How to select pharmacologic treatments to manage recidivism risk in sex offenders

Finasteride is approved for treating benign prostatic hyperplasia and androgenetic alopecia. It works by preventing conversion of testosterone to dihydrotestosterone (DHT) by the type II isoenzyme.²¹ Serum DHT contributes to male sexual behavior and predicts frequency of orgasms in healthy volunteers.²² Although there have been no studies of finasteride in sex offenders, it may be more acceptable to patients than other hormonal treatments and have a theoretical benefit in reducing sexual drive. Clinically, some patients describe increased control over urges without substantial side effects. Because there is no evidence supporting finasteride use in sex offenders, consider this medication only on an individual basis or as a possible adjunctive treatment.

Cyproterone acetate (CPA) is a synthetic steroid that blocks androgen receptors.^3,23 Some evidence supports its use in treating sex offenders,²⁴ although this agent is not available in the United States. For more information about CPA, see Box.

Medroxyprogesterone acetate (MPA), a derivative of progesterone, lowers serum testosterone by inhibiting its production through reducing pituitary luteinizing hormone (LH).²⁴ The typical dose range for use in sex offenders is 100 to 600 mg/d orally or 100 to 700 mg IM every week,³ although some authors suggest giving similar doses every 2 weeks.⁴

Side effects of MPA include hypersomnia; neurasthenia; weight gain; hot flashes; gynecomastia; increased scalp hair; and decreased erections, ejaculate volume, spermatogenesis, and body and facial hair. The drug decreases testosterone levels by about 50%. Positive effects include reduced interest in and energy spent on pursuing sexual goals, but preservation of nondeviant sexual arousal.⁴

MPA has been shown to effectively decrease deviant sexual arousal and recidivism. In a study of 100 patients receiving MPA (average 250 mg IM every 2 weeks) for an average of 3 years, only 1 re-offended while taking MPA.⁴

In a 5-year follow-up study²⁵ of 275 men, subjects were classified into high risk/treatment with MPA, 200 to 400 mg IM every 2 weeks, and low risk/nontreatment groups. A portion of the high risk/treatment group did not receive MPA. No sexual re-offenses occurred among high-risk subjects who received MPA, whereas the recidivism rate was 18% among high-risk subjects who did not receive MPA. Subjects in the low risk/nontreatment group had a recidivism rate of 15%, which suggests the need for more liberal use of antiandrogens. One major confounding factor was that subjects in the high risk/treatment group had to report every 2 weeks for injections; this may have resulted in closer follow-up, monitoring, and support, which may have contributed to lower recidivism.

Gonadotropin-releasing hormone (GNRH) agonists. The terms gonadotropin-releasing hormone and luteinizing-releasing hormone are used interchangeably. Most body testosterone is produced and released by Leydig cells in the testes in response to stimulation by LH released by the pituitary gland. LH release is controlled by the pulsatile release of GNRH from the hypothalamus. GNRH agonists are high-potency analogs of GNRH that work by causing an initial surge of LH followed by down-regulation of gonadotroph cells, a drop in LH, and a drop in testosterone to castration levels.

The GNRH analogs leuprolide, goserelin, and triptorelin are used to treat paraphiliacs and sexual offenders.²⁰ Leuprolide typically is dosed at 7.5 mg IM every month, 22.5 mg IM every 3 months, or 30 mg IM every 4 months. Goserelin is provided as a subcutaneous implant/depot injected as 3.6 mg every month or 10.8 mg every 3 months.

Triptorelin is FDA-approved as treatment for advanced prostate cancer. Triptorelin is given in depot formulation as 3.75 mg IM every month or in a long-acting form as 11.25 mg IM every 3 months.

When starting these medications, an initial surge of LH and testosterone can last up to 3 weeks.²⁶ Theoretically, this could worsen paraphiliac interests. Many practitioners will use a testosterone blocker such as flutamide, 250 mg tid, for the initial weeks of treatment.

Side effects of the GNRH agonists are similar. Most patients initially experience hot flashes. A systemic literature review²⁷ reported:

• weight gain
• perspiration
• gynecomastia
• urinary incontinence
• hot flashes
• decreased growth of facial and body hair
• asthenia
• erectile failure
• muscle tenderness
• frequent bone demineralization.

Rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported, possibly related to an underlying pituitary adenoma.²⁸

In a literature review that totalled 118 patients,²⁷ GNRH agonists significantly decreased erections, ejaculations, paraphiliac fantasies, and paraphiliac behavior. Patients also reported feeling more relaxed, and recidivism rates were low. Some patients who failed to respond to CPA and MPA responded to GNRH agonists. Subsequent studies found similar results.^29,30