54 research outputs found
CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism?
No full textIntroduction It is controversial whether or not testing the length of the androgen receptor polymorphism in clinical practice is useful for correct diagnosis and treatment of hypogonadism. AimTo describe the molecular and clinical implications of testing the length of the androgen receptor polymorphism for treatment of hypogonadism in both male and female subjects. MethodsA systematic Medline search was conducted using several terms related to and including the terms androgen receptor, CAG-repeat polymorphism, male hypogonadism, female hypogonadism, and neurodegenerative disease. Main Outcome MeasuresClinical evidence that demonstrates the importance of CAG repeat number investigation in male and female hypogonadism. Results A thorough review of the clinical utility of CAG repeat polymorphism investigation in men and women with hypogonadism is presented. Conclusions The role of AR CAG repeat number investigation in hypogonadism (male and female) is not yet established in the clinical practice. In both sexes, a role during clinical management of hormonal replacement therapies may be hypothesized, but the CAG repeat number's relationship with the presence or absence of hypogonadal symptoms remains unclear. Pharmacogenomic investigations of the AR polymorphism may be a future option to tailor testosterone titration individually and to better identify subjects as potentially more or less responsive to treatments; also, investigation may be important to individually predict beneficial and side effects in special subpopulations, specifically, obese men and postmenopausal women. Francomano D, Greco EA, Lenzi A, and Aversa A. CAG repeat testing of androgen receptor polymorphism: Is this necessary for the best clinical management of hypogonadism? J Sex Med 2013;10:2373-2381
Effects of Five-Year Treatment with Testosterone Undecanoate on Metabolic and Hormonal Parameters in Ageing Men with Metabolic Syndrome
No full textMetabolic and hormonal modifications after long-term testosterone (T) treatment have never been investigated. 20 hypogonadal men (mean T = 241 ng/dL-8.3 nmol/L) with metabolic syndrome (MS, mean age 58) were treated with T-undecanoate injections every 12 weeks for 60 months. 20 matched subjects in whom T was unaccepted or contraindicated served as controls. Primary endpoints were variations from baseline of metabolic and hormonal parameters. In T-group, significant reductions in waist circumference (-9.6 ± 3.8 cm, P < 0.0001), body weight (-15 ± 2.8 Kg, P < 0.0001), and glycosylated hemoglobin (-1.6 ± 0.5%, P < 0.0001) occurred, along with improvements in insulin sensitivity (HOMA-I; -2.8 ± 0.6, P < 0.0001), lipid profile (total/HDL-cholesterol ratio -2.9 ± 1.5, P < 0.0001), systolic and diastolic blood pressure (-23 ± 10 and -16 ± 8 mm Hg, P < 0.0001, resp.), and neck and lumbar T-scores (+0.5 ± 0.15 gr/cm(2), P < 0.0001; +0.7 ± 0.8, P < 0.0001, resp.). Also, serum vitamin D (+14.0 ± 1.3 ng/mL, P < 0.01), TSH (- 0.9 ± 0.3 mUI/mL, P < 0.01), GH (0.74 ± 0.2 ng/mL, P < 0.0001), and IGF1 (105 ± 11 ng/mL, P < 0.01) levels changed in T-group but not in controls. Normalization of T levels in men with MS improved obesity, glycemic control, blood pressure, lipid profile, and bone mineral density compared with controls. Amelioration in hormonal parameters, that is, vitamin D, growth hormone, and thyrotropin plasma levels, were reported
Is testosterone treatment dangerous for the cardiovascular system in older hypogonadal men?
No full textThe relationship between testosterone deficiency syndrome (TDS) and men's vascular health has a great impact in the modern approach to the aging male. There is good evidence that low testosterone (T) is associated with erectile dysfunction (ED) and that ED is a strong marker for cardiovascular risk; also, TDS is frequently associated with increased cardiovascular and all-cause mortality. Noteworthy, the occurrence of increased levels of glucose, total cholesterol, low-density lipoprotein, pro-inflammatory cytokines, and myointimal carotid thickness may be associated with reduced T levels especially in cardiac older frail men. Screening for low T should be mandatory in high risk groups including those with type 2 diabetes, metabolic syndrome and obesity. The rising demand from patients to be treated for ED associated with TDS will increase the prescribing of T and facilitate future long-term studies on its impact on cardiovascular disease (CVD). Recent studies suggest warnings with regard to T prescription in older frail men, but we regret that these studies had consistent bias in inclusion criteria and statistical evaluation. Data from studies conducted in more selected populations suggest that T replacement therapy may improve multiple surrogate markers for CVD as well as reducing cardiovascular mortality. After analyzing the most important studies' limitation, we can conclude that at present there is insufficient evidence of a causal relationship between T therapy and adverse cardiovascular outcomes to support against T supplementation in older hypogonadal frail men
Cardiometabolic complications after androgen deprivation therapy in a man with prostate cancer: effects of three years intermittent testosterone supplementation
No full textAndrogen deprivation therapy (ADT) for prostate carcinoma (PCa) may cause cardiometabolic complications unless intermittent androgen blockade (IAB) is instituted. An 80-year-old man was diagnosed intermediate grade (Gleason 4+3) PCa and was treated with continuous ADT with triptorelin plus bicalutamide. After 6 months of treatment, he experienced an acute myocardial infarction and one month after hospitalization he came to our outpatient clinic for fatigue, weight gain and hyperglycemia. Due to iatrogenic hypogonadism, we decided to proceed with IAB, but after three months ADT withdrawal his serum testosterone (T) was still 0.5 ng/mL. Due to very low concomitant PSA levels (0.1 ng/mL) he was then proposed intermittent T-gel supplementation (Tostrex®) which was initiated according to the following scheme: 6 months on and three months off. T-gel dose was titrated tri-weekly in order to achieve T plasma levels below 3.49 ng/mL. After six months on, his serum T raised to a mean value of 2.0 ng/mL without increments in PSA. After overall twelve months on, his serum T peaked to a mean value of 3.0 ng/mL while a delay in PSA rise was seen after 24 mo (0.6 ng/mL) but remained stable until the last observation carried forward (LOCF), at 45 months. No clinical and biochemical PCa progression were observed at LOCF. Reversion of iatrogenic metabolic syndrome started after six mo of T supplementation without using any add-on treatment. This case provides support that once regression of PCa growth is attained, T supplementation may be administered in well differentiated PCa, especially if IAB is not successful in reverting iatrogenic hypogonadism and its associated cardiac and metabolic complications
Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study
No full textIntroduction. Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease. Aim. To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11 nmol/L or free T at or below 250 pmol/L). Methods. This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57 +/- 8) were randomized (4:1) to receive TU 1,000 mg (every 12 weeks) or placebo (PLB) gel (3-6 g/daily) for 24 months. Main Outcome Measures. Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP). Results. At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P < 0.001), CIMT (P < 0.0001), and hsCRP (P < 0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P < 0.0001) and 58% (P < 0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P < 0.0001), visceral fat mass (P < 0.0001), and improvement in HOMA-IR without changes in body mass index (BMI). Conclusions. TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events. Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, and Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late onset hypogonadism and metabolic syndrome: Results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med 2010;7:3495-3503
Peripheral Arterial Tonometry to Measure the Effects of Vardenafil on Sympathetic Tone in Men with Lifelong Premature Ejaculation
No full textTo elucidate whether adrenergic overtone is involved in the pathophysiology of men with
lifelong (LL) premature ejaculation (PE), we investigated differences in reactive hyperemia
index (RHI) responses by using peripheral arterial tonometry (PAT). 20 men with LL-PE (18–40 years) were enrolled in an 8-week, double-blind, placebo-controlled, crossover study and compared with 10 age-matched controls without LL-PE. Primary endpoints were PAT modifications induced by vardenafil 10 mg on demand. Secondary endpoints were the
improvement in intravaginal ejaculatory latency time (IELT) as measured by the stopwatch technique and variations in anxiety scores at Stai-X1 for state-anxiety and Stai-X2 for trait-anxiety. At baseline, men with LL-PE showed higher RHI variation (), Stai-X1 and Stai X2 scores (, resp.), and prolactin levels () compared with controls. Vardenafil treatment markedly reduced RHI variation in men with LL-PE ()
when compared with placebo. Mean changes in geometric IELT were higher after taking
vardenafil (0.6 ± 0.3 versus 4.5 ± 1.1 min, ) when compared with placebo. STAI-X1 and STAI-X2 scores fell within the normal range after treatment with vardenafil (). Vardenafil was an effective treatment in men with LL-PE; improvements of IELT may be due to increased NO production which is able to reduce adrenergic overactivity and anxiety levels
Weight Loss by Multidisciplinary Intervention Improves Endothelial and Sexual Function in Obese Fertile Women
No full textIntroduction Weight loss in sexually active women improves their quality of life. At present, no studies have investigated whether weight loss may affect female sexual function in severe obese women. Aim The aim of this study was to investigate the effects of different programs of weight loss on female sexual dysfunction complaints and on endothelial function in premenopausal obese females. Methods Forty-four out of overall 80 obese fertile women (age 1849 years; mean 36 years) were enrolled because of sexual complaints at Female Sexual Function Index-6 (FSFI-6 score 19). Patients were then allocated to different treatments of 8 weeks duration each: an intensive residential program with hypocaloric diet plus controlled physical exercise along with lifestyle modifications at a specialized clinic (Group A, N=23) and a non-intensive outpatient clinic program consisting of hypocaloric diet and physical exercise at home (Group B, N=21). Afterward, overall patients were allocated to an extended 8-week follow-up period consisting of outpatient clinic controlled diet plus physical exercise at home. Main Outcome Measures Primary end points were modifications of FSFI-6 scores and endothelial function as measured by reactive hyperemia (RHI) with EndoPat-2000. Secondary end points were modifications in body composition as measured by dual-energy X-ray absorptiometry (DEXA). Results After 16 weeks, FSFI-6 score and the frequency of sexual activity were significantly higher in Group A compared with Group B (P<0.01), and significant improvements in arousal, lubrication, and satisfaction sub-domain scores were also found (P<0.01). Group A showed improvements in RHI (P<0.01) and marked improvement in homeostasis model assessment of insulin resistance (P<0.001), anthropometric parameters as weight (P<0.01), body mass index (P<0.01), fat mass (P<0.0001), and percentage of fat mass (P<0.005) compared with Group B. A relationship between peak insulin (P<0.0001) and RHI (P<0.001) vs. FSFI-6 scores was found, respectively. Conclusions A multidisciplinary approach to female obesity appears to be superior to conventional outpatient clinic to produce weight loss and to improve several aspects of sexual dysfunction in obese women. Such changes might be related to persistent improvements in endothelial function and in insulin resistance. Aversa A, Bruzziches R, Francomano D, Greco EA, Violi F, Lenzi A, and Donini LM. Weight loss by multidisciplinary intervention improves endothelial and sexual function in obese fertile women. J Sex Med 2013; 10: 1024-1033
An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors
No full textIntroduction: Phosphodiesterase type 5 inhibitors (PDE5-i) are used for the oral treatment of erectile dysfunction (ED). Since the launch of sildenafil more than 15 years ago, new molecules have become available. At present, in addition to tadalafil and vardenafil, there are three other drugs, udenafil, avanafil and mirodenafil, marketed in some countries which appear to be promising. Areas covered: The clinical pharmacological differences in dosage and side effects of all PDE5-i are evaluated. Expert opinion: All PDE5-i are equally effective and safe for the treatment of ED. On-demand use of any PDE5-i is also safe for patients with comorbid conditions. Tadalafil seems to be the preferred drug by patients and physicians, probably due to its peculiar pharmacological profile that makes sexual intercourse more spontaneous for the patients. Preliminary data suggest that the use of vardenafil may also be beneficial in cases of ED associated with premature ejaculation. Daily treatment is another option in men with ED and documented vascular or prostate disease. In geriatric or in difficult-to-treat populations, the evaluation of testosterone plasma levels will help to predict the efficacy of any PDE5-i. Remarkably, when such drugs are withdrawn for any reason, ED most often continues to occur because of the presence of an underlying disease. © 2013 Informa UK, Ltd
Cardiovascular effect of testosterone replacement therapy in aging male
No full textCardiovascular diseases (CVD) are the most important causes of morbidity and mortality in the developed and developing world. Particularly, coronary heart disease is the commonest cause of death worldwide. Testosterone (T) is an anabolic hormone with putative beneficial effects on men's health and restoration of normal T levels in deficient men represents an important key-point of male well-being. In the lasts years it has emerged a possible linkage between androgen deficiency and CVD. Many studies noted that T deficiency might contribute to increased risk of CVD. Furthermore, androgen deficiency is frequently associated with increased levels of glucose, total cholesterol, low-density lipoprotein, increased production of pro-inflammatory cytokines, and increased thickness of the arterial wall that all contribute to worsen endothelial function. The clinical and epidemiological studies discussed in this section give an update on the interplay between late onset hypogonadism (LOH) and CVD. The linkage between androgen deficiency and men's vascular health has a great impact in the modern approach to the ageing male, and should be further investigated to determine the therapeutic potential of androgens in men with vascular disease. (www.actabiomedica.it). © Mattioli 1885
Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study
No full textPurpose Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Methods 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. Results At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r(2) = -0.46, p < 0.001 and r(2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r(2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. Conclusions In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained
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