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Background/Aim: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. Patients and Methods: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. Results: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. Conclusion: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib.

Considerable research has shown that testosterone regulates many physiological systems, modulates clinical disorders, and contributes to health outcome. However, studies on the interaction of testosterone levels with depression and the antidepressant effect of testosterone replacement therapy in hypogonadal men with depression have been inconclusive. Current findings indicate that low circulating levels of total testosterone meeting stringent clinical criteria for hypogonadism and testosterone deficiency induced by androgen deprivation therapy are associated with increased risk for depression and current depressive symptoms. The benefits of testosterone replacement therapy in men with major depressive disorder and low testosterone levels in the clinically defined hypogonadal range remain uncertain and require further investigation. Important considerations going forward are that major depressive disorder is a heterogeneous phenotype with depressed individuals differing in inherited polygenic determinants, onset and clinical course, symptom complexes, and comorbidities that contribute to potential multifactorial differences in pathophysiology. Furthermore, polygenic mechanisms are likely to be critical to the biological heterogeneity that influences testosterone-depression interactions. A genetically informed precision medicine approach using genes regulating testosterone levels and androgen receptor sensitivity will likely be essential in gaining critical insight into the role of testosterone in depression.

Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men. ispartof: REVIEWS IN ENDOCRINE & METABOLIC DISORDERS vol:23 issue:6 pages:1173-1208 ispartof: location:Germany status: published

Objective: This study aimed to investigate the frequency of sexual dysfunction and the effect of short-term testosterone replacement therapy on sexual functions in congenital hypogonadism patients. Furthermore, we sought to reveal the consistency of the self-report scales used for the diagnosis of sexual dysfunction and the relationship between biochemical parameters. Materials and methods: The study was conducted on 47 young male patients aged above 18 years who were diagnosed with hypogonadotropic hypogonadism. Short (IIEF-5) and long (IIEF-15) forms of the International Index of Erectile Function and Arizona Sexual Experiences Scale (ASEX) were applied before treatment under the supervision of a physician. The patients’ blood pressure, height, and weight were measured, and their luteinizing hormone (LH), FSH, and total testosterone levels were recorded. Patients who started their treatments were called for a follow-up checkup after 6 months. Their blood pressure, height, and weight were measured by reapplying the ASEX, IIEF-5, and IIEF-15. In addition, their LH, FSH, and total testosterone levels in the biochemical tests were rerecorded. Results: In this study, the sexual dysfunction status of patients diagnosed with hypogonadotropic hypogonadism before and after treatment was evaluated using the ASEX, IIEF-15, and IIEF-5 scales. A decrease in sexual dysfunction was observed in all three scales after treatment compared with that before treatment. The IIEF-5 and IIEF-15 scales were found to be uncorrelated in terms of the pretreatment values but were correlated in terms of the post-treatment values. Although a correlation was observed between ASEX and IIEF-5 before treatment, no correlation was detected between ASEX and IIEF-15. After the treatment, ASEX was found to be correlated with both IIEF-5 and IIEF-15. The results of the scales indicated the correlation in all categories, except the pretreatment results of the IIEF-15 scale. Conclusion: The results of the current study demonstrated a significant improvement in the sexual function of hypogonadism patients undergoing short-term testosterone therapy. The ASEX, IIEF-5, and IIEF-15 scales used in the diagnosis and follow-up of sexual dysfunction were useful for evaluating sexual functions in hypogonadotropic hypogonadism patients.

Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels

In the present study, the initial treatment efficiency of combination therapy using testosterone replacement therapy (TRT), herbal medicine and phosphodiesterase 5 inhibitors (PDE5i) in male patients with late-onset hypogonadism (LOH) were assessed. A total of 21 patients were enrolled and after 12 weeks, the clinical efficacy was evaluated based on improvement of LOH symptoms via laboratory parameters and several questionnaires, including the Ageing Males' Symptoms (AMS) scale. The overall AMS scores, as well as the psychological, physical and sexual AMS factors prior to and after treatment in the TRT, testosterone enanthate (T enanthate) monotherapy and T enanthate + PDE5i treatment groups were significantly improved. In the herbal medicine group, only the AMS physiological factors were significantly improved after treatment compared with the baseline. The improvement of the overall AMS scores, as well as the physiological and sexual AMS factors, were significantly negatively correlated with the free testosterone (FT) value prior to treatment. In conclusion, treatment with combination therapy using TRT, herbal medicine and PDE5i improved AMS scores in patients with LOH syndrome. Particularly in patients with LOH syndrome and low FT, the symptoms were significantly improved following combination therapy.

Klinefelter syndrome (KS) is a common cause of non-obstructive azoospermia (NOA). Advances in fertility preservation (FP) techniques, such as the use of microdissection testicular sperm extraction (micro-TESE), have improved sperm retrieval rates (SRR) up to 40–50% in this population. Age has been suggested to have an impact on FP, postulating that sperm production may deteriorate over time due to germ cell loss. As such, sperm retrieval for patients with KS at a younger age has been proposed to further improve SRR; however, whether such practice pragmatically improves SRR is yet to be determined, and controversy remains with concerns over trauma caused by FP procedures on further impairment of testicular function. There has also been a debate on the ethics of performing FP procedures in the pediatric population. Optimizing FP for patients with KS invariably requires a holistic multidisciplinary approach. This review aimed to evaluate the latest evidence in performing FP in pediatric patients with KS, and discuss the controversy surrounding such practice. Hormonal changes in patients with KS during childhood and the use of hormonal manipulation to optimize SSR in this population have also been reviewed.

Testosterone replacement therapy (TRT) is recommended for the treatment of most cases of male hypogonadism. Transdermal testosterone (T) gels are commonly used in clinical practice; however, there is little evidence concerning how to monitor dosage to bring and maintain serum T levels in the normal physiologic range.We examined 30 hypogonadal patients undergoing treatment with 40 mg/day transdermal 2% testosterone gel. After a week from treatment onset, all patients underwent a total of four measurements to assess serum total T, bioavailable T and free T at + 2 h (samples A and A') and + 23 h (samples B and B').No significant difference was found concerning total, free and bioavailable T between the two samples taken at the same time points (A vs A' and B vs B'). A repeated-measures mixed effects regression model showed significantly lower serum levels of total, free and bioavailable T at + 23 h compared to + 2 h (total T, β = - 3.050 ± 0.704, p 0.001; free T, β = - 85.187 ± 22.746, p 0.001; bioavailable T, β = - 1.519 ± 0.497, p = 0.003) without a significant between-sample variability. Serum T 3.5 ng/ml at + 2 h was reached in 21/30 patients (70%), but only 11 (36.7%) still had adequate serum T at + 23 h.Assessment of TRT with transdermal gels at its peak and at its minimum could be useful in providing a finely tailored treatment for hypogonadal men, both preventing supra-physiological levels and maintaining adequate concentrations through the day.

Introduction Hypogonadotropic hypogonadism is a common disorder associated with type 2 diabetes. Hypogonadotropic hypogonadism in type 2 diabetic patients requires further assessment to understand the etiology, and the possible consequences, complications, and treatment This study aims to highlight the testosterone level in type 2 diabetes mellitus (DM). Moreover, it further emphasizes the association of testosterone with the duration of DM. Materials and method This case-control survey was conducted from September 2020 to March 2021 in the outpatient department of internal medicine in a tertiary care hospital in Pakistan. The experiment group included 200 diabetic male participants aged between 30 and 69 years. In the control group, 200 participants without DM were enrolled in the study. The venous blood sample was collected via phlebotomy and sent to the laboratory to test for total testosterone level. Results The mean total testosterone level was significantly lower in diabetic patients compared to the non-diabetic patients (8.9 ± 5.1 mmol/L vs. 14.1 ± 7.2 mmol/L; p-value

Opioids play a pivotal role in managing chronic pain with increasing prescription rates over the last few years. Hence, it is crucial to focus on the adverse effects of narcotics, and one of the lesser-known side effects is hypogonadism. Opioids act on the hypothalamus, pituitary, and directly on the gonads affecting serum testosterone levels. Narcotic-induced androgen insufficiency contributes to sexual dysfunction, infertility, hyperalgesia, and involving various body functions overall, affecting the quality of life. Opioid-induced hypogonadism is very challenging to diagnose for the clinicians, as the patients often under-report the symptoms. There are no established guidelines to analyze androgen insufficiency and dealing with their manifestations successfully. We did a substantial search in PubMed and Google Scholar, using various combinations of keywords to collect data to evaluate the impacts of opioids on serum testosterone levels. This study aims to highlight the clinical significance of opioid-induced androgen deficiency and the diagnostic techniques to recognize and credible treatment alternatives, including testosterone replacement therapy. Health care providers should screen the patients routinely for the signs and symptoms and monitor them often for the hormonal changes to select the patients cautiously for testosterone replacement therapy.

Background. Epidemiological data report that male hypogonadism may play a role in cognitive impairment in elderly. However, the effect of testosterone replacement therapy (TRT) on cognitive abilities in this cluster of patients has not been well established. Methods. PubMed/MEDLINE, Google Scholar, Cochrane Library, and Web of Science were searched by using free text words and medical subject headings terms related with “male hypogonadism”, “late-onset hypogonadism”, elderly, cognition, “mild cognitive impairment”, memory, “testosterone replacement therapy” used in various combinations according to the specific clinical questions. Original articles, reviews, and randomized controlled trials written in English were selected. Results. A long-term TRT could improve specific cognitive functions, such as verbal and spatial memory, cognitive flexibility, and physical vitality. However, randomized controlled trials do not provide positive results, and in most of the cases TRT might not induce beneficial effects on cognitive function in elderly men. Discussion and conclusions. Since the lengthening of life expectancy, the prevalence rate of cognitive decline in elderly men is expected to increase remarkably over the next decade with considerable healthcare and economical concerns. Therefore, this remains a relevant clinical topic and further investigations are needed for clarifying the role of TRT especially in elderly men with hypogonadism.

Since the male secondary sex characters, libido and fertility are attributed to their major androgen hormone testosterone, the sub-optimum levels of testosterone in young adults may cause infertility and irregularities in their sexual behaviour. Such deficiency is often secondary to maladies involving testes, pituitary or hypothalamus that could be treated with an administration of exogenous testosterone. In the last few decades, the number of testosterone prescriptions has markedly increased to treat sub-optimal serum levels even though its administration in such conditions is not yet approved. On account of its associated cardiovascular hazards, the food and drug authority in the United States has issued safety alerts on testosterone replacement therapy (TRT). Owing to a great degree of conflict among their findings, the published clinical trials seem struggling in presenting a decisive opinion on the matter. Hence, the clinicians remain uncertain about the possible cardiovascular adversities while prescribing TRT in hypogonadal men. The uncertainty escalates even further while prescribing such therapy in older men with a previous history of cardiovascular ailments. In the current review, we analysed the pre-clinical and clinical studies to evaluate the physiological impact of testosterone on cardiovascular and related parameters. We have enlisted studies on the association of cardiovascular health and endogenous testosterone levels with a comprehensive analysis of epidemiological studies, clinical trials, and meta-analyses on the cardiovascular risk of TRT. The review is aimed to assist clinicians in making smart decisions regarding TRT in their patients.

Testosterone is an anabolic hormone that is responsible for the development of male sex organs. It also increases muscle mass and fortifies bone density. In addition to being responsible for primary sexual characteristics at birth and puberty (development and changes of sexual organs such as uterus, vagina, penis, and testes), testosterone is also involved in maintaining secondary sexual characteristics. Patients with low testosterone who are symptomatic should be treated with testosterone replacement therapy (TRT) once the diagnosis has been confirmed. The goal of treatment is to improve the symptoms including the physical, sexual, and cognitive health with the aim being to keep the testosterone in the mid-normal limit of the reference range. Male hypogonadism has been increasingly diagnosed and treated in elderly males since the last decade. A proportionate increase in the prescription of testosterone has been seen as well. The relationship of testosterone levels with cardiovascular (CV) outcomes is challenging and has shown conflicting results. Moreover, in patients with established CV disease, those with high CV risk factors including diabetes, or those with significant risk factors for atherosclerotic CV disease (ASCVD), the benefits of TRT should be weighed against the risks of replacement. Risks and benefits of TRT should be discussed with every patient prior to starting or restarting the procedure.

Background: According to the literature, parenteral testosterone replacement therapy (TRT)-induced polycythaemia is associated with cardiovascular events. No or minimal data exist for the prevalence of TRT-induced polycythaemia in lateonset hypogonadism (LOH) patients from South Africa. Polycythaemia is the side effect most frequently associated with parental TRT formulations. Design: This was a quantitative, observational, descriptive, retrospective study. Setting: The study setting was a private practice male clinic in Emalahleni. Subject: An all-inclusive sampling method was used. Outcome measures: The main outcome measure for polycythaemia was haematocrit (Hct). An Hct percentage of > 50% at month 3 (post-treatment initiation) constituted a positive diagnosis for polycythaemia. For the rise in total testosterone (TT) and Hct, the variance was used as documented between pre- and post-treatment initiation. Results: The prevalence of polycythaemia was 34%. A statistically significant increase in both TT and Hct was observed. The Cohen’s d effect size was 0.68 and 0.73, respectively, for TT and Hct. Conclusion: Depot-testosterone undecanoate parenteral formulation induces polycythaemia in LOH patients, where the rise in TT demonstrates the effectiveness of therapy

Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double‐blinded, placebo‐controlled study, we investigated the effects of six‐month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were estimated by transmission electron microscopy. Insulin sensitivity (insulin‐stimulated Rd) and body composition were assessed by euglycemic‐hyperinsulinemic clamp and dual X‐ray absorptiometry, respectively. TRT significantly increased total testosterone levels, BioT, and lean body mass (LBM) (p < 0.05), whereas percent body fat decreased (p < 0.05), and insulin sensitivity was unchanged. Baseline mitochondrial volume fraction correlated inversely with percent body fat (ρ = −0.43; p = 0.003). Δ‐mitochondrial fraction correlated positively with Δ‐total testosterone (ρ = 0.70; p = 0.02), and Δ‐glycogen fraction correlated inversely with Δ‐LBM (ρ = −0.83; p = 0.002) during six‐month TRT, but no significant changes were observed in mitochondrial, glycogen, and LD volume fractions during TRT and ST. In conclusion, in this exploratory small‐scale study, the beneficial effects of six‐month TRT on total testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six‐month ST or combined three‐month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD fractions compared to placebo. However, further studies with a larger sample size are needed.

Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male repro- ductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is com- monly seen in ageing males, and has a complex relationship as a risk factor and a comorbidity in age-related noncommunicable chronic diseases (NCDs), such as obesity, metabolic syndrome, type 2 diabetes, and malignancy. Oxidative stress, as a significant contributor to the ageing process, is a common feature between ageing and NCDs, and the related comorbidities, including hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia, and chronic inflammation. Oxidative stress may also be a mediator of hypogonadism in males. Consequently, the management of oxidative stress may represent a novel therapeutic approach in this context. Therefore, this narrative review aims to discuss the mechanisms of age-related oxidative stress in male hypogonadism associated with NCDs and discusses current and potential approaches for the clinical management of these patients, which may include conventional hormone replacement therapy, nutrition and lifestyle changes, ad-herence to the optimal body mass index, and dietary antioxidant supplementation and/or phyto-medicines. info:eu-repo/semantics/openAccess

We present a patient receiving Testopel® implants whose serum testosterone levels, as measured by a CDC certified assay, were accurately predicted by a multi-compartmental model. This is the first time a model has predicted measured serum testosterone levels within 4% of values calculated. To our knowledge, it was also the first time a pharmacokinetic model allowed patient targeted serum levels (peak/trough/average) to be reached within three months., Highlights • Pharmacokinetic model assists in rapid and accurate Testopel® therapy. • HoSt approved assay enables accurate targeting of serum testosterone levels. • Mean, trough, & peak serum testosterone levels calculated with pharmacokinetic model. • Serum testosterone levels predicted from Testopel® absorption and elimination.

Introduction The role of testosterone (T) replacement therapy (TRT) in men is still conflicting. In particular, safety concerns and cardiovascular (CV) risk related to TRT have not been completely clarified yet. Similarly, the clear beneficial effects of TRT are far to be established. Aim To systematically and critically analyze the available literature providing evidence of the benefit-risk ratio derived from TRT in aging men. Methods A comprehensive PubMed literature search was performed to collect all trials, either randomized controlled trials (RCTs) or observational studies, evaluating the effects of TRT on different outcomes. Main Outcome Measure Whenever possible, data derived from RCTs were compared with those resulting from observational studies. In addition, a discussion of the available meta-analyses has been also provided. Results Data derived from RCT and observational studies clearly documented that TRT can improve erectile function and libido as well as other sexual activities in men with hypogonadism (total T Clinical Implications Before prescribing TRT, hypogonadism (total T Strength & Limitations When correctly diagnosed and administered, TRT is safe, and it can improve several aspects of sexual function. However, its role in complicated vasculogenic erectile dysfunction is limited. Conversely, TRT is not recommended for weight reduction and metabolic improvement. Further well-powered studies are advisable to better clarify TRT for long-term CV risk and prostate safety in complicated patients as well as in those curatively treated for prostate cancer. Conclusion TRT results in sexual function improvement when men with hypogonadism (total T

Klinefelter syndrome (KS), karyotype 47, XXY, is a common cause of hypogonadism in males. Patients with this condition often experience symptoms of gonadal failure, which can precipitate gender identity challenges. Treatment with testosterone replacement therapy (TRT) can combat these symptoms by improving sexual function, muscle mass, bone health, and virilization, thereby enhancing the quality of life (QOL). Although TRT is often employed in patients with KS, there is a concern that the application of exogenous testosterone may increase the risk of prostate adenocarcinoma development and progression. We report the case of a 58-year-old male with KS who is also diagnosed with prostate adenocarcinoma and wished to remain on TRT post-radiation therapy in support of his gender identity and QOL. We describe the challenges this patient faced when balancing a rising prostate-specific antigen level and risk of cancer recurrence with his QOL.

Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of symptoms are attributed to LOH, but the most common association is that of sexual dysfunction. LOH has recently come under greater scrutiny with the widespread use of testosterone therapy, and concerns regarding the efficacy and safety of testosterone replacement therapy have been raised. In particular, the cardiovascular safety and the beneficial effects of testosterone replacement therapy on general health have been questioned. This review will give an overview of the current evidence for the relationship of LOH and male sexual dysfunction.

Male hypogonadism is a clinical syndrome characterized by low testosterone and symptoms of androgen deficiency. Prostate cancer remains a significant health burden and cause of male mortality worldwide. The use of testosterone replacement therapy drugs is rising year-on-year for the treatment of androgen deficiency and has reached global proportions. As clinicians, we must be well versed and provide appropriate counseling for men prior to the commencement of testosterone replacement therapy. This review summarizes the current clinical and basic science evidence in relation to this commonly encountered clinical scenario. There is gathering evidence that suggests, from an oncological perspective, that it is safe to commence testosterone replacement therapy for men who have a combination of biochemically confirmed androgen deficiency and who have either had definitive treatment of their prostate cancer or no previous history of this disease. However, patients must be made aware and cautioned that there is a distinct lack of level 1 evidence. Calls for such studies have been made throughout the urological and andrological community to provide a definitive answer. For those with a diagnosis of prostate cancer that remains untreated, there is a sparsity of evidence and therefore clinicians are “pushing the limits” of safety when considering the commencement of testosterone replacement therapy.

The article presents a review of the literature, which indicate the current understanding of the clinical significance of late onset hypogonadism and types of its correction. The results of studies demonstrate the efficacy and safety of hormone replacement therapy. The authors point to the need for health care professionals to understand and see the benefits of substitution treatment. But the priority in the appointment and monitoring of therapy should be for the urologist and endocrinologist.

Objectives: Differences in testosterone replacement therapy (TRT) gel products may affect patient satisfaction, quality-of-life, and treatment response and adherence. This study investigated preferences for TRT gel in terms of formulation and administration. Methods: 525 male adults aged 45 years and over completed a discrete choice experiment. Respondents made repeated choices between two hypothetical testosterone gel treatments described according to four attributes: form, ease of use, impact of use on showering/swimming, and location/dosage of the application. Choice data were analyzed using a latent class model. Results: Three preference classes were identified. Respondents across all classes displayed a preference for the gel being dispensed in smaller units with accurate dosing, waiting shorter times after the gel application before swimming/showering, and using 2.5 gm of gel to be applied to the inner thigh/abdomen as opposed 5 gm to shoulder/abdomen. The importance of these characteristics differed across classes, with preference class membership predicted by age and education level. For instance, younger men (aged 45–64 years) were more likely to belong to a class that prioritized reduced waiting time before being able to undertake activities. Formulation was not an important driver of choice. Conclusions: Preferences demonstrate a predilection for TRT gel dispensed in small units allowing precise dosing, shorter waiting time after application, and application to the inner thigh/abdomen. However, the strength of importance of these characteristics differs between men. This study highlights the attributes of TRT gel considered important to patient subgroups, and which may ultimately affect treatment response, medication adherence, and patient quality-of-life.

Testosterone has a variety of functions and is commonly used in older men to treat symptoms of hypogonadism, such as decreased libido, decreased mood and erectile dysfunction. Despite its positive effects on sexual function, it has a negative effect on fertility. Exogenous testosterone therapy can negatively affect the hypothalamic-pituitary gonadal axis and inhibit the production of follicle stimulating hormone and luteinizing hormone. The purpose of this review is to discuss the contra-ceptive properties of testosterone therapy and to discuss strategies to increase testosterone in men with the desire to preserve fertility.

The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non-significantly manner (MD, −0.85; 95% CI, −1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, −0.16; 95% CI, −0.29 to −0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, −1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, −0.62 to 0.82; P=0.78) or bone mineral density (MD, −0.01; 95% CI, −0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate-specific antigen (PSA) (MD, 0.10; 95% CI, −0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, −0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well-tolerated and safe for men with hypogonadism who are exhibiting PSA levels of

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.

Klinefelter syndrome (KS) is associated with increased incidence of thrombotic events. Hypofibrinolysis is associated with increased risk of thromboembolism. Although testosterone replacement therapy (TRT) inhibits the hypofibrinolysis, it can still cause thrombosis paradoxically due to increased dose and duration of use. Herein, we present a case of a young male diagnosed with KS who was taking testosterone. The dose was increased to boost the energy levels, and the patient presented with abdominal pain. Computed tomography (CT) of the abdomen showed extensive portal vein thrombosis. He was started on enoxaparin followed by apixaban. Studies need to be done regarding the need for thromboembolism prophylaxis in patients on TRT.

Purpose of Review Previously considered an absolute contraindication, the use of testosterone therapy in men with prostate cancer has undergone an important paradigm shift. Recent data has changed the way we approach the treatment of testosterone deficiency in men with prostate cancer. In the current review, we summarize and analyze the literature surrounding effects of testosterone therapy on patients being treated in an active surveillance protocol as well as following definitive treatment for prostate cancer. Recent Findings The conventional notion that defined the relationship between increasing testosterone and prostate cancer growth was based on limited studies and anecdotal case reports. Contemporary evidence suggests testosterone therapy in men with testosterone deficiency does not increase prostate cancer risk or the chances of more aggressive disease at prostate cancer diagnosis. Although the studies are limited, men who received testosterone therapy for localized disease did not have higher rates of recurrences or worse clinical outcomes. Current review of the literature has not identified adverse progression events for patients receiving testosterone therapy while on active surveillance/watchful waiting or definitive therapies. Summary The importance of negative effects of testosterone deficiency on health and health-related quality of life measures has pushed urologists to re-evaluate the role testosterone plays in prostate cancer. This led to a paradigm shift that testosterone therapy might in fact be a viable option for a select group of men with testosterone deficiency and a concurrent diagnosis of prostate cancer.

Background Atrial fibrillation ( AF ) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone ( TT ) levels were associated with a higher incidence of AF . In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF . To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy ( TRT ) in patients with low testosterone. Methods and Results Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT ), group 2 had TRT without normalization of TT levels (nonnormalized TRT ), and group 3 did not receive TRT (no TRT ). Propensity score–weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post‐ TRT levels of TT and the incidence of AF . Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81–0.99, P =0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70–0.89, P =0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78– 1.0009, P =0.0675) in incidence of AF . Conclusions These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF .

Summary The purpose of the study was to evaluate whether testosterone replacement therapy improves muscle mechanical and physical function in addition to increasing lean leg mass and total lean body mass in aging men with type 2 diabetes and lowered bio-available testosterone (BioT) levels. Thirty-nine men aged 50–70 years with type 2 diabetes and BioT levels

Male hypogonadism, defined as an inadequate production of testosterone (T), is associated with a greater morbidity and mortality. Epidemiological studies identified T deficiency as a risk factor for cardiovascular disease. Also, low serum T levels impact on glucose homeostasis through a worse glucose uptake, utilization, and disposal, and the general negative impact on metabolism. The aim of this review is to provide a comprehensive and updated overview of the effects of T replacement therapy on metabolic and cardiovascular systems and prostate tissue in patients with hypogonadism, including molecular mechanisms through which T exerts its actions. Furthermore, recent findings on novel coronavirus disease (COVID-19) epidemiology have shown a greater mortality in male compared with female patients and a role of T in promoting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection of the host cells has been demonstrated. Hence, the secondary aim of this review is to provide preliminary indications on the management in patients with COVID-19.

Aims and Methods This was a 6-month, open label, multinational, observational study in hypogonadal men treated with daily titrated dose of 50, 75, or 100 mg 1% testosterone gel (AndroGel®) in community practice. Primary outcome was effect of treatment on hypogonadal symptoms and quality of life as assessed by Aging Males’ Symptoms (AMS) scale. Secondary objectives included erectile dysfunction (International Index of Erectile Function [IIEF]), fatigue (Multidimensional Fatigue Inventory [MFI]), and surrogates for body composition (waist circumference, body mass index [BMI]). Results Seven hundred and ninety-nine of the 1053 men enrolled had follow-up data at 6 months, 81.2% had ≥1 testosterone value in the normal range during the study. Substantial and significant improvements were observed in mean AMS score (−29%), IIEF score (+115.7%), and MFI scores (−21.5%). Further beneficial effects were significant decreases in mean BMI (−0.8 kg/m2) and waist circumference (−3.3 cm). Younger age quartiles showed greater improvements in AMS, MFI, BMI, and waist circumference than older quartiles. IIEF scores, however, did not differ significantly by age category. Conclusions Substantial improvements in hypogonadal symptoms, quality of life, fatigue, erectile dysfunction, and libido/sexual desire were observed. Adverse drug reactions were experienced by 7.5% of the safety population over the 6-month study period.

Evidence suggests that providers are not adhering to current testosterone replacement therapy guidelines when treating male hypogonadism. Understanding the diagnosis and management of this condition is further complicated by conflicting recommendations among available guidelines. NPs must select and follow the best guideline recommendations available to optimally treat male hypogonadism., Evidence suggests that providers are not adhering to current testosterone replacement therapy guidelines when treating male hypogonadism. Understanding diagnosis and management is further complicated by conflicting recommendations among available guidelines. NPs must select and follow the best guideline recommendations available to optimally treat this condition.

A low testosterone level and hypogonadism are associated with cardiovascular disease. Aging, chronic health problems, and obesity are all associated with a low testosterone level as well as the presence and severity of cardiovascular disease. Testosterone is increasingly prescribed for patients with clinical hypogonadism and a low testosterone level. The information we have is still contradictory regarding testosterone replacement therapy (TRT) and its association with adverse cardiovascular events. Older patients and patients who are susceptible to cardiovascular diseases could be at risk with a testosterone prescription. This is a review of the literature to discuss the cardiovascular safety of TRT. WOS:000418480800016 28990951

AIM To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men.

There is no conclusive evidence as to whether patients with testosterone deficiency (TD) who benefit from testosterone treatment (TRT) must continue the treatment for the rest of their lives. In some patients, the effect of TRT does not maintained after stopping TRT and, some patients show no significant TD symptoms, with normal testosterone levels after TRT cessation. Therefore, we investigated the predictive factors of response maintenance after TRT cessation. A total of 151 men with TD who responded to TRT were followed up for six months after TRT discontinuation. Ninety-two patients (Group I) failed to show response maintenance, 59 patients (Group II) had a maintained response. The groups did not differ in baseline characteristics or the type of TRT (oral, gel, short/long-acting injectables). However, TRT duration was significantly longer (10.7 vs. 5.2 months), and peak total testosterone (TT) level was significantly higher (713.7 vs. 546.1 ng/dL), in Group II than in Group I. More patients regularly exercised in Group II than in Group I (45.8% vs. 9.8%, p &lt, 0.001). A multivariate logistic regression analysis revealed that exercise (B = 2.325, odds ratio = 10.231, p &lt, 0.001) and TRT duration (B = 0.153, Exp(B) = 1.166, p &lt, 0.001) were independent predictive factors of response maintenance. In men with TD who respond to TRT, longer treatment periods can improve the response durability after TRT cessation, regardless of the type of TRT. Additionally, regular exercise can increase the probability of maintaining the response after TRT cessation.

Testosterone deficiency is common in men with chronic obstructive pulmonary disease (COPD) and may exacerbate their condition. Research suggests that testosterone replacement therapy (TRT) may have a beneficial effect on respiratory outcomes in men with COPD. To date, however, no large-scale nationally representative studies have examined this association. The objective of the study was to assess whether TRT reduced the risk of respiratory hospitalizations in middle-aged and older men with COPD. We conducted two retrospective cohort studies. First, using the Clinformatics Data Mart—a database of one of the largest commercially insured populations in the United States—we examined 450 men, aged 40–63 years, with COPD who initiated TRT between 2005 and 2014. Second, using the national 5% Medicare database, we examined 253 men, aged ≥66 years, with COPD who initiated TRT between 2008 and 2013. We used difference-in-differences (DID) statistical modeling to compare pre- versus post-respiratory hospitalization rates in TRT users versus matched TRT nonusers over a parallel time period. DID analyses showed that TRT users had a greater relative decrease in respiratory hospitalizations compared with nonusers. Specifically, middle-aged TRT users had a 4.2% greater decrease in respiratory hospitalizations compared with nonusers (−2.4 decrease vs. 1.8 increase; p = 0.03); and older TRT users had a 9.1% greater decrease in respiratory hospitalizations compared with nonusers (−0.8 decrease vs. 8.3 increase; p = 0.04). These findings suggest that TRT may slow disease progression in patients with COPD. Future studies should examine this association in larger cohorts of patients, with particular attention to specific biological pathways.

There has been a recent dramatic shift in our understanding of the relationship between androgens and prostate cancer (PCa). Whereas for several decades it had been assumed that higher serum testosterone (T) concentrations would lead to ever-greater PCa growth, current literature indicates that PCa growth is unaffected by changes in serum T throughout most of the naturally occurring range. A Saturation Model has been proposed to explain how prostate tissue can be exquisitely sensitive to changes in serum T at the very low end of the concentration range, but appears indifferent to such changes above the near-castrate range. This has special applicability to T-deficient men, since this means that T therapy may not be nearly as risky as once assumed. Indeed, one of the more interesting changes over the last several years has been the growing acceptance of the use of T therapy in men with a prior history of PCa, with early data indicating minimal risk of cancer recurrence or progression. Provocative new evidence suggests that it is not high serum T that is problematic for PCa, butlowserum T that is associated with worrisome cancer features and outcomes, such as high Gleason score, advanced stage of presentation, and increased risk of biochemical recurrence after surgery. It will be interesting to see what changes will occur in this rapidly changing field over the next several years.

Introduction: Testosterone treatment has evolved rapidly over the past 25 years as new, more effective and convenient methods have become available. This study reports experience with seven different methods, introduced on the market in the UK. Aim: To establish the symptom response when testosterone treatment was initiated on the basis of clinical features and symptoms of androgen deficiency, and the resulting endocrine, biochemical and physiological responses. Methods: Of 2693 patients attending the 3 Men’s Health Centers – The UK Androgen Study (UKAS), 2247 were treated. Treatments included pellet implants, oral testosterone undecanoate (Testocaps), mesterolone (Proviron), testosterone gel (Testogel), testosterone scrotal cream (Andromen) and scrotal gel (Tostran). Results: There was no correlation between initial testosterone level, initial symptom score or the success of treatment as defined by adequate resolution of symptoms. Despite the diverse endocrine patterns produced, the testosterone preparations appear equally safe over prolonged periods, with either no change or improvement of cardiovascular risk factors, especially in lowering cholesterol and diastolic blood pressure. Conclusions: It is suggested that because of excessive reliance on laboratory measures of androgens and undue safety concerns, many men who could benefit from symptom relief, improvement in related clinical conditions and given preventive medical benefits remain untreated.

Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p

Testosterone replacement therapy (TRT) is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction.

Male hypogonadism is a clinically and biochemically defined the disease of men with serum testosterone (T) levels below the reference ranges of young man and with symptoms of T deficiency (TD). Morbidity and mortality of TD and the method to treat TD are different by the onset age or reserving fertility. Therefore, diagnostic skills and treatment methods should be set the age, desire (fertility or not) and situation of the patient. The main symptom is sexual dysfunction, anemia, reduced muscle mass and strength, metabolic syndrome, reduction of bone density and lessening of general performance, depressed mood, cardiovascular disease and infertility in young man got married. The diagnosis of hypogonadism is based on the presence of symptoms or signs, TD, and serum T levels. Young adult who need fertility should be treated in to both directions to recover fertility and overcome the low T relating diseases. In the patient who has late onset hypogonadism, we have to target the symptoms and signs, change of body composition and morbidity and mortality. We also have to consider the testosterone replacement therapy (TRT) inducing pathophysiological changes such as polycythemia, blood viscosity, and aggravated benign prostatic hyperplasia (BPH) inducing lower urinary tract symptoms (LUTS) and malignant prostate diseases before and after TRT. I would like to introduce the diagnostic algorithm for the hypogonadal patient before and after TRT. Before TRT for baseline, we have to check anthropometry, CBC, blood chemistry for metabolic syndrome, total T, free T, prostate specific antigen (PSA), transrectal prostate ultrasonography (TRUS), and questionnaires. For the follow-up after TRT, the anthropometry, blood viscosity, in addition CBC, total testosterone, free testosterone, PSA, TRUS, and questionnaires including voiding and erectile status. A semen analysis in the secondary hypogonadal patient who wants fertility has to be considered. I recommend that sample collection for T measurement occur between 7 and 11 a.m. or within 3 h after waking in the shift workers. Measurement of the repeated T and SHBG with calculated free or bioavailable T should be performed to men with TDS and equivocally low T levels when he is needed TRT. For the follow-up, T, PSA, hematocrit, blood viscosity, semen analysis (want baby) and questionnaires should be assessed at 3 and 6 months after onset of TRT and then annually thereafter if stable. A digital rectal examination should be performed at baseline, at 6 months and then annually following onset of TRT. A TRUS should be performed at baseline, at 12 months and then annually following onset of TRT. The interval to recheck has to be differed by the age, duration of the TRT and developing morbidity and mortality. I recommend assessment of response and AE at 3, 6 months after onset of TRT and then annually thereafter.

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm(2); femoral BMD= 0.847 ± 0.117 g/cm(2)). TU induced a significant improvement of bone mass after 36 months (lumbar BMD=1.053 ± 0.145 g/cm(2); p < 0.002; femoral BMD=0.989 ± 0.109; p < 0.003 g/cm(2)) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r(2) = 0.66, p < 0.0001) and femoral (r(2) =0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.

Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule., Video abstract