Hypogonadism and male obesity: Focus on unresolved questions
Open accessAbstract
Summary: Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations in men and presents as one of the strongest predictors of receiving testosterone treatment. While low circulating total testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin, more marked obesity can lead to genuine hypothalamic‐pituitary‐testicular axis ( HPT ) suppression. HPT axis suppression is likely mediated via pro‐inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities. Whether oestradiol‐mediated negative hypothalamic‐pituitary feedback plays a pathogenic role requires further study. Although the obesity‐hypogonadism relationship is bidirectional, the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity. In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis. In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone. In randomized controlled clinical trials ( RCT s), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass. Short‐term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone. However, longer term, larger RCT s designed for patient‐important outcomes and potential risks are required. Until such trials are available, testosterone treatment cannot be routinely recommended for men with obesity‐associated nonclassical hypogonadism. Lifestyle measures or where indicated bariatric surgery to achieve weight loss, and optimization of comorbidities remain first line.
AI snapshot
Written from the paper’s full text.
TL;DR
This perspective reviews unresolved questions in obesity-associated male hypogonadism, arguing that obesity suppresses the hypothalamic-pituitary-testicular axis more substantially than low testosterone promotes adiposity. It concludes that weight loss remains first-line and that testosterone treatment cannot be routinely recommended for obesity-associated nonclassical hypogonadism until longer, larger trials with patient-important outcomes are available.
Key findings
- Obesity is the single most important factor associated with low testosterone. In EMAS (3369 men aged 40–79 years), obese men had a 5.1 nmol/L (30%) lower total testosterone and a 53.7 pmol/L (18%) lower calculated free testosterone than lean men; obesity was associated with a 13-fold increased risk of nonclassical/late-onset hypogonadism, versus a 5.2-fold increase with ≥2 comorbidities.
- The relationship is bidirectional, but obesity effects appear dominant: a bidirectional Mendelian randomization analysis in 7446 Caucasian men predicted that reducing BMI from 30 to 25 kg/m² would increase circulating testosterone by 13%, whereas genetically instrumented testosterone was not associated with BMI. Bariatric surgery increased total testosterone by 8.73 nmol/L [6.51–10.95], while testosterone treatment in RCTs did not reduce body weight but modestly reduced fat mass by 1.6 kg and increased lean mass by 1.6 kg.
- In a 56-week RCT of obese men with low testosterone (mean total testosterone 6.9 nmol/L) on a very low energy diet, testosterone versus placebo did not augment weight loss but produced greater fat mass reduction (−2.9 kg [−5.7, −0.2]), greater visceral fat reduction (−2678 mm² [−5180, −176]), and preservation of lean mass (+3.4 kg [1.3, 5.5]); benefits were not sustained 20 months after treatment cessation.
- SERMs and aromatase inhibitors raise testosterone but lack demonstrated clinical benefit. In the largest anastrozole RCT (88 obese men ≥60 years), testosterone rose from 11.2 to 18.2 nmol/L, but there were no between-group differences in symptoms, body composition, strength, or lipids, and spine BMD decreased significantly after 12 months.
Methods
- Narrative perspective/review based on PubMed searches using the terms “testosterone,” “androgen,” “obesity,” “hypogonadism,” “selective oestrogen receptor modulator,” “aromatase inhibitor,” “oestradiol,” “leptin,” and “kisspeptin,” from inception to March 2018.
- The paper focuses on selected unresolved questions and explicitly excludes basic clinical assessment/biochemical evaluation, management of associated comorbidities such as sleep apnoea, and detailed discussion of testosterone treatment risks in nonclassical hypogonadism.
- Evidence discussed includes observational studies, randomized controlled trials, preclinical studies, and Mendelian randomization; no new primary data are presented.
Limitations
- The author states this perspective is not intended to cover all mechanistic and clinical aspects of obesity-associated hypogonadism and excludes several important areas, including basic assessment, comorbidity management, and risks of testosterone treatment in nonclassical hypogonadism.
- The paper notes limitations of cited studies: early studies were small and cross-sectional; large population-based studies had less detailed clinical assessment; the Mendelian randomization analysis was cross-sectional, relied on single testosterone concentrations, and lacked body composition data; and RCT benefits in selected men with markedly low testosterone cannot be extended to unselected obese men.
- Evident from the text: this is a narrative review without a systematic search or meta-analysis, so conclusions depend on selected literature and the author’s interpretation.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 54 cited sources checked · 0 supported · 0 flagged
- Premisecitation
Testosterone concentrations in nonclassical hypogonadism typically range from 8-12 nmol/L.
“Testosterone concentrations in nonclassical hypogonadism typically range from 8-12 nmol/L.40”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] source
Not checked in the free run.
- Interpretationcitation
In older men with comorbidities, obesity is strongly associated with nonclassical hypogonadism.
“In summary, these population-based studies suggest that in older men with comorbidities, obesity is strongly associated with nonclassical hypogonadism.”
Quote in the paperSubstantial claim - Interpretationreasoning
The effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity.
“the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity.”
Quote in the paperSubstantial claim - Interpretationreasoning
More marked obesity can lead to genuine hypothalamic-pituitary-testicular axis (HPT) suppression.
“more marked obesity can lead to genuine hypothalamic-pituitary-testicular axis (HPT) suppression.”
Quote in the paperNot a substantial claim - Premisecitation
The relationship between low testosterone and obesity is bidirectional.
“It is most commonly stated that the relationship between low testosterone and obesity is bidirectional.”
Quote in the paperSubstantial claim
- Premisecitation
Obesity is the single most important factor associated with low testosterone, overriding the effects of age and comorbidities.
“These studies have confirmed that obesity is the single most important factor associated with low testosterone, overriding the effects of age and comorbidities.28,29”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisenone given
In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis.
“In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis.”
Quote in the paperNot a substantial claim - Premisenone given
Short-term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone.
“Short-term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone.”
Quote in the paperSubstantial claim - Interpretationreasoning
In otherwise healthy young to middle-aged men, marked obesity (generally class 3, BMI ≥ 40 kg/m2) is required to genuinely suppress the HPT axis at the biochemical level.
“Overall, these studies suggested that in otherwise healthy young to middle-aged men, marked obesity (generally class 3, BMI ≥ 40 kg/m 2 ) is required to genuinely suppress the HPT axis at the biochemical level”
Quote in the paperSubstantial claim - Premisecitation
Obesity has emerged as one of the strongest predictors of receiving testosterone treatment in middle-aged US American men.
“obesity has emerged as one of the strongest predictors of receiving testosterone treatment in middle-aged US American men. 2”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
Not checked in the free run.
- Interpretationcitation
Reversal of HPT axis suppression with weight loss suggests a pathogenic role for excess adipose tissue.
“While exact mechanisms are unknown, the reversal of HPT axis suppression with weight loss 43,46,47 suggests a pathogenic role for excess adipose tissue.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisenone given
In most men, at least 10% of weight loss is required to achieve an increase in circulating testosterone.
“In most men, at least 10% of weight loss is required to achieve an increase in circulating testosterone.”
Quote in the paperNot a substantial claim - Premisecitation
In the RCT by Ng Tang Fui et al. (reference 91), metabolically favourable changes in body composition from testosterone treatment did not augment weight loss-associated improvements in glucose metabolism.
“Interestingly, in this RCT, 91 the metabolically favourable changes in body composition consequent to testosterone treatment did not augment weight loss-associated improvements in glucose metabolism, consistent with testosterone treatment RCTs that did not incorporate weight loss measures.51,52”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Mechanistic studies support the concept that obesity, especially if marked, leads to genuine hypogonadism.
“Overall, these mechanistic studies support the concept that obesity, especially if marked, leads to genuine hypogonadism.”
Quote in the paperSubstantial claim - Interpretationreasoning
Circulating leptin and testosterone could interact in a self-perpetuating cycle promoting adiposity and reproductive dysfunction.
“Overall the data suggest that circulating leptin and testosterone could interact in a self-perpetuating cycle promoting adiposity and reproductive dysfunction.”
Quote in the paperSubstantial claim - Premisecitation
Weight loss is associated with marked increases in circulating testosterone that rise in proportion to the amount of weight lost.
“Weight loss is associated with marked increases in circulating testosterone that rise in proportion to the amount of weight lost.46”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [46] source
Not checked in the free run.
- Interpretationreasoning
Testosterone treatment needs to be given long term to maintain benefits.
“This suggests, consistent with other studies, 103,104 that testosterone treatment needs to be given long term to maintain benefits.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Testosterone treatment improved constitutional symptoms and sexual function over and above the effects of weight loss alone in the same RCT.
“However, testosterone treatment improved constitutional symptoms and sexual function over and above the effects of weight loss alone.101”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [101] source
Not checked in the free run.
- Interpretationreasoning
The benefits reported with testosterone treatment in this cohort cannot be extended to unselected obese men.
“Therefore, the benefits reported with testosterone treatment in this cohort 91,101 cannot be extended to unselected obese men.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Among obese US American men, total testosterone ranged from 11.5 to 12.2 nmol/L and free testosterone from 176 to 193 pmol/L, depending on diabetic status.
“among obese US American men, they ranged from 11.5 nmol/L to 12.2 nmol/L and 176 pmol/L to 193 pmol/L, respectively, depending on diabetic status.30”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] source
Not checked in the free run.
- Premisecitation
SERMs and AIs are ineffective in classical hypogonadotrophic hypogonadism.
“SERMs and AIs require residual hypothalamic-pituitary responsiveness for their action and they are therefore ineffective in classical hypogonadotrophic hypogonadism.106”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [106] source
Not checked in the free run.
- Premisenone given
Obesity-associated hypogonadism is functional.
“However, as discussed above, obesity-associated hypogonadism is functional and the question arises as to whether SERMs and AIs could be effective in this context.”
Quote in the paperNot a substantial claim - Premisecitation
SERMs and AIs require residual hypothalamic-pituitary responsiveness for their action.
“SERMs and AIs require residual hypothalamic-pituitary responsiveness for their action and they are therefore ineffective in classical hypogonadotrophic hypogonadism.106”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [106] source
Not checked in the free run.
- Premisecitation
In the large T Trials, sexual function improved modestly with testosterone treatment.
“In the large T Trials, sexual function improved modestly with testosterone treatment,”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] source
Not checked in the free run.
- Premisecitation
There were no differences in testosterone concentrations between previously testosterone- and placebo-treated men.
“There were no differences in testosterone concentrations between previously testosteroneand placebo-treated men, 92”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [92] source
Not checked in the free run.
- Interpretationcitation
Relatively short-term (56 weeks) testosterone treatment was not associated with a prolonged iatrogenic suppression of the HPT axis.
“suggesting that relatively short-term (56 weeks) testosterone treatment was not associated with a prolonged iatrogenic suppression of the HPT axis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [92] source
Not checked in the free run.
- Premisecitation
The reduction in LH and testosterone secretion in response to SERMs or AIs in older men is exacerbated by obesity.
“and this is exacerbated by obesity 108”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [108] source
Not checked in the free run.
- Interpretationcitation
Even older men with a relatively high comorbid burden (37% had diabetes and 15% a previous myocardial infarction) can respond to testosterone.
“suggesting that even older men with a relatively high comorbid burden (37% had diabetes and 15% a previous myocardial infarction) can respond to testosterone.37”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] source
Not checked in the free run.
- Premisecitation
Experimental studies demonstrate reduced LH and testosterone secretion in response to SERMs or AIs in older compared to young men.
“Experimental studies demonstrate reduced LH and testosterone secretion in response to SERMs 27,72 or AIs 107 in older compared to young men,”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
The reduction in LH and testosterone secretion in response to SERMs or AIs in older men is exacerbated by a proinflammatory state.
“and a proinflammatory state 24 that commonly coexists with obesity.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] source
Not checked in the free run.
- Premisecitation
In an RCT in older men with long-standing diabetes (mean duration 8-9 years) and a high comorbid burden, testosterone treatment did not improve androgen deficiency-like symptoms or sexual function.
“Interestingly, in an RCT using the same questionnaires as Ng Tang Fui's study, 91,101 but in a cohort of older men with long-standing diabetes (mean duration 8-9 years) and a high comorbid burden, testosterone treatment did not improve androgen deficiency-like symptoms or sexual function.105”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [105] source
Not checked in the free run.
- Premisecitation
In a recent cross-over RCT among 24 middle-aged obese men with impaired glucose tolerance or diabetes and baseline testosterone <10.4 nmol/L, clomiphene treatment for 3 months produced modest but significant improvements in fasting glucose and insulin resistance (by HOMA-IR).
“A recent cross-over RCT among 24 middle-aged obese men with impaired glucose tolerance or diabetes and baseline testosterone <10.4 nmol/L reported modest but significant improvements in fasting glucose and insulin resistance (by HOMA-IR) after 3 months of clomiphene treatment, but this small study requires confirmation.114”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [114] source
Not checked in the free run.
- Premisecitation
A proinflammatory state commonly coexists with obesity.
“a proinflammatory state 24 that commonly coexists with obesity.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] source
Not checked in the free run.
- Premisecitation
AIs reduce bone density.
“Moreover, as discussed below, AIs reduce bone density.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [110] source
Not checked in the free run.
- Premisecitation
The increase in SHBG with SERMs may limit testosterone bioavailability.
“In contrast to testosterone treatment, SERMs via oestrogen-like actions in the liver may reduce insulin-like growth factor-1, potentially reducing anabolism, while the increase in SHBG may limit testosterone bioavailability.109”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] source
Not checked in the free run.
- Premisecitation
Smaller RCTs have similarly reported that despite robust increases in testosterone, AIs had no effect on a large array of psychological and somatic measures in men with age- or obesity-associated reductions in testosterone.
“Smaller RCTs have similarly reported that despite robust increases in testosterone, AIs had no effect on a large array of psychological and somatic measures in men with age-or obesity-associated reductions in testosterone.[116][117][118]”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationnone given
Changes in adiposity can have marked effects on the HPT axis.
“While the relationship between obesity and the HPT axis is to a certain extent bidirectional, changes in adiposity can have marked effects on the HPT axis, whereas changes in circulating testosterone have relatively modest effects on body composition.”
Quote in the paperSubstantial claim - Interpretationnone given
Nonspecific androgen deficiency-like symptoms in men with more modest obesity may at least in part be caused by comorbidities.
“Many men with more modest degrees of obesity have reductions primarily in total testosterone, and their nonspecific androgen deficiency-like symptoms may at least in part be caused by comorbidities.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Androgen deficiency-like features are less specific in older men with comorbidities.
“While in otherwise healthy younger men, only severe obesity, BMI ≥ 40 kg/m, 2 leads to genuine HPT axis suppression, older men with comorbidities may be susceptible with lesser degrees of adiposity; however, androgen deficiency-like features are less specific in these older men.”
Quote in the paperSubstantial claim - Interpretationnone given
Marked obesity can lead to genuine biochemical hypogonadism.
“It is clear that marked obesity can lead to genuine biochemical hypogonadism, but the evidence for patientimportant clinical consequences is comparatively less well established.”
Quote in the paperSubstantial claim - Interpretationnone given
Adipose tissue-derived factors such as leptin, pro-inflammatory cytokines and oestradiol play roles in the regulation of the HPT axis and their hypothalamic targets.
“Both mechanistic and clinical studies have shed new light on the roles for adipose tissue-derived factors such as leptin, pro-inflammatory cytokines and oestradiol in the regulation of the HPT axis and their hypothalamic targets.”
Quote in the paperSubstantial claim - Interpretationnone given
In markedly obese men, substantial loss of excess body weight is very effective in restoring eugonadism.
“In markedly obese men, substantial loss of excess body weight is very effective in restoring eugonadism, but lifestyle measures are less effective and difficult to sustain.”
Quote in the paperNot a substantial claim - Interpretationnone given
Short-term studies have shown that testosterone treatment in selected men may have modest benefits, even additive to diet alone.
“While lifestyle modifications should remain first-line therapeutic measures, short-term studies have shown that testosterone treatment in selected men may have modest benefits, even additive to diet alone.”
Quote in the paperNot a substantial claim - Interpretationnone given
Older men with comorbidities may be susceptible to genuine HPT axis suppression with lesser degrees of adiposity.
“While in otherwise healthy younger men, only severe obesity, BMI ≥ 40 kg/m, 2 leads to genuine HPT axis suppression, older men with comorbidities may be susceptible with lesser degrees of adiposity; however, androgen deficiency-like features are less specific in these older men.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The relationship between obesity and the HPT axis is to a certain extent bidirectional.
“While the relationship between obesity and the HPT axis is to a certain extent bidirectional, changes in adiposity can have marked effects on the HPT axis, whereas changes in circulating testosterone have relatively modest effects on body composition.”
Quote in the paperSubstantial claim - Interpretationnone given
In otherwise healthy younger men, only severe obesity (BMI ≥ 40 kg/m2) leads to genuine HPT axis suppression.
“While in otherwise healthy younger men, only severe obesity, BMI ≥ 40 kg/m, 2 leads to genuine HPT axis suppression, older men with comorbidities may be susceptible with lesser degrees of adiposity; however, androgen deficiency-like features are less specific in these older men.”
Quote in the paperNot a substantial claim - Interpretationnone given
Many men with more modest degrees of obesity have reductions primarily in total testosterone.
“Many men with more modest degrees of obesity have reductions primarily in total testosterone, and their nonspecific androgen deficiency-like symptoms may at least in part be caused by comorbidities.”
Quote in the paperNot a substantial claim - Interpretationnone given
Changes in circulating testosterone have relatively modest effects on body composition.
“While the relationship between obesity and the HPT axis is to a certain extent bidirectional, changes in adiposity can have marked effects on the HPT axis, whereas changes in circulating testosterone have relatively modest effects on body composition.”
Quote in the paperNot a substantial claim
- May combine two claims. 24
- Classified as probably not a substantial claim. 5
May combine two claims.
PremisecitationIn EMAS, obesity was associated with a 13-fold increased risk of nonclassical or late-onset hypogonadism, whereas the presence of 2 or more comorbidities increased the risk of LOH risk by only 5.2-fold.
“In EMAS, obesity was associated with a 13-fold increased risk of nonclassical or late-onset hypogonadism (LOH) defined as the syndromic coexistence of sexual dysfunction and low testosterone concentrations, whereas the presence of 2 or more comorbidities increased the risk of LOH risk by only 5.2-fold.35”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based). May combine two claims.
Interpretationnone givenHPT axis suppression is likely mediated via pro-inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities.
“HPT axis suppression is likely mediated via pro-inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisenone givenIn randomized controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass.
“In randomized controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisenone givenLifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone.
“In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone givenTestosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin.
“testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationWhile weight loss is difficult to achieve, sustaining weight loss and maintaining the associated increases in testosterone is even more difficult.
“These studies confirmed what is known; that while weight loss is difficult to achieve, sustaining weight loss and maintaining the associated increases in testosterone is even more difficult.”
Quote in the paperSubstantial claimMay combine two claims.
PremisereasoningChanges in circulating testosterone induced either by testosterone deprivation or testosterone treatment have limited effects on body weight; instead, changes in circulating testosterone mostly modulate body composition, albeit modestly.
“In contrast, changes in circulating testosterone concentrations induced either by testosterone deprivation or testosterone treatment have limited effects on body weight; instead, changes in circulating testosterone mostly modulate body composition, albeit modesty.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
InterpretationreasoningHypothalamic resistance to leptin stimulation combined with preserved testicular sensitivity to leptin inhibition may contribute to HPT axis suppression in male obesity.
“Therefore, it is possible that hypothalamic resistance to leptin stimulation combined with preserved testicular sensitivity to leptin inhibition may contribute to HPT axis suppression in male obesity.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationBMI has a causal effect on testosterone, whereas testosterone does not impact BMI.
“Consistent with the foregoing discussion, the authors concluded that BMI has a causal effect on testosterone, whereas testosterone does not impact BMI.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [59] source
Not checked in the free run.
May combine two claims.
InterpretationcitationTestosterone treatment did not augment diet-associated weight loss, but it prevented the diet-associated loss in lean mass.
“Thus, although testosterone treatment did not augment diet-associated weight loss, it prevented the diet-associated loss in lean mass.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenKey adipose-derived factors postulated to mediate obesity-associated HPT axis suppression include oestradiol, leptin and pro-inflammatory cytokines.
“Key adiposederived factors postulated to mediate obesity-associated HPT axis suppression include oestradiol, leptin and pro-inflammatory cytokines.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationTestosterone treatment modestly reduces fat mass by 1.6 kg [2.5,0.6] and increases lean mass by 1.6 kg [0.6-2.6].
“Instead, testosterone treatment modestly reduces fat mass by 1.6 kg [2.5, 0.6] and increases lean mass by 1.6 kg [0.6-2.6].50”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [50] source
Not checked in the free run.
May combine two claims.
PremisecitationBariatric surgery is associated with an increase in total testosterone of 8.73 nmol/L [6.51-10.95] together with increases in gonadotropins and free testosterone, suggesting a genuine reactivation of the HPT axis.
“Bariatric surgery is associated with an increase in total testosterone of 8.73 nmol/L [6.51-10.95]together with increases in gonadotropins and free testosterone, suggesting a genuine reactivation of the HPT axis.47”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] source
Not checked in the free run.
May combine two claims.
InterpretationreasoningObesity-associated hypogonadism is functional and therefore potentially reversible.
“However, in contrast to classical hypogonadism, obesity-associated hypogonadism is functional and therefore potentially reversible.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationWhen re-evaluated 20 months after the end of the RCT, testosterone treatment effects on body composition were not sustained, and former between-group differences in fat and lean mass were no longer apparent.
“When re-evaluated 20 months after the end of the RCT, 91,101 the testosterone treatment effects on body composition were not sustained, and the former between-group differences in fat and lean mass were no longer apparent.92”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [92] source
Not checked in the free run.
May combine two claims.
PremisecitationIn the obese subgroup of the EMAS cohort, mean total and free testosterone concentrations were 13.5 nmol/L and 280 pmol/L.
“in the obese subgroup of the EMAS cohort, mean total and free testosterone concentrations were 13.5 nmol and 280 pmol/L, 102”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [102] source
Not checked in the free run.
May combine two claims.
InterpretationreasoningIn older men with multiple comorbidities, androgen deficiency-like symptoms are less specific, and sexual dysfunction is more likely to be contributed to by nonendocrine causes compared to younger and healthier men.
“This discrepancy is consistent with the notion that in older men with multiple comorbidities, androgen deficiency-like symptoms are less specific, and that sexual dysfunction is more likely to be contributed to by nonendocrine causes compared to younger and healthier men.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn the largest RCT, despite substantial increases in testosterone from 11.2 nmol/L to 18.2 nmol/L with anastrozole, there were no between-group differences in symptoms, body composition, strength or lipid levels.
“Despite substantial increases in testosterone from 11.2 nmol/L to 18.2 nmol/L with anastrozole, there were no between-group differences in symptoms, body composition, strength or lipid levels.115”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [115] source
Not checked in the free run.
May combine two claims.
PremisecitationEnclomiphene is the trans-isomer of clomiphene and a relatively pure oestradiol antagonist.
“Enclomiphene, the trans-isomer of clomiphene is a relatively pure oestradiol antagonist, 113”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [113] source
Not checked in the free run.
May combine two claims.
InterpretationcitationThe differential effect on gonadotrophins likely resulted in maintenance of a normal sperm count in enclomiphene-treated men whereas sperm count was modestly reduced from a normal baseline in testosterone-treated men.
“It is likely that this differential effect on gonadotrophins resulted in maintenance of a normal sperm count in enclomiphenetreated men whereas sperm count was modestly reduced from a normal baseline in testosterone-treated men.71”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [71] source
Not checked in the free run.
May combine two claims.
PremisecitationBMD at the spine decreased significantly after 12 months of anastrozole, presumably because of the decrease in circulating oestradiol.
“Of concern, BMD at the spine decreased significantly after 12 months of anastrozole, presumably because of the decrease in circulating oestradiol.110”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [110] source
Not checked in the free run.
May combine two claims.
PremisecitationIn men receiving enclomiphene, gonadotrophin concentrations increased; in men receiving testosterone, gonadotrophins decreased.
“In men receiving enclomiphene, gonadotrophin concentrations increased and in men receiving testosterone gonadotrophins decreased.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [71] source
Not checked in the free run.
May combine two claims.
PremisecitationSERMs via oestrogen-like actions in the liver may reduce insulin-like growth factor-1, potentially reducing anabolism.
“In contrast to testosterone treatment, SERMs via oestrogen-like actions in the liver may reduce insulin-like growth factor-1, potentially reducing anabolism, while the increase in SHBG may limit testosterone bioavailability.109”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] source
Not checked in the free run.
May combine two claims.
Interpretationnone givenLifestyle measures are less effective and difficult to sustain for restoring eugonadism in markedly obese men.
“In markedly obese men, substantial loss of excess body weight is very effective in restoring eugonadism, but lifestyle measures are less effective and difficult to sustain.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationOestradiol may be important for sexual function, prevention of abdominal adiposity, and insulin sensitivity.
“In addition to bone health, 119 oestradiol may be important for of sexual function, prevention of abdominal adiposity 68 and insulin sensitivity.69,120”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationUncontrolled case series reported increases in testosterone and improvements in self-reported sexual function and androgen deficiency-like symptoms in SERM-treated men.
“Uncontrolled case series, reviewed elsewhere,111 variously reported not only increases in testosterone, but also improvements in selfreported sexual function and androgen deficiency-like symptoms in SERM-treated men.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [111] source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenTestosterone treatment needs to be maintained long-term, and possibly indefinitely to sustain a benefit.
“Testosterone treatment needs to be maintained long-term, and possibly indefinitely to sustain a benefit.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationDespite robust increases in testosterone with clomiphene (from 8.3 nmol/L to 19.1 nmol/L), sexual function assessed by self-reporting and by nocturnal tumescence did not improve.
“Despite robust increases in testosterone with clomiphene (from 8.3 nmol/L to 19.1 nmol/L), sexual function assessed by self-reporting and by nocturnal tumescence did not improve.112”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [112] source
Not checked in the free run.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Obesity is often associated with lowered testosterone and low to normal gonadotrophin concentrations; however, whether this reflects causality, reverse causality, or merely in-common risk factors remains unclear.
“Obesity is often associated with lowered testosterone and low to normal gonadotrophin concentrations; however, whether this reflects causality, reverse causality, or merely in‐common risk factors remains unclear. 56 , 57”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [56]
Marked obesity (BMI > 35 kg/m2) may lead to genuine suppression of the HPT axis.
“However, marked obesity (body mass index (BMI) > 35 kg/m2) may lead to genuine suppression of the HPT axis. 56”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [56]
Additional contributing factors to obesity-mediated HPT axis suppression include paternal genetics, leptin resistance, and obesity-associated elevations in pro-inflammatory cytokines.
“Additional contributing factors include paternal genetics, 68 leptin resistance, 69 and obesity‐associated elevations in pro‐inflammatory cytokines (reviewed in Grossmann 56 ).”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [56]
Cites
Health effects of overweight and obesity in 195 countries over 25 years
Collaborators, T. G. 2. O. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1614362 · Cited by 7,918 · see citing works
Identification of late-onset hypogonadism in middle-aged and elderly men
Wu, F. C. W., Tajar, A., Beynon, J. M., Pye, S. R., Silman, A. J., Finn, J. D., O'Neill, T. W., Bartfai, G., Casanueva, F. F., Forti, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0911101 · Cited by 1,544 · see citing works
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 · see citing works
Testosterone Replacement in Older Hypogonadal Men: A 12-Month Randomized Controlled Trial
Sih, R., Morley, J. E., Kaiser, F. E., Perry, H. M., Patrick, P., & Ross, C. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.6.3988 · Cited by 920 · see citing works
Effects of Testosterone Treatment in Older Men
Snyder, P. J., Bhasin, S., Cunningham, G. R., Matsumoto, A. M., Stephens-Shields, A. J., Cauley, J. A., Gill, T. M., Barrett-Connor, E., Swerdloff, R. S., Wang, C., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1506119 · Cited by 890 · see citing works
Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men
Finkelstein, J. S., Lee, H., Burnett-Bowie, S.-A. M., Pallais, J. C., Yu, E. W., Borges, L. F., Jones, B. F., Barry, C. V., Wulczyn, K. E., Thomas, B. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1206168 · Cited by 782 · see citing works
Obesity Pathogenesis: An Endocrine Society Scientific Statement
Schwartz, M. W., Seeley, R. J., Zeltser, L. M., Drewnowski, A., Ravussin, E., Redman, L. M., & Leibel, R. L. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00111 · Cited by 727 · see citing works
Isidori, A. M., Giannetta, E., Greco, E. A., Gianfrilli, D., Bonifacio, V., Isidori, A., Lenzi, A., & Fabbri, A. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02339.x · Cited by 695 · see citing works
Tajar, A., Forti, G., O'Neill, T. W., Lee, D. M., Silman, A. J., Finn, J. D., Bartfai, G., Boonen, S., Casanueva, F. F., Giwercman, A., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1796 · Cited by 604 · see citing works
Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels
Isidori, A. M., Caprio, M., Strollo, F., Moretti, C., Frajese, G., Isidori, A., & Fabbri, A. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6082 · Cited by 560 · see citing works
Singh, R., Artaza, J. N., Taylor, W. E., Gonzalez-Cadavid, N. F., & Bhasin, S. (2003) · Endocrinology · doi:10.1210/en.2003-0741 · Cited by 555 · see citing works
The contribution of bone to whole-organism physiology
Karsenty, G., & Ferron, M. (2012) · Nature · doi:10.1038/nature10763 · Cited by 537 · see citing works
Increased Estrogen Production in Obese Men*
SCHNEIDER, G. T., Kirschner, M. A., Berkowitz, R. D., & Ertel, N. H. (1979) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-48-4-633 · Cited by 507 · see citing works
Insulin sensitivity during combined androgen blockade for prostate cancer
Smith, M. R., Lee, H., & Nathan, D. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2507 · Cited by 493 · see citing works
Kelly, D. M., & Jones, T. H. (2015) · Obesity Reviews · doi:10.1111/obr.12282 · Cited by 487 · see citing works
Low testosterone levels are common and associated with insulin resistance in men with diabetes
Grossmann, M., Thomas, M. C., Panagiotopoulos, S., Sharpe, K., MacIsaac, R. J., Clarke, S., Zajac, J. D., & Jerums, G. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2177 · Cited by 468 · see citing works
Self-citationLow serum testosterone and sex-hormone-binding-globulin in massively obese men
GLASS, A. R., SWERDLOFF, R. S., BRAY, G. A., DAHMS, W. T., & ATKINSON, R. L. (1977) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-45-6-1211 · Cited by 430 · see citing works
Corona, G., Rastrelli, G., Monami, M., Saad, F., Luconi, M., Lucchese, M., Facchiano, E., Sforza, A., Forti, G., Mannucci, E., et al. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0955 · Cited by 414 · see citing works
Travison, T. G., Araujo, A. B., Kupelian, V., O’Donnell, A. B., & McKinlay, J. B. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1859 · Cited by 410 · see citing works
Camacho, E. M., Huhtaniemi, I. T., O'Neill, T. W., Finn, J. D., Pye, S. R., Lee, D. M., Tajar, A., Bartfai, G., Boonen, S., Casanueva, F. F., et al. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0890 · Cited by 392 · see citing works
Weinheimer, E. M., Sands, L. P., & Campbell, W. W. (2010) · Nutrition Reviews · doi:10.1111/j.1753-4887.2010.00298.x · Cited by 391 · see citing works
Wabitsch, M., Blum, W. F. P., Muche, R., Braun, M., Hube, F., Rascher, W., Heinze, E., Teller, W. M., & Hauner, H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119595 · Cited by 360 · see citing works
Testosterone concentrations in diabetic and nondiabetic obese men
Dhindsa, S., Miller, M. G., McWhirter, C. L., Mager, D. E., Ghanim, H., Chaudhuri, A., & Dandona, P. (2010) · Diabetes Care · doi:10.2337/dc09-1649 · Cited by 352 · see citing works
Low Testosterone in Men with Type 2 Diabetes: Significance and Treatment
Grossmann, M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0118 · Cited by 350 · see citing works
Self-citationZUMOFF, B., STRAIN, G. W., MILLER, L. K., ROSNER, W., SENIE, R., SERES, D. S., & ROSENFELD, R. S. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-4-929 · Cited by 349 · see citing works
Vermeulen, A. (1993) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.76.5.1140 · Cited by 346 · see citing works
The hypothalamus-pituitary-gonad axis: Tales of mice and men
Kaprara, A., & Huhtaniemi, I. T. (2017) · Metabolism · doi:10.1016/j.metabol.2017.11.018 · Cited by 332 · see citing works
Tajar, A., Huhtaniemi, I. T., O'Neill, T. W., Finn, J. D., Pye, S. R., Lee, D. M., Bartfai, G., Boonen, S., Casanueva, F. F. F., Forti, G., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2513 · Cited by 318 · see citing works
Derby, C. A., Zilber, S., Brambilla, D., Morales, K. H., & McKinlay, J. B. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02560.x · Cited by 315 · see citing works
Lowered testosterone in male obesity: Mechanisms, morbidity and management
Grossmann, M., Tang Fui, M., & Dupuis, P. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.122365 · Cited by 293 · see citing works
Self-citationDhindsa, S., Ghanim, H., Batra, M., Kuhadiya, N. D., Abuaysheh, S., Sandhu, S., Green, K., Makdissi, A., HEJNA, J. M., Chaudhuri, A., et al. (2015) · Diabetes Care · doi:10.2337/dc15-1518 · Cited by 285 · see citing works
Expression of Functional Leptin Receptors in Rodent Leydig Cells1
Caprio, M., Isidori, A. M., Carta, A. R., Moretti, C., Dufau, M. L., & Fabbri, A. (1999) · Endocrinology · doi:10.1210/endo.140.11.7088 · Cited by 270 · see citing works
Handelsman, D. J. (2013) · Medical Journal of Australia · doi:10.5694/mja13.10111 · Cited by 253 · see citing works
Lower endogenous androgens predict central adiposity in men
Khaw, K., & Barrett-Connor, E. L. (1992) · Annals of Epidemiology · doi:10.1016/1047-2797(92)90012-f · Cited by 247 · see citing works
Grossmann, M., & Matsumoto, A. M. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3580 · Cited by 246 · see citing works
Self-citationCouillard, C. (2000) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.3.1026 · Cited by 237 · see citing works
Leptin inhibits testosterone secretion from adult rat testis in vitro
Tena‐Sempere, M., Pinilla, L., Gonzalez, L., Diéguez, C., Casanueva, F. F., & Aguilar, E. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1610211 · Cited by 231 · see citing works
Singh, A. B., Hsia, S. H., Alaupovic, P., Sinha‐Hikim, I., Woodhouse, L. J., Buchanan, T. A., Shen, R., Bross, R., Berman, N., & Bhasin, S. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.1.8172 · Cited by 225 · see citing works
Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men
Tsai, E., Boyko, E. J., Leonetti, D., & Fujimoto, W. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801183 · Cited by 221 · see citing works
Pathogenesis of the decreased androgen levels in obese men.
Giagulli, V. A., Kaufman, J. M., & Vermeulen, A. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.4.7962311 · Cited by 215 · see citing works
Decreased Pituitary-Gonadal Secretion in Men with Obstructive Sleep Apnea
Luboshitzky, R., Aviv, A., Hefetz, A., Herer, P., Shen‐Orr, Z., Lavie, L., & Lavie, P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.7.8663 · Cited by 211 · see citing works
Guo, F., Moellering, D. R., & Garvey, W. T. (2014) · Obesity · doi:10.1002/oby.20585 · Cited by 202 · see citing works
Huhtaniemi, I. T., Tajar, A., Lee, D. M., O’Neill, T. W., Finn, J. D., Bártfai, G., Boonen, S., Casanueva, F. F., Giwercman, A., Han, T. S., et al. (2012) · European Journal of Endocrinology · doi:10.1530/eje-11-1051 · Cited by 200 · see citing works
Gonadal steroid–dependent effects on bone turnover and bone mineral density in men
Finkelstein, J. S., Lee, H., Leder, B. Z., Burnett-Bowie, S.-A. M., Goldstein, D. W., Hahn, C. W., Hirsch, S. C., Linker, A., Perros, N., Servais, A. B., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84137 · Cited by 198 · see citing works
Kamischke, A., Kemper, D., Castel, M., Luthke, M., Rolf, C., Behre, H. M., MAGNUSSEN, H., & Nieschlag, E. (1998) · European Respiratory Journal · doi:10.1183/09031936.98.11010041 · Cited by 195 · see citing works
Obesity and testicular function
Mah, P., & Wittert, G. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.06.007 · Cited by 179 · see citing works
Mild hypogonadotropic hypogonadism in obese men
Strain, G. W., Zumoff, B., Kream, J., Strain, J. J., Deucher, R., Rosenfeld, R. S., Levin, J., & Fukushima, D. K. (1982) · Metabolism · doi:10.1016/0026-0495(82)90175-5 · Cited by 174 · see citing works
Andersson, A., Jensen, T. K., Juul, A., Petersen, J. H., Jørgensen, T., & Skakkebæk, N. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2633 · Cited by 174 · see citing works
The relationship between testosterone and molecular markers of inflammation in older men.
Maggio, M. C., Basaria, S. S., Ceda, G. P., Blè, A., Ling, S. M., Bandinelli, S., Valenti, G., & Ferrucci, L. (2005) · PubMed · Cited by 169 · see citing works
Allan, C. A., & McLachlan, R. I. (2010) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e3283398ee2 · Cited by 168 · see citing works
Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample
Hall, S. A., Esche, G. R., Araujo, A. B., Travison, T. G., Clark, R. V., Williams, R. E., & McKinlay, J. B. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0021 · Cited by 167 · see citing works
Manfredi-Lozano, M., Roa, J., & Tena-Sempere, M. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.07.008 · Cited by 162 · see citing works
The Effect of Weight Loss on Reproductive Hormones in Obese Men*
STANIK, S., DORNFELD, L. P., MAXWELL, M. H., VIOSCA, S. P., & KORENMAN, S. G. (1981) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-53-4-828 · Cited by 156 · see citing works
Obesity and late-onset hypogonadism
Corona, G., Vignozzi, L., Sforza, A., Mannucci, E., & Maggi, M. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.06.031 · Cited by 154 · see citing works
Krasnoff, J. B., Basaria, S., Pencina, M. J., Jasuja, G. K., Vasan, R. S., Ulloor, J., Zhang, A., Coviello, A., Kelly-Hayes, M., D'Agostino, R. B., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2680 · Cited by 152 · see citing works
Guay, A. T. (1995) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.80.12.3546 · Cited by 150 · see citing works
Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels
Leder, B. Z., Rohrer, J. L., Rubin, S. D., Gallo, J., & Longcope, C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031467 · Cited by 149 · see citing works
O’Connor, D. B., Archer, J., & Wu, F. C. W. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031354 · Cited by 149 · see citing works
Saad, F., Aversa, A., M. Isidori, A., & J. Gooren, L. (2012) · Current Diabetes Reviews · doi:10.2174/157339912799424573 · Cited by 148 · see citing works
Guay, A. T., Bansal, S., & Heatley, G. J. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.12.8530597 · Cited by 146 · see citing works
Burnett-Bowie, S.-A. M., McKay, E. A., Lee, H., & Leder, B. Z. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0739 · Cited by 146 · see citing works
Hildreth, K. L., Barry, D. W., Moreau, K. L., Vande Griend, J., Meacham, R. B., Nakamura, T., Wolfe, P., Kohrt, W. M., Ruscin, J. M., Kittelson, J., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3695 · Cited by 140 · see citing works
Grossmann, M., Hoermann, R., Wittert, G., & Yeap, B. B. (2015) · Clinical Endocrinology · doi:10.1111/cen.12664 · Cited by 139 · see citing works
Self-citationDepressed Plasma Testosterone and Fractional Binding of Testosterone in Obese Males*
Amatruda, J. M., Harman, S. M., Pourmotabbed, G., & LOCKWOODF, D. H. (1978) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-47-2-268 · Cited by 132 · see citing works
Saad, F., Yassin, A., Doros, G., & Haider, A. (2016) · International Journal of Obesity · doi:10.1038/ijo.2015.139 · Cited by 131 · see citing works
Low Estradiol Concentrations in Men With Subnormal Testosterone Concentrations and Type 2 Diabetes
Dhindsa, S., Furlanetto, R. W., Vora, M., Ghanim, H., Chaudhuri, A., & Dandona, P. (2011) · Diabetes Care · doi:10.2337/dc11-0208 · Cited by 128 · see citing works
Ng Tang Fui, M., Prendergast, L. A., Dupuis, P., Raval, M., Strauss, B. J., Zajac, J. D., & Grossmann, M. (2016) · BMC Medicine · doi:10.1186/s12916-016-0700-9 · Cited by 124 · see citing works
Self-citationGeorge, J. T., Veldhuis, J. D., Tena‐Sempere, M., Millar, R. P., & Anderson, R. A. (2012) · Clinical Endocrinology · doi:10.1111/cen.12103 · Cited by 123 · see citing works
Testosterone suppression in opioid users: A systematic review and meta-analysis
Bawor, M., Bami, H., Dennis, B. B., Plater, C., Worster, A., Varenbut, M., Daiter, J., Marsh, D. C., Steiner, M., Anglin, R., et al. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.01.038 · Cited by 123 · see citing works
Hoyos, C. M., Killick, R., Yee, B. J., Grunstein, R. R., & Liu, P. Y. (2012) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2012.04413.x · Cited by 118 · see citing works
Zumoff, B., Miller, L. K., & Strain, G. W. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00186-0 · Cited by 118 · see citing works
Short- and Long-Term Effects of Clomiphene Citrate on the Pituitary-Testicular Axis
SANTEN, R. J., LEONARD, J. M., SHERINS, R. J., GANDY, H. M., & PAULSEN, C. A. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-33-6-970 · Cited by 116 · see citing works
Morelli, A., Sarchielli, E., Comeglio, P., Filippi, S., Vignozzi, L., Marini, M., Rastrelli, G., Maneschi, E., Cellai, I., Persani, L., et al. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.09.017 · Cited by 107 · see citing works
Expression of Functional Leptin Receptors in Rodent Leydig Cells
Caprio, M. (1999) · Endocrinology · doi:10.1210/en.140.11.4939 · Cited by 102 · see citing works
Khoo, J., Tian, H.-H., Tan, B., Chew, K., Ng, C.-S., Leong, D., Teo, R. C.-C., & Chen, R. Y.-T. (2013) · The Journal of Sexual Medicine · doi:10.1111/jsm.12154 · Cited by 101 · see citing works
Testosterone and glucose metabolism in men: current concepts and controversies
Grossmann, M. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0393 · Cited by 101 · see citing works
Self-citationEriksson, J., Haring, R., Grarup, N., Vandenput, L., Wallaschofski, H., Lorentzen, E., Hansen, T., Mellström, D., Pedersen, O., Nauck, M., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0176277 · Cited by 101 · see citing works
O'Connell, M. D. L., Roberts, S. A., Srinivas-Shankar, U., Tajar, A., Connolly, M. J., Adams, J. E., Oldham, J. A., & Wu, F. C. W. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1167 · Cited by 98 · see citing works
Attenuated release of biologically active luteinizing hormone in healthy aging men.
Urban, R. J., Veldhuis, J. D., Blizzard, R. M., & Dufau, M. L. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113412 · Cited by 93 · see citing works
The treatment of hypogonadism in men of reproductive age
Kim, E. D., Crosnoe, L., Bar-Chama, N., Khera, M., & Lipshultz, L. I. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.10.052 · Cited by 89 · see citing works
Male late-onset hypogonadism: pathogenesis, diagnosis and treatment
Huhtaniemi, I., & Forti, G. (2011) · Nature Reviews Urology · doi:10.1038/nrurol.2011.47 · Cited by 88 · see citing works
Kim, E. D., McCullough, A., & Kaminetsky, J. (2016) · BJU International · doi:10.1111/bju.13337 · Cited by 81 · see citing works
Sanchez-Garrido, M. A., Ruíz-Pino, F., Manfredi-Lozano, M., León, S., García-Galiano, D., Castano, J. P., Luque, R. M., Romero‐Ruíz, A., Castellano, J. M., Diéguez, C., et al. (2014) · Endocrinology · doi:10.1210/en.2013-1584 · Cited by 78 · see citing works
Burnett‐Bowie, S. M., Roupenian, K. C., Dere, M. E., Lee, H., & Leder, B. Z. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03327.x · Cited by 73 · see citing works
Turnbull, A. V., & RIVIER, C. L. (1997) · Endocrinology · doi:10.1210/endo.138.3.5019 · Cited by 72 · see citing works
Weight loss is a major contributor to improved sexual function after bariatric surgery
Mora, M., Aranda, G. B., de Hollanda, A., Flores, L., Puig-Domingo, M., & Vidal, J. (2013) · Surgical Endoscopy · doi:10.1007/s00464-013-2890-y · Cited by 70 · see citing works
Cheung, A. S., Hoermann, R., Dupuis, P., Joon, D. L., Zajac, J. D., & Grossmann, M. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0200 · Cited by 69 · see citing works
Self-citationGianatti, E. J., Dupuis, P., Hoermann, R., Zajac, J. D., & Grossmann, M. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1872 · Cited by 67 · see citing works
Self-citationVeldhuis, J., Yang, R., Roelfsema, F., & Takahashi, P. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3611 · Cited by 65 · see citing works
Effects of Dehydroepiandrosterone and Atamestane Supplementation on Frailty in Elderly Men
Muller, M., van den Beld, A. W., van der Schouw, Y. T., Grobbee, D. E., & Lamberts, S. W. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2433 · Cited by 62 · see citing works
Katznelson, L. J., Robinson, M. W., Coyle, C. L., Lee, H., & Farrell, C. E. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02291 · Cited by 62 · see citing works
Low testosterone and anaemia in men with type 2 diabetes
Grossmann, M., Panagiotopolous, S., Sharpe, K., MacIsaac, R. J., Clarke, S., Zajac, J. D., Jerums, G., & Thomas, M. C. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03357.x · Cited by 60 · see citing works
Self-citationIgaz, P., Salvi, R., Rey, J.-P., Glauser, M., Pralong, F., & Gaillard, R. (2006) · Endocrinology · doi:10.1210/en.2005-0729 · Cited by 59 · see citing works
Agonistic and Antagonistic Effects of Clomiphene Citrate and Its Isomers1
Clark, J. H., & Guthrie, S. C. (1981) · Biology of Reproduction · doi:10.1095/biolreprod25.3.667 · Cited by 58 · see citing works
Ohlsson, C., Hammarstedt, A., Vandenput, L., Saarinen, N., Ryberg, H., Windahl, S. H., Farman, H. H., Jansson, J.-O., Movérare-Skrtic, S., Smith, U., et al. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2017 · Cited by 55 · see citing works
Sanchez-Garrido, M. A., Ruíz-Pino, F., Velasco, I., Barroso, A., Fernandois, D., Heras, V., Manfredi-Lozano, M., Vazquez, M. J., Castellano, J. M., Roa, J., et al. (2017) · Endocrinology · doi:10.1210/en.2017-00705 · Cited by 55 · see citing works
Kumagai, H., Yoshikawa, T., Zempo‐Miyaki, A., Myoenzono, K., Tsujimoto, T., Tanaka, K., & Maeda, S. (2017) · Hormone and Metabolic Research · doi:10.1055/s-0043-117497 · Cited by 51 · see citing works
Yassin, A., Almehmadi, Y., Saad, F., Doros, G., & Gooren, L. (2016) · Clinical Endocrinology · doi:10.1111/cen.12936 · Cited by 49 · see citing works
Aromatase Inhibition Reduces Insulin Sensitivity in Healthy Men
Gibb, F. W., Homer, N. Z. M., Faqehi, A. M. M., Upreti, R., Livingstone, D. E., McInnes, K. J., Andrew, R., & Walker, B. R. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-4146 · Cited by 49 · see citing works
Veldhuis, J. D., Liu, P. Y., Keenan, D. M., & Takahashi, P. Y. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00450.2011 · Cited by 48 · see citing works
Loves, S., de Jong, J., van Sorge, A., Telting, D., Tack, C. J., Hermus, A., Westerterp, K., & de Boer, H. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0190 · Cited by 45 · see citing works
Pelusi, C., Giagulli, V. A., Baccini, M., Fanelli, F., Mezzullo, M., Fazzini, A., Bianchi, N., Carbone, M. D., De Pergola, G., Mastroroberto, M., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0183369 · Cited by 45 · see citing works
Jasuja, G. K., Bhasin, S., Reisman, J. I., Hanlon, J. T., Miller, D. R., Morreale, A. P., Pogach, L. M., Cunningham, F. E., Park, A., Berlowitz, D. R., et al. (2017) · Journal of General Internal Medicine · doi:10.1007/s11606-016-3940-7 · Cited by 44 · see citing works
The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men
Allan, C. A., Strauss, B. J., Burger, H., Forbes, E. A., & McLachlan, R. I. (2006) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2006.tb00639.x · Cited by 43 · see citing works
TENOVER, J. S., & BREMNER, W. J. (1991) · Journal of Andrology · doi:10.1002/j.1939-4640.1991.tb00265.x · Cited by 41 · see citing works
Ng Tang Fui, M., Hoermann, R., Prendergast, L. A., Zajac, J. D., & Grossmann, M. (2017) · International Journal of Obesity · doi:10.1038/ijo.2016.242 · Cited by 40 · see citing works
Self-citationHuang, G., Pencina, K. M., Li, Z., Basaria, S., Bhasin, S., Travison, T. G., Storer, T. W., Harman, S. M., & Tsitouras, P. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02545 · Cited by 40 · see citing works
Ghanim, H., Dhindsa, S., Abuaysheh, S., Batra, M., Kuhadiya, N. D., Makdissi, A., Chaudhuri, A., & Dandona, P. (2018) · European Journal of Endocrinology · doi:10.1530/eje-17-0673 · Cited by 39 · see citing works
Evidence for Hypogonadism in Massively Obese Males Due to Decreased Free Testosterone
Kley, H. K., Deselaers, T., & PEERENBOOM, H. (1981) · Hormone and Metabolic Research · doi:10.1055/s-2007-1019359 · Cited by 37 · see citing works
Ng Tang Fui, M., Hoermann, R., Zajac, J. D., & Grossmann, M. (2017) · Clinical Endocrinology · doi:10.1111/cen.13385 · Cited by 37 · see citing works
Self-citationModulation of Leydig cell testosterone production by secretory products of macrophages
Afane, M., Dubost, J., Sauvezie, B., Issoual, D., Dosgilbert, A., Grizard, G., & Boucher, D. (2009) · Andrologia · doi:10.1111/j.1439-0272.1998.tb01149.x · Cited by 36 · see citing works
Veldhuis, J. D., & Iranmanesh, A. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0834 · Cited by 36 · see citing works
Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status
Fui, M. N. T., Hoermann, R., Cheung, A. S., Gianatti, E., Zajac, J. D., & Grossmann, M. (2013) · Andrology · doi:10.1111/j.2047-2927.2013.00124.x · Cited by 33 · see citing works
Self-citationShort-Term Estrogen Withdrawal Increases Adiposity in Healthy Men
Chao, J., Rubinow, K. B., Kratz, M., Amory, J. K., Matsumoto, A. M., & Page, S. T. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1482 · Cited by 25 · see citing works
Neurokinin 3 receptor antagonism decreases gonadotropin and testosterone secretion in healthy men
Skorupskaite, K., George, J. T., Veldhuis, J. D., Millar, R. P., & Anderson, R. A. (2017) · Clinical Endocrinology · doi:10.1111/cen.13445 · Cited by 25 · see citing works
Turnbull, A. V. (1997) · Endocrinology · doi:10.1210/en.138.3.1008 · Cited by 25 · see citing works
Handelsman, D. J., & Swerdloff, R. S. (1985) · Clinics in Endocrinology and Metabolism · doi:10.1016/s0300-595x(85)80066-9 · Cited by 24 · see citing works
Testosterone and depressive symptoms among men in the Diabetes Prevention Program
Kim, C., Barrett-Connor, E. L., Aroda, V. R., Mather, K. J., Christophi, C. A., Horton, E. S., Pi-Sunyer, X., Bray, G. A., Labrie, F., & Golden, S. H. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.06.009 · Cited by 24 · see citing works
Birzniece, V., Sata, A., Sutanto, S., & Ho, K. K. Y. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1477 · Cited by 22 · see citing works
Effect of Testosterone Treatment on Adipokines and Gut Hormones in Obese Men on a Hypocaloric Diet
Fui, M. N. T., Hoermann, R., & Grossmann, M. (2017) · Journal of the Endocrine Society · doi:10.1210/js.2017-00062 · Cited by 22 · see citing works
Self-citationTestosterone and All-Cause Mortality in Older Men: The Role of Metabolic Syndrome
Laouali, N., Brailly‐Tabard, S., Helmer, C., Ancelin, M., Tzourio, C., Singh‐Manoux, A., Dugravot, A., Elbaz, A., Guiochon‐Mantel, A., & Canonico, M. (2018) · Journal of the Endocrine Society · doi:10.1210/js.2018-00005 · Cited by 19 · see citing works
López, D. S., Qiu, X., Advani, S., Tsilidis, K. K., Khera, M., Kim, J. J., Morgentaler, A., Wang, R. J., & Canfield, S. E. (2017) · Clinical Endocrinology · doi:10.1111/cen.13501 · Cited by 17 · see citing works
Trials of testosterone replacement reporting cardiovascular adverse events
Basaria, S. S., & Gagliano‐Jucá, T. (2018) · Asian Journal of Andrology · doi:10.4103/aja.aja_28_17 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Corona, G., Goulis, D. G., Huhtaniemi, I., Zitzmann, M., Toppari, J., Forti, G., Vanderschueren, D., & Wu, F. C. (2020) · Andrology · doi:10.1111/andr.12770 · Cited by 431 · see citing works
Salonia, A., Capogrosso, P., Boeri, L., Cocci, A., Corona, G., Dinkelman-Smit, M., Falcone, M., Jensen, C. F., Gül, M., Kalkanli, A., et al. (2025) · European Urology · doi:10.1016/j.eururo.2025.04.010 · Cited by 174 · see citing works
Late‐onset hypogonadism: metabolic impact
Grossmann, M., Ng Tang Fui, M., & Cheung, A. S. (2020) · Andrology · doi:10.1111/andr.12705 · Cited by 95 · see citing works
Self-citationTatem, A. J., Beilan, J., Kovac, J. R., & Lipshultz, L. I. (2020) · The World Journal of Men's Health · doi:10.5534/wjmh.190002 · Cited by 66 · see citing works
La Vignera, S., Cannarella, R., Galvano, F., Grillo, A., Aversa, A., Cimino, L., Magagnini, C. M., Mongioì, L. M., Condorelli, R. A., & Calogero, A. E. (2021) · Endocrine · doi:10.1007/s12020-020-02518-8 · Cited by 36 · see citing works
Fontana, A., Vieira, J. G., Vianna, J. M., Bichowska, M., Krzysztofik, M., Wilk, M., & Reis, V. M. (2023) · PLOS ONE · doi:10.1371/journal.pone.0288730 · Cited by 22 · see citing works
Venkatesh, V. S., Grossmann, M., Zajac, J. D., & Davey, R. A. (2022) · Obesity Reviews · doi:10.1111/obr.13429 · Cited by 22 · see citing works
Self-citationVery low‐calorie ketogenic diet rapidly augments testosterone levels in non‐diabetic obese subjects
Cignarelli, A., Santi, D., Genchi, V. A., Conte, E., Giordano, F., Di Leo, S., Natalicchio, A., Laviola, L., Giorgino, F., & Perrini, S. (2023) · Andrology · doi:10.1111/andr.13357 · Cited by 19 · see citing works
- Authors
- Grossmann, M.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Grossmann, Mathis
- ORCID
- Grossmann, Mathis
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2018-05-16
- Volume
- 89
- Issue
- 1
- Pages
- 11-21
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2800549049
- Cited by
- 164
- References
- 123
- Citations by year
- 2026: 30 · 2025: 22 · 2024: 14 · 2023: 23 · 2022: 18 · 2021: 17 · 2020: 18 · 2019: 19 · 2018: 3
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (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 › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- male obesity, hypogonadism, androgen deficiency, sex hormone-binding globulin, leptin signaling, inflammatory cytokines, bariatric surgery, weight loss, testosterone treatment, body composition, lifestyle intervention
- MeSH terms
- Body Weight, Humans, Hypogonadism, Male, Obesity, Testosterone
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
