CoChat
Sign Up
Cited by 101Hormonal and reproductive studiesHypothalamic control of reproductive hormonesGrowth Hormone and Insulin-like Growth Factors

Effects of liraglutide on obesity-associated functional hypogonadism in men

Open access
Jensterle, M, Podbregar, A, Goricar, K, Gregoric, N, Janez, A·2019·Endocrine Connections
DOI 10.1530/ec-18-0514PMC PMC6391904
Open this paper in CoChat — free account

Abstract

Lifestyle measures (LSMs) should be the first-line approach offered for obesity-related functional hypogonadism (FH). When LSMs fail, the role of testosterone replacement treatment (TRT) is unclear. GLP1 receptor agonist liraglutide is linked to progressive and sustained weight loss. A potential direct impact of GLP1 on hypothalamus-pituitary-testicular (HPT) axis was reported in animal models. We aimed to compare the effects of liraglutide and TRT on FH in obese men that had been poor responders to LSM, by means of reversal of FH and weight reduction. We designed a 16-week prospective randomized open-label study with 30 men (aged 46.5 ± 10.9 years, BMI 41.2 ± 8.4 kg/m 2 , mean ± s.d. ) that were randomized to liraglutide 3.0 mg QD (LIRA) or 50 mg of 1% transdermal gel QD (TRT). Sexual function and anthropometric measures were assessed. Fasting blood was drawn for determination of endocrine and metabolic parameters followed by OGTT. Model-derived parameters including HOMA IR and calculated free testosterone (cFT) were calculated. Total testosterone significantly increased in both arms (+5.9 ± 7.2 in TRT vs +2.6 ± 3.5 nmol/L in LIRA) and led to improved sexual function. LIRA resulted in a significant increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) ( P < 0.001 for between-treatment effect). Subjects treated with LIRA lost on average 7.9 ± 3.8 kg compared with a 0.9 ± 4.5 kg loss in TRT ( P < 0.001). Metabolic syndrome was resolved in two patients in LIRA and in no subjects in TRT. Liraglutide was superior to TRT in improving an overall health benefit in men with obesity-associated FH after LSM failed.

AI snapshot

Written from the paper’s full text.

TL;DR

In a 16-week randomized open-label pilot of 30 obese men with functional hypogonadism who had failed lifestyle measures, liraglutide 3.0 mg/day and transdermal testosterone both raised total testosterone and improved sexual function, but liraglutide produced greater weight loss and increased LH/FSH whereas testosterone suppressed gonadotropins. Liraglutide was concluded to be superior to testosterone replacement for overall health benefit in this population.

Key findings

  • Total testosterone increased in both arms: +5.9 ± 7.2 nmol/L with testosterone replacement (TRT) vs +2.6 ± 3.5 nmol/L with liraglutide (LIRA), with no significant between-group difference (P = 0.239). Sexual function improved in both arms, with no significant between-treatment differences for libido (P = 0.762), morning erections (P = 0.550), or ejaculations (P = 0.204).
  • Gonadotropins diverged significantly: LIRA increased LH (+0.7 ± 1.2 IU/L) and FSH (+0.9 ± 1.8 mIU/L), while TRT suppressed LH (−2 ± 1.3 IU/L) and FSH (−3.2 ± 1.7 mIU/L); between-treatment P < 0.001 for both.
  • LIRA produced greater weight loss than TRT: abstract reports 7.9 ± 3.8 kg vs 0.9 ± 4.5 kg (P < 0.001); Table 2 reports −8 ± 4 kg vs −1 ± 5 kg (P < 0.001). BMI change was −2.6 ± 1.3 vs −0.3 ± 1.4 kg/m² (P < 0.001), and waist circumference change was −5 ± 5 vs −2 ± 4 cm (P = 0.035).
  • Metabolic syndrome resolved in 2 patients in LIRA and 0 in TRT. HbA1c decreased significantly in LIRA, with a significant between-treatment difference favoring LIRA (P = 0.004); HOMAIR decreased significantly in TRT (P = 0.033) but not in LIRA (P = 0.754).

Methods

  • 16-week prospective randomized open-label pilot study of 30 middle-aged obese men with functional hypogonadism who had been poor responders to lifestyle measures; participants were randomized to liraglutide 3.0 mg QD s.c. (LIRA, N = 15) or 50 mg of 1% transdermal testosterone gel QD (TRT, N = 15), with lifestyle measures actively promoted in both groups.
  • Assessments at baseline and study end included sexual function self-reports (morning erections, ejaculations, libido scored 1–3), the Aging Male Syndrome (AMS) scale, endocrine parameters (total testosterone, SHBG, LH, FSH, calculated free and bioavailable testosterone), anthropometric measures, and metabolic parameters including OGTT, HOMAIR, HbA1c, and lipids.
  • Statistical analysis used Wilcoxon signed-rank tests for related samples and Mann–Whitney tests for independent groups, with P < 0.05 considered significant.

Limitations

  • The authors state that conclusions are limited by a small sample size and short-term observation, and that libido and sexual function were not measured with validated tools.
  • The authors note that 11 of 30 subjects had type 2 diabetes, which could independently affect the HPT axis, although diabetes presence was balanced between groups and well controlled.
  • Evident from the text: the study was open-label and did not include a placebo arm, so expectancy effects cannot be excluded; it was also a pilot study, limiting generalizability.

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

Integrity signals

Registry

Crossref · 10.1530/ec-18-0514

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 51 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Libido significantly improved in both the testosterone replacement and liraglutide arms.

    “Libido and sexual functions were significantly improved in both arms.”
    • Also stated in: § Symptoms and signs of FH · plain
      “In TRT arm, libido as reported by self-measurement increased from 1.0 ± 0.0 to 2.2 ± 0.7 scores (P = 0.003). In LIRA, libido increased from 1.1 ± 0.3 to 1.8 ± 0.6 scores (P = 0.003).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The aging male syndrome score significantly improved in the testosterone replacement arm.

    “AMS score was significantly improved in TRT (Table 1).”
    • Also stated in: § Results · plain
      “| AMS | 40.6 ± 9.9 | 31.5 ± 5.7 | 0.002 | 43.4 ± 12.4 | 37.6 ± 12.3 [1] | 0.157 | 0.616 |”
    Quote in the paperNot a substantial claim
  • Findingown data

    After 16 weeks, all patients with impaired glucose tolerance at baseline had normal glucose tolerance.

    “Two men in LIRA and two in TRT had IGT at the beginning of the study. After 16 weeks all of them had normal glucose tolerance.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Hematocrit did not rise over 52% during either intervention.

    “Ht did not rise over 52% during either intervention from 0.44 ± 0.03 to 0.46 ± 0.03 in TRT or from 0.46 ± 0.04 to 0.45 ± 0.03 in TRT.”
    Quote in the paperNot a substantial claim
  • Findingown data

    None of the patients in the liraglutide arm reported hypoglycemic events.

    “None of the patients in LIRA reported hypoglycemic events.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 25

  • May combine two claims.

    Findingown data

    There were no significant between-treatment differences in libido, morning erections, or ejaculations.

    “There were no significant between-treatment differences for any parameters (P = 0.762 for libido, P = 0.550 for morning erections, P = 0.204 for ejaculations).”
    Quote in the paperSubstantial claim

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

    Findingown data

    In the liraglutide arm, three patients with type 2 diabetes at baseline reported lowering of insulin doses after 16 months.

    “Five patients in LIRA and six patients in TRT had type 2 diabetes at baseline. After 16 months, three patients in LIRA reported lowering of insulin doses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Total testosterone significantly increased in both the liraglutide and testosterone replacement arms, with no significant difference between groups.

    “Total testosterone significantly increased in both arms (+5.9 ± 7.2 in TRT vs +2.6 ± 3.5 nmol/L in LIRA) and led to improved sexual function.”
    • Also stated in: § Endocrine changes · plain
      “Total testosterone significantly increased in both arms, with no significant differences between groups.”
    • Also stated in: § Endocrine changes · plain
      “| Total testosterone (nmol/L) | 5.9 ± 7.2 | 2.6 ± 3.5 | 0.239 |”
    Quote in the paperSubstantial claim

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

    Findingown data

    In the testosterone replacement arm, one man progressed from normal glucose tolerance to type 2 diabetes mellitus.

    “In TRT one man progressed from normal glucose tolerance to type 2 diabetes mellitus.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Nausea was reported by four, headache by one, and stomach pain by two patients in the liraglutide arm.

    “Nausea was reported by four, headache by one and stomach pain by two patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Hematocrit and PSA did not increase significantly in either treatment arm.

    “Ht and PSA did not increase significantly in either arm.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    HOMAIR score and fasting insulin decreased in the testosterone replacement arm.

    “HOMAIR score and fasting insulin decreased in TRT.”
    • Also stated in: § Results · plain
      “| HOMAIR score | 9.1 ± 6.4 | 5.4 ± 3.3 [1] | 0.033 | 9 ± 6.5 [1] | 7.9 ± 6 [1] | 0.754 | 0.880 |”
    • Also stated in: § Results · plain
      “| Insulin 0 min OGTT (mU/L) | 24.7 ± 13.3 | 17.9 ± 8.4 [2] | 0.016 | 31.6 ± 19.4 [1] | 29 ± 18.9 [2] | 0.556 | 0.287 |”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The most frequent adverse events in the liraglutide arm were mild to moderate, transient, and gastrointestinal in nature.

    “The most frequent adverse events in LIRA were mild to moderate, transient and gastrointestinal in nature.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Metabolic syndrome was resolved in two men treated with LIRA, while no such changes were observed in TRT.

    “Metabolic syndrome was resolved in two men treated with LIRA, while no such changes were observed in TRT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Liraglutide reduced weight and waist circumference.

    “We demonstrated that liraglutide had modest effect on testosterone levels, potential to improve sexual symptoms irrespective of modest increase in total testosterone, reversed the HPT axis suppression, reduced weight and waist circumference and improved glycemic control.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LIRA improved glycemic control, resulting in a significant decrease in HbA1c.

    “As expected, LIRA improved glycemic control resulting in a significant decrease in HbA1c.”
    • Also stated in: § Discussion · boosted
      “We demonstrated that liraglutide had modest effect on testosterone levels, potential to improve sexual symptoms irrespective of modest increase in total testosterone, reversed the HPT axis suppression, reduced weight and waist circumference and improved glycemic control.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: A complex bidirectional relationship between dysglycemia and the HPT axis was controlled in one direction.

  • May combine two claims.

    Interpretationown data

    Testosterone replacement therapy improved sexual functions, total testosterone levels, and HOMAIR.

    “TRT improved sexual functions, total testosterone levels and HOMAIR.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Treatment with liraglutide in an anti-obesity dose resulted in significant improvement of sexual symptoms, increase in total testosterone concentrations, recovery of the HPT axis, reduction of anthropometric measures of obesity, and improvement of glycemic control.

    “Treatment with liraglutide in an anti-obesity dose resulted in significant improvement of sexual symptoms, increase in total testosterone concentrations, recovery of HPT axis, reduction of anthropometric measures of obesity and improvement of glycemic control.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: In clinical practice, lifestyle measures often fail.
    • Rests on an assumption: The impact of liraglutide on obesity-related functional hypogonadism has not yet been addressed in a prospective clinical study.

  • May combine two claims.

    Study design and conductown data

    The study was a 16-week prospective randomized open-label trial in which 30 men were randomized to liraglutide or testosterone replacement therapy.

    “We designed a 16-week prospective randomized open-label study with 30 men (aged 46.5 ± 10.9 years, BMI 41.2 ± 8.4 kg/m2, mean ± s.d.) that were randomized to liraglutide 3.0 mg QD (LIRA) or 50 mg of 1% transdermal gel QD (TRT).”
    • Also stated in: § Study protocol · plain
      “We conducted a 16-week prospective randomized open-label study with 30 eligible men who were randomized to liraglutide 3.0 mg QD s.c. (LIRA arm) and 50 mg of 1% transdermal gel QD (TRT arm).”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Total testosterone was measured by coated tube RIA with within and between assay coefficients of variation of 1.05% and 5.75%.

    “Total testosterone levels were measured by coated tube RIA (DiaSorin S. p. A., Salluggia, Italy and Diagnostic Products Corporation, Los Angeles, CA, USA, respectively). Within and between assays, coefficients of variation for testosterone were 1.05 and 5.75%.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study was registered with ClinicalTrials.gov identifier Nbib3619330.

    “The study is registered with ClinicalTrials.gov identifier: Nbib3619330.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In middle-aged obese men with low testosterone subjected to a rigorous weight loss program, men not receiving testosterone replacement therapy lost adipose tissue and lean body mass, whereas weight loss in testosterone-treated men was almost exclusively due to loss of body fat.

    “One study in middle-aged obese men with low testosterone subjected to a rigorous weight loss program has reported that men not receiving TRT lost adipose tissue and lean body mass, whereas weight loss in testosterone-treated men was almost exclusively due to loss of body fat (6).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Ng Tang Fui M Prendergast LA Dupuis P Raval M Strauss BJ Zajac JD Grossmann M. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Medicine 2016 14 153 (10.1186/s12916-016-0700-9) 27716209 PMC5054608 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Obesity causes functional hypogonadism due to suppression of the hypothalamus-pituitary-testicular axis that is potentially reversible.

    “Obesity causes functional hypogonadism (FH) due to suppression of hypothalamus-pituitary-testicular (HPT) axis that is potentially reversible (1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Wu FC Tajar A Pye SR Silman AJ Finn JD O’Neill TW Bartfai G Casanueva F Forti G Giwercman A, et al Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. Journal of Clinical Endocrinology and Metabolism 2008 93 2737– 2745. (10.1210/jc.2007-1972) 18270261 source

      Not checked in the free run.

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

    Study design and conductcitation

    The Slovene version of the aging male syndrome scale was translated according to international methodological recommendations for linguistic and cultural adaptation.

    “Translation of Slovene version was performed in congruence with international methodological recommendations for linguistic and cultural adaptation of HRQoL measures using the English version as source language to ensure cross-cultural equivalence among countries. Six steps of the translation process were followed as recommended (16).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Heinemann LA Saad F Zimmermann T Novak A Myon E Badia X Potthoff P T’Sjoen G Pollanen P Goncharow NP, et al The Aging Males’ Symptoms (AMS) scale: update and compilation of international versions. Health and Quality of Life Outcomes 2003 1 15 (10.1186/1477-7525-1-15) 12747807 PMC155679 source

      Not checked in the free run.

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

    Study design and conductown data

    HbA1c was assessed by high-performance liquid chromatography with within and between assay coefficients of variation of 1.67% and 2.27%.

    “HbA1 was assessed by high-performance liquid chromatography (D-100; Bio-Rad Laboratories). Within and between assays, coefficients of variation for HbA1c were 1.67 and 2.27%.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Combination of testosterone replacement therapy and lifestyle measures is superior to lifestyle measures alone in increasing insulin sensitivity, glycemic control, muscle mass and reducing liver fat.

    “Only few studies to date reported that combination of TRT and LSM is superior to LSM alone in increasing insulin sensitivity, glycemic control, muscle mass and reducing liver fat (4, 5).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Heufelder AE Saad F Bunck MC Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. Journal of Andrology 2009 30 726– 733. (10.2164/jandrol.108.007005) 19578132 source

      Not checked in the free run.

    • cites [5] Hoyos CM Yee BJ Phillips CL Machan EA Grunstein RR Liu PY. Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial. European Journal of Endocrinology 2012 167 531– 541. (10.1530/EJE-12-0525) 22848006 source

      Not checked in the free run.

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

    Study design and conductnone given

    Insulin was determined by immunoradiometric assay with within and between assay coefficients of variation of 3.6% and 3.8%.

    “Insulin was determined by immunoradiometric assay (Biosource Europe S.A., Nivelles, Belgium). Within and between assays, coefficients of variation for insulin were 3.6 and 3.8%.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    SHBG, LH and FSH were determined with a chemiluminescent immunoassay with within and between assay coefficients of variation ranging from 1.2 to 4.0% and 1.8 to 4.3%.

    “Sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined with a chemiluminescent immunoassay (Immulite 2000 XPi Analyzer; Siemens Healthcare). Within and between assays, coefficients of variation for the applied method ranged from 1.2 to 4.0% and 1.8 to 4.3%.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Five per cent of weight loss with lifestyle modification was associated with a 2 nmol/L increase in total testosterone and no increase in free testosterone.

    “Five per cent of weight loss with LSM was associated with the 2 mmol/L increase of total testosterone and no increase of free testosterone (21)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Roy CN Snyder PJ Stephens-Shields AJ Artz AS Bhasin S Cohen HJ Farrar JT Gill TM Zeldow B Cella D, et al Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Internal Medicine 2017 177 480– 490. (10.1001/jamainternmed.2016.9540) 28241237 PMC5433757 source

      Not checked in the free run.

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

    Premisecitation

    GLP1 receptor agonists are linked to progressive and sustained weight loss in subjects with or without diabetes.

    “GLP1 receptor agonists are linked to progressive and sustained weight loss in subjects with or without diabetes (7).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Vilsboll T Christensen M Junker AE Knop FK Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012 344 d7771 (10.1136/bmj.d7771) 22236411 PMC3256253 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The observed magnitude of increase in total testosterone in patients treated with liraglutide was slightly greater than expected for the amount of weight reduction, although they remained hypogonadal by laboratory standards.

    “The observed magnitude of the increase in total testosterone in our patients who had been treated with liraglutide was slightly greater than expected for the amount of WR, although they remained hypogonadal by laboratory standards.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The suppression of the HPT axis in functional hypogonadism associated with obesity is considered to be an adaptive response to weight variation.

    “The suppression of HPT axis in FH associated with obesity is considered to be an adaptive response to the weight variation (25).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Wu F Zitzmann M Heiselman D Donatucci C Knorr J Patel AB Kinchen K. Demographic and clinical correlates of patient-reported improvement in sex drive, erectile function, and energy with testosterone solution 2. Journal of Sexual Medicine 2016 13 1212– 1219. (10.1016/j.jsxm.2016.05.010) 27329542 source

      Not checked in the free run.

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

    Premisecitation

    Upon refeeding, GLP1 increased, perhaps aiding the recovery of LH secretion.

    “Upon refeeding period GLP1 increased, perhaps aiding the recovery of LH secretion (14).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Greco D. Normal pregnancy outcome after first-trimester exposure to liraglutide in a woman with type 2 diabetes. Diabetic Medicine 2015 32 e29– e30. (10.1111/dme.12726) 25683470

      Not checked in the free run.

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

    Premisecitation

    Intracerebroventricular injection of GLP1 increased the levels of LH in rats.

    “Intracerebroventricular injection of GLP1 increased the levels of LH in rats (30).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Jeibmann A Zahedi S Simoni M Nieschlag E Byrne MM. Glucagon-like peptide-1 reduces the pulsatile component of testosterone secretion in healthy males. European Journal of Clinical Investigation 2005 35 565– 572. (10.1111/j.1365-2362.2005.01542.x) 16128863 source

      Not checked in the free run.

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

    Premisecitation

    Some studies and meta-analyses highlighted that TRT may reduce body weight in obese men.

    “While some studies and meta-analyses highlighted that TRT may reduce body weight in obese men (34, 35, 36, 37)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [34] Jones TH Arver S Behre HM Buvat J Meuleman E Moncada I Morales AM Volterrani M Yellowlees A Howell JD, et al Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study) Diabetes Care 2011 34 828– 837. (10.2337/dc10-1233) 21386088 PMC3064036 source

      Not checked in the free run.

    • cites [35] Hackett G Cole N Bhartia M Kennedy D Raju J Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. Journal of Sexual Medicine 2013 10 1612– 1627. (10.1111/jsm.12146) 23551886 source

      Not checked in the free run.

    • cites [36] Corona G Monami M Rastrelli G Aversa A Sforza A Lenzi A Forti G Mannucci E Maggi M. Type 2 diabetes mellitus and testosterone: a meta-analysis study. International Journal of Andrology 2011 34 528– 540. (10.1111/j.1365-2605.2010.01117.x) 20969599 source

      Not checked in the free run.

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

    Premisecitation

    LH increased with weight reduction in a magnitude-dependent manner.

    “It has been reported previously that LH increased with WR in magnitude-dependent manner (8).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Ponce OJ Spencer-Bonilla G Alvarez-Villalobos N Serrano V Singh-Ospina N Rodriguez-Gutierrez R Salcido-Montenegro A Benkhadra R Prokop LJ Bhasin S, et al The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials. Journal of Clinical Endocrinology and Metabolism 2018 103 1745– 1754. (10.1210/jc.2018-00404) 29562341 source

      Not checked in the free run.

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

    Premisecitation

    Some animal studies demonstrated the potential involvement of GLP1 in the direct regulation of the hypothalamus-pituitary system.

    “some animal studies demonstrated the potential involvement of GLP1 in the direct regulation of the hypothalamus-pituitary system.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [30] Jeibmann A Zahedi S Simoni M Nieschlag E Byrne MM. Glucagon-like peptide-1 reduces the pulsatile component of testosterone secretion in healthy males. European Journal of Clinical Investigation 2005 35 565– 572. (10.1111/j.1365-2362.2005.01542.x) 16128863 source

      Not checked in the free run.

    • cites [14] Greco D. Normal pregnancy outcome after first-trimester exposure to liraglutide in a woman with type 2 diabetes. Diabetic Medicine 2015 32 e29– e30. (10.1111/dme.12726) 25683470 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Severe obesity (BMI>38) is characterized by reduction of serum testosterone, its free fraction, and quality and quantity of LH secretion.

    “especially the severe form of obesity (BMI>38) is characterized by reduction of serum T, its free fraction and quality and quantity of LH secretion (26).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Giagulli VA Kaufman JM Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. Journal of Clinical Endocrinology and Metabolism 1994 79 997– 1000. (10.1210/jcem.79.4.7962311) 7962311 source

      Not checked in the free run.

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

    Premisecitation

    Several adipokines were proposed as negative mediators on the reproductive axis.

    “Several adipokines were proposed as negative mediators on the reproductive axis (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Michalakis K Mintziori G Kaprara A Tarlatzis BC Goulis DG. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism: Clinical and Experimental 2013 62 457– 478. (10.1016/j.metabol.2012.08.012) 22999785 source

      Not checked in the free run.

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

    Premisecitation

    In response to fasting, rats' hypothalamic GLP1 content significantly decreased when there was a rapid reduction in pituitary LH.

    “in response to fasting, the rats’ hypothalamic GLP1 content significantly decreased when there was a rapid reduction in pituitary LH.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Greco D. Normal pregnancy outcome after first-trimester exposure to liraglutide in a woman with type 2 diabetes. Diabetic Medicine 2015 32 e29– e30. (10.1111/dme.12726) 25683470

      Not checked in the free run.

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

    Premisecitation

    With weight loss of more than 15%, LH increased by 2.2 IU.

    “With weight loss of more than 15% LH increased for 2.2 IU (8).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Ponce OJ Spencer-Bonilla G Alvarez-Villalobos N Serrano V Singh-Ospina N Rodriguez-Gutierrez R Salcido-Montenegro A Benkhadra R Prokop LJ Bhasin S, et al The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials. Journal of Clinical Endocrinology and Metabolism 2018 103 1745– 1754. (10.1210/jc.2018-00404) 29562341 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    Several additional causes can have a key role in bringing about functional hypogonadism.

    “Moreover, several additional causes can have a key role in bringing about this clinical condition (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Vermeulen A Kaufman JM Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 1996 81 1821– 1826. (10.1210/jcem.81.5.8626841) 8626841 source

      Not checked in the free run.

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

    Premisecitation

    The degree of weight reduction predicted improved erectile function, whereas changes in testosterone level did not.

    “another study reported that the degree of WR predicted improved erectile function, whereas changes in testosterone level did not (24)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Seftel AD Mack RJ Secrest AR Smith TM. Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning. Journal of Andrology 2004 25 963– 972. (10.1002/j.1939-4640.2004.tb03169.x) 15477371 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    The presence of type 2 diabetes was balanced between the groups and well controlled throughout the study.

    “However, the presence of type 2 diabetes was balanced between the groups and well controlled throughout the study.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The conclusions are limited by a small sample size and short-term observation.

    “The conclusions are limited by a small sample size and short-term observation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Few randomized, double-blind placebo controlled trials and a meta-analysis of RCT studies have not confirmed that TRT reduces body weight in obese men.

    “few randomized, double-blind placebo controlled trials and a meta-analysis of RCT studies (38) have not confirmed those encouraging results (15, 39, 40).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [38] Corona G Giagulli VA Maseroli E Vignozzi L Aversa A Zitzmann M Saad F Mannucci E Maggi M. THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study. European Journal of Endocrinology 2016 174 R99– R116. (10.1530/EJE-15-0262) 26537862 source

      Not checked in the free run.

    • cites [15] Bhasin S Cunningham GR Hayes FJ Matsumoto AM Snyder PJ Swerdloff RS Montori VM & Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2010 95 2536– 2559. (10.1210/jc.2009-2354) 20525905 source

      Not checked in the free run.

    • cites [39] Wang C Jackson G Jones TH Matsumoto AM Nehra A Perelman MA Swerdloff RS Traish A Zitzmann M Cunningham G. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care 2011 34 1669– 1675. (10.2337/dc10-2339) 21709300 PMC3120209 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Libido and sexual function were not measured with validated tools, and therefore could be inaccurate.

    “Libido and sexual function were not measured with validated tools, and therefore could be inaccurate.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    A compelling number of clinical studies demonstrated that TRT led to improvement in glycemic control and insulin sensitivity, whereas some failed to confirm these observations.

    “A compelling number of clinical studies demonstrated that TRT led to improvement in glycemic control and insulin sensitivity (4, 5, 37, 42), whereas some failed to confirm these observations (43).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [4] Heufelder AE Saad F Bunck MC Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. Journal of Andrology 2009 30 726– 733. (10.2164/jandrol.108.007005) 19578132 source

      Not checked in the free run.

    • cites [5] Hoyos CM Yee BJ Phillips CL Machan EA Grunstein RR Liu PY. Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial. European Journal of Endocrinology 2012 167 531– 541. (10.1530/EJE-12-0525) 22848006 source

      Not checked in the free run.

    • cites [37] Hackett G Cole N Bhartia M Kennedy D Raju J Wilkinson P & BLAST Study Group. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study. Journal of Sexual Medicine 2014 11 840– 856. (10.1111/jsm.12404) 24308723 source

      Not checked in the free run.

43 of 43

  • The paper relies on this without support.

    In clinical practice, lifestyle measures often fail.

    “yet in clinical practice LSM often fails.”

  • The paper relies on this without support.

    Testosterone replacement therapy appears to improve body composition and glycometabolic profile without clearly affecting weight loss.

    “On the other hand, testosterone replacement therapy (TRT) appears to improve body composition and glycometabolic profile without clearly affecting weight lost as well as its role after a trail of unsuccessful LSM is unclear.”

  • The paper relies on this without support.

    The role of testosterone replacement therapy after unsuccessful lifestyle measures is unclear.

    “On the other hand, testosterone replacement therapy (TRT) appears to improve body composition and glycometabolic profile without clearly affecting weight lost as well as its role after a trail of unsuccessful LSM is unclear.”

  • The paper relies on this without support.

    The impact of liraglutide on obesity-related functional hypogonadism has not yet been addressed in a prospective clinical study.

    “Despite the fact that the prevalence of FH in obese male population is increased by 13-fold (8), the impact of liraglutide on obesity-related FH has not yet been addressed in a prospective clinical study.”

  • The authors state this as an assumption.

    A complex bidirectional relationship between dysglycemia and the HPT axis was controlled in one direction.

    “We assumed that a complex bidirectional relationship between dysglycemia and HPT was controlled in one direction.”
5 of 5

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?

  • In a 16-week trial in obese hypogonadal men with sexual symptoms and poor responses to lifestyle measures, liraglutide but not testosterone therapy induced a 6% reduction in weight.

    “Liraglutide, but not TTh, induced a 6% reduction in weight.”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [49]

  • In the same trial, both liraglutide and testosterone therapy ameliorated sexual symptoms and significantly increased total testosterone, although the increase was greater with testosterone gel (5.9 vs. 2.6 nmol/L with liraglutide).

    “Both treatments ameliorated sexual symptoms and increased significantly TT, although the increase was more evident with T gel (5.9 vs. 2.6 nmol/L with liraglutide).”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [49]

  • In the same trial, testosterone therapy further reduced luteinizing hormone levels, whereas liraglutide marginally improved it (0.7 mU/L).

    “As expected, TTh further reduced LH levels, whereas liraglutide marginally improved it (0.7 mU/L).”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [49]

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.

  • Follow-up is described as both 16 weeks and 16 months

    Minor

    The study is described as lasting 16 weeks, but the metabolic-parameters section places a follow-up observation after 16 months.

  • Two different hematocrit changes are both attributed to TRT

    Minor

    The adverse-events section assigns two different baseline-to-endpoint hematocrit series to the TRT arm. In the context of a comparison of both arms, one appears to have been assigned the wrong arm label.

  • PSA exclusion threshold conflicts with baseline PSA levels

    Minor

    An exclusion threshold of 3 ng/L equals 0.003 μg/L. Both reported baseline group means exceed that threshold, although these participants were enrolled.

3 of 3

Cites

Flagged first, then by citations

1 of the 46 references couldn’t be matched to a known paper.

Research works printed but not linked: 42

  1. 2015, Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats, Gynecological Endocrinology, 31, 196, 10.3109/09513590.2014.975686 · DOI · Paper page
  2. 2003, Measuring inconsistency in meta-analyses, BMJ, 327, 557, 10.1136/bmj.327.7414.557 · DOI · Paper page
  3. 2011, Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study), Diabetes Care, 34, 828, 10.2337/dc10-1233 · DOI · Paper page
  4. 2018, The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials, Journal of Clinical Endocrinology and Metabolism, 103, 1745, 10.1210/jc.2018-00404 · DOI · Paper page
  5. 2013, Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis, European Journal of Endocrinology, 168, 829, 10.1530/eje-12-0955 · DOI · Paper page
  6. 2008, Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations, European Journal of Endocrinology, 159, 507, 10.1530/eje-08-0601 · DOI · Paper page
  7. 2003, The Aging Males’ Symptoms (AMS) scale: update and compilation of international versions, Health and Quality of Life Outcomes, 1, 15, 10.1186/1477-7525-1-15 · DOI · Paper page
  8. 2017, Association of testosterone levels with anemia in older men: a controlled clinical trial, JAMA Internal Medicine, 177, 480, 10.1001/jamainternmed.2016.9540 · DOI · Paper page
  9. 2013, Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study, European Journal of Endocrinology, 168, 445, 10.1530/eje-12-0890 · DOI · Paper page
  10. 2011, Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes, Diabetes Care, 34, 1669, 10.2337/dc10-2339 · DOI · Paper page
  11. 2016, Demographic and clinical correlates of patient-reported improvement in sex drive, erectile function, and energy with testosterone solution 2, Journal of Sexual Medicine, 13, 1212, 10.1016/j.jsxm.2016.05.010 · DOI · Paper page
  12. OF ENDOCRINE DISEASE Testosterone supplementation and body composition results from a meta - analysis study of https org, THERAPY European Journal Endocrinology, 99
  13. 2016, Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial, International Journal of Obesity, 40, 1310, 10.1038/ijo.2016.52 · DOI · Paper page
  14. 2000, Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling, Endocrinology, 141, 752, 10.1210/endo.141.2.7326 · DOI · Paper page
  15. GrecoD, Normal pregnancy outcome after first - trimester exposure to liraglutide in a woman with type diabetes https org, Diabetic Medicine, 29
  16. 2005, Glucagon-like peptide-1 reduces the pulsatile component of testosterone secretion in healthy males, European Journal of Clinical Investigation, 35, 565, 10.1111/j.1365-2362.2005.01542.x · DOI · Paper page
  17. 2008, Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study, Journal of Clinical Endocrinology and Metabolism, 93, 2737, 10.1210/jc.2007-1972 · DOI · Paper page
  18. 2018, Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis, Lancet Diabetes and Endocrinology, 6, 105, 10.1016/s2213-8587(17)30412-6 · DOI · Paper page
  19. 2011, Type 2 diabetes mellitus and testosterone: a meta-analysis study, International Journal of Andrology, 34, 528, 10.1111/j.1365-2605.2010.01117.x · DOI · Paper page
  20. 2003, Follow-up report on the diagnosis of diabetes mellitus, Diabetes Care, 26, 3160, 10.2337/diacare.26.11.3160 · DOI · Paper page
  21. 2017, A perspective on middle-aged and older men with functional hypogonadism: focus on holistic management, Journal of Clinical Endocrinology and Metabolism, 102, 1067, 10.1210/jc.2016-3580 · DOI · Paper page
  22. 2005, Diabetes (db/db) mutation-induced endometrial epithelial lipoapoptosis: ultrastructural and cytochemical analysis of reproductive tract atrophy, Reproductive Biology and Endocrinology, 3, 15, 10.1186/1477-7827-3-15 · DOI · Paper page
  23. 1999, A critical evaluation of simple methods for the estimation of free testosterone in serum, Journal of Clinical Endocrinology and Metabolism, 84, 3666, 10.1210/jcem.84.10.6079 · DOI · Paper page
  24. 2013, The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review, Metabolism: Clinical and Experimental, 62, 457, 10.1016/j.metabol.2012.08.012 · DOI · Paper page
  25. 2018, The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes, Aging Male, 21, 158, 10.1080/13685538.2018.1468429 · DOI · Paper page
  26. 1996, Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males, Journal of Clinical Endocrinology and Metabolism, 81, 1821
  27. 2015, Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism, Andrology, 3, 1094, 10.1111/andr.12099 · DOI · Paper page
  28. 2018, Testosterone replacement therapy: for whom, when and how?, Metabolism: Clinical and Experimental, 86, 69, 10.1016/j.metabol.2018.03.007 · DOI · Paper page
  29. 2016, Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial, BMC Medicine, 14, 153, 10.1186/s12916-016-0700-9 · DOI · Paper page
  30. 2009, Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone, Journal of Andrology, 30, 726, 10.2164/jandrol.108.007005 · DOI · Paper page
  31. 2015, Efficacy of liraglutide for weight loss among patients With Type 2 diabetes: the SCALE diabetes randomized clinical trial, JAMA, 314, 687, 10.1001/jama.2015.9676 · DOI · Paper page
  32. 1985, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man, Diabetologia, 28, 412, 10.1007/bf00280883 · DOI · Paper page
  33. 2015, A randomized, controlled trial of 3.0 mg of liraglutide in weight management, New England Journal of Medicine, 373, 11, 10.1056/nejmoa1411892 · DOI · Paper page
  34. 2003, Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin, Endocrinology, 144, 4484, 10.1210/en.2003-0457 · DOI · Paper page
  35. 2004, Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning, Journal of Andrology, 25, 963, 10.1002/j.1939-4640.2004.tb03169.x · DOI · Paper page
  36. 2012, Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials, BMJ, 344, d7771, 10.1136/bmj.d7771 · DOI · Paper page
  37. 2003, Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway, Endocrinology, 144, 5081, 10.1210/en.2003-0741 · DOI · Paper page
  38. 2014, Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study, Journal of Sexual Medicine, 11, 840, 10.1111/jsm.12404 · DOI · Paper page
  39. 2014, Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial, Journal of Clinical Endocrinology and Metabolism, 99, 3821, 10.1210/jc.2014-1872 · DOI · Paper page
  40. 2012, Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial, European Journal of Endocrinology, 167, 531, 10.1530/eje-12-0525 · DOI · Paper page
  41. 2013, Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes, Journal of Sexual Medicine, 10, 1612, 10.1111/jsm.12146 · DOI · Paper page
  42. 1994, Pathogenesis of the decreased androgen levels in obese men, Journal of Clinical Endocrinology and Metabolism, 79, 997

Cited by

Sorted by citations

Related

Authors
Jensterle, M., Podbregar, A., Goricar, K., Gregoric, N., & Janez, A.
Affiliations
  • Ljubljana University Medical Centre (SI)
  • Univerzitetni Rehabilitacijski Inštitut (SI)
  • 3University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Pharmacogenetics Laboratory, Ljubljana, Slovenia
  • 1Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
ORCID
Jensterle, M
Venue
Endocrine Connections
Publisher
Bioscientifica
Published
2019-03
Volume
8
Issue
3
Pages
195-202
ISSN
2049-3614 (ISSN-L)
DOI
10.1530/ec-18-0514
PMC
PMC6391904
OpenAlex
W2911630547
Semantic Scholar
9a92191699daf0fdeda59f722f3a085a4688f35f
Cited by
101
References
46
Citations by year
2026: 17 · 2025: 22 · 2024: 17 · 2023: 13 · 2022: 13 · 2021: 6 · 2020: 7 · 2019: 6
FWCI
6.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Connections (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
liraglutide, testosterone replacement therapy, GLP-1 receptor agonists, hypothalamic-pituitary-testicular axis, luteinizing hormone, follicle-stimulating hormone, weight loss, sexual function, metabolic syndrome

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