Testosterone therapy in late-life major depression in males.
BACKGROUND
Major depression associated with aging in males may improve with anabolic/androgenic steroid therapy. The efficacy and safety of testosterone therapy in the treatment of depression in elderly hypogonadal males is inconclusive. The following study identifies a subgroup of elderly depressed males who may benefit from testosterone therapy.


METHODS
Participants included 16 elderly eugonadal males with major depressive disorder (DSM-IV criteria) and a Hamilton Rating Scale for Depression (HAM-D) score > 18. Following a single-blind 2-week placebo lead-in, patients were randomly assigned to treatment with either a physiologic dose of testosterone cypionate (TC), 100 mg/week, or supraphysiologic dose of 200 mg/week IM for 6 weeks. Psychometric testing was carried out at entry into the study, at the TC injection baseline, and every 2 weeks thereafter. Tests included an objective measurement, the HAM-D, and the Buss-Durkee Hostility Inventory.


RESULTS
One patient meeting inclusion criteria responded during the placebo lead-in; thus, 15 patients were randomly assigned to treatment (100 mg/week, N = 8; 200 mg/week, N = 7). There was a 42% decrease in the mean HAM-D scores from 20.1 to 11.9 (p <.0001). However, the majority of the change was due to improvement in the 10 late-onset (< or = 45 years old) depression patients, whose mean HAM-D score decreased from 19.8 to 9.3 (53%), versus the 5 early-onset depression patients, whose mean HAM-D score decreased from 20.8 to 17.0 (18%) (p =.0110). The TC dose did not affect the response. Similar HAM-D decreases of 43% and 41% occurred for the respective 100- and 200-mg/week doses. The HAM-D responder analysis found that none of 5 early-onset patients had HAM-D response, whereas 6 (60%) of 10 late-onset patients responded (p =.025). Similarly, none of the early-onset patients experienced a remission whereas 5 (50%) of the late-onset patients were categorized as remitters (p =.053). Correlations between the peak and mean total testosterone concentrations and HAM-D change scores suggested that only minimal TC doses were required to produce an antidepressant effect.


CONCLUSIONS
These data suggest that testosterone therapy would best be limited to men with late-onset depression. The findings suggest that short-term therapy with TC is safe. Long-term treatment safety is unknown. Psychiatrists using testosterone therapy should ascertain that patients have been recently valuated for prostate cancer. If testosterone therapy is initiated, serial serum prostate-specific antigen sampling should be used for monitoring patients' prostate status.
Perry
Paul J
PJ
Division of Clinical Pharmacy, College of Pharmacy, University of Iowa, Iowa City 52242, USA. paul-perry@uiowa.edu
Yates
William R
WR
Williams
Richard D
RD
Andersen
Arnold E
AE
MacIndoe
John H
JH
Lund
Brian C
BC
Holman
Timothy L
TL
D045930:Anabolic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*
D045930:Anabolic Agents; D013739:Testosterone; C016131:testosterone 17 beta-cypionate