Abstract
Background: Testosterone (T) level declines progressively with age. Psychiatric symptoms
of T deficiency (e.g., dysphoria, fatigue, irritability, low libido) are also symptoms
of depression, and appear to be variably expressed.
Methods: We assessed independent measures of hypothalamic-pituitary-gonadal axis functioning,
i.e., total T level and androgen receptor (AR) CAG repeat length (CAG RL), a genetic
trait marker associated with AR function; and depression (diagnosed by above-threshold
score on the Center for Epidemiologic Studies-Depression Scale [CES-D]) in 1000 men
(mean age = 62.6 years; SD = 8.3) who participated in the Massachusetts Male Aging
Study.
Results: There were 110 (11%) men with “depression” (CES-D score ≥ 16) in the analysis
sample. Neither total T level nor CAG RL was associated with depression in bivariate
analyses. Among men with shorter CAG RLs, the percentage of men with depression was
21.6% in the lowest subgroup of total T (defined by quintiles) and 4.2% in the highest
subgroup of total T. This was confirmed in simple logistic regression models with
depression as the dependent variable and continuous total T as the predictor, run
separately within the three CAG RL subgroups: depression was significantly and inversely
associated with total T in men with shorter CAG RLs but not in men with moderate and
longer CAG RLs.
Conclusions: CAG isotype, a genetic trait marker of androgen receptor function, may
mediate the expression of the central nervous system effects of T deficiency in men.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The relationship between depressive symptoms and male erectile dysfunction.Psychosom Med. 1998; 60: 458-465
- Bioavailable testosterone and depressed mood in older men.J Clin Endocrinol Metab. 1999; 84: 573-577
- Testosterone and men’s depression.J Health Soc Behav. 1999; 40: 130-140
- Does collecting repeated blood samples from each subject improve the precision of estimated steroid hormone levels?.J Clin Epidemiol. 1996; 49: 345-350
- CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk.Br J Cancer. 1999; 8: 672-676
- The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function.Nucleic Acids Res. 1994; 22: 3181-3186
- Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups.Genomics. 1992; 12: 241-253
- The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.J Clin Endocrinol Metab. 1994; 79: 1310-1316
- Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men.J Endocrinol. 1999; 162: 137-142
- Cloning of human androgen receptor complementary DNA and localization to the X chromosome.Science. 1988; 240: 327-330
- The questionable physiologic and epidemiologic basis for a male climacteric syndrome.Maturitas. 1989; 11: 103-115
- Andropause.J Urol. 2000; 163: 705-712
- Use of a self-report symptom scale to detect depression in a community sample.Am J Psychiatry. 1980; 137: 1081-1084
- Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes.Arch Gen Psychiatry. 1994; 51: 375-382
- Effects of supraphysiologic doses of testosterone on mood and aggression in normal men. A randomized controlled trial.Arch Gen Psychiatry. 2000; 57: 133-140
- The Center for Epidemiologic Studies Depression Scale.Am J Psychiatry. 1983; 140: 41-46
- Estrogens and androgens.Neuropsychopharmacology. 2000; 23 (Abstract): S56-S56
- Low testosterone levels in elderly men with dysthymic disorder.Neuropsychopharmacology. 2000; 23 (Abstract): S147
Seidman SN, Spatz E, Roose SP (in press b): Testosterone replacement for depressed men: Randomized clinical trial. J Clin Psychiatry. 62.
- The prevalence and incidence of depression in older hypogonadal men. Abstract presented at the American Association of Geriatric Psychiatry Annual Meeting. 2001
- Transcriptional activation and nuclear targeting signals of the human androgen receptor.J Biol Chem. 1991; 266: 510-518
- Domain functions of the androgen receptor.J Steroid Biochem Mol Biol. 1992; 43: 37-41
- Age-associated testosterone decline in men.Am J Psychiatry. 1998; 155: 1310-1318
- Ageing of the hypothalamo-pituitary-testicular axis in men.Horm Res. 1995; 43: 25-28
- Testosterone replacement therapy improves mood in hypogonadal men—a clinical research center study.J Clin Endocrinol Metab. 1996; 81: 3578-3583
- Psychosexual effects of three doses of testosterone in cycling and normal men.Biol Psychiatry. 1999; 45: 254-260
Article info
Publication history
Accepted:
March 16,
2001
Received in revised form:
March 13,
2001
Received:
December 6,
2000
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.