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Objectives To review the latest innovations and advances in testosterone treatments including their advantages and disadvantages and to address important issues in testosterone therapy (TTh). Methods This review was conducted according to the Preferred Reporting Items for Systemic Reviews and Meta-analyses guidelines. The PubMed, MEDLINE, Scopus and Cochrane databases were searched using specifically related key words. The identified studies were screened for inclusion criteria that included studies discussing one of the four objectives of the systematic review: 1) cut–off references, 2) prevention/remission of type II diabetes mellitus (T2DM), 3) duration of treatment, and 4) prostate, lower urinary tract symptoms, prostate health, or cancer. The search was limited to the past 15 years. Any studies were not written in English were excluded. Results The initial literature search retrieved 393 studies. After screening four studies were removed due to duplication, 360 studies were further excluded after reviewing the title, abstract or the whole manuscript due to different exclusion criteria or being not focussed on the objective. Finally, 29 studies were included in the review. One study discussed the cut–off value, four studies discussed the effect of testosterone replacement therapy (TRT) on the control of T2DM, four studies on duration of TRT, and 20 studies discussed the effects of TRT on the prostate Conclusions Numerous studies have demonstrated the benefits of TTh in overtly hypogonadal men. There are several possible administration routes for testosterone treatment. Each approach has advantages and disadvantages, and the choice of the method of TRT will often be determined by patient preference or co-medication (no intramuscular injections in patients under coumarin or similar anticoagulants). Although new developments are promising, it seems that among the available treatments, only transdermal gel delivery and long-acting injectable testosterone undecanoate provide pharmacokinetic behaviour that gives a steady state level within a physiological range.

Objectives Testosterone therapy (TTh) is the main treatment for elderly men with hypogonadism. No evidence of the long-term effectiveness of TTh on renal function is reported to date. Methods In this study, we evaluated the long-term TTh of testosterone undecanoate (TU) administration on renal function parameters in 496 symptomatic hypogonadal men, with T levels ≤350 ng/dL. The treatment group (T-group) consisted of 312 patients and obtained TU 1000 mg for 12 weeks followed by 6-week intervals and for up to 8 years. The remaining 184 hypogonadal men, who opted against TTh, served as a control group (C-group). The two groups were similar in criteria prior to treatment. We evaluated renal function by calculating serum creatinine, urea, uric acid, and glomerular filtration rate (GFR) according to Mayo Clinic guidelines for 8 years. This study obeys the ethical guidelines of German medical association according to Section 15 of the Professional Code, document for AY- Ref. EK/CH/AU signed on Jun 2015. Results During the study period, the T-group exhibited lower levels of urea (47.0 ± 11.8 to 34.0 ± 13.9 mg/dL), uric acid (6.57 ± 1.2 to 5.49 ± 1.5 mg/dL), serum creatinine (0.90 ± 0.10 to 1.12 ± 0.9 mg/dL), and higher-level in GFR (87.0 ± 12.9 to 98.0 ± 8.0 mL/min/1.73 m2), which were significant. Alternatively, the C-group exhibited an increase in their serum creatinine (1.16 ± 0.31 to 1.19 ± 0.58 mg/dL), an increase in uric acid (5.54 ± 1.2 to 5.44 ± 1.7 mg/dL), and a decrease in GFR (92.0 ± 20.1 to 87.0 ± 26.1 mL/min/1.73 m2). A total of 25 deaths (7.8%) was recorded in the T-group, among them 11 (44%) were cardiovascular. On the other hand, 28 patients (15.2%) died in C-group and all deaths (100%) were found to cardiovascular causes. Conclusion The results suggest that long-term TTh could improve renal function in hypogonadal men comparing to slight deterioration observed in patients without intervention. In addition to reduce mortality in cardiovascular patients, almost to the half., Highlights • Long-term testosterone treatment improves mainly the metabolic parameters in the hypogonadal men. • Long-term testosterone treatment shows an increase in GFR, thus improving kidney function. • Decreased cardiovascular events in long-term testosterone group would directly improves the cardiorenal function.

Mustafa Alwani,1,2 Aksam Yassin,2– 4 Raidh Talib,2 Ahmad Al-Qudimat,2 Omar Aboumarzouk,2 Raed M Al-Zoubi,2,5 Farid Saad,6 Karim S Haider,7 Abdulla Al Ansari2 1Jordan University of Science and Technology, School of Medicine, Irbid, Jordan; 2Hamad Medical Corporation, Department of Surgery, Division of Urology/Andrology and Section of Surgical Research, Doha, Qatar; 3Weill Cornell Medical College, New York, NY, USA; 4Weill Cornell Medical College, Doha, Qatar; 5Jordan University of Science and Technology, Department of Chemistry, Irbid, Jordan; 6Dresden International University, Center of Medicine and Health Sciences, Dresden, Germany; 7Klinikum Bremen-Mitte, Department of Urology, Bremen, GermanyCorrespondence: Aksam Yassin Rathausallee 94 A, Norderstedt-Hamburg, 22846, GermanyTel +49 40 526 21 57Fax +49 40 526 28 20Email yassin@t-online.dePurpose: Erectile dysfunction (ED) is associated with testosterone deficiency and is a symptom of functional hypogonadism. A correlation between ED and cardiovascular disease (CVD) has been recognized, and ED has been proposed as an early marker of CVD. However, the relationship between ED and CVD risk in hypogonadism requires clarification and whether testosterone therapy (TTh) can be a beneficial treatment strategy, but long-term data are limited. This study investigates long-term TTh in men with hypogonadism and ED with a history of CVD.Methods: Seventy-seven patients with a history of CVD and diagnosed with functional hypogonadism and erectile dysfunction (erectile function domain score < 21 on the International Index of Erectile Function questionnaire (IIEF questions 1– 5)) were enrolled and TTh effects on anthropometric and metabolic parameters investigated for a maximum duration of 12 years. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. Eight-year data were analysed. Data collection registry started in November 2004 till January 2015.Results: In hypogonadal men receiving TTh, IIEF increased by 5.4 (p< 0.001). Total weight loss was 23.6 ± 0.6 kg after 8 years. HbA1c had declined by an average of 2.0% (P< 0.0001). Total cholesterol levels significantly declined following TTh after only 1 year (P< 0.0001), and HDL increased from 1.6± 0.5 at baseline to 2± 0.5 mmol/L following 8 years of TTh (P< 0.0001). SBP decreased from 164± 14 at baseline to 133± 9 mmHg, signifying a reduction of 33± 1 mmHg (P< 0.0001).Conclusion: In hypogonadal men with a history of CVD, TTh improves and preserves erectile function over prolonged periods with concurrent sustained improvements in cardiometabolic risk factors. Measuring ED and testosterone status may serve as an important male health indicator predicting subsequent CVD-related events and mortality and TTh may be an effective add-on treatment in secondary prevention of cardiovascular events in hypogonadal men with a history of CVD.Keywords: functional hypogonadism, testosterone therapy, erectile function, cardiovascular disease