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Cited by 84Hormonal and reproductive studiesHeart Failure Treatment and ManagementDiabetes, Cardiovascular Risks, and Lipoproteins

The Effect of Testosterone on Insulin Sensitivity in Men with Heart Failure

Open access
Malkin, Chris J., Jones, T. Hugh, Channer, Kevin S.·2007·European Journal of Heart Failure
DOI 10.1016/j.ejheart.2006.04.006
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Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

In men with moderate-to-severe chronic heart failure, testosterone therapy improved fasting insulin sensitivity as measured by HOMA-IR compared with placebo. Testosterone also increased total body mass and reduced percent body fat, without changing glucose or insulin area under the curve after an oral glucose challenge.

Key findings

  • Testosterone reduced HOMA-IR versus placebo: mean treatment effect −1.9 ± 0.8, p = 0.03 (95% CI −0.16 to −3.6), indicating improved fasting insulin sensitivity.
  • Testosterone increased total body mass by +1.5 ± 0.5 kg (p = 0.008) and decreased percent body fat by −0.8 ± 0.3% (p = 0.02).
  • At baseline, HOMA-IR correlated with percent fat mass (r = 0.84, p = 0.0001) and body mass index (r = 0.79, p = 0.01), but not with measures of heart failure severity.
  • There were no differences in the area under the treatment curves for insulin or glucose after a 75 g oral glucose load; for insulin, AUC was 8845 vs 9124, p = 0.8.

Methods

  • Single-blind placebo-controlled crossover trial in 13 men with moderate-to-severe stable chronic heart failure (ejection fraction 30.5 ± 1.3; NYHA class II/III/IV 1/10/2); 14 were randomized and 1 was withdrawn, leaving complete data from 13.
  • Patients had two 4-week treatment phases with a 4-week washout between phases; they were randomized to testosterone first or placebo first, then crossed over. Testosterone was given as Sustanon 250 by deep intramuscular injection, two injections 2 weeks apart.
  • Primary outcome was HOMA-IR from fasting glucose and insulin; secondary outcomes included body composition by bioelectrical impedance and glucose tolerance to a standard 75 g oral glucose load. Analysis used delta values, between-group comparisons, t-tests or Mann-Whitney tests, and correlation coefficients.

Limitations

  • The paper states the sample size was small, there were no prior studies on which to calculate a power equation, the data were insufficient to compare cachectic versus non-cachectic subgroups, and the clinical impact of these metabolic effects has not yet been tested in a heart failure population.
  • Evident from the text: the trial was single-blind rather than double-blind, each treatment phase lasted only 4 weeks, the sample was composed of elderly men, and the study did not assess clinical outcomes or prognosis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.ejheart.2006.04.006

Cites

17 of 17 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 10 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The reduction in HOMA-IR with testosterone was not correlated with total testosterone (r = -0.38, p = 0.2).

    “The reduction in HOMA-IR was inversely correlated with the increase in bioavailable testosterone (rP= À 0.58, p = 0.04) but not total testosterone (rP= À 0.38, p = 0.2).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In men with moderate to severe chronic heart failure, testosterone therapy reduced the HOMA-IR index of fasting insulin sensitivity compared with placebo (mean treatment effect -1.9 ± 0.8, p = 0.03, 95% CI -0.16 to -3.6).

    “Testosterone reduced HOMA-IR (À 1.9 T 0.8, p = 0.03) indicating improved fasting insulin sensitivity.”
    • Also stated in: § 3.2. Fasting insulin sensitivity · plain
      “The mean treatment effect [and 95% confidence intervals] of testosterone on HOMA-IR was a reduction (À 1.9 T 0.8, p = 0.03) [À 0.16 to À 3.6] compared to placebo.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: HOMA-IR provides a valid index of insulin resistance in patients with heart failure, although its validation was performed in non-heart-failure populations.
  • Findingown data

    Testosterone therapy increased total body mass compared with placebo in men with chronic heart failure (+1.5 ± 0.5 kg, p = 0.008).

    “Testosterone also increased total mass (+ 1.5 T 0.5 kg, p = 0.008)”
    • Also stated in: § 3.3. Body composition · plain
      “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).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Testosterone therapy decreased percentage body fat compared with placebo in men with chronic heart failure (-0.8 ± 0.3%, p = 0.02).

    “and decreased body fat (À 0.8 T 0.3%, p = 0.02)”
    • Also stated in: § 3.3. Body composition · plain
      “the percentage fat mass reduced with testosterone compared to placebo (Table 2).”
    Quote in the paperNot a substantial claim
  • Findingown data

    At baseline, HOMA-IR was positively correlated with percentage fat mass in men with chronic heart failure (r = 0.84, p = 0.001).

    “At baseline HOMA-IR correlated with measures of body fat [% fat mass (rP= 0.84, p = 0.0001)”
    • Also stated in: § 3. Results · plain
      “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)”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 10
  • May combine two claims. 15

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of the fourteen patients randomised, 3 had frank diabetes and 8 had impaired glucose tolerance by WHO biochemical criteria.

    “Of the fourteen patients randomised, 3 had frank diabetes and 8 had impaired glucose tolerance by these criteria.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both total and bioavailable testosterone levels rose significantly with active testosterone therapy.

    “Both total and bioavailable testosterone levels rose significantly with active therapy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The mean baseline total testosterone was 14.1 nmol/L, at the lower end of the normal range (11-35 nmol/L).

    “The mean total testosterone was 14.1 nmol/L at the lower end of the normal range (11-35 nmol/L).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The testosterone treatment was well tolerated and there were no adverse effects on serum electrolytes.

    “The drug was well tolerated by the subjects.”
    • Also stated in: § 3.1. Safety · plain
      “There were no adverse effects on serum electrolytes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    HOMA-IR has been validated against the euglycaemic clamp in non-heart-failure populations and provides a useful and repeatable index of insulin resistance.

    “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].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Bonora, 2000, 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 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Complete data were available from 13 of the 14 randomised patients.

    “Complete data were available from 13 patients”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Resistance to insulin occurs in chronic heart failure and is related to prognosis.

    “Resistance to insulin occurs in chronic heart failure (CHF) and is related to prognosis.”
    • Also stated in: § 1. Introduction · plain
      “the degree of insulin resistance directly influenced prognosis [9].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Doehner, 2005, Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure, J Am Coll Cardiol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The trial was a single-blind placebo-controlled crossover study.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    There were no treatment/period effects of significance and no statistical difference between the baseline data of the testosterone and placebo phases (p > 0.2).

    “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).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    To ensure accuracy, fasting insulin and glucose were measured as the mean of 3 serum samples taken every 15 min after a minimum 10-h overnight fast.

    “To ensure accuracy we used the mean of 3 serum samples taken every 15 min after a minimum 10-h overnight fast.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Patients were randomised to testosterone-first or placebo-first using computer generated random numbers.

    “Patients were randomised to Ftestosterone first_ or Fplacebo first_ using computer generated random numbers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Placebo was given as 0.9% normal saline and drugs were drawn up in a separate clinical room away from the patient in identical syringes.

    “Placebo was given as 0.9% normal saline; drugs were drawn up in a separate clinical room away from the patient in identical syringes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Measurement of body composition by bioelectrical impedance is accurate in healthy and morbid populations and is a reliable alternative to dual energy X-ray absorptiometry.

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Uszko-Lencer, 2005, Measuring body composition in chronic heart failure: a comparison of methods, Eur J Heart Fail

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    No prior studies existed on which to calculate a power equation, so the sample size was estimated from Simon et al.'s study of 12 men, planning to recruit 14 patients.

    “There were no studies on which to calculate a power equation since this population has never been studied before.”
    • Also stated in: § 2.6. Statistical analysis · hedged
      “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Simon, 2001, 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 source

      Not checked in the free run.

    • Rests on an assumption: A heart failure population would have lower androgen levels and more severe insulin resistance than the healthy men in Simon et al.'s study.

  • May combine two claims.

    Premisecitation

    There is some evidence that testosterone replacement is beneficial and improves functional status in men with chronic heart failure.

    “there is some evidence that testosterone replacement is beneficial and improves functional status in men with CHF [5,6].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] Pugh, 2004, Testosterone treatment for men with chronic heart failure, Heart source

      Not checked in the free run.

    • cites [6] Malkin, 2006, Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial, Eur Heart J source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A cross-sectional study of patients with heart failure found that 43% had manifest disorders of glucose metabolism ranging from frank diabetes to impaired glucose sensitivity.

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Kontoleon, 2003, Hormonal profile in patients with congestive heart failure, Int J Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The primary action of testosterone is on body composition, with improvements in insulin sensitivity associated with reduced body fat.

    “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.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: HOMA-IR provides a valid index of insulin resistance in patients with heart failure, although its validation was performed in non-heart-failure populations.

  • May combine two claims.

    Interpretationown data

    In these patients with chronic heart failure, the reduction of body fat contributed primarily to the improvement of insulin sensitivity, though this may not be the only mechanism.

    “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.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: HOMA-IR provides a valid index of insulin resistance in patients with heart failure, although its validation was performed in non-heart-failure populations.
18 of 18

  • The paper relies on this without support.

    A heart failure population would have lower androgen levels and more severe insulin resistance than the healthy men in Simon et al.'s study.

    “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”

  • The paper relies on this without support.

    HOMA-IR provides a valid index of insulin resistance in patients with heart failure, although its validation was performed in non-heart-failure populations.

    “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].”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Testosterone treatment reduces insulin resistance in obese men, men with heart failure, and type 2 diabetic subjects.

    “Testosterone treatment has also been shown to reduce insulin resistance in obese men (23,24), men with heart failure (25), and type 2 diabetic subjects (26).”

    From Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes (2007) · cites this paper as [25]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Body-fat confidence interval is not centred on its mean effect

    Minor

    The reported confidence-interval endpoints have a midpoint of −0.6, rather than the reported mean effect of −0.8. This exceeds rounding at the printed precision.

    Reported -0.8 · recomputed -0.6

  • Different baseline mean total testosterone values

    Minor

    The results give a baseline mean of 14.1 nmol/L, while Table 1 gives 14.3 nmol/L.

  • Glucose-challenge dose differs by a factor of 1,000

    Minor

    The methods specify a 75 g oral glucose challenge, but the figure text calls it a 75mg challenge.

  • Different p-values for the same body-fat correlation

    Minor

    The abstract and results report the same baseline correlation with percent fat mass but give p-values of 0.0001 and 0.001, respectively.

  • PSA mean equals the reported maximum despite a lower minimum

    Minor

    Table 1 gives a mean PSA of 2.1 and a range of 0.3-2.1. A mean cannot equal the maximum when at least one observation is below it.

5 of 5

Cites

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Related

Authors
Malkin, C. J., Jones, T. H., & Channer, K. S.
Affiliations
  • Royal Hallamshire Hospital (GB)
  • Barnsley Hospital (GB)
Corresponding author
Channer, Kevin S.
Venue
European Journal of Heart Failure
Publisher
Oxford University Press (OUP)
Published
2007-01-01
Volume
9
Issue
1
Pages
44-50
ISSN
  • 1388-9842 (ISSN-L)
  • 1879-0844
DOI
10.1016/j.ejheart.2006.04.006
OpenAlex
W2074853632
Semantic Scholar
2c08c66a447096f23894164453c51081ade3ccd8
Cited by
84
References
17
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 10 · 2013: 4 · 2012: 8
FWCI
3.85
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • European Journal of Heart Failure (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
testosterone replacement therapy, insulin resistance, chronic heart failure, HOMA-IR, body composition, lean body mass, fat mass, glucose tolerance, men
MeSH terms
Aged, Aged, 80 and over, Blood Glucose, Blood Pressure, Creatinine, Fasting, Heart Failure, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Placebos, Testosterone, Body Mass Index, Single-Blind Method, Cross-Over Studies

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