Eric Meuleman

Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study)

OBJECTIVE This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12). RESULTS TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate. CONCLUSIONS Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.

Predictors of success with neuromodulation in lower urinary tract dysfunction : results of trial stimulation in 100 patients

Chronic lower urinary tract dysfunction can be treated by sacral neuro-stimulation. Clinical parameters for selection of patients for this expensive and invasive treatment modality are not well defined to date. Therefore, before implantation of a permanent stimulator, the effect is tested by temporary implantation of a wire electrode connected to an external stimulator. According to the literature, many patients do not respond during temporary implantation and a mean of 25% of the patients with a permanent stimulator implanted fail to respond as well. To improve patient selection, we attempted to define clinical parameters to predict the outcome of sacral neuro-stimulation in 100 consecutive patients who were tested with temporary sacral stimulation. A total of 34 patients achieved a complete cure on trial stimulation. It appeared that detrusor overactivity and urethral instability responded best but they were not predictors of success. We conclude that neither gender, patient age, history nor diagnosis are predictors of success in sacral neuro-stimulation of lower urinary tract dysfunction.

Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST Study)

INTRODUCTION Addition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels. AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant. METHODS A multicenter, multinational, double-blind, placebo-controlled study of 173 men, 45-80 years, nonresponders to treatment with different PDE5-Is, with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double-blind, placebo-controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory. Main Outcomes Measures.  Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question). RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5-Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5-I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤ 3 ng/mL.

Sexual dysfunction after renal replacement therapy.

The existence of a sexual problem as the subjective evaluation of sexual function was assessed with a simple questionnaire. Those questioned were patients undergoing dialysis treatment (n = 400) or with a functioning renal transplant (RTx; n = 300) and both men and women in the general Dutch population (n = 591). In the Dutch control population, 8.7% of the men and 14.9% of the women reported a sexual problem, showing a significant gender difference but unrelated to age. In patients, the prevalence of a sexual problem was significantly greater (hemodialysis, men, 62.9%; women, 75.0%; peritoneal dialysis, men, 69.8%; women, 66.7%; renal transplantation, men, 48.3%; women, 44.4%). In RTx recipients, sexual problems were significantly less prevalent than in patients undergoing dialysis (P < 0.001). Only in male patients was an association between prevalence of a sexual problem and age found. The results of the simple questionnaire were sufficiently validated when 102 of 104 patients confirmed their responses in a subsequent structured interview. This study shows that the prevalence of sexual problems in patients undergoing renal replacement therapy is high and clinically relevant.

An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation

To develop a contemporary, evidence‐based definition of premature ejaculation (PE).

Erectile Dysfunction in Diabetic Men: The Neurological Factor Revisited

In the literature the importance of the neurological factor in the etiology of erectile dysfunction in patients with diabetes mellitus is subject to debate. We report on the findings of neurophysiological investigations in 27 impotent and 30 potent diabetic patients, as well as 102 impotent nondiabetic patients. Additionally, hormonal and vascular evaluations were done. The neurophysiological evaluations consisted of assessment of somatic as well as autonomic sensory nerves, by measuring the latencies of somatosensory evoked potentials of the posterior tibial and pudendal nerves, and of the bulbocavernosus and urethro-anal reflexes. The results show a higher incidence of more severe peripheral and autonomic sensory neuropathy in impotent diabetic men. Also, a preponderance of abnormal intracavernous pharmacological tests, suggesting vasculogenic impotence, was found in impotent diabetic patients. No important endocrinological differences were found among the 3 groups under investigation. Significant differences occurred for plasma glucose and glycosylated hemoglobin. We conclude that diabetic urogenital sensory neuropathy has a crucial role in the etiology of diabetic impotence. Angiopathy seems to be of secondary importance. The results show that poor diabetes regulation is associated with diabetic impotence.

Assessment of penile blood flow by duplex ultrasonography in 44 men with normal erectile potency in different phases of erection.

Duplex ultrasonography is important in the diagnosis of vasculogenic erectile dysfunction. We measured the ultrasonographic parameters of cavernous blood flow in different phases of penile erection. We examined 44 volunteers with normal erectile potency. Doppler spectra of the cavernous artery were obtained in a time-dependent manner after intracavernous administration of papaverine. Following intracavernous pharmacological stimulation, the Doppler spectrum alters according to a specific pattern indicating the different hemodynamic phases of erection. Peak flow velocity and acceleration time, measured in the early post-injection phase, may be used to grade arterial inflow. The difference between resistance index in the pre-injection and late post-injection phases may be used to estimate veno-occlusive function. References values are defined.

Hypoactive sexual desire disorder: An underestimated condition in men.

HSDD is associated with a wide variety of biological and psychological causes [1]. At present, no single instrument for diagnostically assessing HSDD prevails [3]. Sexual healthcare providers who wish to be alert to a diagnosis of HSDD are advised to pose direct and unambiguous questions to their patients, to probe for aspects of sexual desire and motivation. Patients often will not reveal sexual problems unless explicitly invited [4]. Collateral information may be obtained through questionnaires, completed before or after the consultation. Several reliable and valid questionnaires are available for assessing sexual desire problems, with easy-to-follow instructions. The Sexual Desire Inventory [5] was designed specifically to measure level of sexual desire, the International Index of Erectile Function [6] provides a subscale to measure sexual desire, and the Golombok Rust Inventory of Sexual Satisfaction [7–9] provides subscales of sexual avoidance, and of infrequency of sexual contact.

Penile Sensory Disorders in Erectile Dysfunction: Results of a Comprehensive Neuro-Urophysiological Diagnostic Evaluation in 123 Patients

A total of 123 patients with complaints of erectile dysfunction and no clinically overt neurological disease underwent a comprehensive neuro-urophysiological diagnostic evaluation. The results were compared with those obtained in 50 healthy volunteers. Data gathered consisted of somatosensory evoked potentials from the posterior tibial nerve (tibial evoked potential) and from the dorsal penile nerve (pudendal evoked potential). Also, 2 sacral reflex latencies were measured (bulbocavernosus reflex and urethro-anal reflex). A total of 58 patients (47%) had at least 1 abnormal neuro-urophysiological measurement. Neuro-urophysiological abnormalities were found more frequently in older patients. The tibial evoked potential was abnormal in 30 patients (24%), pudendal evoked potential in 21 (17%), bulbocavernosus reflex in 26 (21%) and urethro-anal reflex in 32 (26%). It was concluded that somatosensory disturbances constitute an important part of neuro-urophysiological abnormalities. Our results suggest a relationship between erectile dysfunction and subclinical, age-related (penile) sensory disorders. Our study corroborates the importance of penile sensibility for erectile (patho)physiology as suggested by others and supports the concept of sensory deficit impotence as an important cause of erectile dysfunction.

Is increased CAG repeat length in the androgen receptor gene a risk factor for male subfertility

PURPOSE Increased length of the CAG repeat in the androgen receptor gene may be related to male subfertility. Expansion to 38-62 CAG repeats leads to the neurodegenerative disorder with male infertility called Kennedys disease. Recently it was suggested that slight expansion is related to male subfertility. In this study we investigated the association of male subfertility with the length of CAG repeats in the androgen receptor. MATERIALS AND METHODS CAG repeat length in the androgen receptor gene was investigated in 75 subfertile men, who were mainly candidates for intracytoplasmic sperm injection. Sperm parameters varied from azoospermia to severe oligoasthenoteratozoospermia. The control group consisted of 70 men who predominantly had bladder cancer. DNA was isolated from peripheral blood and genotyping was performed with polymerase chain reaction based methods. RESULTS No statistically significant difference in the mean length of the CAG repeat plus or minus standard deviation was noted in subfertile men and controls (22.2 +/- 3.1 and 21.7 +/- 3.4, respectively). The length of the CAG repeat in the androgen receptor was not related to the degree of impaired spermatogenesis or clinical characteristics of the subfertile men. CONCLUSIONS Increased length of CAG repeats in the androgen receptor gene is not a risk factor for male subfertility.