ISCRIVITI A ISSAM ITALIA

Testosterone e Diabete: Studio d'intervento

Riferimenti bibliografici: Diabetes Care 34:828-837, 2011

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 ANDMETHODS?The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men withtype 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 026 (phase 1; no changes in medication allowed).Medication changes were allowed in phase 2 (months 6212). 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, 20.446%; 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 beneficialeffects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS. Autori: T. HUGH JONES, FRCP ,STEFAN ARVER, HERMANN M. BEHRE, MD 4 JACQUES BUVAT, ERIC MEULEMAN,IGNACIO MONCADA, ANTONIO MARTIN MORALES, MAURIZIO VOLTERRANI, ANN YELLOWLEES, JULIAN D. HOWELL, MB, BS, FRCS, MFPM 11 KEVIN S. CHANNER, MD, FRCP 12 TIMES INVESTIGATORS*

Indirizzo: http://care.diabetesjournals.org/content/34/4/828.full.pdf+html

Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline

Riferimenti bibliografici: J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59

2.3 Older men with low serum testosterone concentration 2.3.A Recommendation We recommend against a general policy of offering testosterone therapy to all older men with low testosterone levels. (1) We suggest that clinicians consider offering testosterone therapy on an individualized basis to older men with low testosterone levels on more than one occasion and clinically significant symptoms of androgen deficiency, after explicit discussion of the uncertainty about the risks and benefits of testosterone therapy. (2) The panelists disagreed on serum testosterone levels below which testosterone therapy should be offered to older men with symptoms. Depending on the severity of clinical manifestations, some panelists favored treating symptomatic older men with a testosterone level below the lower limit of normal for healthy young men [280-300 ng/dl (9.7-10.4 nmol/liter)]; others favored a level less than 200 ng/dl (6.9 nmol/liter). The panelists who favored treating men who had values less than 300 ng/dl were more influenced by the observation that men who have values below that level often have symptoms that might be attributable to low testosterone. The panelists who favored not treating unless the serum testosterone was as low as 200 ng/dl were more influenced by the lack of testosterone treatment effects in randomized clinical trials when subjects had pretreatment values of 300 ng/dl but suggestions of beneficial effects when the pretreatment values were closer to 200 ng/dl. The lack of definitive studies precludes an unequivocal recommendation and emphasizes the need for additional research. 2.3.B Evidence Several cross-sectional and longitudinal studies demonstrate that serum total and free testosterone concentrations in men fall with increasing age (7, 8, 9, 84, 103, 104, 114, 115). Although the fall is gradual, by the eighth decade, according to one study, 30% of men had total testosterone values in the hypogonadal range, and 50% had low free testosterone values (8). The rate of age-related decline in serum testosterone levels varies in different individuals and is affected by chronic disease, adiposity, and medications (7, 9, 114, 115, 116, 117). Testosterone trials in older men In randomized, placebo-controlled trials of 3 months to 3 yr in older men with low-normal to low testosterone concentrations, testosterone administration was associated with varying degrees of elevation in testosterone levels (68, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131). Overall, testosterone trials in older men were characterized by small sample size, inclusion of healthy older men with low or low-normal testosterone levels who were asymptomatic, variable dosing regimens, and the use of surrogate outcomes; these studies did not have sufficient power to detect either meaningful gains in patient-important outcomes or changes in prostate and cardiovascular event rates (68, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131). Bone mineral density We did not find any trials reporting the effect of testosterone on bone fractures. A systematic review of randomized, placebo-controlled trials of 1- to 3-yr duration that evaluated effects on bone mineral density and were published before March 2005 yielded inconsistent and imprecise results (118, 120, 122, 132); these trials showed a moderate treatment effect on lumbar bone mineral density (0.4 SD units; 95% CI, 0.1, 0.7), equivalent to an increase in lumbar bone density of 2% (95% CI, 0.5, 3.3) (132). These trials ruled out a moderate-to-large testosterone effect on femoral neck bone density (0.0 SD units; 95% CI, -0.3, 0.3). Body composition In our systematic review, testosterone therapy was associated with a significantly greater increase in LBM (2.7 kg; 95% CI, 1.6, 3.7) and a greater reduction in fat mass (-2.0 kg; 95% CI, -3.1, -0.8) than placebo (125). The body weight change did not differ significantly between groups (-0.6 kg; 95% CI, -2.0, 0.8) (125). Muscle strength and physical function Testosterone therapy was associated with a greater improvement in grip strength than placebo (3.3 kg; 95% CI, 0.7, 5.8) (125). Changes in lower-extremity muscle strength and measures of physical function were reported in only a few studies and were inconsistent. Some studies reported no changes in performance-based measures of physical function (68, 119, 121), whereas one study reported improvement in a composite measure of physical function (121). Most of the studies included men who had no functional limitations and used measures of physical function that had a low ceiling. Sexual function. Two placebo-controlled trials yielded imprecise results regarding the effect of testosterone on overall sexual satisfaction (0.2 SD units; 95% CI, -0.02, 0.57) (4). Quality of life. Four placebo-controlled randomized trials reported on testosterone's effect on quality of life (119, 129, 133, 134). The results were inconsistent across trials and imprecise. However, testosterone therapy was associated with significantly greater improvement in the physical function domain score than was placebo (0.5 SD units; 95% CI, 0.03, 0.9) (125). Depression. The effects of testosterone therapy on depression have been inconsistent across trials. A recent systematic review of randomized trials reported significantly greater improvements in depression scores in testosterone-treated men than in placebo-treated men (135). However, several randomized trials have found no significant effects of testosterone therapy on depression in older men with low or low-normal testosterone levels (127, 133). The inconsistent and imprecise results limit the inferential strength. Cognition. Three placebo-controlled, randomized trials (130, 133, 136), one of which studied patients with Alzheimer's dementia and low testosterone levels (136), reported imprecise effects on several dimensions of cognition, none of which was significant after pooling. Adverse outcomes associated with testosterone therapy. In a systematic review of 19 randomized trials to determine the risks of adverse events associated with testosterone therapy in older men (77), the combined rate of all prostate events was significantly greater in testosterone-treated men than in placebo-treated men (odds ratio, 1.78; 95% CI, 1.07, 2.95). Rates of prostate cancer, PSA greater than 4 ng/ml, and prostate biopsies were higher in the testosterone group than in the placebo group, although differences between groups were not statistically significant (77). Testosterone-treated men were nearly four times more likely than placebo-treated men to experience hematocrit above 50% (odds ratio, 3.69; 95% CI, 1.82, 7.51). The frequency of cardiovascular events, sleep apnea, or death did not differ significantly between groups. Thus, testosterone therapy of older men was associated with a higher risk of detecting prostate events and hematocrit above 50% than was placebo (77). A meta-analysis by Haddad et al. (3) of studies found through October 2004 enrolling older men with low testosterone levels yielded insignificant changes in major lipid fractions [total cholesterol standardized mean difference (SMD), -0.22 (-0.71 to 0.27); low-density lipoprotein cholesterol SMD, 0.06 (-0.30 to 0.42); high-density lipoprotein cholesterol SMD, 0.04 (-0.39 to 0.40); and triglycerides SMD, -0.27 (-0.61 to 0.08)]. 2.3.C Values The recommendation not to treat asymptomatic older men with age-related decline in testosterone level places a lower value on the unproven, potential benefits of testosterone therapy and a higher value on avoiding the burdens of testosterone administration, monitoring, and cost, as well as on unknown long-term risks. 2.3.D Remarks Physicians should recognize considerable disagreement among experts on this issue because of the lack of evidence base to reach consensus recommendations (35, 36, 125). Nonspecific age-related symptoms and low T levels often coexist in older men without a clear causal link. Neither the safety nor the efficacy of T therapy in older men with low testosterone level has been demonstrated. Should clinicians and their patients choose testosterone therapy, we suggest that clinicians aim at achieving total testosterone levels in the lower part of the normal range of young men [400-500 ng/dl (14.0-17.5 nmol/liter)]. Autori: Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society.

Indirizzo: http://jcem.endojournals.org/cgi/reprint/95/6/2536

Gonadal status and physical performace in older men

Riferimenti bibliografici: The Aging Male 2011; 14(1): 42-47

Autori: M. Maggio, GP. Ceda, F. Lauretani, S. Bandinelli, EJ. Matter, JM. Guralnik, S. Basaria, C. Cattabiani, M. Luci, E. Dall'Aglio, R.Volpi, G.Valenti, L. Ferrucci

An aging world - the role of the International Society of Men's Health and Aging and its European harm

Riferimenti bibliografici: The Aging Male. 2009; 12(4): 119-121

Autori: B. Lunenfeld

Emerging cardiometabolic complications of androgen deprivation therapy

Riferimenti bibliografici: The Aging Male. 2010; 13(1): 1-9

Autori: K.Choong , S. Basaria