Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men

Table 1

Naturalistic and cross-sectional studies in nonselected samples of patients.

Author, year	Type of study	Sample size	Age	Outcome measures	Results
Barrett-Connor et al. [64]	Cross-sectional population-based study	856 men	Range: 50–89 yrs	Association between BDI and BT or DHT	BDI scores were inversely associated with BT and DHT. BT were 17% lower for men with categorically defined depression than levels observed in all other men.
T’Sjoen et al. [105]	Naturalistic	236 male outpatients in 1997 and 192 in 2000	All patients were 70+ yrs. Range: 73.5–78.5 yrs in 1997; 76.0–81.0 yrs in 2000	Association between GDS and TT, FT, estradiol, DHEAS, AR gene CAG-repeat length	No relationship between the GDS and FT or TT in 1997. The GDS did not correlate with AR gene CAG-repeat length. The GDS of 1997 correlated significantly with (free) estradiol and with DHEAS. The analysis in 2000 confirmed a lack of association between GDS and androgen levels or AR gene CAG-repeat length. The association between GDS and (free) estradiol and DHEAS was not observed in the subgroup of men studied in 2000. Changes in FT and serum (free) estradiol levels between 1996 and 2000 were not related to GDS score in 2000.
Strasser et al. [55]	Naturalistic	48 patients with cancer who had received no major antineoplastic intervention for at least 2 weeks	Range: 20–79 yrs; Median: 59 yrs	Association between HAM-D and hypogonadism	64% of patients had hypogonadism, which was correlated with HAM-D score.
Spetz et al. [43]	Cross sectional	370 men	Range: 55 to 75 yrs; median: 62 yrs	Blood concentrations of T and BT	Men reporting deterioration in work performance had significantly lower T (16.6 nmol/L) and BT (6.9 nmol/L) than men without this problem (18.8 nmol/L and 7.9 nmol/L, resp.). Men reporting decreased strength and/or endurance had lower concentrations of BT than men without the same complaint (7.2 nmol/L and 8.0 nmol/L, resp.). Men suffering from hot flushes had lower T (15.1 nmol/L) and BT (6.58 nmol/L) compared with men who either had flushes but were not bothered by them or men without any flushes (17.6 nmol/L and 7.63 nmol/L).
Kratzik et al. [54]	Naturalistic	669 manual workers	Range: 43–67 years	Association between BT, BMI and BDI scores	There was a U-shaped (quadratic) association between BT and BDI. Obese and underweight men with high BT had an increase BDI score. Men with low BT levels had an increased BDI score and eugonadal men with normal T levels have the lowest risk of depression.
Morsink et al. [53]	Prospective cohort udy	2855 well-functioning elderly men (1406) and women (1449)	All aged aged 70–79 yrs; Mean: 73.8 yrs (men); 73.5 yrs (women)	Associations between TT, FT, DHEAS and CES-D scores	Significant inverse association between DHEAS and the CES-D for men and women. In men, there was a borderline significant inverse association between TT and depressive symptoms. For men, those in the lowest quartile of DHEAS and TT had significantly more depressive symptoms than those in the other quartiles.
Makhlouf et al. [52]	Naturalistic	157 men referred to an erectile dysfunction specialty clinic	Range: 21–85 yrs; Median = 53 yrs	Scores of 22 or higher on the CES-D (overt depression)	Hypogonadal men were 1.94 times more likely to have overt depression scores compared to eugonadal counterparts.
Fukai et al. [50]	Cross-sectional	108 men and 100 women	Range: 70–95 yrs; Mean:82±7yrs (men);81±6yrs (women)	Associations between GDS and TT, FT, DHEA, DHEAS, Estradiol	Linear regression model of hormone levels on functional scores unadjusted and adjusted for age, and age and body mass index indicated that in men the GDS was not associated with hormone levels.
Hintikka et al. [47]	Naturalistic	59 men with adverse mental symptoms (AMS) and 57 asymptomatic (AS) men from the Finnish National Population Register	Mean: 55.9±8.6 yrs for AMS and 56.3±10.4 yrs for AS	Hypogonadism (FT < 160 pmol/L)	AMS more often had hypogonadism; BDI score and HAM-D correlated negatively with FT in the entire sample.
Wu et al. [7]	Naturalistic	Random population sample of 3,369 men at eight European centers	Mean: 59.7±0.3 yrs	Associations between TT and FT, and items from the SF-36 and the BDI	Sadness (SF-36), loss of energy (BDI), and fatigue were significantly associated with FT but not with TT. The probability of symptoms increased with decreased levels of T. The thresholds for TT were approximately 160 pmol/L for both sadness and fatigue.
Jankowska et al. [49]	Cross-sectional	Study population: 163 men with stable systolic chronic heart failure (CHF), and 316 healthy men living in the same area	Range: 35–80 yrs (controls) Mean:60±10yrs (CHF)	Associations between BDI and TT or DHEAS	There were no differences in serum TT levels between the healthy men and the men with CHF when evaluated according to BDI score. Men with CHF had lower serum DHEAS as compared with healthy men in subsequent groups according to BDI score. Lower TT and DHEAS were associated with depressive symptoms in men with CHF.
Wong et al. [106]	Naturalistic	1147 community-dwelling elderly men, aged	65+ yrs	Associations between GDS, DHEA, TT, FT, estradiol, and SHBG	DHEA was significantly associated with GDS score. No association was seen between depressive symptoms and TT, FT, estradiol levels or SHBG levels.
Berglund et al. [56]	Naturalistic	3413 men participating in the fifth Tromsø study in 2001	Range:60±14yrs	Associations between the Hopkins Symptom Checklist-10 (SCL-10) scores and T	Men with T levels in the lowest 10th percentile, had increased SCL-10 score compared to men with higher T levels. However, men with more pronounced symptoms indicating mental disorder did not have lower testosterone levels.
Halabi et al. [63]	Cross-sectional	104 men with COPD; 36 of whom had significant depressive symptoms (GDS ≥ 11)	All 55+ yrs. Mean:66±1; (depressed),71±1; (nondepressed):	Associations between GDS and hypogonadism	Prevalence of hypogonadism was greater in patients with severe depressive symptoms (GDS ≥ 19) than in those with mild depressive symptoms (GDS = 11–18) (62% versus 26%). After controlling for confounders, however, gonadal state was not associated with severe depressive symptoms.

T: testosterone; BT: bioavailable testosterone; FT: free testosterone; DHEA: dehydroepiandrosterone; DHEAS: dehydroepiandrosterone sulphate; SHBG: sex hormone-binding globulin; BMI: body mass index; HAM-D: Hamilton scale for depression; BDI: Beck depression inventory; CES-D: center for epidemiologic studies depression scale; GDS: geriatric depression scale.