OPTIMIZING ANTILIBIDINAL TREATMENT WITH MEDROXYPROGESTERONE ACETATE

Abstract

To the Editor: Sexual disinhibition in demented patients is not a common problem1–3 but can be a tremendously disruptive one for all concerned. Medroxyprogesterone acetate (MPA) has been shown to be effective for and well tolerated by such patients, generally in modest doses.3,4 The mechanism of action seems to be suppression of follicle-stimulating hormone and luteinizing hormone secretion at the pituitary level, leading to decreased testosterone production and decreased libido.2 Although there is some contrary evidence,5 reduction in serum testosterone levels seems to correlate with behavioral improvement. We recently cared for a seemingly refractory patient in whom monitoring of serum testosterone levels ultimately led to successful treatment with a fairly high dose of MPA. A 76-year-old man with a 15-year history of alcoholic dementia had had ongoing problems with sexually disinhibited behavior for about 10 years. These behaviors included masturbating publicly and verbal and physical sexual advances toward women and had resulted in multiple hospitalizations and discharges from assisted living facilities. Medical history was noncontributory, and there was no evidence of hypersexual or paraphilic behavior or psychiatric illness (other than alcoholism) before the onset of the dementia. Mental status examination was significant for deficits in memory and executive function; there was no evidence of mania or psychosis. The sexual behavior had failed to respond to various neuroleptics and mood stabilizers in the past but had remitted for 5 years with paroxetine, although ultimately the behavior recurred for unclear reasons and failed to respond significantly to substitution of intramuscular MPA in doses as high as 300 mg per week. MPA was titrated as high as 600 mg per week, and paroxetine was ultimately reintroduced, but the sexual behavior did not improve significantly. At this point, a serum testosterone level of 72.1 ng/dL was noted. The MPA dosage was increased to 750 mg per week, and repeat testosterone level was 48.4 ng/dL. At that dosage, the sexual behavior improved markedly; there have been no further sexual advances toward women in the past 2 months, and he masturbates only rarely and discreetly in his room. This patient responded to a much higher dose of MPA than other demented patients reported in the literature; Cooper3 used a fixed dose of 300 mg weekly, and Weiner et al.4 used doses of 100 mg to 200 mg every other week. We found that monitoring testosterone levels helped to explain the patient's apparent refractoriness and to guide successful treatment. This experience was similar to that of others; Cooper5 reported a mean 90% reduction in serum testosterone levels in his successfully treated patients (we unfortunately did not check a pretreatment testosterone level in our patient), and Cordoba and Chapel6 reported testosterone levels reduced “nearly to female values” (25ng/dL–90 ng/dL,7) in their younger, nondemented patient. Serious sexual disinhibition is a potentially devastating problem in demented individuals, leading to hospitalization, restrictive placements, and potential legal liability; MPA can be effective in such patients, and monitoring of serum testosterone levels may be a useful strategy for optimizing treatment.