitant administration of calcium and vitamin D or a biphosphonate drug indicated for osteoporosis such as alendronate (Fosamax). They also speculated that a lower dose of triptorelin might reduce the incidence of side effects while maintaining the benefit of reduced abnormal sexual behavior. They said that the side-effect profile of triptorelin is relatively limited compared with the array of medroxyprogesterone side effects that include weight gain, lethargy, nightmares, hyperglycemia and leg cramps.
In an accompanying editorial, John Bradford, M.B., Ch.B., of the Royal Ottawa Hospital, Ottawa, Canada, indicated that the decrease in normal sexual behavior that accompanies reduction in deviant sexual interests is not an insignificant side effect (Bradford, 1998). "This effect is relevant because the aim of treating men with paraphilia should be not only suppression of deviant sexual interests but also the replacement of these interests with normal interests in sexual relationships with consenting adults."
While this therapeutic goal would seem to lie more within the scope of supportive psychotherapy than within the action of medications that counter androgen-dependent behavior, Bradford's own studies have indicated that cyproterone may exert some differential effects on the patterns of sexual arousal (Bradford and Pawlak, 1993). Antiandrogens like cyproterone or medroxyprogesterone may also be useful in initial combination with a GnRH analog, Bradford suggested, to counter the possible increase in libido and abnormal sexual thoughts during the first four to six weeks of GnRH treatment when serum testosterone concentrations are elevated.
An additional limitation to using medications to chemically castrate sexual offenders, besides posing a controversial civil rights issue, was conveyed by the California Psychiatric Association to that state legislature in 1996. This was prior to the California assembly passing the first bill in the United States to allow state judges to order such treatment for repeat sex crime offenders. In a letter to the sponsoring assemblyman, the association pointed out that while the medications may be effective for sexually motivated predators, they can be expected to be less effective for the greater number of sex crime offenders who are motivated by a passion for violence.
