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Original Research

Open Access


  • Kazuyoshi Shigehara1
  • Yuki Kato1
  • Shohei Kawaguchi2
  • Masashi Ijima1
  • Kouji Izumi1
  • Yoshifumi Kadono1
  • Hiroyuki Konaka2
  • Mikio Namiki3
  • Atsushi Mizokami1

1Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

2Department of Urology, Kanazawa Red Cross Hospital, Kanazawa, Japan

3Department of Urology, Hasegawa Hospital, Toyama, Japan

DOI: 10.31083/jomh.v16i4.208 Vol.16,Issue 4,October 2020 pp.65-71

Published: 01 October 2020

*Corresponding Author(s): Kazuyoshi Shigehara E-mail:

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Background and objective 

This study assessed the short-term effects of testosterone replacement therapy (TRT) on some risk predic-tors for arteriosclerosis among men with late-onset hypogonadism (LOH).

Materials and methods 

A total of 25 patients with LOH who received TRT for 6 months and 21 patients without TRT were enrolled in the present study. Information regarding the following parameters were collected: Aging Males’ Symptoms scale, Sexual Health Inventory for Men (SHIM), International Prostatic Symptom Score, waist circumfer-ence, and some laboratory data, including fasting blood sugar, hemoglobin A1c (HbA1c), low-density lipo-protein cholesterol, triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP) values, and arteriosclerosis index (AI), at baseline and after 6 months. Patients in the TRT group had received intramuscular injections of testosterone enanthate (250 mg) every month for 6 months while those in the control group received no testosterone treatment during this trial.


No significant differences were observed in any baseline patient characteristics between both groups. After 6 months, the TRT group exhibited significant improvements in SHIM scores (from 10.1 to 13.1; p = 0.00563), hs-CRP values (from 0.157 to 0.103 mg/dL; p = 0.00753), and the AI (from 2.10 to 1.95 mg/dL; p = 0.0429), with a significant decrease in AMS scale (from 44.3 to 41.8; p = 0.0388). The control group dis-played no significant changes in all parameters. No patient in the TRT group had additional interventions or medications worsening their urinary symptoms.


TRT for 6 months among men with LOH contributed to significant improvements in three predictive fac-tors for arteriosclerosis. Further studies including long-term TRT are expected to demonstrate the preven-tive effects of testosterone for arteriosclerosis among Japanese men with LOH syndrome.


arteriosclerosis; C-reactive protein; erectile dysfunction; late-onset hypogonadism; testoster-one replacement therapy

Cite and Share

Kazuyoshi Shigehara,Yuki Kato,Shohei Kawaguchi,Masashi Ijima,Kouji Izumi,Yoshifumi Kadono,Hiroyuki Konaka,Mikio Namiki,Atsushi Mizokami. SHORT-TERM EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY ON RISK PREDICTORS FOR ARTERIOSCLEROSIS AMONG MEN WITH LATE-ONSET HYPOGONADISM: A CASE–CONTROL STUDY. Journal of Men's Health. 2020. 16(4);65-71.


1. Lunenfeld B, Mskhalaya G, Zitzmann M, et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male 2015;18:5–15. 1004049

2. Blaya R, Thomaz LD, Guilhermano F, et al. Total testosterone levels are correlated to metabolic syn-drome components. Aging Male 2016;19:85–9.

3. Grosman H, Rosales M, Fabre B, et al. Association between testosterone levels and the metabolic syn-drome in adult men. Aging Male 2014;17:161–5.

4. Hisasue S. Contemporary perspective and manage-ment of testosterone deficiency: Modifiable factors and variable management. Int J Urol 2015;22:1084–


5. Nian Y, Ding M, Hu S, et al. Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: A meta-anal-ysis of randomized controlled trials. Andrologia 2017;49(4).

6. Shigehara K, Konaka H, Nohara T, et al. Effects of testosterone replacement therapy on metabolic syndrome among Japanese hypogonadal men: A subanalysis of a prospective randomised controlled trial (EARTH study). Andrologia 2018;50(1).

7. Deng C, Zhang Z, Li H, et al. Analysis of cardiovas-cular risk factors associated with serum testoster-one levels according to the US 2011-2012 National Health and Nutrition Examination Survey. Aging Male 2019;22:121–8. 38.2018.1479387

8. Schouten BW, Bohnen AM, Bosch JL, et al. Erectile dysfunction prospectively associated with cardiovascular disease in the Dutch general pop-ulation: Results from the Krimpen Study. Int J Impot Res 2008;20:92–9.

9. Yassin AA, Akhras F, El-Sakka AI, et al. Cardiovascular diseases and erectile dysfunction: The two faces of the coin of androgen deficiency. Andrologia 2011;43:1–8.

10. Sabatine MS, Morrow DA, Jablonski KA, et al. Prognostic significance of the centers for disease control/American Heart Association high- sensitivity

C- reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 2007;115:1528–36.

11. Mertz DP. Atherosclerosis-index (LDL/HDL): Risk indicator in lipid metabolism disorders. Med Klin 1980;75:159–61.

12. Namiki M, Akaza H, Shimazui T, et al. Working committee on clinical practice guidelines for late-onset hypogonadism; Japanese Urological Association/Japanese Society for Study of Aging Male. Clinical practice manual for late-onset hypo-gonadism syndrome. Int J Urol 2008;15:377–88.

13. Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, et al. Prediction of cardio-vascular events and all-cause mortality with erectile dysfunction: A systematic review and meta- analysis of cohort studies. Circ Cardiovasc Qual Outcomes 2013;6:99–109.

14. Gazzaruso C, Solerte SB, Pujia A, et al. Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: A potential protective role for statins and 5-phosphodi-esterase inhibitors. J Am Coll Cardiol 2008;51:2040–


15. Montorsi P, Ravagnani PM, Galli S, et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: The COBRA trial. Eur Heart J 2006;27:2632–9.

16. Pye SR, Huhtaniemi IT, Finn JD, et al. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab 2014;99:1357–66. https://doi. org/10.1210/jc.2013-2052

17. Saad F, Caliber M, Doros G, et al. Long-term treat-ment with testosterone undecanoate injections in men with hypogonadism alleviates erectile dys-function and reduces risk of major adverse car-diovascular events, prostate cancer, and mortality. Aging Male 2019;20:1–12. 3685538.2019.1575354

18. Shores M, Smith NL, Forsberg CW, et al. Testosterone treatment and mortality in men with low testoster-one. J Clin Endocrin Metab 2012;97:2050–8.

19. Garcia JA, Sanchez PE, Fraile C, et al. Testosterone undecanoate improves erectile dysfunction in hypo-gonadal men with the metabolic syndrome refrac-tory to treatment with phosphodiesterase type 5 inhibitors alone. Andrologia 2011;43:293–6.

20. Kaplan SA, Johnson-Levonas AO, Lin J, et al. Elevated high sensitivity C-reactive pro-tein levels in aging men with low testoster-one. Aging Male 2010;13:108–12. https://doi. org/10.3109/13685530903440424

21. Shigehara K, Konaka H, Ijima M, et al. The correla-tion between highly sensitive C-reactive protein lev-els and erectile function among men with late-onset hypogonadism. Aging Male 2016;19:239–43.

22. Yassin A, Almehmadi Y, Saad F, et al. Effects of intermission and resumption of long-term testoster-one replacement therapy on body weight and meta-bolic parameters in hypogonadal in middle- aged and elderly men. Clin Endocrinol (Oxf) 2016;84:107–14.

23. Traish AM, Haider A, Doros G, et al. Long-term tes-tosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: An observa-tional, long-term registry study. Int J Clin Pract 2014;68:314–29.

24. Lee EY, Yang Y, Kim HS, et al. Effect of visit-to-visit LDL-, HDL-, and non-HDL-cholesterol variability on mortality and cardiovascular outcomes after per-cutaneous coronary intervention. Atherosclerosis 2018;279:1–9. 2018.10.012

25. Packard CJ, Ford I, Robertson M, et al. Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation 2005;112: 3058–65. AHA.104.526848

26. Kawakami R, Matsumoto I, Shiomi M, et al. Role of the low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol ratio in pre-dicting serial changes in the lipid component of cor-onary plaque. Circ J 2017;81:1439–46. https://doi. org/10.1253/circj.CJ-16-1209

27. Traish AM, Abdou R, Kypreos KE. Androgen defi-ciency and atherosclerosis: The lipid link. Vascul Pharmacol 2009;51:303–13. vph.2009.09.003

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