CoChat
Sign Up
Cited by 250Hormonal and reproductive studiesMenopause: Health Impacts and TreatmentsSexual function and dysfunction studies

Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life

Open access
Malkin, C J, Pugh, P J, Morris, P D, Kerry, K E, Jones, R D, Jones, T H, Channer, K S·2004·Heart
DOI 10.1136/hrt.2003.021121PMC PMC1768369
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia, adverse clotting profiles, obesity, and insulin resistance. Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease. Objective: This randomised single blind placebo controlled crossover study compared testosterone replacement therapy (Sustanon 100) with placebo in 10 men with ischaemic heart disease and hypogonadism. Results: Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l. After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025), time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 (54) seconds (p = 0.002), and mood scores assessed with validated questionnaires all improved. Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor α with delta values of −0.41 (0.54) mmol/l (p = 0.04) and −1.8 (2.4) pg/ml (p = 0.05) respectively. Conclusion: Testosterone replacement therapy in hypogonadal men delays time to ischaemia, improves mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor α.

AI snapshot

Written from the paper’s full text.

TL;DR

In 10 hypogonadal men with coronary disease and angina, one month of intramuscular testosterone (Sustanon 100) improved time to ischaemic threshold on treadmill testing and mood compared with placebo, and reduced total cholesterol and TNFα. This small single-blind crossover proof-of-concept study did not confirm a significant improvement in angina symptoms.

Key findings

  • Time to 1 mm ST segment depression increased by 81 (48) seconds in the testosterone phase versus 7.2 (32) seconds in the placebo phase; the mean difference between testosterone and placebo was 74 (54) seconds (95% CI 35.4 to 112.6; p = 0.002).
  • Trough testosterone concentrations rose significantly versus placebo: total testosterone by 4.8 (6.6) nmol/l (p = 0.05) and bioavailable testosterone by 3.8 (4.5) nmol/l (p = 0.025).
  • Testosterone was associated with reductions in total cholesterol (printed delta 20.41 (0.54) mmol/l; p = 0.04) and serum TNFα (printed delta 21.8 (2.4) pg/ml; p = 0.05).
  • Mood questionnaires improved: Beck depression inventory difference −4.8 (6.1) (p = 0.007) and androgen deficiency screen difference −3.1 (3.3) (p = 0.015); Seattle angina score change did not reach significance (p = 0.14).

Methods

  • Randomised, single-blind, placebo-controlled crossover study in men with coronary artery disease (>70% stenosis of a major coronary artery or previous proven myocardial infarction) and typical angina, recruited from a male andrology clinic with a clinical need for testosterone replacement.
  • Of 12 screened, 11 were randomised and 10 completed; participants received intramuscular Sustanon 100 (1 ml, 100 mg testosterone/ml) every two weeks or placebo (1 ml 0.9% saline) for one month, followed by a one-month washout and crossover.
  • Assessments at weeks 0, 4, 8, and 12 included Bruce protocol treadmill exercise testing with primary endpoint time to 1 mm ST segment depression, blood tests, and validated questionnaires; biological data were analysed with paired t tests and questionnaire scores with Wilcoxon matched-pair tests.

Limitations

  • The paper states that patients did not present with symptoms of androgen deficiency but were found to be hypogonadal during a cross-sectional observational study; it could not confirm a beneficial effect on angina symptoms, the Seattle angina questionnaire only approached significance, patients were not required to complete symptom diaries, and the protocol precluded analysis of angina threshold because treadmill tests stopped at 1 mm ST segment depression.
  • The paper notes the study was single blind, though ECG data were recorded with the Marquette 002E software package, effectively eliminating observer bias; it also notes the testosterone dose may have been inadequate for some patients and uptitration may be required.
  • Evident from the text: the completed sample was very small (10 men), treatment phases were short (one month), and all patients were on concomitant antianginal medications and statins, which may limit generalisability.

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

Integrity signals

Registry

Crossref · 10.1136/hrt.2003.021121

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    After one month of testosterone, trough bioavailable testosterone increased significantly compared with placebo by mean 3.8 (4.5) nmol/l (p = 0.025).

    “After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025)”
    Quote in the paperSubstantial claim
  • Findingown data

    Baseline total testosterone in the 10 hypogonadal men with ischaemic heart disease was 4.2 (0.5) nmol/l.

    “Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Baseline bioavailable testosterone in the 10 hypogonadal men with ischaemic heart disease was 1.7 (0.4) nmol/l.

    “Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l.”
    Quote in the paperNot a substantial claim
  • Findingown data

    After one month of testosterone, trough total testosterone increased significantly compared with placebo by mean 4.8 (6.6) nmol/l (p = 0.05).

    “After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025)”
    Quote in the paperSubstantial claim
  • Interpretationown data

    The present study adds to accumulating evidence that testosterone may have a beneficial anti-inflammatory action.

    “The present study therefore adds to the accumulating evidence that testosterone may have a beneficial anti-inflammatory action.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 7
  • Classified as probably not a substantial claim. 31
  • May combine two claims. 27

  • The quote only partly states this claim.

    Findingown data

    Compared with placebo, testosterone reduced Beck depression inventory scores significantly (difference -4.8, p = 0.007).

    “Compared with placebo there were reductions in Beck depression inventory scores, general health screening score, and androgen deficiency screening scores (fig 3).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Testosterone treatment was associated with a significant reduction in total cholesterol compared with placebo, delta -0.41 (0.54) mmol/l (p = 0.04).

    “Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor a with delta values of 20.41 (0.54) mmol/l (p = 0.04) and 21.8 (2.4) pg/ml (p = 0.05) respectively.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Testosterone treatment induced a small but significant rise in packed cell volume compared with placebo.

    “Compared with placebo, testosterone therapy also induced small but significant rises in haemoglobin and packed cell volume but reductions in serum TNFa and total cholesterol (fig 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a trend to reduction of Seattle angina questionnaire score with testosterone compared with placebo, but it did not reach significance.

    “There was a trend to reduction of the Seattle angina questionnaire score, but this did not reach significance.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Testosterone treatment induced a small but significant rise in haemoglobin compared with placebo.

    “Compared with placebo, testosterone therapy also induced small but significant rises in haemoglobin and packed cell volume but reductions in serum TNFa and total cholesterol (fig 2).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Serum PSA rose slightly from 1.01 (1.3) to 1.10 (1.4) mg/l (p = 0.03) over the trial.

    “As expected serum PSA measured at screening and at the end of the trial rose slightly (from 1.01 (1.3) to 1.10 (1.4) mg/l, p = 0.03)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingown data

    Compared with placebo, testosterone reduced general health screening questionnaire scores, but the difference did not reach significance (difference -3.1, p = 0.075).

    “Compared with placebo there were reductions in Beck depression inventory scores, general health screening score, and androgen deficiency screening scores (fig 3).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Compared with placebo, testosterone reduced androgen deficiency in the adult male screening scores significantly (difference -3.1, p = 0.015).

    “Compared with placebo there were reductions in Beck depression inventory scores, general health screening score, and androgen deficiency screening scores (fig 3).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Compared with placebo, testosterone increased time to 1 mm ST segment depression by mean 74 (54) seconds (95% CI 35.4 to 112.6; p = 0.002).

    “The mean difference in exercise time between testosterone therapy and placebo was 74 (54) seconds (95% confidence interval (CI) 35.4 to 112.6 seconds).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Testosterone treatment was associated with a significant reduction in serum TNFa compared with placebo, delta -1.8 (2.4) pg/ml (p = 0.05).

    “Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor a with delta values of 20.41 (0.54) mmol/l (p = 0.04) and 21.8 (2.4) pg/ml (p = 0.05) respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The reduction in LDL cholesterol was not significant and no reduction was seen in HDL cholesterol.

    “The reduction in LDL cholesterol was not significant and no reduction was seen in HDL cholesterol, which may be due to effects on insulin sensitivity.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    No serious adverse effects other than a small rise in PSA were reported.

    “No other adverse effects were reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The patients did not present with symptoms of androgen deficiency; they were found to be hypogonadal during a cross sectional observational study.

    “The patients in this study did not present with symptoms of androgen deficiency; they were found to be hypogonadal during a cross sectional observational study.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] 2003, J Am Coll Cardiol

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Major improvements in mood were reported by all patients and hypogonadal symptoms were abolished in three.

    “Major improvements in mood were reported by all patients and hypogonadal symptoms were abolished in three.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no new symptoms of prostatic outflow obstruction and the final PSA concentration remained within the age-adjusted normal range.

    “however, there were no new symptoms of prostatic outflow obstruction and the final concentration of PSA remained well within the age adjusted normal range (, 4.5 mg/l).”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    The overall level of patient satisfaction was high.

    “The overall level of patient satisfaction was high.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no serious adverse effects other than a small rise in PSA, which was expected in this hypogonadal cohort.

    “There were no serious adverse effects other than a small rise in PSA, which was expected in this hypogonadal cohort.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    All treadmill tests were supervised by a cardiac technician with one investigator present.

    “All treadmill tests were supervised by a cardiac technician with one investigator (CJM) present.”
    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 conductown data

    Of 12 patients screened, one did not meet ECG criteria and 11 were randomly assigned; one withdrew after elective coronary artery bypass, and complete data were available for 10 patients.

    “Of 12 patients screened, one patient did not meet accepted ECG criteria during exercise treadmill testing and 11 were randomly assigned to treatment.One study patient underwent an elective coronary artery bypass earlier than expected and was withdrawn from the study.Complete data were available for 10 patients”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The lack of HDL cholesterol reduction may be due to effects on insulin sensitivity.

    “The reduction in LDL cholesterol was not significant and no reduction was seen in HDL cholesterol, which may be due to effects on insulin sensitivity.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The protocol precluded analysis of angina threshold because treadmill tests were terminated at the onset of 1 mm ST segment depression.

    “Furthermore, the protocol precluded an analysis of angina threshold, since treadmill tests were terminated at the onset of 1 mm ST segment depression.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    From previous work with eugonadal men showing a 37% increase in time to 1 mm ST segment depression with testosterone, 12 participants were calculated to be needed to detect a 50% increase in a crossover study with 80% power and 5% significance.

    “From previous work with eugonadal men, in which we found a 37% increase in time to 1 mm ST segment depression with testosterone, we calculated that for hypogonadal men 12 participants would be needed to detect a 50% increase in a crossover study protocol, with 80% power and 5% significance.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    No changes were made to antianginal medication for four weeks before or during the trial.

    “No changes were made to antianginal medication for four weeks before or during the trial.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    This study gives further supportive evidence of the antiischaemic and anti-inflammatory effect of testosterone.

    “This study gives further supportive evidence of the antiischaemic and anti-inflammatory effect of testosterone.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Patients were blinded to the identity of the injection and the drug was drawn up away from the patient.

    “Patients were blinded to the identity of the injection and the drug was drawn up away from the patient.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    It is possible that a positive effect on features of the insulin resistance syndrome attenuated the expected reduction in HDL cholesterol in this cohort.

    “Given that in our cohort all were hypogonadal, 50% were diabetic, and the mean body mass index was 31.3 kg/m 2 it is possible that a positive effect on features of the insulin resistance syndrome attenuated the expected reduction in HDL cholesterol”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Time to 1 mm ST segment depression was measured from computer derived analysis, effectively eliminating observer bias.

    “Time to 1 mm ST segment depression was measured from computer derived analysis effectively eliminating observer bias.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Baseline results of each crossover phase were examined and tested for period or treatment period interaction; when no interaction was found, data were deemed suitable for further analysis.

    “The baseline results of each crossover phase were examined and tested for period or treatment period interaction.When no such interaction was found data were deemed suitable for further analysis.”
    Quote in the paperSubstantial claim

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

    Interpretationown data

    The dose of testosterone used may have been inadequate for some patients and uptitration may be required to abolish hypogonadal symptoms in the remainder.

    “The dose of testosterone used in the study may have been inadequate for some of our patients and uptitration of dose may be required to abolish hypogonadal symptoms in the remainder.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Drug order was allocated by blocks of computer generated random numbers.

    “Drug order was allocated by blocks of computer generated random numbers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Testosterone therapy induced a reduction in serum total cholesterol, with no other significant effects on other lipid profiles.

    “Testosterone therapy induced a reduction in serum total cholesterol, with no other significant effects seen on other lipid profiles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The study was a randomised, single blind, placebo controlled crossover trial of testosterone replacement versus placebo in men with hypogonadism and coronary heart disease.

    “This was a randomised, single blind crossover study of testosterone replacement therapy versus placebo in men with hypogonadism and coronary heart disease.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    An interaction between testosterone and hydroxymethyl glutaryl coenzyme A reductase inhibitors cannot be excluded.

    “In addition, we cannot exclude an interaction with testosterone and the hydroxymethyl glutaryl coenzyme A reductase inhibitors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    The effects in the present study were seen in the presence of concomitant antianginal medications, whereas in some earlier studies angina medications were withdrawn.

    “Furthermore, the effects in the present study were seen in the presence of concomitant antianginal medications, whereas in some earlier studies angina medications were withdrawn.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Although a positive effect on inducible myocardial ischaemia was recorded, a beneficial effect on the symptom of angina could not be confirmed.

    “Although a positive effect on inducible myocardial ischaemia was recorded we could not confirm a beneficial effect on the symptom of angina.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Most studies report that testosterone therapy causes reductions in HDL cholesterol, although this effect is absent or less apparent in elderly, hypogonadal, or obese men.

    “Most studies report that testosterone therapy causes reductions in HDL cholesterol, 18 19 although this effect is absent or less apparent in elderly, hypogonadal, or obese men.20 21”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [18] 2002, Horm Metab Res source

      Not checked in the free run.

    • cites [19] 1996, Clin J Sport Med source

      Not checked in the free run.

    • cites [20] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Given that testosterone therapy is of benefit to eugonadal men with coronary disease, hormone replacement for hypogonadal men would be expected to be of even greater benefit.

    “Given that testosterone therapy is of benefit to eugonadal men with coronary disease it would be expected that hormone replacement for hypogonadal men would be of even greater benefit.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    The populations of men in prior testosterone studies were randomly chosen and not selected on the basis of endogenous hormone concentrations.

    “The populations of men in these studies were randomly chosen and not selected on the basis of endogenous hormone concentrations.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In most studies testosterone effects modest reductions of total and LDL cholesterol.

    “Despite some conflicting data, in most studies testosterone effects modest reductions of total and LDL cholesterol.22-24”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [22] source

      Not checked in the free run.

    • cites [23] 1998, Horm Metab Res source

      Not checked in the free run.

    • cites [24] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Potentially beneficial reductions in total cholesterol and reductions of TNFa were seen on testosterone treatment.

    “Finally, potentially beneficial reductions in total cholesterol and reductions of TNFa were seen on testosterone treatment.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Testosterone therapy is reported to improve insulin resistance and components of the metabolic syndrome in obese men and in men with low testosterone.

    “Testosterone therapy is reported to improve insulin resistance and components of the metabolic syndrome in obese men 26 and in men with low testosterone.27”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] 1992, Eur J Med

      Not checked in the free run.

    • cites [27] 2001, Diabetes Care

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Atherosclerosis is acknowledged to be a disease of chronic inflammation.

    “Atherosclerosis is acknowledged to be a disease of chronic inflammation.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Case reports and randomised controlled trials of androgen therapy in inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus have found androgens improve clinical status and reduce inflammatory markers.

    “There are several case reports and randomised controlled trials of androgen therapy in patients with inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus in which androgens have been found to improve clinical status and reduce inflammatory markers.[33][34][35]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [33] source

      Not checked in the free run.

    • cites [34] source

      Not checked in the free run.

    • cites [35] source

      Not checked in the free run.

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

    Premisecitation

    A recent meta-analysis supported findings that testosterone effects modest reductions of total and LDL cholesterol.

    “A recent meta-analysis supported these findings.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] source

      Not checked in the free run.

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

    Premisecitation

    In live mice, gonadectomy and injection of bacterial endotoxin resulted in increased TNF production, which was reduced by hormone replacement.

    “In live mice, gonadectomy and injection of bacterial endotoxin resulted in increased TNF production, which was reduced by hormone replacement.40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] source

      Not checked in the free run.

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

    Premisecitation

    The reduced frequency of autoimmune disease in men compared with women has been attributed to the antiinflammatory effect of androgens compared with oestrogens.

    “The reduced frequency of autoimmune disease in men compared with women has been attributed to the antiinflammatory effect of androgens compared with oestrogens.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] source

      Not checked in the free run.

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

    Premisecitation

    TNFa is both a marker and a mediator of atherosclerotic plaque development and complications.

    “TNFa is both a marker and a mediator of atherosclerotic plaque development and complications.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    TNFa is a pro-inflammatory cytokine and is increased in infective and inflammatory diseases.

    “TNFa is a pro-inflammatory cytokine and is increased in infective and inflammatory diseases.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    There is considerable evidence from laboratory and clinical studies that testosterone has immune modulating effects.

    “there is considerable evidence from laboratory and clinical studies that testosterone has immune modulating effects.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Serum TNFa is greatly increased during acute coronary syndromes but is also increased to a lesser degree in stable chronic angina and is a marker of future events.

    “Serum TNFa is greatly increased during acute coronary syndromes but is also increased to a lesser degree in stable chronic angina and is a marker of future events.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the past 30 years, at least six studies of various design have reported effects of androgen therapy on coronary ischaemia; all but one reported a beneficial effect.

    “In the past 30 years, at least six studies of various design have reported the effects of androgen therapy on coronary ischaemia 14-16 44-46 ; all but one have reported a beneficial effect.46”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [14] source

      Not checked in the free run.

    • cites [15] source

      Not checked in the free run.

    • cites [16] source

      Not checked in the free run.

51 of 51

  • The paper relies on this without support.

    The British National Formulary advises caution if considering prescription of testosterone therapy to men with known cardiac disease.

    “Indeed, the British National Formulary advises caution if considering prescription of testosterone therapy to men with known cardiac disease.”

  • The authors state this as an assumption.

    Testosterone's anti-ischaemic action is based on its vasodilator effect.

    “Testosterone has been shown in numerous studies to be a vasodilator [11][12][13] and we presume this to be the basis of its anti-ischaemic action.”
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?

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. 2003, J Am Coll Cardiol, 41, 344
  2. 1992, Eur J Med, 1, 329
  3. 2001, Diabetes Care, 24, 149
  4. 1993, Chin Med J (Engl), 106, 415

Cited by

Sorted by citations

Related

Authors
Malkin, C. J., Pugh, P. J., Morris, P. D., Kerry, K. E., Jones, R. D., Jones, T. H., & Channer, K. S.
Affiliations
  • Royal Hallamshire Hospital (GB)
  • University of Sheffield (GB)
Corresponding author
Channer, K S
Venue
Heart
Publisher
BMJ
Published
2004-07-14
Volume
90
Issue
8
Pages
871-876
ISSN
  • 1355-6037 (ISSN-L)
  • 1468-201X
DOI
10.1136/hrt.2003.021121
PMC
PMC1768369
OpenAlex
W2148126950
Semantic Scholar
1ea556e9c5adb18c1d91f34298ee576e96e5e8cf
Cited by
250
References
51
Citations by year
2026: 1 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 15 · 2014: 15 · 2013: 12 · 2012: 19
FWCI
7.88
Type
journal article
Language
en
Open access
Locations
  • Heart (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
Keywords
testosterone replacement therapy, hypogonadism, angina pectoris, coronary artery disease, quality of life, mood, total cholesterol, TNF-α, exercise-induced ST-segment depression
MeSH terms
Androgens, Angina Pectoris, Exercise Test, Humans, Hypogonadism, Injections, Intramuscular, Male, Middle Aged, Myocardial Infarction, Testosterone, Exercise, Single-Blind Method, Treatment Outcome, Myocardial Ischemia, Cross-Over Studies, Hormone Replacement Therapy, Coronary Stenosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review