World J Mens Health.  2016 Dec;34(3):194-199. 10.5534/wjmh.2016.34.3.194.

Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome

• Jung HJ
• Shin HS

• KMID: 2364202
• DOI: http://doi.org/10.5534/wjmh.2016.34.3.194

Abstract

PURPOSE
We aimed to evaluate the effect of testosterone replacement therapy (TRT) on cognitive function and depression in men with testosterone deficiency syndrome.
MATERIALS AND METHODS
We carried out a prospective, placebo-controlled trial involving 106 men with total testosterone levels <3.3 ng/mL and symptoms of hypogonadism. Based on whether the patients received TRT (injection with 1,000 mg testosterone undecanoate) or a placebo (advice to modify lifestyle), the study population was divided into a TRT group (n=54) and a control group (n=52).
RESULTS
The age among patients in the TRT and control groups was 56.7±12.6 years and 57.8±11.4 years, respectively (p> 0.05). At baseline, no significant differences between the TRT and control groups were noted regarding serum testosterone or prostate-specific antigen levels, or regarding the scores for aging symptoms (Aging Males' Symptoms scale), erectile function (5-item International Index of Erectile Function questionnaire), cognitive function (Korean Mini-Mental State Examination), and depression (Beck Depression Inventory). At 8 months after intervention total serum testosterone levels and erectile function scores had significantly increased (p<0.05), whereas the scores for aging symptoms and depression had significantly decreased (p<0.05) in the TRT group; no significant improvement in any parameters was noted for the control group. Notably, significant improvement in cognitive function was noted among patients with cognitive impairment at baseline (cognitive function score <25) who received TRT.
CONCLUSIONS
TRT may be considered in men with testosterone deficiency syndrome if low testosterone levels are associated with depression or cognitive impairment.

Keyword

Cognition; Depression; Testosteron

MeSH Terms

Aging
Cognition
Cognition Disorders
Depression*
Humans
Hypogonadism
Male
Prospective Studies
Prostate-Specific Antigen
Testosterone*
Prostate-Specific Antigen
Testosterone

Figure

• 

  Fig. 1 Changes in clinical parameters at 8 months after intervention with either testosterone replacement therapy (TRT group, n=54) or placebo (control group, n=52) in patients with testosterone deficiency syndrome. At 8 months after intervention, the improvement in total testosterone levels, IIEF-5 score, AMS score, and BDI score was significantly higher (*) in the TRT group than in the control group. *p<0.05 compared with control group. Qmax: maximal urinary flow rate, PVR: postvoid residual volume, IIEF-5: 5-item version of the International Index of Erectile Function questionnaire, AMS: Aging Males' Symptoms, BDI: Beck Depression Inventory, K-MMSE: Korean Mini-Mental State Examination.

• 

  Fig. 2 Overview of K-MMSE scores for patients with testosterone deficiency syndrome, stratified according to whether they received testosterone replacement therapy (TRT group, n=13) or a placebo (control group, n=12). Only data for patients with cognitive impairment at baseline (K-MMSE score <25) are given. At 8 months after intervention, the K-MMSE scores improved significantly (*) in the TRT group but not in the control group. *p<0.05 compared with baseline values. K-MMSE: Korean Mini-Mental State Examination.

Reference

1. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006; 166:1660–1665.

2. Schroeder ET, Zheng L, Ong MD, Martinez C, Flores C, Stewart Y, et al. Effects of androgen therapy on adipose tissue and metabolism in older men. J Clin Endocrinol Metab. 2004; 89:4863–4872.

3. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002; 87:5001–5007.

4. Finas D, Bals-Pratsch M, Sandmann J, Eichenauer R, Jocham D, Diedrich K, et al. Quality of life in elderly men with androgen deficiency. Andrologia. 2006; 38:48–53.

5. Berglund LH, Prytz HS, Perski A, Svartberg J. Testosterone levels and psychological health status in men from a general population: the Tromsø study. Aging Male. 2011; 14:37–41.

6. Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc. 2003; 51:101–115. discussion 115.

7. Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009; 15:289–305.

8. Seidman SN, Spatz E, Rizzo C, Roose SP. Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. J Clin Psychiatry. 2001; 62:406–412.

9. Muller M, Aleman A, Grobbee DE, de Haan EH, van der Schouw YT. Endogenous sex hormone levels and cognitive function in aging men: is there an optimal level? Neurology. 2005; 64:866–871.

10. Cherrier MM, Craft S, Matsumoto AH. Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. J Androl. 2003; 24:568–576.

11. Kenny AM, Bellantonio S, Gruman CA, Acosta RD, Prestwood KM. Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci. 2002; 57:M321–M325.

12. Kang Y, Na DL, Hahn S. A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients. J Korean Neurol Assoc. 1997; 15:300–308.

13. McDowell I. Measuring health: a guide to rating scales and questionnaires. 3rd ed. New York: Oxford University Press, Inc.;2006.

14. Zitzmann M, Weckesser M, Schober O, Nieschlag E. Changes in cerebral glucose metabolism and visuospatial capability in hypogonadal males under testosterone substitution therapy. Exp Clin Endocrinol Diabetes. 2001; 109:302–304.

15. Azad N, Pitale S, Barnes WE, Friedman N. Testosterone treatment enhances regional brain perfusion in hypogonadal men. J Clin Endocrinol Metab. 2003; 88:3064–3068.

16. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001; 58:1985–1992.

17. Cherrier MM, Matsumoto AM, Amory JK, Asthana S, Bremner W, Peskind ER, et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005; 64:2063–2068.

18. Lunenfeld B, Nieschlag E. Testosterone therapy in the aging male. Aging Male. 2007; 10:139–153.

19. Morley JE. Testosterone replacement in older men and women. J Gend Specif Med. 2001; 4:49–53.

20. Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003; 160:105–111.

21. Barrett-Connor E, Von Mühlen DG, Kritz-Silverstein D. Bio-available testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab. 1999; 84:573–577.