Table 2. Effect of testosterone therapy on AD and cognitive impairment.
| Study | Patients | Age (y)a | Study | Therapy | Duration | Outcomes |
|---|---|---|---|---|---|---|
| Resnick et al, 2017 [77] | 788 men, impaired sexual function | 65 | RCT | T gel with a dose to maintain the physiological plasma level | 4 years | No association with improved memory or other cognitive functions. |
| Wahjoepramono et al, 2016 [78] | 44 men | ≥50 | RCT | T gel 50 mg | 24 weeks and 4 weeks washout | Significant improvement in general cognitive functioning. |
| Huang et al, 2016 [79] | 308 men with low T | 60 | RCT multicenter study | T gel 7.5 g of 1% | 36 months | T administration did not improve cognitive function. |
| Asih et al, 2015 [80] | 44, older men | 61±7.7 | RCT | Transdermal T (50 mg/d) |
24 weeks | Significant increases in plasma androgens levels. No changes in plasma amyloid-beta. Dementia is not investigated. |
| Cherrier et al, 2015 [81] |
351 men community | 70.5±8.2 | RCT | T gel (50 to 100 mg/d) |
3 months | Modest improvement in verbal memory and depression symptoms. |
| 37 with MCI and low T | ||||||
| Borst et al, 2014 [82] | 60 hypogonadal men | 70.8 | RCT | T-enanthate (125 mg/wk) |
12 months | Small improvements in depressive symptoms and visuospatial cognition. |
| Young et al, 2010 [83] | 26 young 62 older | 25–35 | RCT | GnRH agonist, T-gel 75 and 100 mg | 6 weeks | Free T positively correlated to spatial cognition while estradiol negatively correlated with working memory. |
| 60–80 | ||||||
| Emmelot-Vonk et al, 2008 [84] | 237 healthy men with a low T leve | 60–80 | RCT | T undecenoate 80 mg | 6 months | Cognitive function and bone mineral density did not change. |
| Vaughan et al, 2007 [85] | 65 healthy men | RCT | 200 mg of T every 2 weeks with 5 mg of finasteride daily (T+F), or placebo | 36 months | No clinically significant effect on tests of cognitive function. | |
| Maki et al, 2007 [86] | 15 normal men | 66–87 | RCT | T enanthate (200 mg i.m. every other week) |
3 months | Decreased verbal memory and altered relative activity in medial temporal and prefrontal regions. |
| Cherrier et al, 2007 [87] | 57 eugonadal men | 67±11 | RCT | T enanthate i.m. 50, 100, or 300 mg/wk | 6 weeks | No significant changes in memory. |
| Lu et al, 2006 [88] | 16 men with mild AD | RCT | T gel (75 mg) | 24 weeks | T replacement therapy improved the quality of life in AD patients. T had minimal effects on cognition. | |
| Haren et al, 2005 [89] | 76 healthy men | 60 | RCT | T undecanoate 80 mg twice daily | 12 months | Not affect scores on visuospatial tests or mood and quality of life scales. |
| Kenny et al, 2004 [90] | 11 men with cognitive decline | 80±5 | RCT | 200 mg every 3 weeks | 12 weeks | No significant changes in behavior, function, depression, or cognitive performance. |
| Tan et al, 2003 [91] | 36 men with AD | RCT | Intramuscular T 200 mg every 2 weeks | 12 months | ADAScog, MMSE, and CDT improved significantly in treated patients. | |
| 10 hypogonadal | ||||||
| O’Connor et al, 2001 [92] | 30 healthy eugonadal men and 7 hypogonadal men | RCT | 200 mg of T enanthate i.m. weekly | 8 weeks | Increased T has a differential effect on cognitive function, inhibiting spatial abilities while improving verbal fluency. | |
| Cherrier et al, 2001 [93] | 25 healthy men | RCT | T enanthate 100 mg weekly | 6 weeks | Short-term T administration enhances cognitive function. |
AD: Alzheimer’s disease, RCT: randomized controlled trial, T: testosterone, MCI: mild cognitive impairment, GnRH: gonadotropin-releasing hormone, ADAScog: Alzheimer’s Disease Assessment Scale Cognitive Subscale, MMSE: Mini-Mental Status Examination, CDT: clock drawing test.
aValues are presented as mean only or mean±standard deviation.