Aksam Yassin

Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss.

Hypogonadism is associated with increased fat mass and reduced muscle mass, which contributes to obesity and health risks, such as cardiovascular disease. Testosterone treatment of hypogonadal men improves muscle mass and reduces fat mass; however, many of these studies are of short duration. Thus, the long‐term effects of testosterone on body anthropometry are not known.

Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone.

Until a decade ago the ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus, lower urinary tract symptoms and erectile dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but there is a growing awareness that these entities are not disparate and, to improve the health of the ageing male, require an integral approach. There is an inter‐dependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower‐than‐normal testosterone levels. A new concept of the role of testosterone in male physiology suggests that testosterone plays also a significant role in the development and maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part and parcel of this approach.

Lower urinary-tract symptoms and testosterone in elderly men

ObjectivesThe objective was to examine the effects of testosterone administration on symptom scores of lower urinary tract symptoms (LUTS).MethodsThe literatures on the epidemiological association between the metabolic syndrome, erectile failure and (LUTS) were reviewed.ResultsIn men with the metabolic syndrome and erectile failure, often lower-than-normal testosterone levels are found. This is less clear for men with LUTS, but the relationship between testosterone and LUTS might be indirect and based on the association of the metabolic syndrome with an overactivity of autonomic nervous system. This overactivity may play a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary factors in aging men. Androgen receptors are present in the epithelium of the urethra and the bladder. Testosterone may play a role in the reflex activity of the autonomic nervous system in the pelvis, or may interact with postsynaptic non-genomic receptors suppressing detrusor activity. Human neurons in the wall of the bladder contain nitric oxide synthase. Similar to the penis, testosterone has an impact on nitric oxide synthase.ConclusionsSome studies investigating the effects of normalizing testosterone levels in elderly men have found a positive effect on variables of the metabolic syndrome and, simultaneously, on scores of the International Prostate Symptoms Score (IPSS) which is worthy of further investigation in randomized, controlled and sufficiently powered clinical trials.

Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters

Abstract Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function – erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.

Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from 5-Year Median Followup of 3 Registries

PURPOSEnAlthough there is no evidence that testosterone therapy increases the risk of prostate cancer, there is a paucity of long-term data. We determined whether the incidence of prostate cancer is increased in hypogonadal men receiving long-term testosterone therapy.nnnMATERIALS AND METHODSnIn 3 parallel, prospective, ongoing, cumulative registry studies 1,023 hypogonadal men received testosterone therapy. Two study cohorts were treated by urologists (since 2004) and 1 was treated at an academic andrology center (since 1996). Patients were treated when total testosterone was 12.1 nmol/l or less (350 ng/dl) and symptoms of hypogonadism were present. Maximum followup was 17 years (1996 to 2013) and median followup was 5 years. Mean baseline patient age in the urological settings was 58 years and in the andrology setting it was 41 years. Patients received testosterone undecanoate injections in 12-week intervals. Pretreatment examination of the prostate and monitoring during treatment were performed. Prostate biopsies were performed according to EAU guidelines.nnnRESULTSnNumbers of positive and negative biopsies were assessed. The incidence of prostate cancer and post-prostatectomy outcomes was studied. A total of 11 patients were diagnosed with prostate cancer in the 2 urology settings at proportions of 2.3% and 1.5%, respectively. The incidence per 10,000 patient-years was 54.4 and 30.7, respectively. No prostate cancer was reported by the andrology center. Limitations are inherent in the registry design without a control group.nnnCONCLUSIONSnTestosterone therapy in hypogonadal men does not increase the risk of prostate cancer. If guidelines for testosterone therapy are properly applied, testosterone treatment is safe in hypogonadal men.

Effects of testosterone gel followed by parenteral testosterone undecanoate on sexual dysfunction and on features of the metabolic syndrome

The effects of administration of testosterone (T) gel, resulting in plasma T levels in the low range of reference values, followed by testosterone undecanoate (TU), producing plasma T levels in the mid‐normal range, were measured in 27 hypogonadal men aged 47–74u2003years. T gel had positive effects on the International Index of Erectile Function, the Aging Males’ Symptoms Scale and International Prostate Symptoms Score and on the metabolic syndrome. The improvement was larger when TU was administered and plasma T levels were higher. The reduction in waist circumference and plasma cholesterol were larger with TU than with T gel, while the increases in plasma high‐density lipoprotein and sex hormone binding globulin (an indicator of the severity of the metabolic syndrome) were larger with TU than with T gel. Both T gel and TU appeared safe on prostate parameters. Plasma haemoglobin and haematocrit were elevated but remained in the normal range. The assumption that treatment with T is adequate when achieved plasma levels of T are within the reference range is no longer tenable. Some androgen‐dependent biological functions require higher plasma T levels than others, and, moreover, these thresholds differ among men.

Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men.

Purpose To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. Materials and Methods A total of 561 hypogonadal men from two registry studies were divided into age groups of ≤65 years (group Y, n=450; range, 32-65 years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. Results Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. Conclusions The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH.

Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadal elderly men: real-life experience from an observational registry study.

Subnormal levels of testosterone are associated with significant negative health consequences, with higher risks of all‐cause and cardiovascular mortality. The numbers of studies reporting on the benefits of normalisation of testosterone is increasing but longer‐term data on (elderly) men receiving testosterone treatment are almost nonexistent. In this single‐centre, cumulative, prospective, registry study, 115 hypogonadal men (mean age 59.05 years) received injections with testosterone undecanoate in 12‐week intervals for up to 10 years. Waist circumference, body weight and mean BMI dropped progressively with statistical significance versus previous year for 7 years and, respectively, 8 years for weight and body mass index. Similarly, fasting glucose displayed a significant decrease after the first year continuing to decrease thereafter. A decline in HbA1c, from 6.4% to 5.6% (mean <6%), was observed from year 2 on, together with a decrease in the ratio of triglycerides:high‐density lipoprotein (HDL), a surrogate marker of insulin resistance, with an increase in HDL levels. The total cholesterol:HDL ratio and non‐HDL cholesterol declined significantly. A decrease was also observed in systolic and diastolic blood pressure, with a decrease in levels of the inflammation marker C‐reactive protein. No major adverse cardiovascular events were observed throughout the study.

Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency

Traditionally, clinical conditions synonymous with the ageing male included cardiovascular disease (CVD), type 2 diabetes mellitus (DM) and sexual dysfunction, and were widely regarded as independent clinical entities. Over the last decade, interrelationship of clinical conditions has been convincingly demonstrated. Declining testosterone levels in the elderly, once regarded as an academic endocrinological question, appear to be central to the listed pathologies. It is now clear that erectile dysfunction is an expression of endothelial dysfunction. Testosterone deficiency is associated with an increased incidence of CVD and DM. The latter is often the sequel of the metabolic syndrome. Visceral obesity, a pivotal characteristic of the metabolic syndrome, suppresses the hypothalamic–pituitary–testicular axis leading to diminished testosterone production. Conversely, substantial androgen deficiency leads to signs and symptoms of metabolic syndrome. It is erroneous not to include testosterone measurements in the progress of the CVD, DM and erectile dysfunction. These conditions correlate strongly with testosterone deficiency.

Effects of intermission and resumption of long‐term testosterone replacement therapy on body weight and metabolic parameters in hypogonadal in middle‐aged and elderly men

In addition to primary and secondary (‘classical’) hypogonadism, hypogonadism occurring in middle‐aged and elderly men has been recognized. There is evidence that restoring T levels to normal improves body weight, serum lipids and glucose levels.