A review of the National Library of Medicine’s more than 9 million articles includes overwhelming evidence that Testosterone does NOT cause an increased incidence of Heart Disease, or Heart Attack. In fact the opposite is true. Researchers from the University of Florence, Italy, Sapienza, Rome, and Hospitals in Bologna and Florence, recently performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of Testosterone Supplementation (TS) on Cardiovascular-related problems.
As highlighted in Reference number 1 below, this “analysis, performed on the largest number of studies collected so far, indicate that Testosterone Supplementation (TS) is not related to any increase in CV risk, even when composite or single adverse events were considered. In Randomized Clinical Trials (RCTs) performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed. Expert opinion: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease.
Low Testosterone is associated with significant illness, including congestive heart disease, heart attacks, strokes, metabolic syndrome, diabetes, prostate cancer, and more. Here is the top then most recent finding of the last 2 months.
Reference 1
Expert Opin Drug Saf. 2014 Aug 19:1-25. [Epub ahead of print]
Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis.
Corona G1, Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, Maggi M.
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Abstract
Introduction: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events. Areas covered: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed. Expert opinion: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease.
KEYWORDS:
cardiovascular risk; mortality; randomized clinical trial; testosterone
PMID: 25139126 [PubMed – as supplied by publisher]
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Ref 2
Int J Cardiol. 2014 Aug 4. pii: S0167-5273(14)01287-X. doi: 10.1016/j.ijcard.2014.07.077. [Epub ahead of print]
Androgen attenuates cardiac fibroblasts activations through modulations of transforming growth factor-β and angiotensin II signaling.
Chung CC1, Hsu RC2, Kao YH3, Liou JP4, Lu YY5, Chen YJ6.
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Abstract
BACKGROUND: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-β and angiotensin (Ang) II signaling.
METHODS: Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350g) cardiac fibroblasts with and without incubation with testosterone (10nM) and co-administration of TGF-β1 (10ng/ml) or Ang II (100nM) by cell migration analysis, proliferation assay, soluble collagen measurement, zymographic analysis, immunofluorescence microscopy, real-time PCR and Western blot.
RESULTS: Compared to those without testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-β1, or had less collagen production with Ang II. Testosterone-treated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-β1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-β1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-β1 or Ang II treatment.
CONCLUSION: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF-β1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
KEYWORDS:
Angiotensin; Fibroblasts; Heart failure; Testosterone; Transforming growth factor
PMID: 25125004 [PubMed – as supplied by publisher]
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Ref 3
Biomed Res Int. 2014;2014:392432. doi: 10.1155/2014/392432. Epub 2014 Jul 6.
Beneficial effects of testosterone therapy on functional capacity, cardiovascular parameters, and quality of life in patients with congestive heart failure.
Mirdamadi A1, Garakyaraghi M2, Pourmoghaddas A2, Bahmani A1, Mahmoudi H3, Gharipour M4.
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Abstract
Background. According to the present evidences suggesting association between low testosterone level and prediction of reduced exercise capacity as well as poor clinical outcome in patients with heart failure, we sought to determine if testosterone therapy improves clinical and cardiovascular conditions as well as quality of life status in patients with stable chronic heart failure. Methods. A total of 50 male patients who suffered from congestive heart failure were recruited in a double-blind, placebo-controlled trial and randomized to receive an intramuscular (gluteal) long-acting androgen injection (1 mL of testosterone enanthate 250 mg/mL) once every four weeks for 12 weeks or receive intramuscular injections of saline (1 mL of 0.9% wt/vol NaCl) with the same protocol. Results. The changes in body weight, hemodynamic parameters, and left ventricular dimensional echocardiographic indices were all comparable between the two groups. Regarding changes in diastolic functional state and using Tei index, this parameter was significantly improved. Unlike the group received placebo, those who received testosterone had a significant increasing trend in 6-walk mean distance (6MWD) parameter within the study period (P = 0.019). The discrepancy in the trends of changes in 6MWD between study groups remained significant after adjusting baseline variables (mean square = 243.262, F index = 4.402, and P = 0.045). Conclusion. Our study strengthens insights into the beneficial role of testosterone in improvement of functional capacity and quality of life in heart failure patients.
PMID: 25110677 [PubMed – in process] PMCID: PMC4109421 Free PMC Article
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Ref 4
Clin Interv Aging. 2014 Jul 23;9:1175-86. doi: 10.2147/CIA.S48918. eCollection 2014.
Off-label use of hormones as an antiaging strategy: a review.
Samaras N1, Papadopoulou MA2, Samaras D3, Ongaro F1.
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Abstract
Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. Finally, we argue on future perspectives of such protocols as part of everyday practice.
KEYWORDS: Anti-aging; dehydroepiandrosterone; estrogen; growth hormone; progesterone; testosterone
PMID: 25092967 [PubMed – in process] PMCID: PMC4116364 Free PMC Article
Ref 5
Obes Res Clin Pract. 2014 Jul-Aug;8(4):e339-49. doi: 10.1016/j.orcp.2013.10.005. Epub 2013 Nov 5.
Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: An observational study.
Haider A1, Saad F2, Doros G3, Gooren L4.
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Abstract
BACKGROUND: Treatment of obesity with diet and exercise may have short-term success but longer-term maintenance of weight loss is less successful. Obesity is associated with a reduction of serum testosterone, and, vice versa, a reduction in serum testosterone is associated with obesity and features of the metabolic syndrome.
OBJECTIVE: To investigate whether restoring serum testosterone to normal in hypo-gonadal obese men is beneficial with regard to weight loss and improvement of the metabolic syndrome.
METHODS: A prospective registry accumulated to 181 men over five years (mean serum testosterone 10.06±1.3nmol/L (N>12.1), body mass index (BMI) ≥30kg/m(2). Of these men, 72 had diabetes mellitus type 2. All received parenteral testosterone undecanoate 1000mg/12 weeks for up to five years.
RESULTS: Waist circumference (cm) decreased from 111.2±7.54 to 100.46±7.1, weight (kg) from 114.71±11.59 to 93.2±8.49, BMI (kg/m(2)) from 36.72±3.72 to 30.2±2.59 (all variables statistically significant vs. baseline (p<0.0001) and each year compared to the previous year (p<0.0001)). In the 72 diabetic men, waist circumference (cm) decreased from 112.93±7.16 to 101.48±7.24, weight (kg) from 116.94±11.62 to 94.42±9.42, BMI (kg/m(2)) from 37.71±3.5 to 30.95±2.69 (all variables statistically significant vs. baseline (p<0.0001) and each year compared to the previous year (p<0.0001)). In all men serum glucose, HbA1c, lipid profiles and blood pressure improved significantly. Testosterone treatment as assessed by hemoglobin, hematocrit, serum prostate specific antigen (PSA) and occurrence of prostate cancer was acceptably safe.
CONCLUSIONS: Normalizing serum testosterone in obese hypogonadal men, also in those with diabetes type 2, improved their metabolic state.
Copyright © 2013 Asian Oceanian Association for the Study of Obesity. All rights reserved.
KEYWORDS: Diabetes mellitus type 2; Obesity; Testosterone; Waist circumference; Weight loss
PMID: 25091355 [PubMed – in process]
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Ref 6
Expert Opin Pharmacother. 2014 Sep;15(13):1903-26. doi: 10.1517/14656566.2014.944896. Epub 2014 Jul 31.
Injectable testosterone undecanoate for the treatment of hypogonadism.
Corona G1, Maseroli E, Maggi M.
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Abstract
INTRODUCTION:
Injectable testosterone undecanoate (TU) is a long-acting testosterone (T) formulation available for the treatment of male hypogonadism (HG) since 2003.
AREAS COVERED: The efficacy and safety of injectable TU are assessed, as obtained by meta-analyzing available evidence. An extensive Medline, Embase and Cochrane search was performed. All uncontrolled and placebo-controlled randomized clinical trials (RCTs), evaluating the effect of injectable TU on different outcomes, were included. Of the 98 retrieved articles, 33 were included in the study. Among those, 11 were placebo-controlled RCTs. Injectable TU was significantly associated with a reduction of fat mass and HbA1c in both controlled and uncontrolled trials, in particular when hypogonadal subjects were enrolled. Similar results were observed for the improvement of erectile function. In addition, TU ameliorated several other outcomes, including blood pressure, lipid profile, waist circumference and body mass index in uncontrolled studies, but these data were not confirmed in placebo-controlled trials. The treatment was well tolerated and no risk of prostate cancer or cardiovascular disease was observed.
EXPERT OPINION: Injectable TU is a safe and effective treatment for male HG. The possibility of a therapeutic intervention just four to five times per year frees the patient, at least partially, from having a chronic condition, thus maintaining a positive, active role in self-caring.
KEYWORDS: erectile dysfunction; obesity; testosterone undecanoate; weight loss
PMID: 25080279 [PubMed – in process]
Ref 7
Int J Impot Res. 2014 Jul 31. doi: 10.1038/ijir.2014.29. [Epub ahead of print]
Testosterone therapy and mortality risk.
Eisenberg ML1, Li S2, Herder D3, Lamb DJ3, Lipshultz LI3.
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Abstract
Recent data suggest an increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date, there are no long-term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine whether TT altered the risk of all-cause mortality in men. We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine mortality. Of the 509 men who met inclusion criteria, 284 were on TT and 225 did not use testosterone. Age (mean 54 years) and follow-up time (mean 10 years) were similar for both groups. In all, 19 men died-10 (4.4%) men not on TT and 9 (3.2%) men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (hazard ratio 0.92, 95% confidence interval 0.36-2.35, P=1.0). There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy. International Journal of Impotence Research advance online publication, 31 July 2014; doi:10.1038/ijir.2014.29.
PMID: 25078049 [PubMed – as supplied by publisher]
Ref 8
Arch Iran Med. 2014 Aug;17(8):545-50. doi: 014178/AIM.005.
The Association between Premature Coronary Artery Disease and Level of Testosterone in Young Adult Males.
Alkamel A, Shafiee A, Jalali A, Boroumand M, Nozari Y.
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Abstract
OBJECTIVE: Low testosterone levels in men have been associated with an increased risk of cardiovascular disease. We aimed to identify the association between serum testosterone level and premature coronary artery disease (CAD) and its predictors in young adult males.
METHODS: In this cross sectional study, consecutive male candidates for coronary angiography with unstable angina, no previous CAD and age ≤45 years were included. Serum levels of free (FT) and total testosterone (TT) as well as demographic and cardiovascular characteristics were compared between the CAD-positive and normal coronary subjects. The cutoff point for low TT was 2.5 ng/L. Additionally, the relationships between all the variables and the number of affected vessels and FT and TT and predictors of CAD were assessed.
RESULTS: In this study, 191 patients with premature CAD were compared with 94 normal coronary subjects. Patients in the CAD group were significantly older (41.59 ± 3.79 versus 39.27 ± 4.97 years; P-value < 0.01), and had higher rates of diabetes mellitus (P-value = 0.04) and dyslipidemia (P-value = 0.01). Serum levels of FT and TT were significantly lower in the CAD group than the normal coronary subjects (P-value < 0.01 for both). The rate of subjects with low TT increased by the number of the affected vessels (p-value for trend <0.01) and there was a significant correlation between the Gensini score and FT and TT (r = -0.37, P-value < 0.01 and r = -0.34, P-value < 0.01, respectively). After adjustment for confounders, the association between low TT and CAD remained significant (Odds ratio = 4.30, 95% confidence interval: 1.99-9.32; P-value ≤ 0.001) CONCLUSION: Low levels of testosterone were associated with premature CAD and its severity in young adults.
PMID: 25065277 [PubMed – in process] Free full text
Ref 9
Exp Hypertens. 2014 Jul 22:1-8. [Epub ahead of print]
Testosterone is associated with the cardiovascular autonomic response to a stressor in healthy men.
Ramesh S1, Wilton SB, Holroyd-Leduc JM, Turin TC, Sola DY, Ahmed SB.
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Abstract
Abstract Objective: Men have high cardiovascular risk and unfavourable cardiac autonomic tone compared to premenopausal women. The role of sex hormones in control of autonomic tone is unclear. We sought to determine the association between sex hormones and cardiosympathovagal tone at baseline and in response to a physiological stressor. Methods: Forty-eight healthy subjects (21 men, 27 premenopausal women) were studied in high-salt balance. Cardiac autonomic tone was assessed by heart rate variability, calculated by spectral power analysis (low frequency (LF, a measure of sympathetic modulation), high frequency (HF, a measure of vagal modulation) and LF:HF (a measure of cardiosympathovagal balance)) at baseline and in response to graded Angiotensin II (AngII) infusion (3 ng/kg/min × 30 min, 6 ng/kg/min ×30 min) were measured. The primary outcome was association between endogenous sex hormone levels and measures of cardiac autonomic tone. Results: All subjects had sex hormone levels in the normal range. No associations were observed between sex hormones and baseline cardiac autonomic tone in men or women. Men with lower testosterone levels, however, were unable to maintain both cardiosympathetic (p = 0.045) and cardiovagal tone (p = 0.035) in response to AngII even after adjustments for covariates. No association was observed between estradiol and progesterone and cardiac autonomic response to AngII in either sex. Conclusion: An unfavourable shift in the cardiac autonomic tone in men with lower testosterone levels was observed in response to a stressor. Understanding the role of sex hormones in modulation of cardiac autonomic tone may help guide risk reduction strategies in men.
KEYWORDS:
Cardiac autonomic tone; heart rate variability; sex hormones
PMID: 25050935 [PubMed – as supplied by publisher]
Ref 10
2014 Sep;79(1):52-57. doi: 10.1016/j.maturitas.2014.06.016. Epub 2014 Jun 30.
Late onset hypogonadism of men is not equivalent to the menopause.
Saad F1, Gooren LJ2.
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Abstract
Some men between the ages 45 and 60 years develop complaints and symptoms reminiscent of menopausal complaints in women. So, parallels were sought between the changes in female and male endocrinology during that period of life. Indeed, men do show a decline of serum testosterone from age 40 to 50 years onwards but it is a slow decline of 1-2% per year and over time it may amount to hypogonadism. The mechanism of a decline in serum testosterone in men does not resemble the menopause; it is partially an aging neuroendocrine system with a less efficient testosterone production but equally or more important, the result of inhibition of testosterone production by metabolic factors in relation to visceral obesity. These effects are in part reversible with weight loss. A hypogonadal state in aging men has deleterious effects. Mortality of all causes is highest in men with low testosterone impacting on their metabolic state leading to diabetes mellitus, cardiovascular disease, osteoporosis, and sexual dysfunction. Normalization of testosterone in aging hypogonadal men has a beneficial effect on the above pathologies. The fear that testosterone treatment of elderly men would lead to prostate disease has not been substantiated in studies. So, while men do not have a ‘menopause’, testosterone deficiency in old age deserves serious attention.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
PMID: 25042874 [PubMed – as supplied by publisher]
Ref 11
J Clin Endocrinol Metab. 2009 Jul;94(7):2482-8. doi: 10.1210/jc.2008-2650. Epub 2009 Apr 28.
Low serum testosterone and estradiol predict mortality in elderly men.
Tivesten A1, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellström D, Ohlsson C.
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Abstract
CONTEXT: Age-related reduction of serum testosterone may contribute to the signs and symptoms of aging, but previous studies report conflicting evidence about testosterone levels and male mortality. No large prospective cohort study has determined a possible association between serum estradiol and mortality in men.
OBJECTIVE: The main objective was to examine the association between serum testosterone and estradiol and all-cause mortality in elderly men.
DESIGN, SETTING, AND PARTICIPANTS: We used specific gas chromatography-mass spectrometry to analyze serum sex steroids at baseline in older men who participated in the prospective population-based MrOS Sweden cohort (n = 3014; mean age, 75 yr; range, 69-80 yr).
MAIN OUTCOME MEASURE: All-cause mortality by serum testosterone and estradiol levels.
RESULTS: During a mean follow-up period of 4.5 yr, 383 deaths occurred. In multivariate hazards regression models, low levels (within quartile 1 vs. quartiles 2-4) of both testosterone [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.29-2.12] and estradiol (HR, 1.54; 95% CI, 1.22-1.95) associated with mortality. A model including both hormones showed that both low testosterone (HR, 1.46; 95% CI, 1.11-1.92) and estradiol (HR, 1.33; 95% CI, 1.02-1.73) predicted mortality. Risk of death nearly doubled (HR, 1.96; 95% CI, 1.46-2.62) in subjects with low levels of both testosterone and estradiol compared with subjects within quartiles 2-4 of both hormones.
CONCLUSIONS: Elderly men with low serum testosterone and estradiol have increased risk of mortality, and subjects with low values of both testosterone and estradiol have the highest risk of mortality.
Ref 12
Circulation. 2007 Dec 4;116(23):2694-701. Epub 2007 Nov 26.
Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study.
Khaw KT1, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N.
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Abstract
BACKGROUND: The relation between endogenous testosterone concentrations and health in men is controversial.
METHODS AND RESULTS: We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone ( approximately 1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years.
CONCLUSIONS: In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
PMID: 18040028 [PubMed – indexed for MEDLINE] Free full text