Testosterone Replacement Reduces Mortality by Jeffrey Dach MD
A new study just published in the Journal of Clinical Endocrinology & Metabolism April 11, 2012 by Molly Shores examined a cohort of 1,031 men (Veterans) over 4 years. All 1,031 had low testosterone (below 250), and a subgroup of 398 of the men were treated with testosterone supplementation. At the end of the observation period the treated men had 10.3% mortality compared to 20.7% for the untreated men.
Testosterone supplementation reduced mortality in half.
Jeffrey Dach MD
Links and References
Testosterone Treatment and Mortality in Men with Low Testosterone Levels by
Molly M. Shores, Nicholas L. Smith, Christopher W. Forsberg, Bradley D. nawalt and Alvin M. Matsumoto -
The Journal of Clinical Endocrinology & Metabolism April 11, 2012 jc.2011-2591
Author Affiliations Veterans Affairs (VA) Puget Sound Health Care System (M.M.S., N.L.S., C.W.F., A.M.M.), Seattle, Washington 98108; VA Epidemiologic Research and Information Center, (N.L.S., C.W.F.) and VA Geriatric Research, Education, and Clinic Center (A.M.M.), Seattle, Washington 98108; Departments of Psychiatry and Behavioral Sciences (M.M.S.), Epidemiology (N.L.S.), and Medicine (B.D.A., A.M.M.), University of Washington, Seattle, Washington 98105; and Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98101
Address all correspondence and requests for reprints to: Molly M. Shores, M.D., Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, S-116PES, Seattle, Washington 98108. E-mail: email@example.com.
Context: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known.
Objective: The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels.
Design: This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori.
Setting: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers.
Patients: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [≤250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005.
Main Outcome Measure: Total mortality in testosterone-treated compared with untreated men was measured.
Results: Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (P<0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42–0.88; P = 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease.
Conclusions: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment.
testo in aodm
Diabetes Care August 2011 vol. 34 no. 8 1771-1777
Low Free Testosterone Levels Are Associated With All-Cause and Cardiovascular Mortality in Postmenopausal Diabetic Women
Elisabeth Wehr 1Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University Graz, Graz, Austria
OBJECTIVE Hyperandrogenemia is associated with cardiovascular risk factors in women but evidence about the relationship of testosterone levels with mortality is sparse. We aimed to evaluate whether total testosterone (TT), free testosterone (FT), and sex hormone–binding globulin (SHBG) are associated with all-cause and cardiovascular mortality in a cohort of postmenopausal women.
RESEARCH DESIGN AND METHODS We measured TT and SHBG levels in 875 postmenopausal women who were referred for coronary angiography (during 1997–2000). FT was calculated according to the Vermeulen method. The main outcome measures were Cox proportional hazard ratios (HRs) for mortality from all causes and from cardiovascular causes.
RESULTS After a median follow-up time of 7.7 years, 179 women (20.5%) had died. There were 101 deaths due to cardiovascular disease (56.4% of all deaths). We found no association of FT, TT, and SHBG levels with mortality in all postmenopausal women.
In postmenopausal diabetic women, multivariable-adjusted HRs (with 95% CIs) in the fourth compared with the first FT quartile for all-cause and cardiovascular mortality were 0.38 (0.08–0.90), P = 0.025, and 0.28 (0.08–0.90), P = 0.032, respectively. We found no association of TT and SHBG with mortality in diabetic postmenopausal women.
CONCLUSIONS In postmenopausal diabetic women referred for coronary angiography, low FT levels are independently associated with increased all-cause and cardiovascular mortality.
Clin Endocrinol (Oxf). 2012 Feb 22. doi: 10.1111/j.1365-2265.2012.04371.x. [Epub ahead of print]
Combination of low free testosterone and low vitamin D predicts mortality in older men referred for coronary angiography.
Lerchbaum E, Pilz S, Boehm BO, Grammer TB, Obermayer-Pietsch B, März W.
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
Low levels of 25-hydroxyvitamin D (25(OH)D) and free testosterone (FT) are both associated with increased mortality. Experimental studies show a complex interplay of vitamin D and androgen metabolism suggesting that a deficiency of both hormones may be associated with a particularly adverse clinical outcome.
To evaluate the impact of parallel FT and 25(OH)D deficiency in a large cohort of older men.
We measured total testosterone (TT), SHBG, and 25(OH)D levels in 2069 men who were routinely referred for coronary angiography (1997-2000).
MAIN OUTCOME MEASURES
Cox proportional hazard ratios (HRs) (with 95% confidence intervals) for mortality from all causes, cardiovascular, and non-cardiovascular causes according to combined deficiency of FT and 25(OH)D.
In multivariate adjusted analyses, we found an increased risk for all-cause mortality, cardiovascular and non-cardiovascular mortality for men in the lowest FT (HR 1.26 [1.03-1.54], 1.24 [0.96-1.60], and 1.39 [1.00-1.93], respectively) and 25(OH)D quartile (HR 1.77 [1.47-2.13], 1.65 [1.29-2.10], and 1.89 [1.38-2.60] respectively) compared to men in higher FT and 25(OH)D quartiles. There was no independent association of TT levels with mortality. Multivariate adjusted HRs progressively increased with the number of hormones (FT and 25(OH)D) in the lowest quartile (0 vs 2 hormone deficiencies:
2.11 [1.60-2.79] for all cause,
1.77 [1.23-2.55] for cardiovascular, and
2.33 [1.45-3.47] for non-cardiovascular mortality respectively).
A combined deficiency of FT and 25(OH)D is significantly associated with fatal events in a large cohort of men referred for coronary angiography.
AODM= DO NOT TREAT with Testo- weight loss and exercize only
J Clin Endocrinol Metab. 2011 Aug;96(8):2341-53. Epub 2011 Jun 6.
Low testosterone in men with type 2 diabetes: significance and treatment.
Department of Medicine, Austin Health/Northern Health, University of Melbourne, Heidelberg, VIC 3084, Australia. firstname.lastname@example.org
The relationship between testosterone and diabetes in men is an important issue, given that one third of U.S. men aged 65 yr or older have diabetes, with a similar percentage having low testosterone levels.
The medical literature from 1970 to March 2011 was reviewed for key articles.
In population-based studies, low testosterone is commonly associated with type 2 diabetes and the metabolic syndrome, and it identifies men with an adverse metabolic profile. The difference in testosterone levels between men with diabetes compared to men without diabetes is moderate and comparable in magnitude to the effects of other chronic diseases, suggesting that low testosterone may be a marker of poor health. Although the inverse association of testosterone with diabetes is partially mediated by SHBG, low testosterone is linked to diabetes via a bidirectional relationship with visceral fat, muscle, and possibly bone. There is consistent evidence from randomized trials that testosterone therapy alters body composition in a metabolically favorable manner, but changes are modest and have not consistently translated into reductions in insulin resistance or improvements in glucose metabolism.
The key response to the aging, overweight man with type 2 diabetes and subnormal testosterone levels should be implementation of lifestyle measures such as weight loss and exercise, which, if successful, raise testosterone and provide multiple health benefits. Although approved therapy for diabetes should be used, testosterone therapy should not be given to such men until benefits and risks are clarified by adequately powered clinical trials.
Endocrine society - measure testo in AODM Men
J Clin Endocrinol Metab. 2011 Sep;96(9):2643-51.
Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity.
Dandona P, Dhindsa S.
Division of Endocrinology, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA. pdandona@KaleidaHealth.org
Studies over the last few years have clearly established that at least 25% of men with type 2 diabetes have subnormal free testosterone concentrations in association with inappropriately low LH and FSH concentrations.
Another 4% have subnormal testosterone concentrations with elevated LH and FSH concentrations.
The Endocrine Society, therefore, now recommends the measurement of testosterone in patients with type 2 diabetes on a routine basis. The subnormal testosterone concentrations are not related to glycosylated hemoglobin or duration of diabetes, but are associated with obesity, very high C-reactive protein concentrations, and mild anemia.
In addition, subnormal testosterone concentrations in these men are associated with a two to three times elevated risk of cardiovascular events and death in two early studies. Short-term studies of testosterone therapy in hypogonadal men with type 2 diabetes have demonstrated an increase in insulin sensitivity and a decrease in waist circumference. However, the data on the effect of testosterone replacement on glycemic control and cardiovascular risk factors such as cholesterol and C-reactive protein concentrations are inconsistent. As far as sexual function is concerned, testosterone treatment increases libido but does not improve erectile dysfunction and thus, phosphodiesterase inhibitors may be required. Trials of a longer duration are clearly required to definitively establish the benefits and risks of testosterone replacement in patients with type 2 diabetes and low testosterone.
endocrine society Guidelines and testosterone recommendations in AODM Men
Two hormones testo and IGF-1 better predictors of increased mortality when low
Steroids. 2012 Jan;77(1-2):52-8. Epub 2011 Oct 20.
Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor I in adult men.
Friedrich N, Schneider HJ, Haring R, Nauck M, Völzke H, Kroemer HK, Dörr M, Klotsche J, Jung-Sievers C, Pittrow D, Lehnert H, März W, Pieper L, Wittchen HU, Wallaschofski H, Stalla GK.
Institute of Clinical Chemistry and Laboratory Medicine, Ernst Moritz Arndt University, Greifswald, Germany. email@example.com
Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men.
METHODS AND RESULTS
From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n=330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06-1.78), p=0.02] and two hormones [HR 2.88 (95% CI 1.32-6.29), p<0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3-0.7%, p=0.03).
Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.
The Journal of Clinical Endocrinology & Metabolism January 1, 2011 vol. 96 no. 1 38-52
Why Is Androgen Replacement in Males Controversial? Glenn R. Cunningham, M.D., Baylor College of Medicine Houston, Texas 77030.
Until recently, it was thought that testosterone deficiency in middle-aged and older men mainly affected the quality of life, but it was unlikely to affect morbidity or mortality. However, population-based studies indicate that testosterone deficiency predicts future development of type 2 diabetes mellitus (6), metabolic syndrome (7), cardiovascular events (8, 9, 10, 11), mobility limitation (12), frailty (13), and mortality (8, 9, 10, 11). Whether testosterone treatment can improve health and prolong active lifestyles is unknown. No large, multicenter, long-term RPCTs have addressed these issues.
The Journal of Clinical Endocrinology & Metabolism January 1, 2011 vol. 96 no. 1 62-65
Editorial Testosterone Treatment of Older Men—Why Are Controversies Created? Ronald Swerdloff and Christina Wang
Ronald Swerdloff, M.D., Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center California
Milk Thistle and AODM
Diabetes Nutr Metab. 2002 Aug;15(4):222-31.
Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent.
Lirussi F, Beccarello A, Zanette G, De Monte A, Donadon V, Velussi M, Crepaldi G.
Source Department of Medical and Surgical Sciences, University of Padova, Italy.
In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM.
Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress.
Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group.
Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.
Co Q10 in AODM
Eur J Clin Nutr. 2002 Nov;56(11):1137-42.
Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes.
Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD.
Source University of Western Australia Department of Medicine and HeartSearch, Royal Perth Hospital, Perth, Western Australia, Australia. Abstract OBJECTIVE
Our objective was to assess effects of dietary supplementation with coenzyme Q10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects.
SUBJECTS AND DESIGN
Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2x2 factorial intervention.
The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia.
Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg/day), 200 mg fenofibrate each morning, both or neither for 12 weeks.
MAIN OUTCOME MEASURES
We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA(1c)), and on oxidative stress assessed by measurement of plasma F2-isoprostanes.
Fenofibrate did not alter blood pressure, HbA(1c), or plasma F2-isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4+/-0.3 micro mol/l, P<0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic (-6.1+/-2.6 mmHg, P=0.021) and diastolic (-2.9+/-1.4 mmHg, P=0.048) blood pressure and HbA(1c) (-0.37+/-0.17%, P=0.032). Plasma F2-isoprostane concentrations were not altered by CoQ (0.14+/-0.15 nmol/l, P=0.345).
These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F2-isoprostanes.
CoQ10 in Bypass Grafting
J Cardiothorac Vasc Anesth. 2008 Dec;22(6):832-9. Epub 2008 Jun 6.
The role of oral coenzyme Q10 in patients undergoing coronary artery bypass graft surgery. Makhija N, Sendasgupta C, Kiran U, Lakshmy R, Hote MP, Choudhary SK, Airan B, Abraham R.
Department of Cardiac Anaesthesia, Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. firstname.lastname@example.org
Cardiopulmonary bypass (CP is known to induce oxidative stress. Because total antioxidant level is reduced during CPB, the supplementation of an antioxidant might help in attenuating the oxidative stress response. The authors sought to evaluate the efficacy of oral coenzyme Q10, in attenuating the oxidative stress to CPB and altering the clinical outcome in patients undergoing coronary artery bypass graft (CABG) surgery.
A prospective, randomized, single-center clinical study.
A cardiothoracic center of a tertiary hospital.
Thirty patients scheduled for elective CABG surgery.
The study group (n = 15) received oral coenzyme Q10, 150 to 180 mg/d, for 7 to 10 days preoperatively, whereas the control group (n = 15) did not receive any antioxidant or placebo. The anesthesia technique was standardized in both groups. Blood samples for total antioxidant level, blood glucose level, and clinical outcome parameters up to 24 hours postoperatively were compared.
MEASUREMENTS AND MAIN RESULTS
There was no difference in the antioxidant level between the 2 groups at any point of time. However, in the study group, 24 hours after aortic clamp release, it was significantly higher than baseline (p < 0.05). The blood glucose was significantly lower in the study group at aortic clamp removal and 4 hours after clamp removal as compared with the control group (p = 0.01). The study group had significantly fewer reperfusion arrhythmias, lower total inotropic requirement, mediastinal drainage, blood product requirement, and shorter hospital stays compared with the control group.
Oral coenzyme Q10 therapy for 7 to 10 days preoperatively could improve clinical outcome in patients undergoing CABG surgery. A larger study group is recommended for confirmation.
Jeffrey Dach MD
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