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The finding of low circulating testosterone level in men is relatively frequent. The symptoms of hypogonadism are very frequent in the aging men. However, the diagnosis of hypogonadism is often neglected and the opportunity to replace low testosterone in older men is highly debated. The aim of this narrative review is to summarize the steps necessary to formulate a proper diagnosis and to guide toward an individualized treatment. While universally recognized the need to treat the young adults with known causes of pituitary or testicular failure, there are controversies on the cost-benefit of treating testosterone deficiency in older men. Discrepancies among the several available guidelines do not help to clarify the scenario, however, the recent larger clinical trials have shed some light on the fact that testosterone treatment carries some benefit, that is not free from risks. We provide an updated review of the diagnostic hallmarks, the several treatment modalities, with their advantages and disadvantages, and how to individualize and monitor treatment in order to maximize the benefits and minimize the risks. The treatment of male hypogonadism can no longer be downgraded and must become part of the cultural baggage of the endocrinologist. [ABSTRACT FROM AUTHOR]

The abuse of anabolic androgenic steroids (AAS) has remained on the rise despite their well-known deleterious effects. We describe a case of AAS-induced multisystem failure following an extensive history of abuse in a 41-year-old bodybuilder. Furthermore, we review pertinent literature and discuss the different pathophysiologic mechanisms through which AAS affect the heart and other organs. This case points to the possibility of multiorgan involvement and severe cardiac effects of AAS abuse in young individuals who may not have any past medical history. [ABSTRACT FROM AUTHOR]

Male hypogonadism is associated with reduced quality of life and the development of co-morbidities including obesity, diabetes mellitus, and dyslipidaemia. The mainstay of treatment for male hypogonadism is testosterone replacement therapy (TRT). However, TRT has recognised side effects including impaired spermatogenesis and there are concerns regarding its use in men with concurrent cardiovascular disease. Thus, there has been an impetus to develop novel androgen therapies for treating male hypogonadism to mitigate the side effects of TRT. This review will discuss the benefits and adverse effects of TRT, and novel therapies including nasal testosterone, aromatase inhibitors, selective oestrogen receptor modulators, and selective androgen receptor modulators. [ABSTRACT FROM AUTHOR]

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. 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). 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%). 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. • Testosterone supplementation therapy (TST) has been used to treat hypogonadal men with type 2 diabetes mellitus (T2DM) for a long time.. • TST decreases homeostatic model assessments of insulin resistance, HbA1c, fasting glucose, and fasting insulin.. • TST can significantly decrease total cholesterol and triglyceride levels. [ABSTRACT FROM AUTHOR]

Background: It is not unusual for men over 60 years of age to have serum testosterone levels below the lower limits of younger men, prompting a diagnosis of hypogonadism. This study evaluated safety, efficacy, and pharmacokinetics of oral enclomiphene citrate as an alternative to currently available androgen replacement therapies. Methods: Fifty-two subjects were randomized to oral enclomiphene citrate (12.5 mg, 25 mg, or 50 mg), topical testosterone gel (5 g) or oral placebo daily for 14 days. Pharmacodynamic profiles of total testosterone (TT) were obtained on day 1 and day 14 after dosing. Subjects were assessed in a follow-up visit 7-10 days after the final dose. Additional subjects were rescreened and added for a 10-g dose cohort. Results: After 14 days, there was a significant, dose-dependent rise in TT across all doses of enclomiphene citrate and topical testosterone, but not placebo. Supraphysiologic levels of TT were observed in topical testosterone-treated subjects, whereas TT levels were maintained within a desirable range of 400 to 700 ng/dL in enclomiphene citrate-treated subjects. Enclomiphene citrate 25 and 50 mg doses and topical testosterone (10 g) treatment elevated free testosterone levels more at day 14 compared with day 1 than did placebo. Topical testosterone (5 g) was associated with disproportionate increase in dihydrotestosterone (DHT) relative to TT, while enclomiphene citrate resulted in a modest decrease. Enclomiphene citrate was rapidly absorbed and had an elimination half-life of about 10 hours. A non-dose-dependent steady-state level was maximal at the 25 mg dose. The effects of enclomiphene citrate were sustained with daily dosing. Conclusions: Enclomiphene citrate increased total and free testosterone without increasing DHT disproportionately. Changes in luteinizing hormone, follicle stimulating hormone, and the DHT/TT ratio with enclomiphene citrate suggest it normalizes endogenous testosterone production pathways and restores normal testosterone levels in men with secondary hypogonadism within 14 days. [ABSTRACT FROM AUTHOR]

Sexual symptoms are the most specific determinants of low testosterone (T) observed during adulthood. In this narrative review, we summarize the most important evidence supporting the positive relationships between endogenous T levels and sexual activity in the adult male, by using preclinical and clinical observations. In addition, we also report an update of our previous meta-analysis evaluating the effects of T treatment (TRT) on sexual functioning in subjects with T deficiency. Available data indicate that TRT of symptomatic hypogonadal men can improve several aspects of sexual life, including erection. However, the effect is rather modest and lower in subjects with associated metabolic conditions. The specific observed effects are similar to those derived from lifestyle intervention. Since TRT might result in body composition improvement, it is reasonable to suppose that an initial treatment with T can improve the willingness of hypogonadal subjects to perform physical exercise and to adhere to a healthier behavior. Similar data were derived from animal models. However, it should be important to recognize that lifestyle modifications should be the first step to promote weigh reduction. TRT can be combined with lifestyle interventions only in symptomatic hypogonadal subjects especially in the presence of comorbid metabolic conditions. [ABSTRACT FROM AUTHOR]

Late-onset hypogonadism (LOH) is a relatively common conditions affecting the aging male. The aim of this review is to summarize the available evidence regarding LOH and its interaction with general health. LOH is often comorbid to obesity and several chronic diseases. For this reason lifestyle modifications should be strongly encouraged in LOH subjects with obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and good treatment balance of chronic diseases. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. Available evidence seems to suggest that testosterone replacement therapy is able to improve central obesity (subjects with MetS) and glycometabolic control (patients with MetS and T2DM), as well as to increase lean body mass (HIV, chronic obstructive pulmonary disease), along with insulin resistance (MetS) and peripheral oxygenation (chronic kidney diseases). However, it should be recognized that the number of studies on benefits of T supplementation is too limited to draw final conclusions. Longer and larger studies are needed to better clarify the role of TRT in such chronic conditions. [Copyright &y& Elsevier]

Androgens have been implicated in prostate tumourigenesis. However, no association between circulating levels of androgens and prostate cancer risk was found in a recent large pooled analysis of prospective studies. A decreased risk of prostate cancer among men treated with finasteride, a 5α-reductase inhibitor which reduces levels of dihydrotestosterone, was observed in the Prostate Cancer Prevention Trial (PCPT), a large clinical trial. In the PCPT, a higher number of high-grade tumours was found in the finasteride group than in the control group; the reason for this finding is still unclear. Treatment of symptoms of late-onset hypogonadism – such as decreased muscle and bone mass and decreased cognition and libido – has become more prevalent with the advent of new forms of administration of testosterone replacement therapy. One small placebo-controlled study showed no increase in incidence of prostate cancer after 6 months of testosterone therapy, but data on the safety of testosterone replacement therapy remain limited. [Copyright &y& Elsevier]

Abstract: Male andropause, male climacteric or viropause is a condition in which men suffer from complex symptomatology due to low androgen level with aging. After the age of 40 years testosterone level starts declining and andropause corresponds to the age at which a pathogenic threshold is reached. This review summarizes the etiology, consequences, screening, diagnosis, monitoring of androgen deficiency in aging male (ADAM). The pros and cons of testosterone replacement therapy (TRT) in elderly male have been discussed. Currently oral, transdermal, transbuccal, intramuscular, and subcutaneous implants are available for clinical use. The choice is made by physicians based on therapeutic indication and patient preferences. [Copyright &y& Elsevier]

Background: Despite the results of the Testosterone Trials, physicians remain uncomfortable treating men with hypogonadism. Discouraged, men increasingly turn to social media to discuss medical concerns.Objective: The goal of the research was to apply natural language processing (NLP) techniques to social media posts for identification of themes of discussion regarding low testosterone and testosterone replacement therapy (TRT) in order to inform how physicians may better evaluate and counsel patients.Methods: We retrospectively extracted posts from the Reddit community r/Testosterone from December 2015 through May 2019. We applied an NLP technique called the meaning extraction method with principal component analysis (MEM/PCA) to computationally derive discussion themes. We then performed a prospective analysis of Twitter data (tweets) that contained the terms low testosterone, low T, and testosterone replacement from June through September 2019.Results: A total of 199,335 Reddit posts and 6659 tweets were analyzed. MEM/PCA revealed dominant themes of discussion: symptoms of hypogonadism, seeing a doctor, results of laboratory tests, derogatory comments and insults, TRT medications, and cardiovascular risk. More than 25% of Reddit posts contained the term doctor, and more than 5% urologist.Conclusions: This study represents the first NLP evaluation of the social media landscape surrounding hypogonadism and TRT. Although physicians traditionally limit their practices to within their clinic walls, the ubiquity of social media demands that physicians understand what patients discuss online. Physicians may do well to bring up online discussions during clinic consultations for low testosterone to pull back the curtain and dispel myths. [ABSTRACT FROM AUTHOR]