Biological Treatments for Paraphilias and Paraphilia-Related Disorders

Antiandrogen Pharmacotherapy

Although it is the primary goal of various psychotherapeutic interventions to alter deviant or unconventional sexual behavior, currently available pharmacotherapies directly target the intensity of sexual arousal. The antiandrogens cyproterone acetate and medroxyprogesterone acetate were developed during the 1960s and have been used to ameliorate abnormal uterine bleeding in women and to retard the progression of prostatic carcinoma in men. Because these medications have diverse endocrinological and medical effects, it is advisable that patients receiving them have a physical examination and laboratory tests, including a complete blood count, a general serology panel, total testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH).

Antiandrogens are currently the most commonly prescribed agents for the control of repetitive, deviant sexual behaviors and severe PRDs. Although neither cyproterone nor medroxyprogesterone has been specifically approved by the U.S. Food and Drug Administration for the treatment of paraphilias, both agents are available in oral and parenteral preparations. Both can be prescribed in Canada and Europe, but only medroxyprogesterone is available in the United States. In multiple studies, parenterally administered antiandrogens have been shown to reduce recidivism rates in male sexual aggressors (Berlin and Meinecke 1981; Bradford and Pawlak 1993a; Cooper et al. 1992; Federoff et al. 1992; Gagne 1981; Kravitz et al. 1996; Langevin et al. 1979; Maletzky 1991c; Meyer et al. 1992), the group most commonly prescribed these drugs.

Cyproterone acetate inhibits testosterone directly at androgen receptor sites and also exhibits antigonadotrophic effects (Liang et al. 1977). In the drug's oral form, the usual prescribed dosage range is 50-200 mg/day. Parenterally, it is usually administered every 1-2 weeks at dosages of 300-600 mg/injection. Side effects can include weight gain, fatigue, hypersomnia, gallstones, depression, and decreased spermatogenesis and gynecomastia.

Medroxyprogesterone acetate, an analog of progesterone, lowers serum testosterone by reducing the production of testosterone from its precursors and by significantly increasing its metabolic clearance rate from serum by interfering with the binding of testosterone to a sex hormone-binding globulin (Albin et al. 1973). It is most commonly prescribed in the parenteral-depot form and injected weekly or biweekly at dosages ranging from 100-800 mg (usually 200-500 mg). Although less data are available on the use of oral medroxyprogesterone, encouraging results have been reported (Gottesman and Schubert 1993; Langevin et al. 1979) with dosages from 20 to 120 mg/day. Side effects associated with medroxyprogesterone acetate may include weight gain, fatigue, gallstones, hypertension, headaches, hyperglycemia, leg cramps, diminished spermatogenesis, and an increased risk of thrombosis. Rarely, feminization effects, such as breast swelling and changes in hair distribution, may occur during prolonged treatment with either drug. Because antiandrogens diminish serum testosterone and affect its synthesis, these medications are generally not prescribed to adolescent sex offenders.