Skip Navigation

European Journal of Heart Failure 2007 9(1):44-50; doi:10.1016/j.ejheart.2006.04.006
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Malkin, C. J.
Right arrow Articles by Channer, K. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malkin, C. J.
Right arrow Articles by Channer, K. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 European Society of Cardiology

The effect of testosterone on insulin sensitivity in men with heart failure

Chris J. Malkina, T. Hugh Jonesb and Kevin S. Channera,c,*

a Department of Cardiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust Sheffield, S10 2JF, United Kingdom
b Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Barnsley District General Hospital NHS Trust Barnsley, S57 5RT, United Kingdom
c Faculty of Health and Wellbeing, Sheffield Hallam University, Collegiate Crescent Sheffield, S10 2BD, United Kingdom

* Corresponding author. Room M131, Department of Cardiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, S10 2JF. United Kingdom. Tel.: +44 114 271 3472; fax: +44 114 271 2042. E-mail address: Kevin.Channer{at}sth.nhs.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Resistance to insulin occurs in chronic heart failure (CHF) and is related to prognosis. Studies of testosterone in non-(CHF) males suggest that physiological testosterone therapy improves insulin sensitivity. This was a single-blind placebo controlled crossover trial to determine the effect of testosterone replacement on insulin sensitivity in 13 men with moderate to severe CHF (ejection fraction 30.5±1.3). The primary outcome was the homeostatic model index (HOMA-IR) of fasting insulin sensitivity and secondary outcomes were body composition as measured by bioelectrical impedance and glucose tolerance to a standard 75 g oral glucose load. Analysis was performed on the delta values with the treatment effect of placebo compared with that of testosterone.

At baseline HOMA-IR correlated with measures of body fat [% fat mass (rP=0.84, p=0.0001) and body mass index (rP=0.79, p=0.01)] but not with CHF severity. Testosterone reduced HOMA-IR (–1.9±0.8, p=0.03) indicating improved fasting insulin sensitivity. Testosterone also increased total mass (+1.5±0.5 kg, p=0.008) and decreased body fat (–0.8±0.3%, p=0.02).

Testosterone improves fasting insulin sensitivity in men with CHF and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of CHF.

Key Words: Testosterone • Insulin resistance • Chronic heart failure • Hormones

Received June 9, 2005; Revised April 11, 2006; Accepted April 11, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Chronic heart failure (CHF) is precipitated by damage to the myocardium from any cause, but the pathophysiology of chronic CHF involves a distinct metabolic syndrome. This syndrome is important because many of the metabolic changes of heart failure are maladaptive and in the long term damaging to the myocardium. In some cases pharmacological blockade of aspects of this syndrome improve prognosis and symptoms. Inhibition of both the renin-angiotensin system and catecholamines are well studied and therapy with angiotensin converting enzyme inhibitors and beta-blockers is now established in practice. There are a number metabolic changes in heart failure that have been targeted with varying success including serum inflammation- with anti-cytokine antibodies and immunoglobulins, [1] and anaemia with erythropoetin [2]. Anabolic hormones such as testosterone are under expressed in heart failure [3,4] and there is some evidence that testosterone replacement is beneficial and improves functional status in men with CHF [5,6].

The glucose insulin axis is deranged in heart failure; a cross-sectional study of patients with heart failure found that 43% of patients had manifest disorders of glucose metabolism ranging from frank diabetes to impaired glucose sensitivity [3]. Patients with CHF have insulin resistance-defined as relative inability of insulin to promote glucose transport into skeletal muscle and adipose tissue. This observation was first reported in the mid-1990s and further research has confirmed that the impaired action of insulin that was inversely related to the severity of the heart failure, [7] was linked with disturbed skeletal muscle physiology, [8] loss of skeletal muscle bulk [4] and the degree of insulin resistance directly influenced prognosis [9].

In non-heart failure populations at least 7 large cross-sectional epidemiological studies and 4 prospective follow up studies, accumulating several thousand patient years of follow up have all shown an inverse relationship with serum androgens and insulin resistance. Small clinical trials in animals and patients have found that androgen deprivation reduces insulin sensitivity and physiological androgen replacement improves sensitivity [10].

To date there have been no studies examining the effect of testosterone therapy on insulin sensitivity in men with heart failure. Recent randomised controlled trials of testosterone therapy have suggested a beneficial therapeutic effect in heart failure. Acute testosterone therapy reduces peripheral vascular resistance and improves cardiac output [11] and chronic testosterone therapy improves functional capacity and mood in patients with heart failure [5]. In the only major study of testosterone replacement in heart failure a potentially significant trend to reduce fasting glucose levels was observed [6]. In this proof of concept study, we concentrated on a single feature of the CHF metabolic syndrome-insulin resistance. We designed a study to confirm the previous suggestion that testosterone reduced fasting glucose but also to explore the effects of testosterone on insulin resistance and glucose tolerance. The primary outcome was the effect of androgen administration on insulin sensitivity in patients with moderate to severe heart failure.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Trial design
This was a single blind placebo controlled crossover study to assess the effect of testosterone therapy on insulin resistance in men with stable heart failure. The primary outcome was an index of insulin resistance measured with paired samples of glucose and insulin taken prior to and during an oral glucose tolerance test. The secondary outcomes were anthropomorphic measures of body mass including body mass index, lean mass and percent fat mass derived from bioelectrical impedance.

The trial was of three months duration; patients had two treatment phases of 4 weeks with a 4 week washout period between the treatment phases. Each patient was randomised to receive either placebo or testosterone first, after the washout period patients crossed over to the alternate treatment.

2.2. Setting
Cardiology Research Department, Royal Hallamshire Hospital, Sheffield.

Endocrine Assessment Unit, Royal Hallamshire Hospital, Sheffield.

2.3. Subjects
Subjects were men with moderate to severe; stable chronic heart failure of at least 6 months duration recruited from cardiology outpatient clinics. All patients gave written informed consent and the local research ethics committee approved the protocol.

Inclusion criteria were men with moderate to severe symptomatic congestive heart failure as classified by New York Heart Association scale 2-4. Every patient had at least moderate left ventricular dysfunction as assessed by 2D transthoracic echocardiography. Patients were excluded if they had any contraindication to testosterone therapy including elevation of prostate specific antigen beyond the age adjusted normal range, hepatic dysfunction (as evidenced by derangement of liver transaminases or prolonged prothrombin time) and sleep apnoea syndrome. For the purpose of this study patients with confirmed or treated diabetes (insulin, metformin, sulphonylurea) were also excluded.

2.4. Randomisation and drug treatment
Patients were randomised to ‘testosterone first’ or ‘placebo first’ using computer generated random numbers. Treatment was with Sustanon 250 (testosterone propionate 30 mg, testosterone phenylpropionate 60 mg, testosterone isocaproate 60 mg, and testosterone decanoate 100 mg/ml, Organon laboratories) a depot preparation of testosterone was given by deep intramuscular injection. Two intramuscular injections were given 2 weeks apart; the final assessment in each treatment phase was within 10-14 days of the previous injection. This is a regime commonly used as physiological testosterone replacement therapy in men with androgen deficiency and represents 1 month of testosterone therapy. Placebo was given as 0.9% normal saline; drugs were drawn up in a separate clinical room away from the patient in identical syringes.

2.5. Assessment
Patients were screened at baseline with a questionnaire detailing their medical history and concomitant medications. Assessments were always made between 8 am and 11 am after an overnight fast. All concomitant medications such as diuretics, angiotensin converting enzyme inhibitors and beta-blockers were permitted and continued throughout the study without dose adjustment. Subject height and weight were recorded, body mass index was calculated according to the equation [body mass index=mass (kg)/height (metres) 2]. Body composition including lean mass and body fat percentage were recorded by bioelectrical impedance using the TANITA BF-305 body fat analyser (TANITA corporation INC). Subjects were examined for peripheral oedema before determining body fat, body composition was tested when subjects were fasted but hydrated, before 9.30 am in light clothing. Measurement of body composition by electrical impedance is accurate in healthy and morbid populations and has recently been found to be a reliable alternative to dual energy X-ray absorptiometry which is the perceived ideal method of body fat analysis [12].

Insulin sensitivity was calculated using the homeostatic model assessment (HOMA-IR). The perceived ideal investigation of insulin sensitivity is the euglycaemic insulin clamp. This has the disadvantage of being invasive, time consuming and technically difficult but it is still used widely in specialist research centres. The technique is particularly difficult in patients with heart failure because of the inherent risks of fluid retention and pulmonary oedema associated with intra-venous infusions; euglycaemic clamps have rarely been used in patients with severe congestive heart failure. The HOMA index is calculated from the equation [(IfxGf)/22.5] where If is fasting insulin and Gf is fasting glucose. To ensure accuracy we used the mean of 3 serum samples taken every 15 min after a minimum 10-h overnight fast. The homeostatic model assessment (HOMA-IR) has been validated against the euglycaemic clamp (in non-heart failure populations) and has been found to provide a useful and repeatable index of insulin resistance [13]. HOMA-IR is also functionally similar to the Minmod assessment of insulin resistance (both tests use fasting and post glucose challenge measures of glucose and insulin) which has been found to be an independent risk factor for mortality in patients with heart failure [9]. The effects of testosterone therapy on glucose tolerance were tested using a standard oral glucose tolerance test. In this test the patient was required to drink a 75 g glucose solution following a 10-12 h fast with blood sampling at –30, –15, 0, 30, 60, 90, 120 min for the measurement of plasma glucose and insulin.

The serum glucose/insulin levels were plotted against time and comparison of the pre-treatment and post-testosterone curves was made using the trapezium equation to calculate area under the treatment curve.

Blood was taken for measurement of full blood count (FBC), prostate specific antigen (PSA), serum electrolytes and sex hormones. Plasma samples were obtained by centrifugation (20 min at 3000 rpm) and immediately frozen at –20 °C pending further analysis. Total testosterone and sex hormone binding globulin were measured by ELISA, inter- and intra-assay coefficients of the variance were <14% and <10% respectively. Bio-available testosterone was determined by a modification of the method described by Tremblay and Dube, [14] inter- and intra-assay coefficients of variance for this technique were <14% and <12% respectively.

2.6. Statistical analysis
There were no studies on which to calculate a power equation since this population has never been studied before. Simon et al. examined the effect of testosterone replacement therapy in 12 apparently healthy men with low serum testosterone (<11.8 nmol/L) and reported a significant improvement in insulin sensitivity as measured by HOMA-IR [15]. Since a heart failure population would be expected to have lower androgen levels and more severe insulin resistance than the healthy men in Simon's study we estimated that a therapeutic effect could be demonstrated with similar numbers of patients, to allow for patient withdrawals we planned to recruit 14 patients.

All data were tested against a normal distribution using the Kolmogorov-Smirnov test. Parametric data are presented as mean±SEM unless otherwise indicated. The data were first examined to exclude a treatment/period interaction, data from the first treatment period was pooled and tested against the pooled data for the second treatment period; where no such interactions were observed, the data was further validated by ensuring that the baseline data from each treatment (placebo and testosterone) were not statistically different using t-test to compare the baseline values in each case. Analysis was with unpaired t-test for parametric data or a Mann U-Whitney test for non-parametric data. The primary outcome (HOMA-IR) was compared by analysis of the delta using between group analyses of the difference with placebo versus testosterone, secondary outcomes such as mean fasting glucose, mean fasting insulin and percent fat mass were also measured with between group analyses. The analysis of glucose and insulin tolerance to a glucose challenge (using the trapezium rule to determine the area under the treatment curve) was compared using within group analysis using the area under the curve before testosterone treatment versus area after testosterone treatment. Correlations were tested with Pearson correlation coefficient for parametric data or Spearman's rank correlation for non-parametric data and ordinal data. In each case significance at the 5% (0.05) level was sought.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
Eighteen patients were screened and 14 were eventually randomised, one patient was withdrawn after randomisation because he was treated with a long acting somatostatin analogue (for acromegaly) a drug that is known to affect insulin sensitivity. Complete data were available from 13 patients; there were no treatment/period effects of significance and there was no statistical difference between the baseline data of the testosterone and placebo phases (p>0.2). The baseline data are presented in Table 1. The sample comprised a group of elderly males with moderate to severe heart failure. Two patients had fasting glucose levels >6.1 mmol/L indicating impaired fasting glucose tolerance. The levels of serum androgen (total and bioavailable) testosterone were variable ranging from very low to a high physiological range. The mean total testosterone was 14.1 nmol/L at the lower end of the normal range (11-35 nmol/L).


View this table:
[in this window]
[in a new window]

  		Table 1 Baseline data

 
At baseline the HOMA-IR was positively correlated with body mass index (rP=0.79, p=0.01) (Fig. 1) and percent fat mass (rP=0.84, p=0.001) but was not related to any measure of heart failure severity.


Figure 01
View larger version (11K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Baseline correlation of HOMA-IR and body mass index.

 
3.1. Safety
The drug was well tolerated by the subjects. One patient was admitted to hospital with a respiratory tract infection (while on the placebo phase). The placebo treatment phase for this patient was repeated in full to exclude any effect of an intercurrent infection on insulin sensitivity. There were no adverse effects on serum electrolytes.

3.2. Fasting insulin sensitivity
Insulin sensitivity as measured by the HOMA index improved on testosterone compared to placebo. The mean treatment effect [and 95% confidence intervals] of testosterone on HOMA-IR was a reduction (–1.9±0.8, p=0.03) [–0.16 to –3.6] compared to placebo. This effect was explained by a reduction in both the fasting insulin and glucose (see Table 2). The reduction in HOMA-IR was inversely correlated with the increase in bioavailable testosterone (rP=–0.58, p=0.04) but not total testosterone (rP=–0.38, p=0.2).


View this table:
[in this window]
[in a new window]

  		Table 2 Treatment effects of testosterone vs. placebo

 
3.3. Body composition
There was a small but significant increase in total body mass following testosterone, this was not explained by a change in fat mass since the percentage fat mass reduced with testosterone compared to placebo (Table 2).

3.4. Sex hormones
Both total and bioavailable testosterone levels rose significantly with active therapy. The level of replacement was at the high end of the physiological range with the mean post-treatment total testosterone 29.5±4.1 nmol/L (sample range 13.2-55.0 nmol/L) (Table 2).

3.5. Glucose challenge sensitivity
There were no differences in the area under the treatment curves of insulin or glucose following testosterone therapy (Figs. 2 and 3). The World Health Organisation defines diabetes biochemically as an elevation of serum glucose to >11.1 mmol/L following a 75 g oral glucose challenge and impaired glucose tolerance as an elevation of serum glucose to >7.1 mmol/L. Of the fourteen patients randomised, 3 had frank diabetes and 8 had impaired glucose tolerance by these criteria.


Figure 02
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Post-challenge glucose tolerance.

 


Figure 03
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Post-challenge insulin tolerance.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
We have shown that testosterone therapy improves fasting insulin sensitivity in a sample of men with moderately severe heart failure. This effect was accompanied by an increase in total body mass and a reduction in fat mass. The study sample size was small but previous studies (in non-heart failure populations) have shown an effect on insulin sensitivity with small numbers. Simon et al. [15] who wrote the paper on which the present study was modelled reported a statistical improvement in twelve men treated with testosterone or dihydrotestosterone. Our study findings are therefore consistent with the epidemiological evidence and the current prospective data suggesting a beneficial effect of testosterone therapy on insulin sensitivity.

At present the mechanism by which androgens influence the insulin-glucose axis is uncertain. There is considerable evidence that body composition governs insulin sensitivity and that excess visceral fat may induce insulin resistance by flooding hepatic metabolism with fatty acids leading to hepatic and eventually systemic insulin resistance [10]. Testosterone has well documented effects on body metabolism including an increase in lean mass and a reduction in fat mass [10]. The findings of the present study were consistent with this lending support to the notion that the primary action of testosterone is on body composition with improvements in insulin sensitivity associated with reduced body fat. However the insulin resistance of severe heart failure appears to have a different pathophysiology to that of simple obesity or type 2 diabetes, since lean patients with severe heart failure also have insulin resistance and patients with cachexia (defined as a non-oedematous weight loss of ≥5 kg (and >7.5% of previous normal weight in 6 months)) have the most severe insulin resistance of all [4]. In the current study only 3 patients had clinically defined cardiac cachexia and one patient was clinically obese (with a body mass index of 35.3) so our data are insufficient to allow comparison of subgroups of cachectic versus non-cachectic men. Body mass index has an unusual and apparently paradoxical relationship with the prognosis of heart failure. Taking the heart failure population as a whole there is a linear improvement in survival with increased BMI and an elevated BMI is apparently protective in heart failure. However further investigation of this paradox has suggested that the relationship is more complex and that systolic heart failure has a U-shaped relationship whereby both low and high BMI are associated with poor outcome and the linear relationship seen overall is partly confounded by the uniformly bad outcome in cachectic patients with low BMI and a better outcome in patients with obstructive lung disease and simple obesity who have mild heart failure and diastolic dysfunction [16]. An elevated BMI is therefore not necessarily protective in patients with systolic heart failure and insulin resistance is detrimental whatever the baseline BMI [9]. In the present study insulin resistance at baseline correlated with measures of body fat (body mass index, percent fat mass) and not to objective measures of heart failure severity (ejection fraction, New York Heart association class), we believe that in our patients the reduction of body fat contributed primarily to the improvement of insulin sensitivity, although we accept this may not be the only mechanism. The present data and indeed the current literature can not easily distinguish the difference in insulin resistance associated with cachectic men with heart failure and obese men with heart failure; however both are associated with a poor prognosis in heart failure due to systolic dysfunction. Currently there are no trials that have assessed the prognostic outcome of intended weight reduction in CHF or of attempts to improve insulin sensitivity, but these will be important areas of future investigation.

Our data have also reinforced the evidence that abnormalities of the glucose-insulin axis are common in heart failure. Of the fourteen patients randomised only 4 did not manifest diabetes or impaired glucose tolerance. We have confirmed the suggestion in our earlier clinical study that testosterone improves fasting insulin sensitivity although the mechanism seems more related to effects on fat mass rather then a pure effect on the heart failure metabolic syndrome alone.

There is increasing evidence of a beneficial effect of testosterone therapy in CHF; to date testosterone has been shown to improve cardiac output, mood, functional capacity and coronary ischaemia [6,11,17]. In summary, we have shown that in this cohort of men testosterone improves insulin sensitivity, reduces fat mass and may increase lean body mass. Although the clinical impact of these effects has not yet been tested in a heart failure population these data do provide supportive evidence to encourage the use of testosterone therapy in men with chronic heart failure.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Anker S.D., Coats A.J. How to recover from renaissance? The significance of the results of recover, renaissance, renewal and attach. Int J Cardiol (2002) 86(2-3):123–130.[CrossRef][Web of Science][Medline]
  2. van der Meer P., Voors A.A., Lipsic E., van Gilst W.H., van Veldhuisen D.J. Erythropoietin in cardiovascular diseases. Eur Heart J (2004) 25(4):285–291.[Abstract/Free Full Text]
  3. Kontoleon P.E., Anastasiou-Nana M.I., Papapetrou P.D., Alexopoulos G., Ktenas V., Rapti A.C., et al. Hormonal profile in patients with congestive heart failure. Int J Cardiol (2003) 87(2-3):179–183.[CrossRef][Web of Science][Medline]
  4. Anker S.D., Chua T.P., Ponikowski P., Harrington D., Swan J.W., Kox W.J., et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation (1997) 96(2):526–534.[Abstract/Free Full Text]
  5. Pugh P.J., Jones R.D., West J.N., Jones T.H., Channer K.S. Testosterone treatment for men with chronic heart failure. Heart (2004) 90(4):446–447.[Free Full Text]
  6. Malkin C.J., Pugh P.J., West J.N., van Beek E.J., Jones T.H., Channer K.S., et al. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J (2006) 27(1):57–64.[Abstract/Free Full Text]
  7. Swan J.W., Anker S.D., Walton C., Godsland I.F., Clark A.L., Leyva F., et al. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol (1997) 30(2):527–532.[Abstract]
  8. Doehner W., Anker S.D., Coats A.J. Defects in insulin action in chronic heart failure. Diabetes Obes Metab (2000) 2(4):203–212.[CrossRef][Web of Science][Medline]
  9. Doehner W., Rauchhaus M., Ponikowski P., Godsland I.F., von Haehling S., Okonko D.O., et al. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure. J Am Coll Cardiol (2005) 46(6):1019–1026.[Abstract/Free Full Text]
  10. Kapoor D., Malkin C.J., Channer K.S., Jones T.H. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf) (2005) 63(3):239–250.[CrossRef][Medline]
  11. Pugh P.J., Jones T.H., Channer K.S. Acute haemodynamic effects of testosterone in men with chronic heart failure. Eur Heart J (2003) 24(10):909–915.[Abstract/Free Full Text]
  12. Uszko-Lencer N.H., Bothmer F., van Pol P.E., Schols A.M. Measuring body composition in chronic heart failure: a comparison of methods. Eur J Heart Fail (2005).
  13. Bonora E., Targher G., Alberiche M., Bonadonna R.C., Saggiani F., Zenere M.B., et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care (2000) 23(1):57–63.[Abstract]
  14. Tremblay R.R., Dube J.Y. Plasma concentrations of free and non-TeBG bound testosterone in women on oral contraceptives. Contraception (1974) 10(6):599–605.[CrossRef][Web of Science][Medline]
  15. Simon D., Charles M.A., Lahlou N., Nahoul K., Oppert J.M., Gouault-Heilmann M., et al. Androgen therapy improves insulin sensitivity and decreases leptin level in healthy adult men with low plasma total testosterone: a 3-month randomized placebo-controlled trial. Diabetes Care (2001) 24(12):2149–2151.[Free Full Text]
  16. Gustafsson F., Kragelund C.B., Torp-Pedersen C., Seibaek M., Burchardt H., Akkan D., et al. Effect of obesity and being overweight on long-term mortality in congestive heart failure: influence of left ventricular systolic function. Eur Heart J (2005) 26(1):58–64.[Abstract/Free Full Text]
  17. English K.M., Steeds R.P., Jones T.H., Diver M.J., Channer K.S. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation (2000) 102(16):1906–1911.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
G. Caminiti, M. Volterrani, F. Iellamo, G. Marazzi, R. Massaro, M. Miceli, C. Mammi, M. Piepoli, M. Fini, and G. M.C. Rosano
Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study.
J. Am. Coll. Cardiol., September 1, 2009; 54(10): 919 - 927.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
A. M. Traish, F. Saad, R. J. Feeley, and A. Guay
The Dark Side of Testosterone Deficiency: III. Cardiovascular Disease
J Androl, September 1, 2009; 30(5): 477 - 494.
[Abstract] [Full Text] [PDF]

Home page
 Circ Heart FailHome page
L. Sacca
Heart Failure as a Multiple Hormonal Deficiency Syndrome
Circ Heart Fail, March 1, 2009; 2(2): 151 - 156.
[Full Text] [PDF]

Home page
 Eur J Heart FailHome page
E. A. Jankowska, J. Jakubaszko, A. Cwynar, J. Majda, B. Ponikowska, D. Kustrzycka-Kratochwil, K. Reczuch, L. Borodulin-Nadzieja, W. Banasiak, P. A. Poole-Wilson, et al.
Bone mineral status and bone loss over time in men with chronic systolic heart failure and their clinical and hormonal determinants
Eur J Heart Fail, January 1, 2009; 11(1): 28 - 38.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
S. C Larsson and A. Wolk
Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies
Am. J. Clinical Nutrition, September 1, 2007; 86(3): 556 - 565.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
M. Lainscak, W. Doehner, and S. D. Anker
Metabolic disturbances in chronic heart failure: A case for the "macho" approach with testosterone?!
Eur J Heart Fail, January 1, 2007; 9(1): 2 - 3.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Malkin, C. J.
Right arrow Articles by Channer, K. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malkin, C. J.
Right arrow Articles by Channer, K. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?