TESTOSTERONE LEVEL, ANDROGEN RECEPTOR POLYMORPHISM, AND DEPRESSIVE SYMPTOMS IN MIDDLE-AGED MEN





SN Seidman, AB Araujo, SP Roose, JB McKinlay

Columbia University Department of Psychiatry,
NY State Psychiatric Institute, Unit 98,
1051 Riverside Drive, New York, NY 10032




Testosterone (T) level declines progressively in middle-aged and elderly men. Psychiatric symptoms of T deficiency (e.g., dysphoria, fatigue, irritability, low libido), which are also symptoms of depression, appear to be variably expressed. We assessed measures of
hypothalamic-pituitary-gonadal (HPG) axis functioning (total T level and androgen receptor CAG allele repeat frequency -- a genetic trait marker of androgen receptor function) and depression (defined by Center for Epidemiologic Studies-Depression scale (CES-D) score >16) in 1000 men ages 48-79 years (mean=62.6; SD=8.3) who participated in the Massachusetts Male Aging Study. There were 110 (11%) men with depression in the analysis sample. Neither total T nor androgen receptor CAG allele repeat frequency was associated with depression in bi-variate analyses. However, in a multiple logistic regression analysis that included both HPG factors and their interaction, total T (p=0.02), androgen receptor CAG allele frequency (p=0.01), and a term for their interaction (p=0.02) were all associated with depression. Androgen receptor functioning (for which the CAG isotype is a trait marker) may mediate the expression of some psychiatric effects of T deficiency, making some men vulnerable to “hypogonadal depression.”




Key words: hypogonadism, testosterone, depression, androgen receptor







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