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Effects of liraglutide on obesity-associated functional hypogonadism in men
Open accessAbstract
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.
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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.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Symptoms and signs of FH
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Symptoms and signs of FH · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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 |”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Symptoms and signs of FH
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Adverse events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of the patients in LIRA reported hypoglycemic events.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Adverse events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fasting glucose, glucose and insulin after OGTT, LDL and total cholesterol did not consistently decrease in either group.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The between-treatment difference was significant for HbA1c, LIRA being superior to TRT (Table 2).”
- Also stated in: § Endocrine changes · plain
“| HbA1c (%) | 0 ± 0.8 | −0.5 ± 0.5 [1] | 0.004 |”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Endocrine changes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Metabolic syndrome was resolved in two patients in LIRA and in no subjects in TRT.”
- Also stated in: § Metabolic parameters · plain
“Ten men in the liraglutide arm and ten in testosterone arm had metabolic syndrome at baseline. It was resolved in two patients in LIRA and in no subjects in TRT.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Metabolic parameters · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of morning erections per week as reported by self-evaluation increased from 1.4 ± 1.3 to 3.8 ± 2.6 N/week in TRT (P = 0.012) and from 1.4 ± 2.2 to 2.9 ± 2.5 N/week in LIRA (P = 0.017).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Symptoms and signs of FH
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hb1Ac significantly decreased in LIRA.”
- Also stated in: § Endocrine changes · plain
“| HbA1c (%) | 0 ± 0.8 | −0.5 ± 0.5 [1] | 0.004 |”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Endocrine changes · plain
- It may state two separate claims as one. 24
- Probably not a substantial claim. 25
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Symptoms and signs of FH
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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 |”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Endocrine changes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In TRT one man progressed from normal glucose tolerance to type 2 diabetes mellitus.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nausea was reported by four, headache by one and stomach pain by two patients.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Adverse events
Strength:plain· not yet calibratedn = 2Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ht and PSA did not increase significantly in either arm.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Adverse events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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 |”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Metabolic parameters
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most frequent adverse events in LIRA were mild to moderate, transient and gastrointestinal in nature.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Results > Adverse events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Metabolic syndrome was resolved in two men treated with LIRA, while no such changes were observed in TRT.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: A complex bidirectional relationship between dysglycemia and the HPT axis was controlled in one direction.
- Also stated in: § Discussion · boosted
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TRT improved sexual functions, total testosterone levels and HOMAIR.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Study protocol · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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%.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Materials and methods > Assessment of endocrine parameters
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study is registered with ClinicalTrials.gov identifier: Nbib3619330.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Materials and methods > Subjects
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Introduction
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Obesity causes functional hypogonadism (FH) due to suppression of hypothalamus-pituitary-testicular (HPT) axis that is potentially reversible (1).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Introduction
What the sources say
- Not checked yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Materials and methods > Assessment of symptoms and signs of FH
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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%.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Materials and methods > Assessment of metabolic parameters
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Introduction
What the sources say
- Not checked yetcites [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 yetcites [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
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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%.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Materials and methods > Assessment of metabolic parameters
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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%.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Materials and methods > Assessment of endocrine parameters
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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)”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“GLP1 receptor agonists are linked to progressive and sustained weight loss in subjects with or without diabetes (7).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Introduction
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The suppression of HPT axis in FH associated with obesity is considered to be an adaptive response to the weight variation (25).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Upon refeeding period GLP1 increased, perhaps aiding the recovery of LH secretion (14).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Intracerebroventricular injection of GLP1 increased the levels of LH in rats (30).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“While some studies and meta-analyses highlighted that TRT may reduce body weight in obese men (34, 35, 36, 37)”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It has been reported previously that LH increased with WR in magnitude-dependent manner (8).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“some animal studies demonstrated the potential involvement of GLP1 in the direct regulation of the hypothalamus-pituitary system.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Several adipokines were proposed as negative mediators on the reproductive axis (28).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“in response to fasting, the rats’ hypothalamic GLP1 content significantly decreased when there was a rapid reduction in pituitary LH.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“With weight loss of more than 15% LH increased for 2.2 IU (8).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Moreover, several additional causes can have a key role in bringing about this clinical condition (27).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“another study reported that the degree of WR predicted improved erectile function, whereas changes in testosterone level did not (24)”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the presence of type 2 diabetes was balanced between the groups and well controlled throughout the study.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The conclusions are limited by a small sample size and short-term observation.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“few randomized, double-blind placebo controlled trials and a meta-analysis of RCT studies (38) have not confirmed those encouraging results (15, 39, 40).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Libido and sexual function were not measured with validated tools, and therefore could be inaccurate.”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Effects of liraglutide on obesity-associated functional hypogonadism in men > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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.”
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 the citing paper
“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 citing paper
“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 citing paper
“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
MinorThe study is described as lasting 16 weeks, but the metabolic-parameters section places a follow-up observation after 16 months.
“After 16 months, three patients in LIRA reported lowering of insulin doses.”
“We conducted a 16-week prospective randomized open-label study with 30 eligible men”
Two different hematocrit changes are both attributed to TRT
MinorThe 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.
“from 0.44 ± 0.03 to 0.46 ± 0.03 in TRT”
“from 0.46 ± 0.04 to 0.45 ± 0.03 in TRT”
PSA exclusion threshold conflicts with baseline PSA levels
MinorAn exclusion threshold of 3 ng/L equals 0.003 μg/L. Both reported baseline group means exceed that threshold, although these participants were enrolled.
“initial PSA more than 3 ng/L”
“from 0.57 ± 0.33 to 0.59 ± 0.36 μg/L in TRT and from 0.93 ± 0.76 to 0.88 ± 0.66 μg/L in LIRA”
Citations
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,772
A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum
Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6079 · Cited by 3,824
Follow-up report on the diagnosis of diabetes mellitus
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus* (2003) · Diabetes Care · doi:10.2337/diacare.26.11.3160 · Cited by 3,784
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411892 · Cited by 2,724
Bhasin, S., Cunningham, G. R., Hayes, F. J., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., & Montori, V. M. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2354 · Cited by 1,954
Davies, M. J., Bergenstal, R., Bode, B., Kushner, R. F., Lewin, A., Skjøth, T. V., Andreasen, A. H., Jensen, C. B., DeFronzo, R. A., & for the NN8022-1922 Study Group (2015) · JAMA · doi:10.1001/jama.2015.9676 · Cited by 1,198
Vilsboll, T., Christensen, M., Junker, A. E., Knop, F. K., & Gluud, L. L. (2012) · BMJ · doi:10.1136/bmj.d7771 · Cited by 970
Wu, F. C. W., Tajar, A., Pye, S. R., Silman, A. J., Finn, J. D., O'Neill, T. W., Bartfai, G., Casanueva, F., Forti, G., Giwercman, A., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1972 · Cited by 939
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
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- 2003, Follow-up report on the diagnosis of diabetes mellitus, Diabetes Care, 26, 3160, 10.2337/diacare.26.11.3160 · DOI · Paper page
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 1994, Pathogenesis of the decreased androgen levels in obese men, Journal of Clinical Endocrinology and Metabolism, 79, 997
Cited by
Sorted by citations
Items 101–101 of 101
Sellke, N. C., & Eisenberg, M. L. (2026) · International Journal of Impotence Research · doi:10.1038/s41443-026-01325-5
Metadata
- 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)
- 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
- gold
- doi.org
- 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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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 ›
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