Medroxyprogesterone acetate, an analog of progesterone(Drug information on 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 serum sex-hormone binding globulin. It is most commonly prescribed in the parenteral depot form and injected weekly or biweekly in doses ranging from 100 to 800 mg (usually 200 to 500 mg). Although less clinical data exist on oral medroxyprogest-erone, encouraging results have been reported (Gottesman and Schubert) using doses from 20 to 100 mg per day.
Cyproterone acetate inhibits testosterone directly at androgen receptor sites and also exhibits antigonadotrophic effects. In its oral form, the usual prescribed dosage range is 50 to 200 mg per day. Parenterally, it is usually administered every one to two weeks at dosages of 300 to 600 mg per injection.
Testosterone, the principal androgen (sex hormone) produced by the testes, is considered the most important androgen affecting male sexual behavior. The role of testosterone as a primary etiological factor in physical and sexual aggression in men, however, remains ambiguous. The majority of studies of testosterone in male sex offenders reveal that serum total testosterone (i.e., protein bound and unbound) is within normal limits in all but a subgroup of the most violent paraphiliacs (Hucker and Bain). In fact, there are reports of male paraphilias with low baseline serum testosterone (Seim and Dwyer). Despite these data, most men prescribed antiandrogens report a calming effect in both sexual aggression and general irritability, and these agents have become the standard biological intervention for sexually aggressive paraphiliacs. Since the prescription of antiandrogens for paraphilias is still considered an off-label use (i.e., not FDA-approved for that specific use), it is prudent to document informed consent in a patient's record before antiandrogen administration, and to obtain baseline fasting glucose, liver functions, vital signs, serum FSH and total testosterone.
The effect of antiandrogens on sexual desire and associated fantasies, erections, urges and other sexual behaviors is usually evident by two to four weeks after the initiation of pharmacotherapy. Pharmacological tolerance to their effects has not been described, and either agent can be tapered without a rebound increase in sexual or aggressive behaviors. After a period of symptom stabilization, a lower maintenance dose can sometimes be titrated to minimize side effects, and in some cases, to permit a more selective mitigation of deviant sexuality in comparison with conventional sexual desire.
Sexual fantasies and erections usually return approximately two to four weeks after an antiandrogen is gradually tapered, although in some men it may take longer for the effects to be fully reversed.
Although there may not be a linear relationship between lowered serum testosterone and diminished deviant sexual behavior, some investigators seek to lower serum testosterone to prepubertal levels (<100 ng per dL) and others target a 50-percent reduction of circulating testosterone as adequate for a therapeutic effect with less side effects. This clinical feature of monitoring circulating testosterone as well as the parenteral administration of these agents provides a means to assure compliance in men who are court-mandated, are sexual predators or are incapable of taking oral medications reliably to assure that compliance with treatment had been maintained should an offense reoccur. On the other hand, oral MPA or CPA can be utilized with highly motivated males with paraphilias and paraphilia-related disorders (Gottesman and Schubert).
In oral preparation, the daily dose of antiandrogens can be more readily titrated to perhaps preserve "conventional"sexual arousal. Compliance is enhanced because the patient is afforded improved self-efficacy, and the dose can be more easily adjusted during a slow taper phase.
It is common practice that antiandrogen pharmacotherapy is utilized as a therapeutic modality early (e.g., three to 12 months) during cognitive, behavioral and group therapies in the treatment of sex offender paraphiliac patients. In some circumstances, however, antiandrogens have been prescribed for more than a decade with no significant untoward effects and with continued beneficial mitigation of deviant sexual arousal.
