A systematic review on the latest developments in testosterone therapy: Innovations, advances, and paradigm shifts.

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

Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study.

Objectives: To report the association between testosterone treatment in hypogonadal men with hepatic steatosis, non-alcoholic fatty liver disease and cardiovascular disease (CVD). Methods: A prospective study was conducted to assess the physiological and functional performance of the long-term effects of testosterone undecanoate treatment on hepatic steatosis in 496 hypogonadal men. Two groups were studied, the treatment group (T-group) of 312 patients treated with TU 1000 mg every 12 weeks and followed for 8 years, and an untreated control group (C-group) of 184 patients. We evaluated liver functions and Fatty Liver Index (FLI) according to Mayo Clinic parameters and guidelines. Results: The T-group showed a decrease in the FLI (from a mean [SD] of 83.70 [12.15] to 67.12 [19.21]), bilirubin (from a mean [SD] of 1.69 [4.21] to 1.31 [1.91] mg/dL), triglycerides (from a mean [SD] of 254.87 [92.99] to 213.37 [66.91] mg/dL), and gamma-glutamyl-transferase (from a mean [SD] of 39.45 [11.51] to 29.11 [7.68] U/L) over the duration of the study. Other parameters were also reduced in the T-group such as body mass index (from a mean [SD] of 31.59 [4.51] to 29.50 [3.84] kg/m2) and waist circumference (from a mean [SD] of 107.51 [9.95] to 101.86 [9.28] cm). A total of 25 deaths (7.8%) were recorded in the T-group, among them, 11 (44%) were related to CVD. While in the C-group 28 deaths (15.2%) were recorded and all the reported deaths (100%) were related to CVD. Conclusions: The findings suggest that long-term testosterone therapy in hypogonadal men improves liver function. While, the physiological and functional improvements in the liver may be associated with a decrease in CVD-related mortality. Abbreviations ALT: alanine transaminase; AR: androgen receptor; AST: aspartate transaminase; BMI: body mass index; CVD: cardiovascular disease; FLI: Fatty Liver Index; γ-GT: gamma-glutamyl-transferase; MetS: metabolic syndrome; LDL: low-density lipoprotein; NAFLD: non-alcoholic fatty liver disease; RCT: randomised controlled trial; T2DM: type II diabetes mellitus; TT: total testosterone; TTh: testosterone therapy; TU: testosterone undecanoate; WC: waist circumference.

Long-term testosterone therapy improves liver parameters and steatosis in hypogonadal men: a prospective controlled registry study.

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) and both are prevalent in men with testosterone deficiency. Long-term effects of testosterone therapy (TTh) on NAFLD are not well studied. This observational, prospective, cumulative registry study assesses long-term effects of testosterone undecanoate (TU) on hepatic physiology and function in 505 hypogonadal men (T levels ≤350 ng/dL). Three hundred and twenty one men received TU 1000 mg/12 weeks for up to 12 years following an initial 6-week interval (T-group), while 184 who opted against TTh served as controls (C-group). T-group patients exhibited decreased fatty liver index (FLI, calculated according to Mayo Clinic guidelines) (83.6 ± 12.08 to 66.91 ± 19.38), γ-GT (39.31 ± 11.62 to 28.95 ± 7.57 U/L), bilirubin (1.64 ± 4.13 to 1.21 ± 1.89 mg/dL) and triglycerides (252.35 ± 90.99 to 213 ± 65.91 mg/dL) over 12 years. Waist circumference and body mass index were also reduced in the T-group (107.17 ± 9.64 to 100.34 ± 9.03 cm and 31.51 ± 4.32 to 29.03 ± 3.77 kg/m2). There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular related. In contrast, 28 patients (15.2%) died in C-group, and all deaths (100%) were attributed to CVD. These data suggest that long-term TTh improves hepatic steatosis and liver function in hypogonadal men. Improvements in liver function may have contributed to reduced CVD-related mortality.

Testosterone replacement therapy improves the health-related quality of life of men diagnosed with late-onset hypogonadism.

OBJECTIVES: To test the hypothesis that testosterone replacement therapy (TRT) improves the long-term health-related quality of life (HRQoL) of men with late-onset hypogonadism (LOH), as studies have shown that sub-physiological testosterone levels have a negative impact on psychological (e.g. mood, vitality, libido and sexual interest) and physical features (e.g. erectile function and physical strength), all of which contribute to a sense of well-being. PATIENTS AND METHODS: In all, 261 patients (mean age 58 years) diagnosed with LOH were treated with long-acting intramuscular testosterone undecanoate (TU) for up to 5 years. Health quality indicators including the International Prostate Symptom Score (IPSS), the five-item version of the International Index of Erectile Function (IIEF-5), the Aging Males' Symptoms (AMS) scale, and the percentage of patients reporting joint and muscle pain were measured at baseline and at each visit. The means were then plotted over time in parallel with mean total testosterone (TT) levels. RESULTS: Both the mean IPSS and AMS scores fell significantly within the first 3 months and the mean IIEF-5 score and TT levels increased within the first 3 months. All four parameters continued to improve over the course of the trial. The percentage of patients reporting both joint and muscle pain decreased during TRT. CONCLUSIONS: This prospective, observational and longitudinal analysis shows a clear improvement in both psychological and physical characteristics as physiological testosterone levels are reached and maintained contributing to an improvement in the HRQoL in men with diagnosed LOH.

Is there a relationship between the severity of erectile dysfunction and the comorbidity profile in men with late onset hypogonadism?

OBJECTIVE: To determine whether the severity of erectile dysfunction (ED) in a man diagnosed with late-onset hypogonadism (LOH) gives information about his metabolic syndrome state, as patients with LOH often have sexual symptoms and associated cardiovascular and metabolic comorbidities, but the role of ED in predicting the prevalence of comorbid disease in men with low levels of testosterone is currently unknown. PATIENTS AND METHODS: Men (130) diagnosed with LOH and fulfilling the criteria of a total testosterone level of <3.5 ng/mL (<12 nmol/L), and with an erectile function domain score of <21 on the International Index of Erectile Function questionnaire (IIEF, questions 1-5), were enrolled for a subsequent trial of supplementation with testosterone undecanoate. Demographic data were recorded at baseline. The men completed three standardised questionnaires to assess sexual health, including the International Prostate Symptom Score, Ageing Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by the severity of ED, with SHIM scores of 1-7 considered severe, 8-11 moderate, and 12-16 mild to moderate. Levels of serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density and low-density lipoprotein) were assessed, along with plasma fasting glucose and glycated haemoglobin (HbA1c) levels. Body weight, body mass index and waist circumference were also recorded. RESULTS: There was a significant association between the severity of ED and mean weight (P < 0.001), waist circumference (P < 0.001), triglycerides (P = 0.009), total cholesterol (P = 0.027), HbA1c (P < 0.001), fasting glucose (P = 0.003) and AMS scores (P = 0.043). There were no significant differences in testosterone fractions and SHBG levels between the ED subgroups. There was a positive correlation between the prevalence of diabetes mellitus (type 1 and type 2) and the severity of ED in these men (P = 0.018). CONCLUSIONS: The descriptive data showed that a greater severity of ED in men with LOH correlated with an increased waist circumference, hyperglycaemia, hypertriglyceridaemia, hyperlipidaemia, and a history of diabetes mellitus. Severe ED is a prognostic indicator of comorbidities in men with LOH.

Erectile dysfunction is a prognostic indicator of comorbidities in men with late onset hypogonadism.

INTRODUCTION: The role of testosterone deficiency in erectile dysfunction (ED) is increasingly recognized; however, there is a need to clarify the nature of the relationship between ED and late onset hypogonadism (LOH). AIM: In this study, we sought to determine the correlators of ED severity amongst men with LOH. METHODS: 130 patients diagnosed with LOH fulfilling the criteria of total testosterone ≤3.5 ng/ml (<12 nmol/l) and with an erectile function domain score <21 on the International Index of Erectile Function questionnaire (IIEF questions 1-5) were enrolled for a subsequent trial of Testosterone Undecanoate. Demographic data were recorded at baseline. MAIN OUTCOME MEASURES: Subjects completed three standardised questionnaires to assess sexual health including International Prostate Symptom Score (IPSS), Aging Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by ED severity with SHIM scores of 1-7 considered severe ED, 8-11 moderate ED and 12-16 mild to moderate. Serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein) were assessed along with plasma fasting glucose and HbA1c. Weight, BMI and waist circumference were also recorded. RESULTS: A significant association was observed between severity of ED and mean weight (p = 0.000), waist circumference (p = 0.000), triglycerides (p = 0.009), total cholesterol (p = 0.027), HbA1c (p = 0.000), fasting glucose (p = 0.003) and AMS scores (p = 0.043). No significant differences were seen in testosterone fractions and SHBG levels between ED subgroups. A positive correlation existed between the prevalence of diabetes mellitus (type 1 and type 2) and ED severity in this cohort (p = 0.018). CONCLUSIONS: The descriptive data of our cohort show that increased severity of ED within LOH patients correlated with an increased waist circumference, hyperglycemia, hypertriglyceridemia, hyperlipidemia and a history of diabetes mellitus. Severe ED functions as a prognostic indicator of co-morbidities in men with LOH.

Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life.

INTRODUCTION: Late-onset hypogonadism (LOH) is diagnosed when declining testosterone concentrations in the aging male cause unwanted symptoms such as erectile dysfunction (ED), reduced bone density and muscle strength, and increased visceral obesity. Testosterone deficiency is also associated with insulin resistance and the metabolic syndrome (MetS). Restoring testosterone to physiological concentrations has beneficial effects on many of these symptoms; however, it is not known whether these effects can be sustained in the long term. AIMS: To investigate whether treatment with testosterone undecanoate (TU) has a long-term and sustained effect on parameters affected by the MetS in men with LOH and ED, to determine whether long-term testosterone treatment can improve the overall health-related quality of life in these men, and to establish the safety of long-term testosterone treatment. METHODS: Two hundred sixty-one patients (mean age 59.5 ± 8.4 years) diagnosed with LOH and ED were treated with long-acting TU in a prospective, observational, and longitudinal registry study. Men received intramuscular injections of 1,000 mg TU at day 1, at week 6, and every 3 months thereafter. MAIN OUTCOME MEASURES: Parameters affected by the MetS, including obesity parameters (body weight, waist circumference, and body mass index [BMI]), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, HbA1c (glycated hemoglobin), and blood pressure, as well as total testosterone levels and health-related quality of life, were assessed. RESULTS: We found TU significantly improved obesity parameters (body weight, waist circumference, and BMI) and lowered total cholesterol, LDL cholesterol, triglycerides, fasting blood glucose, HbA1c , and blood pressure over the 5-year study. HDL cholesterol was increased. TU treatment resulted in a sustained improvement in erectile function and muscle and joint pain, which contributed to an improvement in long-term health-related quality of life. Furthermore, we found a relationship between health-related quality of life and waist circumference. Finally, we found no evidence that long-term treatment with TU increases the risk of prostate carcinoma. CONCLUSION: Long-term TU in men with LOH and ED reduces obesity parameters and improves metabolic syndrome and health-related quality of life.

Combined testosterone and vardenafil treatment for restoring erectile function in hypogonadal patients who failed to respond to testosterone therapy alone.

INTRODUCTION: The role of testosterone in erectile dysfunction (ED) is increasingly recognized. It is suggested that assessment of testosterone deficiency in men with ED and symptoms of hypogonadism, prior to first-line treatment, may be a useful tool for improving therapy. AIM: In this prospective, observational, and longitudinal study, we investigated the effects of vardenafil treatment as adjunctive therapy to testosterone undecanoate in hypogonadal ED patients who failed to respond to testosterone treatment alone. METHODS: One hundred twenty-nine testosterone deficient (serum total testosterone ≤ 3.4 ng/mL) patients aged 56 ± 3.9 years received intramuscular injections of long-acting parenteral testosterone undecanoate at 3-month intervals for 8 months mean follow-up. MAIN OUTCOME MEASURES: Scores on the International Index of Erectile Function Questionnaire-five items (IIEF-5) and partner survey scores were compared at baseline and posttreatment with testosterone therapy alone or in combination with vardenafil. Patient baseline demographics and concomitant disease were correlated with patients' IIEF-5 scores. RESULTS: Seventy one (58.2%) responded well to monotherapy within 3 months. Nonresponders had lower testosterone levels and higher rates of concomitant diseases and smoking. Thirty-four of the 51 nonresponders accepted the addition of 20 mg vardenafil on demand. Efficacy assessments were measured by the IIEF-erectile function domain (IIEF-EF, questions 1-5 plus 15, 30 points) and partner self-designed survey at baseline after 4-6 weeks and at study end point. Thirty out of 34 patients responded well to this combination. IIEF-EF Sexual Health Inventory for Men score improved from 12 to 24 (P < 0.0001), and partner survey showed significantly higher satisfaction (P < 0.001). These patients reported spontaneous or nocturnal and morning erections or tumescence. No changes in adverse effects were recorded. CONCLUSIONS: These data suggest that combination therapy of testosterone and vardenafil is safe and effective in treating hypogonadal ED patients who failed to respond to testosterone monotherapy.

Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism: 5-year prospective, observational and longitudinal registry study.

PURPOSE: Many men with "late-onset hypogonadism" (LOH) experience lower urinary tract symptoms (LUTS) that can be distressing and may decrease quality of life. LUTS often appear in men when testosterone levels begin to decline, which could be a significant association. We investigated whether testosterone replacement could alleviate LUTS in men with LOH. METHODS: Two hundred and sixty-one hypogonadal patients (mean age 59.5 years) presenting with erectile dysfunction, having also been evaluated for LUTS, received a single testosterone undecanoate injection at day 1, at week 6 and quarterly thereafter. Parameters, including International Prostate Symptom Score (IPSS), post-voiding residual urine volume, transrectal ultrasound, prostate volume and prostate-specific antigen were measured at each treatment visit. Two hundred and fifty-nine patients were included in the full analysis set. These were subsequently divided into weight losers (L ≥ 5 % weight loss at last visit from baseline) and non-losers (NL). t test analyses were used to compare the IPSS means of these subgroups. The potentially confounding effect on IPSS of using the phosphodiesterase-5 inhibitor (PDE5i) vardenafil was also accounted for. RESULTS: Mean IPSS showed a significant decrease with time following initiation of testosterone treatment (p < 0.05). No significant differences were observed in either IPSS between L and NL groups or in mean IPSS between vardenafil users and non-users. CONCLUSION: Testosterone replacement is associated with improvements in LUTS which are not confounded by weight loss or PDE5i. The mechanisms of this association require further investigation.

The role of the urologist in the prevention and early detection of cardiovascular disease.

In this review we identify whether problems encountered in urology, such as erectile dysfunction, have a bearing on general health, in particular cardiovascular health. Testosterone, traditionally regarded as the hormone subserving male reproductive and sexual functioning, appears to have a much wider role. Recent findings show that testosterone is involved in the metabolic control of glucose and lipids, of strength of bone and muscle, and psychological aspects such as mood and energy. Serum testosterone levels decline with ageing, free testosterone levels more so than total testosterone. At least 10 publications have shown that low testosterone levels are associated with an increased risk of death. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. There is a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin levels predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavourable risk profile for the development of diabetes and atherosclerosis, thus also improving risk factors for erectile dysfunction. We conclude that urologists diagnosing and treating erectile problems are in a unique position to include general aspects of men's health in their work, and thus contribute to general health and to cardiovascular health in particular.

Effects of testosterone on the lower urinary tract go beyond the prostate: New insights, new treatment options.

The traditional assumption that the prostate is an organ exquisitely sensitive to androgen action still holds true, but with lower-than-normal circulating levels of testosterone, all androgen receptors are saturated and a further increase in circulating levels of testosterone has no effect on the prostate (saturation model). Prostate disease (prostate cancer and benign prostatic hyperplasia, BPH) usually occur at an age when circulating levels of testosterone are declining, so it is unlikely that they are to be attributed to an excess of testosterone. The bother of BPH is presently subsumed under 'pathology of the lower urinary tract'. Surprisingly, these structures have androgen receptors, and depend for their relaxation on nitric oxide, for which the mechanism, in turn, is aided by androgens. This explains why phosphodiesterase type-5 inhibitors also benefit erectile function and symptoms of the lower urinary tract. Normalisation of testosterone in hypogonadal men favours this action. During the development of the prostate, epithelium and mesenchyme are under the control of testicular androgens, and interact to form an organised secretory organ. Furthermore, many of the disease processes of the prostate have been attributed to androgen action, and consequently, therapies have been aimed at manipulating androgen activity.

Amelioration of penile fibrosis: myth or reality.

Several changes have been reported to occur in the cavernosal tissue and tunica albuginea with aging. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction in the number of smooth muscle cells (SMCs) has been demonstrated in relation to this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance with aging. Chronic ischemia is therefore associated with fibrosis but also with nitric oxide-cGMP reduction. The sensitivity of the α-adrenoceptors on the SMCs increases with aging. Furthermore, androgen deprivation produces penile tissue atrophy, alterations in dorsal nerve structure, alterations in endothelial morphology, reductions in trabecular SM content, increases in deposition of extracellular matrix, and increases in accumulation of adipocytes in the subtunical region of the corpus cavernosum. All of these modifications can explain the prevalence of erectile dysfunction with aging. The aim of this review is to address the underlying etiology of corporal fibrosis, especially aging, cavernosal nerve damage, androgen deprivation, and tunical fibrosis. Finally, we will address the proposed amelioration and reversal of fibrosis in terms of correcting, at least partially, the relative SMC loss that occurs with aging, diabetes, or cavernosal nerve damage and its impact on prevention of erectile dysfunction-associated cavernosal fibrosis.

Erectile dysfunction, cardiovascular diseases and depression: interaction of therapy.

Several studies have revealed the intimate associations between erectile dysfunction (ED), ischemic heart disease (IHD) and depression. Whether the physicians should also screen for the other two components when a patient presents with one component of this triad is still an important question to be answered. These three components had been classified as independent medical conditions managed by unrelated medical services. Recently, the potential effect of medications of each condition on the other conditions had gained a lot of interest. The aim of the current review is to discuss the integrative view of association between cardiovascular diseases, erectile dysfunction and depression, and to address the two direction impact of pharmacotherapy for IHD and depression on erectile function.

Lower urinary-tract symptoms and testosterone in elderly men.

OBJECTIVES: The objective was to examine the effects of testosterone administration on symptom scores of lower urinary tract symptoms (LUTS). METHODS: The literatures on the epidemiological association between the metabolic syndrome, erectile failure and (LUTS) were reviewed. RESULTS: In 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. CONCLUSIONS: Some 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.

Testosterone and erectile dysfunction.

Aging is associated with a decline in several important health factors in men, including libido. Serum testosterone concentrations also decrease with age, and many age-related clinical features are closely associated with androgen deficiency, including erectile function (ED). Approximately 70% of ED is of organic origin, with the major risk factors being diabetes mellitus, hypercholesterolemia, smoking and chronic medical illnesses. These are also established risk factors for atherosclerosis, which is the predominant predisposing factor of vasculogenic ED. The introduction of phosphodiasterase-5 (PDE-5) inhibitors for the treatment of ED made a significant impact both in terms of clinical efficacy, and increasing the awareness of the condition. In spite of this, some patients fail to respond to PDE-5 inhibitors alone. Both animal and clinical studies indicate that testosterone therapy improves both erectile function and the response to PDE-5 inhibitors in patients with ED and hypogonadism. Indeed, interventional studies demonstrate that testosterone replacement therapy improves erectile function in hypogonadal men who have previously failed to respond to PDE-5 inhibitors alone. Furthermore, it has been demonstrated that the full therapeutic potential of PDE5 inhibitors will only become manifest in a eugonadal state. Recent studies have demonstrated a close relationship between testosterone and ED and suggest that testosterone therapy may be a valuable option for an increasing number of affected men. European guidelines recommend that all men presenting with ED should have their testosterone concentrations measured.

Conservative treatment for Peyronie's disease: an update.

Many theories have been proposed to explain the cause of Peyronie's disease (PD); however, the true pathogenesis of PD remains an enigma. As a result, the treatment of PD remains a dilemma and new therapies continue to evolve. The last two decades have witnessed a phenomenal advance in the understanding of the pathophysiology and natural history of PD. The efficacy of conservative treatment for PD is not settled. In this update review the authors provide information of the status of conservative therapy for PD. Conservative treatment is always the initial treatment in most of the cases. This kind of therapy consists of different modalities of treatment such as oral, intralesional or topical therapy. Other treatments including iontophoresis, extracorporeal shock wave, radiotherapy, ultrasound and laser have also been reported.

Improvement of sexual function in men with late-onset hypogonadism treated with testosterone only.

AIM: Late-onset hypogonadism is associated with relatively mild testosterone deficiencies. This study investigated the effects of restoring testosterone levels to normal in men with complaints of low sexual desire and erectile dysfunction. MAIN OUTCOME MEASURES: Sexual function was assessed with the International Index of Erectile Function (IIEF) at baseline and after 24 weeks of testosterone administration. METHODS: Twenty-two hypogonadal men (mean age 58 years) with erectile dysfunction were studied. Fifteen patients had serum testosterone below 6.9 nmol/L, and seven between 7.2 and 11.7 nmol/L (reference values in our laboratory >/=12.0 nmol/L); there were considerable comorbidities. The duration of sexual complaints was on average 3.8 years. Patients received intramuscular long-acting testosterone undecanoate. RESULTS: In all patients, serum testosterone levels were restored to normal within 6-8 weeks. Twelve patients reported a significant improvement in the sexual desire domain (from 4.5 to 8.4) and experienced an improvement in the erectile function domain (from 12 to 25 [Questions 1-5 plus 15)], following treatment with this long-acting testosterone; in 9 of 12 patients, this occurred only after at least 12-24 weeks. The remaining 10 patients reported an improvement of sexual desire (from 4.5 to 7.5), but no significant improvement in the erectile function domain (from 12 to 14). No changes in serum prostate-specific antigen or prostate volume were noticed while receiving this long-acting testosterone preparation. CONCLUSION: Restoring testosterone levels to normal in men with proven subnormal testosterone levels improves libido in most subjects, and erectile function in more than 50% of these men. It may take 12-24 weeks before the effects of testosterone become manifest.

Effects of testosterone on erectile function: implications for the therapy of erectile dysfunction.

Sexual potency declines with age, as does the efficiency of erection. Many studies show that different patterns of erectile dysfunction (ED), varying from occasional inability to obtain a full erection, impairment throughout intercourse and total absence of erectile response, might not be triggered by psychological factors only. Recent research indicates that ED relies on organic causes, and has challenged the development of new therapies. One therapeutic approach in patients who have testosterone deficiency is based on androgen therapy. Thus, we reviewed data on testosterone-induced effects relative to erectile function, summarizing the results from studies reported in 1991-2006 on testosterone therapy in patients with ED and hypogonadism, with a special focus on men not responding to phosphodiesterase-5 (PDE-5) inhibitors. We searched several computerized databases parallel with printed bibliographic references. Many studies have established animal models, which confirm that testosterone is important in modulating the central and peripheral regulation of ED. Testosterone deprivation has a strong negative impact on the structure of penile tissues and erectile nerves, which can be prevented by androgen administration. Combined therapy regimens with PDE-5 inhibitors and testosterone might improve ED in patients with hypogonadism of different causes. Thus, androgen treatment in hypogonadic patients, including those unresponsive to PDE-5 inhibitors, often results in an improvement of ED. Testosterone therapy is safe and convenient, while rapidly correcting low testosterone levels.

Testosterone depot injection in male hypogonadism: a critical appraisal.

Testosterone compounds have been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable testosterone esters have been used for treatment, but they generate supranormal testosterone levels shortly after the 2- to 3-weekly injection interval and then testosterone levels decline very rapidly, becoming subnormal in the days before the next injection. The rapid fluctuations in plasma testosterone are subjectively experienced as disagreeable. Testosterone undecanoate is a new injectable testosterone preparation with a considerably better pharmacokinetic profile. After 2 initial injections with a 6-week interval, the following intervals between two injections are almost always 12-weeks, amounting eventually to a total of 4 injections per year. Plasma testosterone levels with this preparation are nearly always in the range of normal men, so are its metabolic products estradiol and dihydrotestosterone. The "roller coaster" effects of traditional parenteral testosterone injections are not apparent. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters and on sexual functions. Its safety profile is excellent due to the continuous normalcy of plasma testosterone levels. No polycythemia has been observed, and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. There was no impairment of uroflow. Testosterone undecanoate is a valuable contribution to the treatment options of androgen deficiency.

Treatment of sexual dysfunction of hypogonadal patients with long-acting testosterone undecanoate (Nebido).

Recently, testosterone undecanoate (TU), a new parenteral testosterone (T) preparation has been introduced. Two of its distinctive features are (a) its prolonged action: after two initial loading injections 6 weeks apart, usually only one injection every 12 weeks is needed (b) over the full interval between two injections, plasma T levels are in the physiological range. New research presents convincing evidence that T has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, which is, at least, in part reversible upon androgen therapy. Our studies with TU demonstrated that venous leakage could be corrected with T treatment in a number of patients. We further could show that sexual functions, in a substantial number of elderly men, can be restored with treatment with T only. So, these results argue for determination of T levels in elderly men with sexual problems. If the levels are subnormal, T treatment is warranted.