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Cited by 232Hormonal and reproductive studiesAdrenal Hormones and DisordersMenopause: Health Impacts and Treatments

Onset of effects of testosterone treatment and time span until maximum effects are achieved

Open access
Saad, Farid, Aversa, Antonio, Isidori, Andrea M, Zafalon, Livia, Zitzmann, Michael, Gooren, Louis·2011·European Journal of Endocrinology
DOI 10.1530/eje-11-0221PMC PMC3188848
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Abstract

Objective: Testosterone has a spectrum of effects on the male organism. This review attempts to determine, from published studies, the time-course of the effects induced by testosterone replacement therapy from their first manifestation until maximum effects are attained. Design: Literature data on testosterone replacement. Results: Effects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond. Changes in erections/ejaculations may require up to 6 months. Effects on quality of life manifest within 3–4 weeks, but maximum benefits take longer. Effects on depressive mood become detectable after 3–6 weeks with a maximum after 18–30 weeks. Effects on erythropoiesis are evident at 3 months, peaking at 9–12 months. Prostate-specific antigen and volume rise, marginally, plateauing at 12 months; further increase should be related to aging rather than therapy. Effects on lipids appear after 4 weeks, maximal after 6–12 months. Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3–12 months. Changes in fat mass, lean body mass, and muscle strength occur within 12–16 weeks, stabilize at 6–12 months, but can marginally continue over years. Effects on inflammation occur within 3–12 weeks. Effects on bone are detectable already after 6 months while continuing at least for 3 years. Conclusion: The time-course of the spectrum of effects of testosterone shows considerable variation, probably related to pharmacodynamics of the testosterone preparation. Genomic and non-genomic effects, androgen receptor polymorphism and intracellular steroid metabolism further contribute to such diversity.

AI snapshot

Written from the paper’s full text.

TL;DR

This review charts the published time-course of testosterone replacement effects in hypogonadal men, from first manifestation to maximum effect. It finds considerable variation across outcomes, probably related to testosterone preparation pharmacodynamics, genomic and non-genomic effects, androgen receptor polymorphism, and intracellular steroid metabolism.

Key findings

  • Sexual interest/libido appears after 3 weeks and plateaus at 6 weeks; erections/ejaculations may require up to 6 months; depressive mood becomes detectable after 3–6 weeks with a maximum after 18–30 weeks.
  • Erythropoiesis is evident at 3 months and peaks at 9–12 months; PSA and prostate volume rise marginally and plateau at 12 months; lipid effects appear after 4 weeks and are maximal after 6–12 months.
  • Insulin sensitivity may improve within days, but glycemic control effects become evident only after 3–12 months; fat mass, lean body mass, and muscle strength change within 12–16 weeks, stabilize at 6–12 months, and can marginally continue over years; bone effects are detectable after 6 months and continue at least 3 years.
  • Effects on inflammation occur within 3–12 weeks.

Methods

  • Literature review of testosterone replacement data, searching MEDLINE, the Cochrane Library, EMBASE, and Current Contents for 1976–2011, plus bibliographies and references of retrieved/review articles.
  • Inclusion criteria: one active treatment group compared with matched placebo/control, description of the time-course of active treatment, randomization, protocol adherence, and single/double blinding; only peer-reviewed medical journal articles, no abstracts.
  • Main analysis: qualitative synthesis of onset and maximum-effect time points across target systems, summarized in figures.

Limitations

  • The paper states that almost none of the quoted studies were specifically designed to assess the time-course of effects; some studies measured effects only after 3 months, particularly missing earlier libido and erection effects.
  • The paper states that sub-optimal therapeutic regimens or inappropriate patient selection (eugonadal men or men with biochemical but not clinical hypogonadism) may show a different time-course, and the analysis was restricted to testosterone treatment, excluding androgen deprivation therapy.
  • Evident from the text: as a narrative review without meta-analysis, time-course estimates depend on heterogeneous studies, preparations, doses, and follow-up schedules, and no formal quantitative pooling or risk-of-bias assessment is reported.

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

Integrity signals

Registry

Crossref · 10.1530/eje-11-0221

Cites

104 of 104 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 183 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Changes in erections and ejaculations may require up to 6 months.

    “Changes in erections/ejaculations may require up to 6 months.”
    • Also stated in: § Effects on erection/ejaculation · hedged
      “Maximal effects are usually achieved after 3–6 months (72) but may take even up to 1 year in individual cases (71).”
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  • Findingcitation

    Effects of testosterone on glycemic control become evident only after 3-12 months.

    “Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3–12 months.”
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  • Findingcitation

    Insulin sensitivity may improve within a few days of testosterone administration.

    “Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3–12 months.”
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      “And indeed, in an experimental study, stimulation of endogenous testosterone was shown to increase insulin sensitivity within 48 h (49).”
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  • Findingcitation

    Effects of testosterone on inflammation occur within 3-12 weeks.

    “Effects on inflammation occur within 3–12 weeks.”
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  • Findingcitation

    Changes in fat mass, lean body mass, and muscle strength occur within 12-16 weeks of testosterone treatment.

    “Changes in fat mass, lean body mass, and muscle strength occur within 12–16 weeks, stabilize at 6–12 months, but can marginally continue over years.”
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    Findingcitation

    Effects of testosterone on sexual interest appear after 3 weeks and plateau at 6 weeks, with no further increments expected beyond that.

    “Effects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond.”
    • Also stated in: § Effects on libido · plain
      “Effects on libido, sexual desire, sexual thoughts and fantasies and satisfaction with sexual life manifest themselves rather rapidly: after 3 weeks (68) or 30 days (14).”
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    Findingcitation

    Effects of testosterone on quality of life manifest within 3-4 weeks, but maximum benefits take longer.

    “Effects on quality of life manifest within 3–4 weeks, but maximum benefits take longer.”
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    Findingcitation

    Effects of testosterone on depressive mood become detectable after 3-6 weeks, with a maximum after 18-30 weeks.

    “Effects on depressive mood become detectable after 3–6 weeks with a maximum after 18–30 weeks.”
    • Also stated in: § Time-course of effects on psychological variables · hedged
      “It is very likely that the positive effects of testosterone on depressive symptoms start as early as after 3–6 weeks, but will most likely take 18–30 weeks to find the patient with a significant improvement.”
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    Findingcitation

    Prostate-specific antigen and prostate volume rise marginally and plateau at 12 months during testosterone treatment.

    “Prostate-specific antigen and volume rise, marginally, plateauing at 12 months; further increase should be related to aging rather than therapy.”
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    Findingcitation

    Effects of testosterone on erythropoiesis are evident at 3 months and peak at 9-12 months.

    “Effects on erythropoiesis are evident at 3 months, peaking at 9–12 months.”
    • Also stated in: § Time-course of effects on erythropoiesis · plain
      “The effects are apparent after 3 months (14, 35, 40) and a maximum is reached after 9–12 months (35).”
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    Findingcitation

    Effects of testosterone on lipids appear after 4 weeks and are maximal after 6-12 months.

    “Effects on lipids appear after 4 weeks, maximal after 6–12 months.”
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    Findingcitation

    Effects of testosterone on bone are detectable already after 6 months and continue at least for 3 years.

    “Effects on bone are detectable already after 6 months while continuing at least for 3 years.”
    • Also stated in: § Time-course of effects on bone mineral density · hedged
      “From studies analyzing the effects of testosterone administration over as long as 36 months (25, 26) an increase was observed over that time period and it did not become clear whether the maximum effects of testosterone improving bone mineral have been attained after 36 months.”
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    Findingcitation

    Testosterone treatment decreases trunk fat or waist circumference after 3 months, with continuous decline over 24 months.

    “A decrease in trunk fat or waist circumference was noted in a number of studies after 3 months (35, 36) with continuous decline over 24 months (32)”
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    Findingcitation

    In studies of testosterone administration up to 36 months, bone mineral density increases over that period, and it is unclear whether maximum effects are attained after 36 months.

    “From studies analyzing the effects of testosterone administration over as long as 36 months (25, 26) an increase was observed over that time period and it did not become clear whether the maximum effects of testosterone improving bone mineral have been attained after 36 months.”
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    Findingcitation

    Upon testosterone administration, fat mass decreases and lean body mass increases, with total body weight often but not always showing no major changes.

    “Upon testosterone administration there is a decrease in fat mass and an increase in lean body mass and the net result is often, but not always, that total body weight does not show major changes.”
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    Findingcitation

    Effects of testosterone on muscle strength are demonstrable after 12-20 weeks, and maximum effects are attained after 6 or 12 months depending on the achieved testosterone levels.

    “It can be concluded that the effects of testosterone on muscle strength are demonstrable after 12–20 weeks and that depending on the achieved testosterone levels, the maximum effects are attained after 6 or 12 months.”
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    Findingcitation

    Serum triglycerides decrease after 4 weeks and after 3 months of testosterone treatment, with further decrease over 9 or 12 months.

    “The decrease in serum triglycerides follows a similar pattern: after 4 weeks (38), after 3 months (35), and with further decrease over 9 months (41) or 12 months (43).”
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    Findingcitation

    Low-density lipoprotein cholesterol decreases after 3 months, after 40-44 weeks, or after 12 months of testosterone treatment, with a maximum observed after 24 months.

    “The decrease in low-density lipoprotein cholesterol seems somewhat slower: after 3 months (35), after 40–44 weeks, (44) or after 12 months (42) with a maximum observed after 24 months (32).”
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    Findingcitation

    Serum total cholesterol decreases as quickly as after 4 weeks of testosterone treatment, but most studies report a decrease after 3 months.

    “Decreases in serum total cholesterol have been noted as quick as after 4 weeks (38, 39) but most studies have reported a decrease after 3 months (35, 36).”
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    Findingcitation

    Body mass index declines after 6 months of testosterone treatment, with further improvement during an observation period of 2 years.

    “Body mass index as a widely used measure of body composition declined after 6 months with further improvement during an observation period of 2 years (32).”
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    Findingcitation

    Testosterone treatment decreases waist hip ratio after 3 months or after 6 months and 30 weeks.

    “and a decrease in the waist hip ratio after 3 months (31, 36) or after 6 months and 30 weeks respectively (17).”
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    Findingcitation

    High-density lipoprotein cholesterol increases after 3 months, increasing further during 12 months, after 6 months, or close to 1 year, with continuous increase over 24 months.

    “An increase was found to occur after 3 months increasing further during 12 months (43), after 6 months, (35) or close to 1 year (44). Continuous increase was observed over 24 months (32).”
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    Findingcitation

    In men with baseline glucose >110 ng/ml (6.6 mmol/l), serum glucose is reduced after 24 weeks of testosterone treatment, but not significantly in men with baseline glucose <110 ng/ml.

    “In a recent study, this was observed after 24 weeks only in men with baseline glucose >110 ng/ml (6.6 mmol/l) but not significantly in men whose baseline glucose levels were <110 ng/ml (6.6 mmol/l) (40).”
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    Findingcitation

    Serum proinsulin and insulin decrease after 3 or 6 months of testosterone treatment, and HOMA-IR decreases after 3 or 6 months.

    “A decrease in serum proinsulin and insulin was noted after 3 months (43) or 6 months (45), and a decrease in homeostasis model assessment index of insulin resistance (HOMA-IR) after 3 months (36) or 6 months (45–47).”
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    Findingcitation

    HbA1c declines after 3 months of testosterone treatment, with further decrease after 12 months.

    “A decline in HbA1c was observed after 3 months (31, 36, 43) with further decrease after 12 months (43).”
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    Findingcitation

    The interplay between insulin sensitivity, triglyceride levels, and androgens occurs within a week and is not facilitated by changes in body composition alone.

    “Recently, it has been demonstrated that the interplay between insulin sensitivity, triglyceride levels, and androgens is practically immediate, as it occurs within a week, and is not facilitated by changes in body composition alone.”
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    Findingcitation

    Arterial stiffness measured as pulse wave velocity decreases after 48 h, and large artery compliance improves after 3 months of testosterone treatment.

    “A decrease in arterial stiffness measured as pulse wave velocity was measurable after 48 h (58) and in large artery compliance after 3 months (58).”
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    Findingcitation

    In men with chronic heart failure, exercise capacity increases after 12 weeks of testosterone treatment, while cardiac index increases after 180 min.

    “Exercise capacity in men with chronic heart failure increased after 12 weeks (60), whereas the cardiac index (cardiac output related to body surface) had already increased after 180 min.”
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    Findingcitation

    Testosterone administration decreases C-reactive protein after 3 weeks and after 3 months.

    “A decrease in C-reactive protein (CRP) was observed after 3 weeks (63) and in other studies after 3 months (32, 43).”
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    Findingcitation

    Testosterone administration decreases IL6 after 3 weeks and after 16 weeks.

    “Already after 3 weeks of testosterone administration, a decline was noted in IL6 (63) and in another study after 16 weeks (64).”
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    Findingcitation

    Diastolic blood pressure declines after 3-9 months of testosterone treatment, and in some studies systolic blood pressure also declines.

    “In some studies a decline in diastolic blood pressure has been observed, after 3–9 months (22, 35, 41, 44) and in some studies in systolic blood pressure also (35, 44).”
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    Findingcitation

    Asymmetric dimethylarginine declines upon testosterone administration after 10 days or after 4 weeks.

    “Asymmetric dimethylarginine is an endogenous NO synthase inhibitor and appears to decline upon testosterone administration after 10 days (66) or after 4 weeks (67).”
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    Findingcitation

    The percentage of full erections, sexual performance, and satisfaction with erections increase after 30 days of testosterone treatment.

    “An increase in percentage of full erections and sexual performance and satisfaction with erections was noticed after 30 days (14, 69)”
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    Findingcitation

    Ejaculations increase after 2 weeks and sexual activity after 3 weeks of testosterone treatment.

    “an increase of ejaculations and sexual activity after 2 weeks (70) and 3 weeks respectively (68).”
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    Findingcitation

    Increases in IIEF erectile function occur after 3 months, while increases in IIEF sexual desire, intercourse satisfaction, and overall satisfaction appear after 6 weeks.

    “Increases in the IIEF erectile function have been noted after 3 months (35, 40) but increases in IIEF sexual desire, intercourse satisfaction, and overall satisfaction appear already after 6 weeks (40).”
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    Findingcitation

    Maximal effects of testosterone on erection and ejaculation are usually achieved after 3-6 months but may take up to 1 year in individual cases.

    “Maximal effects are usually achieved after 3–6 months (72) but may take even up to 1 year in individual cases (71).”
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    Findingcitation

    Increase in motivation occurs after 30 days of testosterone treatment and is maintained thereafter.

    “There was also an increase in motivation after 30 days which was maintained thereafter (14).”
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    Findingcitation

    Increase in good mood and decrease in bad mood occur after 3 weeks or 30 days of testosterone treatment.

    “Increase in good mood and a decrease in bad mood were noted after 3 weeks (68) or after 30 days (14).”
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    Findingcitation

    Improvements on AMS scores are noted after 1 month, 6 weeks to 3 months, or after 9 months, continuing over a total of 18 months.

    “Improvements on scores on the AMS have been noted after 1 month (38), 6 weeks (40) to 3 months on treatment with parenteral testosterone undecanoate (35) or after 9 months on testosterone gel (74) continuing over a total of 18 months (74).”
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    Findingcitation

    In severely depressed men, effects of testosterone replacement therapy by gel versus placebo are observed within 6 weeks, but the effect is not consistent within the whole group.

    “In a larger set of severely depressed men (n=2×50), effects of testosterone replacement therapy (TRT) by gel versus placebo were observed within 6 weeks. The effect was not consistent within the whole group of patients.”
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    Findingcitation

    Increase in sociability, decrease in anxiety, increase in concentration, and increase in self-confidence are apparent after 3 weeks of testosterone treatment.

    “A number of psychological variables (increase in sociability, decrease in anxiety, increase in concentration, and self-confidence) were apparent after 3 weeks (68).”
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    Findingcitation

    A rise in prostate-specific antigen levels is noticed after 6 months of testosterone treatment, with no significant further increase over the following 24 months.

    “A rise in PSA levels was noticed after 6 months, whereafter over the following 24 months there was no significant further increase (85).”
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    Findingcitation

    A rise in prostate-specific antigen levels is found after 3 months in some studies and only after 12 months in others.

    “Other studies have found a rise of PSA levels after 3 months (40), some only after 12 months (43).”
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    Findingcitation

    Aging itself is a factor in the rise of prostate volume and prostate-specific antigen, and there is no endpoint in the effects of testosterone on the prostate.

    “Upon judging the time-course of effects of testosterone on the prostate, it is of note that aging itself is a factor in the rise of both prostate volume and PSA (84), and there is no endpoint in the effects of testosterone on the prostate.”
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    Findingcitation

    Positive effects of testosterone on depressive symptoms start as early as after 3-6 weeks, but most likely take 18-30 weeks to find a patient with significant improvement.

    “It is very likely that the positive effects of testosterone on depressive symptoms start as early as after 3–6 weeks, but will most likely take 18–30 weeks to find the patient with a significant improvement.”
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    Findingcitation

    In hypogonadal men receiving testosterone plus an aromatase inhibitor, spatial working memory improves within 3 weeks and improves further until week six.

    “These patients exhibited a markedly improved spatial working memory within 3 weeks, improving further until week six (81).”
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    Findingreasoning

    Effects of testosterone on libido and other psychological variables and effects on vasculature occur rather rapidly.

    “Effects on libido and other psychological variables and effects on vasculature occur rather rapidly.”
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    Findingcitation

    Testosterone treatment reduces waist circumference, which appears to be a valid parameter of the degree of visceral obesity.

    “Several studies have indeed confirmed that testosterone treatment reduces waist circumference which, in its simplicity, appears to be a valid parameter of the degree of visceral obesity (91).”
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    Findingown data

    In the authors' own studies, signs and symptoms of the metabolic syndrome improved substantially following administration of long-acting testosterone undecanoate, and improvements in glycemic control and lipids parallel improvements in body composition.

    “In our own studies, signs and symptoms of the metabolic syndrome improved substantially following administration of long-acting testosterone undecanoate (32, 35, 92) and improvements in glycemic control and lipids parallel improvements in body composition.”
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    Findingcitation

    Prostate volume increases after 3 months and after 12 months of testosterone treatment.

    “An increase in prostate volume was noted after 3 months (86) and after 12 months (44).”
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    Findingcitation

    In a study of 123 subjects over 42 months of testosterone gel application, serum prostate-specific antigen significantly increases over the first 6 months and then shows no further significant increases with continued testosterone treatment.

    “In a study of 123 subjects over 42 months of testosterone gel application, there was significant increase in serum PSA over the first 6 months and then no further significant increases with continued testosterone treatment was found (87).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [87] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Upon testosterone administration, there is a positive correlation between blood testosterone concentrations and leg press strength, thigh and quadriceps muscle volume, and levels of hemoglobin and IGF1.

    “In a series of studies, Bhasin et al. (8) have demonstrated that upon testosterone administration, there is a positive correlation between blood testosterone concentrations and leg press strength, thigh, and quadriceps muscle volume, and, further, levels of hemoglobin and IGF1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A 12-week long-acting testosterone administration increases quadriceps isometric strength, maximal voluntary contraction, and isokinetic strength.

    “A study investigating the effect of a 12-week long-acting testosterone administration on maximal exercise capacity and muscle strength found an increase in quadriceps isometric strength, maximal voluntary contraction, and isokinetic strength (peak torque) (12).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] source

      Not checked in the free run.

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

    Premisecitation

    The anabolic response to testosterone can largely be predicted by the dose administered.

    “In a later study, the same group of authors concluded that the anabolic response to testosterone can largely be predicted by the dose administered (9).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Combining testosterone with GH increases total lean body mass and appendicular lean tissue, and composite maximum voluntary strength of upper and lower body muscles increases after 16 weeks.

    “In a study that combined testosterone with GH, total lean body mass increased, as did appendicular lean tissue. Composite maximum voluntary strength of upper and lower body muscles had increased after 16 weeks (11).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Testosterone improves bone mineral density at the lumbar spine compared with placebo, but at the femoral neck improvements are less certain.

    “Testosterone improves bone mineral density at the lumbar spine compared with placebo, but at the femoral neck improvements are less certain (19).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 180 days of treatment with a 1% testosterone gel preparation (50 or 100 mg/day), mean leg press muscle strength increases by 90 days and does not improve further at 180 days.

    “In a study of 180 days of treatment with a 1% testosterone gel preparation (50 or 100 mg/day, contained in 5 or 10 g gel), mean muscle strength in the leg press exercise increased by 90 days and had not improved further at 180 days (14).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Testosterone enanthate 200 mg/2 weeks produces major effects over the first 12 months of administration, with minor increases thereafter.

    “A study administering testosterone enanthate, 200 mg/2 weeks observed major effects to occur over the first 12 months of testosterone administration, thereafter minor increases could be observed (17).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Testosterone treatment for 6 months increases lean body mass and improves lower limb muscle strength.

    “A study similar in design found an increase in lean body mass and an improvement of lower limb muscle strength after 6 months (15).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The metabolic observations of testosterone are most likely attributed to testosterone-induced changes in lipid metabolism and/or altered postreceptor insulin signaling in muscle.

    “Such observations are most likely attributed to testosterone-induced changes in lipid metabolism and/or altered postreceptor insulin signaling in muscle (54) and also improved insulin sensitivity enhancing muscle lipid uptake (55).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [54] source

      Not checked in the free run.

    • cites [55] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Effects of testosterone on muscle and bone involve protein synthesis and are a result of genomic actions of testosterone and therefore rather slow.

    “The effects of testosterone on muscle and bone involve protein synthesis and are a result of genomic actions of testosterone and, therefore, rather slow.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Effects of testosterone on erection occur rather rapidly and may be partially explained by non-genomic effects on vascular penile erectile tissue.

    “Also effects on erection occur rather rapidly and may be partially explained by non-genomic effects on vascular penile erectile tissue (89).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] source

      Not checked in the free run.

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

    Premisenone given

    Earlier studies have shown that there are thresholds for the various actions of testosterone, such that signs and symptoms of testosterone deficiency appear at different threshold values of circulating testosterone.

    “Earlier studies have shown that there are thresholds for the various actions testosterone: in other words signs and symptoms of testosterone deficiency appear at different threshold values of circulating testosterone.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    There is a degree of consensus that elderly men with serum testosterone clearly below the reference ranges and persistent clear clinical signs of hypogonadism may justifiably be treated.

    “There is a degree of consensus that elderly men with serum testosterone clearly below the reference ranges and persistent clear clinical signs of hypogonadism may justifiably be treated (98, 99)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [98] source

      Not checked in the free run.

    • cites [99] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A verdict on treating elderly men with lower than normal testosterone levels can only be reached with large-scale studies including 5000 men over 5 years.

    “a verdict can only be reached with large-scale studies including 5000 men over 5 years (95)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [95] source

      Not checked in the free run.

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

    Premisecitation

    Small-scale studies show benefits and acceptable risks of treating elderly men with lower than normal testosterone levels.

    “Though small-scale studies show benefits and acceptable risks of treating elderly men with lower than normal testosterone levels (46, 97)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46] source

      Not checked in the free run.

    • cites [97] source

      Not checked in the free run.

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

    Premisecitation

    Some biological functions, such as erectile function, are composite in nature, and in addition to testosterone, endothelial function and psychological factors are equally relevant.

    “Some biological functions, like erectile functions are composite in nature, and next to testosterone, endothelial function and psychological factors are equally relevant (2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] source

      Not checked in the free run.

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

    Premisecitation

    It is still hotly debated whether late-onset hypogonadism is a true form of hypogonadism or a decline of serum testosterone associated with the progressive accumulation of health problems with aging, rather independently of the process of aging itself.

    “It is still hotly debated whether this is a true form of hypogonadism, or a decline of serum testosterone associated with the progressive accumulation of health problems with aging (95, 96), but rather independently of the process of aging itself.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [95] source

      Not checked in the free run.

    • cites [96] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    In the present analysis, an attempt was made to select studies of testosterone treatment that provided adequate doses/delivery of testosterone.

    “Finally, in the present analysis it was attempted to select those studies of testosterone treatment that provided adequate doses/delivery of testosterone.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Sub-optimal therapeutic regimens or inappropriate patient selection (eugonadal or men with biochemical but not clinical hypogonadism) may show different time-course of effects.
64 of 64

  • The paper relies on this without support.

    The available controlled studies, despite not being specifically designed to assess onset or time-dependency, allow a reasonable estimation of the time-course of testosterone effects.

    “Nearly all of these studies were not specifically designed to address the onset or time-dependency of effects of testosterone, nevertheless a number of controlled studies with different design and scheduled follow-up, allow a reasonable estimation.”

  • The paper relies on this without support.

    The time-course of the diverse actions of testosterone can be compiled across studies of testosterone administration to hypogonadal men and studies on androgen deprivation.

    “Data to compile a time-course for the diverse actions of testosterone are not easily available. They originate from studies analyzing the effects of testosterone administration to hypogonadal men or, alternatively, from studies on androgen deprivation. The main source of information will be the former category.”

  • The paper relies on this without support.

    Deprivation of testosterone and its time-dependent effects might be totally different from the onset of testosterone action in testosterone treatment, even in the same parameter.

    “However, deprivation of testosterone and the time-dependent effects thereof might be totally different from the onset of testosterone action in testosterone treatment, even in the same parameter.”

  • The paper relies on this without support.

    Sub-optimal therapeutic regimens or inappropriate patient selection (eugonadal or men with biochemical but not clinical hypogonadism) may show different time-course of effects.

    “It is obvious that sub-optimal therapeutic regimens or, alternatively, inappropriate patient selection (eugonadal or men with biochemical but not clinical hypogonadism) may show different time-course of effects.”
4 of 4

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?

  • Obesity-related male hypogonadism is considered a form of hypogonadotropic hypogonadism.

    “Based on these and other studies (53,54), obesity-related male hypogonadism is now considered as a form of hypogonadotropic hypogonadism (see for a review, references (55,56)).”

    From Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis (2013) · cites this paper as [56]

    The Discussion addresses testosterone treatment, visceral obesity and metabolic syndrome, but does not classify obesity-related male hypogonadism as hypogonadotropic. Searches for that classification and for “hypogonadotropic” found the term only in titles in the References, not a passage making the claimed connection; page numbers were unavailable in our copy. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • High BMI seems to repress serum testosterone mainly via central inhibitory effects on gonadotropin secretion.

    “Thus high BMI seems to repress serum T mainly via central inhibitory effects on gonadotropin secretion [38, 41].”

    From Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis (2017) · cites this paper as [41]

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. 1996, 18, 171
  2. 1996, 121, 35
  3. 2007, ENDOCRINE PRACTICE, 16, 629
  4. 2007, 133, 1796
  5. 2002, Clinical Psychology: Science and Practice, 63, 1096

Cited by

Sorted by citations

Related

Authors
Saad, F., Aversa, A., Isidori, A. M., Zafalon, L., Zitzmann, M., & Gooren, L.
Affiliations
  • Gulf Medical University (AE)
  • Sapienza University of Rome (IT)
  • University of Münster (DE)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Corresponding author
Saad, Farid
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2011-11
Volume
165
Issue
5
Pages
675-685
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-11-0221
PMC
PMC3188848
OpenAlex
W2123994640
Semantic Scholar
d5b89a0b7567a3389c8a0477c9569f998d47f246
Cited by
232
References
104
Citations by year
2026: 11 · 2025: 11 · 2024: 12 · 2023: 14 · 2022: 12 · 2021: 18 · 2020: 17 · 2019: 11 · 2018: 12 · 2017: 15 · 2016: 14 · 2015: 23 · 2014: 23 · 2013: 19 · 2012: 17
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
www.bioscientifica.com/journals/reuselicenceeje/ (unspecified)
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
Eli Lilly and Company
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
testosterone replacement therapy, time course of treatment effects, sexual interest, erectile function, quality of life, depressive mood, erythropoiesis, prostate-specific antigen, lipid metabolism, insulin sensitivity, glycemic control, body composition, muscle strength, inflammation, bone metabolism, androgen receptor polymorphism, pharmacodynamics
MeSH terms
Animals, Humans, Male, Testosterone, Time Factors, Treatment Outcome, Hormone Replacement Therapy

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.

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