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Introduction: As an increasingly popular therapeutic option, testosterone replacement therapy (TRT) has gained significant notoriety for its health benefits in indicated populations, such as those suffering from hypogonadism., Areas Covered: Benefits such as improved libido, muscle mass, cognition, and quality of life have led to widened public interest in testosterone as a health supplement. No therapy exists without side effects; testosterone replacement therapy has been associated with side effects such as an increased risk of polycythemia, benign prostate hypertrophy (BPH), prostate cancer, gynecomastia, testicular atrophy, and infertility. Testosterone replacement therapy is often accompanied by several prophylactic co-therapies aimed at reducing the prevalence of these side effects. Literature searches for sections on the clinical benefits and risks associated with TRT were performed to include clinical trials, meta-analyses, and systematic reviews from the last 10 years., Expert Opinion: Data from clinical studies over the last decade suggest that the benefits of this therapy outweigh the risks and result in overall increased quality of life and remission of symptoms related to hypogonadism. With this in mind, the authors of this review suggest that carefully designed clinical trials are warranted for the investigation of TRT in symptomatic age-related hypogonadism.

Andropause is a condition surrounded by controversies, whether it be through its diagnosis or management. As we learn more about the pathophysiology of hypogonadism, our perspectives on the risks and benefits of testosterone therapy have shifted. We attempt to discuss the most modern and relevant points of controversy currently affecting the field. Throughout this review, we discuss the art of diagnosing hypogonadism as well as the association or lack thereof between testosterone replacement therapy and cardiovascular disease, prostate cancer, thrombosis, antiaging effects, exogenous steroid abuse, and diabetes mellitus., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Testosterone supplementation therapy (TST) is a longstanding treatment for hypogonadal men with type 2 diabetes mellitus (T2DM), even though the benefits of TST are variable among trials. This meta-analysis was done to determine the specific role of TST in hypogonadal men with T2DM., Methods: PubMed, Embase, and Google Scholar were queried to discover eligible randomized controlled trials (RCTs) and observational studies. To quantify the specific effects of TST, we estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals (CIs)., Results: Our meta-analysis included 1596 hypogonadal T2DM subjects from 12 randomized controlled trials and one observational study. TST can significantly enhance glycemic control compared to placebo by decreasing homeostatic model assessment of insulin resistance (WMD = -1.55 [-2.65, -0.45]; p = 0.26; I2 = 20.2%), fasting glucose (WMD = -0.35 [-0.79, 0.10]; p = 0.07; I2 = 69.7%), fasting insulin (WMD = -2.88 [-6.12, 0.36]; p = In addition, TST can decrease cholesterol (WMD = -0.28 [-0.47, -0.09] p = 0.0008; I2 = 91%) and triglyceride (WMD = -0.23 [-0.43, -0.03] p = 0.03; I2 = 79.2%). Furthermore, Testosterone therapy is related to a significant rise in total testosterone levels (WMD = 5.08 [2.90, 7.26] p = 0.0002; I2 = 92.9%). Pooling of free testosterone levels indicated a larger increase in the patients who got TST than placebo (WMD = 81.21 [23.87, 138.54] p = 0.07; I2 = 70%)., Conclusion: Our findings suggested that TST can enhance glycemic control and hormone levels and reduce total cholesterol, triglyceride, LDL cholesterol whereas increase HDL cholesterol in hypogonadal T2DM patients. Therefore, in these patients, we propose TST alongside anti-diabetic treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The growing life expectancy in modern societies has raised scientific interest in identifying medical interventions to alleviate age-associated pathologies such as vascular calcification, cognitive decline, sarcopenia, osteoporosis and sexual dysfunction. Although no such single treatment has thus far been established in humans, some clinicians and patients have set their hopes on testosterone replacement therapy (TRT) as a potential "fountain of youth" for aging men. While TRT has proven effective in ameliorating distinct symptoms of late-onset hypogonadism (LOH), its safety remains to be demonstrated. Besides humans, multiple other species exhibit age-related reductions in circulating testosterone levels, raising the question whether such changes are an inherent, pathological feature of growing organismal age or rather reflect an adaptive response. In this manuscript, we apply key principles of evolutionary medicine to testosterone biology and LOH to provide a novel perspective on these two fields. Additionally, we discuss insightful data derived from the animal kingdom to illustrate the plasticity of individual testosterone trajectories across the lifespan, outline cost-benefit-considerations of TRT in LOH and highlight potential caveats of such therapies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Polycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood., Aim: The objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT., Methods: We performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean ± SD for parametric variables and median [interquartile range] for non-parametric values., Outcome: The primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT., Results: 474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P = .002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P = .01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 ± 11.4 years, mean BMI of 32.4 ± 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P = .013)., Clinical Translation: In hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered., Strengths & Limitations: This is a single provider retrospective study and further studies are needed to assess generalizability., Conclusions: In this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA. Lundy SD, Parekh NV, Shoskes DA. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy. J Sex Med 2020;17:1297-1303., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Male hypogonadism is "a clinical syndrome that results from failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic- pituitary-testicular axis". The diagnostic protocol of male hypogonadism includes accurate medical history, physical exam, as well as hormone assays and instrumental evaluation. Basal hormonal evaluation of serum testosterone, LH, and FSH is important in the evaluation of diseases of the hypothalamus-pituitary-testis axis. Total testosterone levels < 8 nmol/l profoundly suggest the diagnosis of hypogonadism. An inadequate androgen status is moreover possible if the total testosterone levels are 8-12 nmol/L. In this "grey zone" the diagnosis of hypogonadism is debated and the appropriateness for treating these patients with testosterone should be fostered by symptoms, although often non-specific. Up to now, no markers of androgen tissue action can be used in clinical practice. The identification of markers of androgens action might be useful in supporting diagnosis, Testosterone Replacement Treatment (TRT) and clinical follow-up. The aim of this review is to analyze the main findings of recent studies in the field of discovering putative diagnostic markers of male hypogonadism in seminal plasma by proteomic techniques. The identified proteins might represent a "molecular androtest" useful as a seminal fingerprint of male hypogonadism, for the diagnosis of patients with moderate grades of testosterone reduction and in the follow-up of testosterone replacement treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as 'late-onset hypogonadism (LOH)'. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered., Materials and Methods: We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy., Results: Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001)., Conclusions: Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Testosterone replacement therapy in men with prostate cancer is controversial, with concern that testosterone can stimulate cancer growth. We evaluated the safety and efficacy of testosterone in hypogonadal men with prostate cancer treated with radical prostatectomy., Materials and Methods: We performed a review of 103 hypogonadal men with prostate cancer treated with testosterone after prostatectomy (treatment group) and 49 nonhypogonadal men with cancer treated with prostatectomy (reference group). There were 77 men with low/intermediate (nonhigh) risk cancer and 26 with high risk cancer included in the analysis. All men were treated with transdermal testosterone, and serum hormone, hemoglobin, hematocrit and prostate specific antigen were evaluated for more than 36 months., Results: Median (IQR) patient age in the treatment group was 61.0 years (55.0-67.0), and initial laboratory results included testosterone 261.0 ng/dl (213.0-302.0), prostate specific antigen 0.004 ng/ml (0.002-0.007), hemoglobin 14.7 gm/dl (13.3-15.5) and hematocrit 45.2% (40.4-46.1). Median followup was 27.5 months, at which time a significant increase in testosterone was observed in the treatment group. A significant increase in prostate specific antigen was observed in the high risk and nonhigh risk treatment groups with no increase in the reference group. Overall 4 and 8 cases of cancer recurrence were observed in treatment and reference groups, respectively., Conclusions: Thus, testosterone therapy is effective and, while followed by an increase in prostate specific antigen, does not appear to increase cancer recurrence rates, even in men with high risk prostate cancer. However, given the retrospective nature of this and prior studies, testosterone therapy in men with history of prostate cancer should be performed with a vigorous surveillance protocol., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Previous work has demonstrated a deficiency in urology resident education when it comes to andrology and male infertility. We analyzed the top 100 most frequently cited and influential articles published on testosterone deficiency and its associated therapy, allowing trainees and clinicians to review and understand the characteristics of impactful literature for self-directed learning purposes. Methods: The ISI Web of Knowledge database was used to find articles on testosterone deficiency, hypogonadism, and replacement therapies. Relevant, peer-reviewed, English articles were included. Article details, including title, citation count, publication year, and more, were gathered. Articles were classified based on content (e.g. clinical outcomes, anatomy, and trends) using defined criteria. Results: The top 300 most cited were reviewed with 100 included. The most cited article had 774 citations, averaging 234 in the top 100. Publication years had peaks in 2003–2004 and 2006–2007. The US led in publications (56), followed by England (16), Germany (14), and Italy (13). Common affiliations included US Department of Veteran Affairs, Veterans Health Administration, RIC Research Education Clinical Center, and University of California System. Articles were categorized as LOE 2 (47), LOE 1 (22), and LOE 5 (21). Articles focused on clinical outcomes (71.7%), anatomy/biomechanics/physiology (14.1%), clinical guidelines (8.1%), and screening (4%). The " Journal of Clinical Endocrinology & Metabolism " published 26 of the top 100 cited articles. Conclusions: This analysis highlights influential articles regarding testosterone deficiency and management. The discussed articles have significant clinical and therapeutic implications for the practicing urologist which may bolster deficits in current resident education. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT)

Testosterone replacement therapy (TRT) has been used to treat hypogonadal males with type 2 diabetes mellitus (T2DM) for a long time, despite variable results. This meta-analysis examines TRT’s role in hypogonadal males with T2DM. The databases PubMed, Embase, and Google Scholar were searched for relevant RCTs and observational studies. Estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals were used to measure the effects of TRT (CIs). When compared to the placebo, TRT improves glycemic management by significantly reducing glycated hemoglobin (HBA1c) levels (WMD = −0.29 [−0.57, −0.02] p = 0.04; I2 = 89.8%). Additionally, it reduces the homeostatic model assessment levels of insulin resistance (WMD = −1.47 [−3.14, 0.19]; p = 0.08; I2 = 56.3%), fasting glucose (WMD = −0.30 [−0.75, 0.15]; p = 0.19; I2 = 84.4%), and fasting insulin (WMD = −2.95 [−8.64, 2.74]; however, these results are non-significant. On the other hand, HBA1c levels are significantly reduced with TRT; in addition, total testosterone levels significantly increase with testosterone replacement therapy (WMD = 4.51 [2.40, 6.61] p = 0.0001; I2 = 96.3%). Based on our results, we hypothesize that TRT can improve glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol levels while raising HDL cholesterol in hypogonadal type 2 diabetes patients. To this end, we recommend TRT for these patients in addition to standard diabetes care.

Lower urinary tract symptoms (LUTS) are caused by higher tension at the bladder neck level (due to fibrosis or stiffness) or benign prostatic hyperplasia, which causes static obstruction of the bladder outlet. Both forms cause a group of symptoms such as hesitancy, intermittency, weak stream, nocturia, urine frequency, and urgency. Additionally, LUTS (obstructive or irritative symptoms) are common in elderly men with hypogonadism, identified as the reduced testes capability in producing sex steroids and sperm, and are categorized as testosterone deficiency. Even though the mode of action (MoA) of testosterone therapy (TTh) on hypogonadal men needs more researched and understanding, the effectiveness of TTh in the development of male genital organs has been reported in several studies. This review shows the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages.

Testosterone replacement therapy (TRT) has been used to treat hypogonadal males with type 2 diabetes mellitus (T2DM) for a long time, despite variable results. This meta-analysis examines TRT's role in hypogonadal males with T2DM. The databases PubMed, Embase, and Google Scholar were searched for relevant RCTs and observational studies. Estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals were used to measure the effects of TRT (CIs). When compared to the placebo, TRT improves glycemic management by significantly reducing glycated hemoglobin (HBA1c) levels (WMD = −0.29 [−0.57, −0.02] p = 0.04; I2 = 89.8%). Additionally, it reduces the homeostatic model assessment levels of insulin resistance (WMD = −1.47 [−3.14, 0.19]; p = 0.08; I2 = 56.3%), fasting glucose (WMD = −0.30 [−0.75, 0.15]; p = 0.19; I2 = 84.4%), and fasting insulin (WMD = −2.95 [−8.64, 2.74]; however, these results are non-significant. On the other hand, HBA1c levels are significantly reduced with TRT; in addition, total testosterone levels significantly increase with testosterone replacement therapy (WMD = 4.51 [2.40, 6.61] p = 0.0001; I2 = 96.3%). Based on our results, we hypothesize that TRT can improve glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol levels while raising HDL cholesterol in hypogonadal type 2 diabetes patients. To this end, we recommend TRT for these patients in addition to standard diabetes care. [ABSTRACT FROM AUTHOR]

Late Onset Hypogonadism (LOH) is a disease associated with advancing age, characterized by symptoms and a deficiency in serum testosterone. It is important to choose which patient suitable for testosterone replacement therapy (TRT), but there is no one consensus that fits for all. After treating patients with testosterone replacement therapy (TRT), several parameters need to be evaluated. A 74-years old male came with chief complaint of difficulty to maintain erection since 2 years ago. PADAM questionnaire was positive, and IIEF-5 score was 6. Physical examination showed an underweight condition. Total testosterone level was 3,65ng/mL, and patient chose to be given TRT instead of evaluating his free testosterone. PDE-5 inhibitor and non-pharmacologic treatment was also given. Follow-up showed that his erection was improved. At which level should testosterone be substituted is still debatable. Several consensuses issued by several organization still cannot be used universally. Study in Indonesia showed that symptoms of LOH had been occur when the testosterone level still in normal range. After giving TRT to our patients, routine follow up is needed. Non pharmacologic treatment also needs to be addressed to improve the outcome. Symptoms of LOH had been occurred even though testosterone level is still in normal range. The consideration made by clinician is the most important thing to be evaluated, whether to give TRT or not. Somatic and laboratory parameters mentioned in this study is important to be evaluated. [ABSTRACT FROM AUTHOR]

Lower urinary tract symptoms (LUTS) are caused by higher tension at the bladder neck level (due to fibrosis or stiffness) or benign prostatic hyperplasia, which causes static obstruction of the bladder outlet. Both forms cause a group of symptoms such as hesitancy, intermittency, weak stream, nocturia, urine frequency, and urgency. Additionally, LUTS (obstructive or irritative symptoms) are common in elderly men with hypogonadism, identified as the reduced testes capability in producing sex steroids and sperm, and are categorized as testosterone deficiency. Even though the mode of action (MoA) of testosterone therapy (TTh) on hypogonadal men needs more researched and understanding, the effectiveness of TTh in the development of male genital organs has been reported in several studies. This review shows the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages. [ABSTRACT FROM AUTHOR]