The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index; 8 of the 43 sources its claims cite were checked for support.
Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies
Open accessAbstract
STUDY QUESTION: What is the degree of intrinsic insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) and the relative contribution of BMI to overall IR based on meta-analysis of gold standard insulin clamp studies? SUMMARY ANSWER: We report an inherent reduction (-27%) of insulin sensitivity (IS) in PCOS patients, which was independent of BMI. WHAT IS ALREADY KNOWN: PCOS is prevalent, complex and underpinned by IR but controversies surround the degree of intrinsic IR in PCOS, the effect of BMI and the impact of the different diagnostic criteria (NIH versus Rotterdam) in PCOS. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of Medline and All EBM databases was undertaken of studies published up to 30 May 2015. Studies were included if premenopausal women diagnosed with PCOS were compared with a control group for IS, measured by the gold standard euglycaemic-hyperinsulinaemic clamp. The systematic review adheres to the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analyses were performed using mixed modelling and magnitude-based inferences expressed as mean effect ±99% CI. We inferred the effect was small, moderate or large relative to a smallest important change of -3.7% or 3.8% derived by standardisation. Effects were deemed unclear when the CI overlapped smallest important positive and negative values. Effects were qualified with probabilities reflecting uncertainty in the magnitude of the true value (likely, 75-95%; very likely, 95-99.5%; most likely, >99.5%). PARTICIPANTS/MATERIALS, SETTING, METHOD: A total of 4881 articles were returned from the search. Of these, 28 articles were included in the meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Overall IS was lower in women with PCOS compared with controls (mean effect -27%, 99% CI ±6%; large, most likely lower). A higher BMI exacerbated the reduction in IS by -15% (±8%; moderate, most likely lower) in PCOS compared with control women. There was no clear difference in IS between women diagnosed by the original National Institutes of Health (NIH) criteria alone compared with those diagnosed by the Rotterdam criteria. Low levels of sex hormone-binding globulin (SHBG) were associated with reduced levels of IS (-10%, ±10%; small, very likely negative), which was not confounded by BMI. LIMITATIONS, REASONS FOR CAUTION: This systematic review and meta-analysis inherited the confounding problems of small sample sizes, missing data (e.g. some hormones, waist and hip girths) and the lack of Rotterdam criteria phenotype reporting, limiting the evidence synthesis and meta-analysis. WIDER IMPLICATIONS OF THE FINDINGS: BMI has a greater impact on IS in PCOS than in controls. SHBG appears a potentially valuable marker of IR in PCOS, whereas testosterone after adjustment for BMI demonstrated an unexpected interplay with IS which warrants further investigation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the National Health & Medical Research Council (NHMRC), grant number 606553 (H.J.T., N.K.S.), as well as Monash University. H.J.T. is an NHMRC Research Fellow. N.K.S. is supported through the Australian Government's Collaborative Research Networks (CRN) programme. The funding bodies played no role in the design, methods, data management or analysis or in the decision to publish. All authors declare no conflict of interests. REGISTRATION NUMBER: N/A.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
8 of 43 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“recent genome-wide association studies in Caucasian (Day et al., 2015;Hayes et al., 2015) and Asian (Chen et al., 2011;Shi et al., 2012) PCOS populations report preservation of genes across both criteria.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Supportedcites Day et al., 2015 source
The Methods (Follow-up studies) report separate analyses using Rotterdam and NIH PCOS criteria. The Results (Genome-wide association signals for PCOS) state that all six significant signals had directionally concordant associations in clinically validated follow-up cases, with no significant heterogeneity by case definition. Day et al. studied women of White European ancestry; the sentence cites separate studies for the Asian populations. (LLM, conf=0.88)
- Supportedcites Hayes et al., 2015 source
The Discussion reports that this European-ancestry study used the NIH phenotype while the Chinese GWAS included additional Rotterdam phenotypes. It also reports nominal replication of seven of eleven previously identified Chinese PCOS SNPs and a shared 9q22.32 locus, supporting overlap in genetic findings across the criteria. The paper does not claim that every associated gene is shared. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites Chen et al., 2011 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The most consistently observed androgenic abnormality in PCOS is elevated 'free testosterone' or calculated free androgen index, which includes SHBG in the equation (Teede et al., 2011).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Partly supportedcites Teede et al., 2011 sourceExperimental — accuracy not yet measured
The Clinical practice points say calculated free testosterone is a commonly measured marker and that the free androgen index is calculated from testosterone and SHBG. The evidence-based recommendation lists both as first-line tests for biochemical hyperandrogenism in PCOS. Neither passage establishes that their elevation is the most consistently observed androgenic abnormality. (LLM, conf=0.86)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Differences in study or subject characteristics, including inherent problems in analysing and reporting data from the euglycaemic-hyperinsulinaemic clamp, recruitment strategies, ethnicity and lifestyle factors (Day et al., 2015) may account for some of the unexplained effects of PCOS on IR.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Partly supportedcites Day et al., 2015 sourceExperimental — accuracy not yet measured
The paper discusses heterogeneity among PCOS cases (opening section; no page available) and differences between self-reported and clinically validated recruitment (Discussion; no page available). It does not discuss problems analysing or reporting euglycaemic-hyperinsulinaemic clamp data, or propose ethnicity and lifestyle differences as explanations for unexplained effects of PCOS on insulin resistance. (LLM, conf=0.83)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
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
“a 10-unit higher BMI in women with PCOS was associated with a -28% (±14%; large, most likely) difference in IS.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Moderating effects of BMI on IS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ 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
“Total testosterone, when the confounding effects of BMI were controlled, had a moderate and very likely effect on IR.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ 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
“There was no clear difference in IS between women diagnosed by the original National Institutes of Health (NIH) criteria alone compared with those diagnosed by the Rotterdam criteria.”
- Also stated in: § Moderating effects of diagnostic criteria as a surrogate for phenotype · plain
“The effect of PCOS on IS was large for both diagnostic criteria groupings and there was no difference between them (Table IV).”
- Also stated in: § Discussion · plain
“PCOS diagnostic criteria had a trivial effect on IR.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Moderating effects of diagnostic criteria as a surrogate for phenotype · 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
“A higher BMI exacerbated the reduction in IS by -15% (±8%; moderate, most likely lower) in PCOS compared with control women.”
- Also stated in: § Discussion · plain
“BMI independently exacerbated IR by 15% in PCOS, and had a greater impact than in controls.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · 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
“Overall IS was lower in women with PCOS compared with controls (mean effect -27%, 99% CI ±6%; large, most likely lower).”
- Also stated in: § Overall relationship between IS and PCOS · plain
“In the first simple meta-analysis model, IS was lower in women with PCOS compared with controls (a large difference; Table IV).”
- Also stated in: § Discussion · plain
“we report that women with PCOS have 27% worse IS as a measure of IR from the gold standard euglycaemic-hyperinsulinaemic clamp, than controls, independent of BMI, age or diagnostic criteria.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Overall relationship between IS and PCOS · 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 control women the difference in IS for women 10 years older was 4% (±33%; unclear, small effect).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Moderating effects of age on IS
Strength:plain· not yet calibratedCausal:correlational· 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
“Higher LH concentrations in women with PCOS tended (unclear effect) to be associated with lower IS”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > IS, SHBG and hormone concentrations
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 25
- The quote only partly states this claim. 1
- Probably not a substantial claim. 18
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“This approach identified three clear outliers (Micic et al., 2007;Yang et al., 2013;Wu et al., 2014).”
- Also stated in: § Publication bias and outliers · plain
“The other two studies were excluded from the meta-analysis (Supplementary Fig. S1).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Publication bias and outliers
What the sources say
- Not checked — no full text of the sourcecites Micic et al., 2007 source
- Supportedcites Yang et al., 2013 source
The citation identifies Yang et al. (2013) as one of the studies the citing authors classified as outliers. Our copy’s Results section reports Yang et al.’s own ZAG study; the outlier classification, correction, and exclusions are the citing authors’ meta-analytic decisions, not findings attributed to Yang et al. (LLM, conf=0.86)
- Not matchedcites Wu et al., 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Publication bias and outliers · plain
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“IR (defined as reduced insulin sensitivity [IS] compared with control women) and hyperandrogenism play key roles in the aetiology (Teede et al., 2007(Teede et al., , 2010)).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Not checked — no full text of the sourcecites Teede et al., 2007 source
- Supportedcites Teede et al., 2010 source
The Introduction section, “Aetiology: insulin resistance and hyperandrogenism,” explicitly identifies hyperandrogenism as an established contributor to PCOS aetiology and insulin resistance as a pathophysiological contributor. It notes that insulin resistance occurs in around 50%–80% of women with PCOS, so the claim does not imply that it is present in every case. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarities in IR may be related to genetic variations that are preserved across these criteria (Chen et al., 2011;Day et al., 2015;Hayes et al., 2015), suggesting a homogenous disease origin linked to insulin-related genes (Shi et al., 2012).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not checked — no full text of the sourcecites Chen et al., 2011 source
- Partly supportedcites Day et al., 2015 sourceExperimental — accuracy not yet measured
The Methods (Follow-up studies; page unavailable) compare PCOS cases defined by Rotterdam and NIH criteria, and the Results (Genome-wide association signals for PCOS; page unavailable) report directionally concordant genetic associations with no significant heterogeneity by case definition. The Results (Mendelian randomization analyses; page unavailable) also link genetically predicted insulin resistance to PCOS risk, but do not show that similarities in insulin resistance across the two diagnostic groups arise from the same variants. The sentence cites Shi et al., not Day et al., for the separate suggestion of a homogeneous disease origin. (LLM, conf=0.86)
- Partly supportedcites Hayes et al., 2015 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports a PCOS susceptibility locus found in both the NIH-phenotype cohort and a Chinese cohort that included additional Rotterdam phenotypes. It does not link that shared locus to similarities in insulin resistance (IR); it says the NIH phenotype has the highest IR risk and emphasizes gonadotropin-related genes. The sentence cites Shi et al., not Hayes et al., for the separate suggestion about insulin-related genes. (LLM, conf=0.84)
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.
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
“Compared with their respective controls, lean and overweight women with PCOS showed lower IS with large and very large magnitudes respectively (Table IV, Fig. 3).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Moderating effects of BMI on IS
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
“Low levels of sex hormonebinding globulin (SHBG) were associated with reduced levels of IS (-10%, ±10%; small, very likely negative), which was not confounded by BMI.”
- Also stated in: § IS, SHBG and hormone concentrations · plain
“The mean lower concentration of SHBG in PCOS compared with controls was associated with a small lower IS, which was not confounded by BMI.”
- Also stated in: § Discussion · boosted
“SHBG had a strong negative association with IR, which was not confounded by BMI.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § IS, SHBG and hormone concentrations · 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
“Compared with their respective controls, younger and older women with PCOS showed lower or much lower IS, respectively (large and very large magnitudes).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Moderating effects of age on IS
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
“FSH concentrations did not differ between PCOS and controls.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
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.
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
“Increasing age adversely impacted IR, yet the impact was trivial when adjusted for BMI and diagnostic criteria.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > 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 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
“Testosterone means were higher in PCOS and were associated with worse IS but the relationship indicates women with less testosterone are more insulin resistant at the same BMI.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > IS, SHBG and hormone concentrations
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
“Older women diagnosed with PCOS had a lower IS compared with younger women with PCOS (a large magnitude), but this effect became small and unclear when BMI and diagnostic criteria were included in the model (Table IV).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Moderating effects of age on IS
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
“while FSH had a trivial relationship with only minor differences in FSH concentration between PCOS and control women.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > IS, SHBG and hormone concentrations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The unexplained residual differences between studies, represented by the random effect, were large (~21%) but fell to moderate, when all predictors were included in the model (Hopkins et al., 2009).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not checked — no full text of the sourcecites Hopkins et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“We also confirm that SHBG is not only lower, but also less variable in PCOS, compared with controls (Jayagopal et al., 2003), with larger studies now needed to derive specific SHBG cut-off ranges to predict IR.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not checked — no full text of the sourcecites Jayagopal et al., 2003 source
Strength:boosted· 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
“We report that PCOS has an intrinsic IR with a 27% lower IS, independent of BMI, with results that are statistically qualitatively 'large' and 'most likely', as defined here.”
- Also stated in: § Discussion · plain
“Overall mean -27, ±6 Large****”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · plain
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
“Here, we address these gaps and advance the field by confirming in a robust systematic review and meta-analysis, that PCOS is underpinned by an intrinsic IR (~27% reduction in IS), independent of BMI and age, as well as across different diagnostic criteria and ethnic groups.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Consensus is yet to be achieved in lean women with PCOS as IR is not consistently demonstrated (Diamanti-Kandarakis and Dunaif, 2012).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Not checked — no full text of the sourcecites Diamanti-Kandarakis and Dunaif, 2012 source
Load-bearingStrength:plain· not yet calibratedTests✓ 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
“two independent reviewers scanned the titles, abstracts and keywords of every record retrieved.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Study selection
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
“Risk of bias of the included studies was assessed by a reviewer using criteria developed a priori (Harris, 2010).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Data extraction and quality assessment
What the sources say
- Not matchedcites Harris, 2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Obesity is known to increase circulating androgen and insulin levels, may increase PCOS prevalence and exacerbates the clinical features of PCOS (Fig. 1; Diamanti-Kandarakis and Dunaif, 2012;Teede et al., 2013).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
Strength:hedged· 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
“IR and hyperinsulinaemia may directly stimulate production of androgens via ovarian tissue steroidogenesis, independently of changes in gonadotrophin concentration (Diamanti-Kandarakis and Dunaif, 2012).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Not checked — no full text of the sourcecites Diamanti-Kandarakis and Dunaif, 2012 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.
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 systematic review adheres to the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.”
- Also stated in: § Materials and Methods · plain
“The methodology adheres to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) Protocols.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Abstract
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.
- Also stated in: § Materials and Methods · plain
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“This suggests a more homogeneous disease and highlights the need for further research into features such as IR in women with Rotterdam diagnosed PCOS (Barber et al., 2007;Panidis et al., 2012).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
Load-bearingStrength:hedged· not yet calibratedTests✓ 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
“The strength of this meta-analysis is the extensive and comprehensive literature search and the focus on studies using gold standard methods to measure IR.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ 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
“A meta-analysis cannot solve inherent confounding problems in included studies, which may exaggerate or underestimate effects.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Strength:plain· 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
“This is in contrast to our current understanding of the interplay between androgens and IR (Diamanti-Kandarakis and Dunaif, 2012).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not checked — no full text of the sourcecites Diamanti-Kandarakis and Dunaif, 2012 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“The recent NIH consensus workshop on PCOS endorsed the Rotterdam criteria as the definitive diagnostic criteria (National Institutes of Health, 2012) and recommended that all studies include analyses by reproductive PCOS phenotype.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not matchedcites National Institutes of Health, 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
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
“There was a lack of available robust trials and challenges of extracting reported data from the included studies as outlined.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“IR can be measured using numerous direct and indirect techniques, including homeostatic model assessment, quantitative insulin sensitivity check index and oral glucose tolerance test-related measures comprising area under the curve for glucose and insulin (Muniyappa et al., 2008).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Not checked — no full text of the sourcecites Muniyappa et al., 2008 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“These are based on fasting or post glucose-load blood glucose and insulin levels, yet lack accuracy and reliability and are inadequate for clinical purposes and mechanistic research where IR is a primary study outcome (Muniyappa et al., 2008).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Not checked — no full text of the sourcecites Muniyappa et al., 2008 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Low SHBG levels are also increased by insulin-sensitising medication (Ehrmann et al., 1997;Moghetti et al., 2000;Moran et al., 2013);”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
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.
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
“Inconsistent reporting of results made it necessary to express variables as factors by dividing the given variable in the PCOS group by that in the respective control group.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“The euglycaemic-hyperinsulinaemic clamp is considered the reference standard to directly measure IS in research settings and can be used to define a specific cut-off level for IR (Muniyappa et al., 2008).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Introduction
What the sources say
- Not checked — no full text of the sourcecites Muniyappa et al., 2008 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The inability to acquire missing data from all eligible studies is not unexpected and deemed part of the meta-analysis process (Kelley et al., 2004).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not checked — no full text of the sourcecites Kelley et al., 2004 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Other key factors may also influence IR in PCOS, including low-grade inflammation (Shorakae et al., 2015) and sympathetic nervous system dysfunction (Diamanti-Kandarakis and Dunaif, 2012;Shorakae et al., 2015) and further research is needed to clarify key mechanisms underpinning IR in PCOS.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
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.
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
“Small sample sizes and missing data limited evidence synthesis and meta-analysis.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > 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
“Also endpoints varied (including units and scales).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
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
“This is consistent with mechanistic studies demonstrating that SHBG production is suppressed by IR and hyperinsulinaemia (Le et al., 2012) and that SHBG concentrations increase with insulin sensitiser treatment (Moghetti et al., 2000).”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
What the sources say
- Not checked — no full text of the sourcecites Moghetti et al., 2000 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.
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
“Furthermore, not all identified studies were included because of difficulties sourcing the required data from original authors.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
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.
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 body of evidence was heterogeneous such that diagnostic criteria were not uniformly applied with many studies only including women with NIH-diagnosed PCOS, and few reporting reproductive phenotypes.”
§ Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemichyperinsulinaemic clamp studies > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The relationships between BMI and insulin sensitivity and between age and insulin sensitivity are linear in the meta-analytic models.
“Fixed effects in the model were either linear numeric variables for BMI and age or a nominal variable for the diagnostic criteria (NIH or Rotterdam).”
The paper relies on this without support.
The diagnostic criteria groupings (NIH versus Rotterdam) are valid surrogates for PCOS phenotype.
“Moderating effects of diagnostic criteria as a surrogate for phenotype”
The paper relies on this without support.
Low SHBG is associated with adverse cardiovascular risk factors, diabetes and metabolic syndrome, independent of obesity.
“Furthermore, low SHBG is associated with adverse cardiovascular risk factors, diabetes and metabolic syndrome, independent of obesity, all important clinical implications of IR in PCOS, suggesting that SHBG may also be a useful clinical marker of metabolic risk in PCOS.”
The paper relies on this without support.
Little prior PCOS literature has reported by phenotype.
“However, little prior PCOS literature has reported by phenotype, necessitating analysis here by diagnostic criteria as a proxy.”
The paper relies on this without support.
Prior studies suggest that women with an NIH diagnosis of PCOS are more insulin resistant than those diagnosed via Rotterdam criteria.
“Prior studies suggest that women with an NIH diagnosis of PCOS are more IR than those diagnosed via Rotterdam criteria.”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A systematic review and meta-analysis of euglycemic-hyperinsulinemic clamp studies found that women with PCOS have a 27% reduction in insulin sensitivity compared to body mass index (BMI) and age-matched controls [155].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [155]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“When the physiology of insulin function is considered to be a quantitative or continuous variable from an evolutionary perspective, it is likely that all women with PCOS, whether obese or lean, have reduced insulin sensitivity [152,155,166].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [155]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the significance of IR as a pathognomonic component of PCOS is an area of debate [153,154,155].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [155]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The level of central adiposity likely plays a key role in cardiometabolic risk, as insulin resistance has been associated with higher levels of central adiposity in the PCOS population [32,34,35,36].”
From Moving beyond Weight: A Narrative Review of the Dietary and Lifestyle Management for Reducing Cardiometabolic Risk in Polycystic Ovary Syndrome (PCOS) (2023) · cites this paper as [32]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Hyperinsulinemia and insulin resistance play important roles in the pathophysiology of PCOS for both normal-weight women and women with obesity (2, 3, 73, 77).”
From Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis (2024) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Having a higher BMI appears to exacerbate insulin resistance by approximately 15% in individuals with PCOS [32].”
From Moving beyond Weight: A Narrative Review of the Dietary and Lifestyle Management for Reducing Cardiometabolic Risk in Polycystic Ovary Syndrome (PCOS) (2023) · cites this paper as [32]
The cited source says what the claim attributes to it.
In the citing paper
“women with PCOS are more likely to be affected by insulin resistance irrespective of body mass index (BMI) (4).”
In the citing paper
“Previous studies found that PCOS women have a significant reduction in insulin sensitivity compared to BMI and age-matched controls [25,39].”
From Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism (2022) · cites this paper as [39]
In the citing paper
“Although the etiology is still unknown, obesity, IR and hyperinsulinemia are cardinal features of PCOS [124].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [124]
In the citing paper
“PCOS, characterized by hyperandrogenism, chronic anovulation and/or sonographic evidence of small cysts in one or both ovaries, is the most common endocrinological disorder among women of reproductive age and the main cause of female infertility [124].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [124]
In the citing paper
“This is independent of weight, but is exacerbated by excess weight gain.7,8”
In the citing paper
“It is widely accepted that increased insulin resistance plays a key role in the pathophysiology of PCOS.”
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.
Adjusted age effect is called both trivial and small
MinorThe discussion calls the BMI- and diagnosis-adjusted age impact trivial, while Table IV labels the corresponding older-versus-younger PCOS effect small and unclear.
“Increasing age adversely impacted IR, yet the impact was trivial when adjusted for BMI and diagnostic criteria.”
“Older PCOS versus younger PCOS -21, ±23 Large (unclear) -7, ±32 ‡ Small (unclear)”
Conclusion reverses the PCOS and control sample counts
MinorThe conclusion assigns 741 participants to PCOS and 1224 to controls; the search-results account assigns those same counts to controls and PCOS, respectively.
“studies (741 women with PCOS and 1224 controls)”
“28 studies (n = 741 controls and n = 1224 PCOS)”
Adjusted BMI effect has the wrong magnitude label
MinorThe paper sets −31% as the threshold for a very large reduction, but labels the adjusted −30% BMI-subgroup effect "Very large." At the reported value, it falls in the large category.
“BMI=32 kg/m 2 (overweight) -31, ±6 Very large**** -30, ±9 † Very large****”
“for reduced IS, the corresponding magnitude thresholds were -3.7, -11, -20 and -31%, respectively.”
Reported age variation is incompatible with the eligibility range
MinorThe table gives one group of eight participants a mean age of 25 years and an age SD of 20 years. An SD that large is impossible if every participant was between 18 and 40 years old, as the selection criteria require.
“Micic et al. (2007) 8, 8 Rotterdam 25 ± 20 22 ± 8”
“participants were premenopausal; 18-40 years of age;”
Two thresholds are given for a very large improvement
MinorThe inferential-statistics section places the very-large improvement threshold at 46%, but the Figure 3 caption places it at 48%.
“For an improvement in IS, magnitude thresholds were 3.8, 12, 25 and 46%, representing small, moderate, large and very large, respectively”
“For an improvement in insulin sensitivity, magnitude thresholds were 3.8, 12, 25, 48 and 120%, representing small, moderate, large, very large and extra large, respectively”
Citations
Cites
Progressive Statistics for Studies in Sports Medicine and Exercise Science
HOPKINS, W. G., MARSHALL, S. W., BATTERHAM, A. M., & HANIN, J. (2009) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31818cb278 · Cited by 9,128
Self-citationGlucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
Fauser, B. C. J. M., Tarlatzis, B. C., Rebar, R. W., Legro, R. S., Balen, A. H., Lobo, R., Carmina, E., Chang, J., Yildiz, B. O., Laven, J. S. E., et al. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.09.024 · Cited by 1,976
Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome
Dunaif, A., Segal, K. R., Futterweit, W., & Dobrjansky, A. (1989) · Diabetes · doi:10.2337/diab.38.9.1165 · Cited by 1,967
Diamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947
March, W. A., Moore, V. M., Willson, K. J., Phillips, D. I. W., Norman, R. J., & Davies, M. J. (2010) · Human Reproduction · doi:10.1093/humrep/dep399 · Cited by 1,799
Muniyappa, R., Lee, S., Chen, H., & Quon, M. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00645.2007 · Cited by 1,643
Teede, H., Deeks, A., & Moran, L. (2010) · BMC Medicine · doi:10.1186/1741-7015-8-41 · Cited by 1,565
Self-citationSterne, J. A. C. (2001) · BMJ · doi:10.1136/bmj.322.7280.226 · Cited by 1,466
Flagged first, then by citations
Research works printed but not linked: 1
- Yang M . A Review of Random Effects Modelling in SAS (Release 8.2). London: London, Centre for Multilevel Modelling, 2003.
Cited by
Sorted by citations
Azziz, R. (2018) · Obstetrics & Gynecology · doi:10.1097/aog.0000000000002698 · Cited by 573
Stener-Victorin, E., Teede, H., Norman, R. J., Legro, R., Goodarzi, M. O., Dokras, A., Laven, J., Hoeger, K., & Piltonen, T. T. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00511-3 · Cited by 495
Self-citationCharacteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics
Glueck, C. J., & Goldenberg, N. (2019) · Metabolism · doi:10.1016/j.metabol.2018.11.002 · Cited by 442
Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing
Sadeghi, H. M., Adeli, I., Calina, D., Docea, A. O., Mousavi, T., Daniali, M., Nikfar, S., Tsatsakis, A., & Abdollahi, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020583 · Cited by 445
“On the other hand, hyperinsulinemia reduces hepatic SHBG [18,32,40,49,52,54–56], increasing free testosterone levels in blood [18,32,52,54,56].”
BackgroundLong-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis
Wekker, V, van Dammen, L., Koning, A., Heida, K. Y., Painter, R. C., Limpens, J., Laven, J. S. E., Roeters van Lennep, J. E., Roseboom, T. J., & Hoek, A. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmaa029 · Cited by 425
“Insulin clamp studies have shown that women with PCOS also have intrinsic insulin resistance, independent of weight, suggesting a higher T2D risk, even in the absence of obesity (Stepto et al., 2013; Cassar et al., 2016).”
BackgroundPolycystic ovarian syndrome (PCOS): Long-term metabolic consequences
Anagnostis, P. G., Tarlatzis, B. C., & Kauffman, R. P. (2017) · Metabolism · doi:10.1016/j.metabol.2017.09.016 · Cited by 445
Zhao, H., Zhang, J., Cheng, X., Nie, X., & He, B. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-022-01091-0 · Cited by 408
“IR and compensatory hyperinsulinaemia (HI) are considered major drivers of PCOS pathophysiology and are involved in the development of hyperandrogenaemia and reproductive dysfunction by various mechanisms [14].”
BackgroundKakoly, N. S., Khomami, M. B., Joham, A. E., Cooray, S. D., Misso, M. L., Norman, R. J., Harrison, C. L., Ranasinha, S., Teede, H. J., & Moran, L. J. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmy007 · Cited by 384
Self-citationArmanini, D., Boscaro, M., Bordin, L., & Sabbadin, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084110 · Cited by 324
“have a significant reduction in insulin sensitivity compared to BMI and age-matched controls [25,39].”
BackgroundTeede, H. J., Khomami, M. B., Morman, R., Laven, J. S. E., Joham, A. E., Costello, M., Patil, M., Rees, D. A., Berry, L., Cree, M. G., et al. (2026) · The Lancet · doi:10.1016/s0140-6736(26)00717-8 · Cited by 446
Self-citationXu, Y., & Qiao, J. (2022) · Journal of Healthcare Engineering · doi:10.1155/2022/9240569 · Cited by 329
Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update
Gnanadass, S. A., Prabhu, Y. D., & Gopalakrishnan, A. V. (2021) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-020-05951-2 · Cited by 305
“Elevated concentration of testosterone and a significantly lower concentration of SHBG has been independently correlated with IR [38].”
BackgroundMediterranean diet nutrients to turn the tide against insulin resistance and related diseases
Mirabelli, M., Chiefari, E., Arcidiacono, B., Corigliano, D. M., Brunetti, F. S., Maggisano, V., Russo, D., Foti, D. P., & Brunetti, A. (2020) · Nutrients · doi:10.3390/nu12041066 · Cited by 272
“PCOS, characterized by hyperandrogenism, chronic anovulation and/or sonographic evidence of small cysts in one or both ovaries, is the most common endocrinological disorder among women of reproductive age and the main cause of female infertility [124].”
BackgroundInfluentialInsulin and the polycystic ovary syndrome
Μacut, D., Bjekić-Macut, J., Rahelić, D., & Doknić, M. (2017) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2017.06.011 · Cited by 273
Polycystic ovary syndrome and risk of type 2 diabetes, coronary heart disease, and stroke
Zhu, T., Cui, J., & Goodarzi, M. O. (2021) · Diabetes · doi:10.2337/db20-0800 · Cited by 226
“MR suggests that low SHBG may be a causal factor for PCOS itself (2,3).”
MethodInfluentialInsulin resistance and PCOS: chicken or egg?
Moghetti, P., & Tosi, F. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01351-0 · Cited by 209
Neven, A., Laven, J., Teede, H., & Boyle, J. (2018) · Seminars in Reproductive Medicine · doi:10.1055/s-0038-1668085 · Cited by 196
Self-citationJeanes, Y. M., & Reeves, S. (2017) · Nutrition Research Reviews · doi:10.1017/s0954422416000287 · Cited by 194
Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials
Unfer, V., Facchinetti, F., Orrù, B., Giordani, B., & Nestler, J. E. (2017) · Endocrine Connections · doi:10.1530/ec-17-0243 · Cited by 220
Polycystic ovary syndrome as a metabolic disease
Helvacı, N., & Yıldız, B. O. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01057-w · Cited by 230
“Insulin resistance in PCOS is independent of but exacerbated by obesity, and increased BMI has a disproportionately greater effect on worsening insulin resistance in women with PCOS compared with control individuals 10 .”
Elkind-Hirsch, K. E., Chappell, N., Shaler, D., Storment, J., & Bellanger, D. (2022) · Fertility and Sterility · doi:10.1016/j.fertnstert.2022.04.027 · Cited by 182
Sex hormone-binding globulin and polycystic ovary syndrome
Zhu, J., Chen, Z., Feng, W., Long, S.-L., & Mo, Z. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.09.010 · Cited by 171
Tosi, F., Bonora, E., & Moghetti, P. (2017) · Human Reproduction · doi:10.1093/humrep/dex308 · Cited by 163
“A meta-analysis of clamp studies concluded that the impairment in insulin action is intrinsic to PCOS and independent of BMI, although obesity exacerbates insulin resistance with a disproportionately greater effect in these women than in controls (Cassar et al., 2016).”
BackgroundResultExercise Interventions in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Patten, R. K., Boyle, R. A., Moholdt, T. T., Kiel, I. A., Hopkins, W. G., Harrison, C. L., & Stepto, N. K. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00606 · Cited by 195
“As per our previous meta-analysis (Cassar et al., 2016) publication bias was assessed by examining a scatter plot of t-statistic associated with each study estimate value contributing to the study-estimate random effect versus log of the standard error of the effect.”
BackgroundMethodSelf-citationInositol in Polycystic Ovary Syndrome: Restoring Fertility through a Pathophysiology-Based Approach
Laganà, A. S., Garzon, S., Casarin, J., Franchi, M. P., & Ghezzi, F. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.09.001 · Cited by 178
“Moreover, BMI independently exacerbates IR in women suffering from PCOS, and has a greater impact on IR in women with PCOS than in controls [69].”
Wang, R., Li, W., Bordewijk, E. M., Legro, R. S., Zhang, H., Wu, X., Gao, J., Morin-Papunen, L. C., Homburg, R., König, T. E., et al. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz029 · Cited by 142
Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome
Sharpe, A., Morley, L. C., Tang, T. H., Norman, R. J., & Balen, A. H. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013505 · Cited by 141
Hiam, D., Moreno‐Asso, A., Teede, H. J., Laven, J. S. E., Stepto, N. K., Moran, L., & Gibson‐Helm, M. E. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8101606 · Cited by 134
“More specifically, most studies examined genetic variants within genes that regulate insulin resistance, which is strongly implicated in the aetiology and reproductive and metabolic health consequences of PCOS [6,7].”
BackgroundSelf-citationHarada, M. (2022) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12487 · Cited by 150
Adipose Tissue Dysfunction in Polycystic Ovary Syndrome
Bril, F., Ezeh, U., Amiri, M., Hatoum, S., Pace, L., Chen, Y.-H., Bertrand, F., Gower, B., & Azziz, R. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad356 · Cited by 123
The diagnosis and treatment of PCOS in adolescents: an update
Witchel, S. F., Burghard, A. C., Tao, R., & Oberfield, S. E. (2019) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000000778 · Cited by 128
Chen, J., Lin, P., Tsai, Y.-R., Yang, Y.-C., & Kang, H. (2019) · Cells · doi:10.3390/cells8111318 · Cited by 129
Xing, C., Zhang, J., Zhao, H., & He, B. (2022) · International Journal of Women's Health · doi:10.2147/ijwh.s344542 · Cited by 118
“SHBG Levels and Hyperinsulinemia in Women with PCOS Approximately 75% of PCOS patients show IR, a prominent PCOS feature.(30) IR is a condition where the response of cells to a given environmental insulin concentration is lower than that of normal controls,(40) varying with tissue type.”
BackgroundPolycystic Ovary Syndrome: Pathophysiology and Therapeutic Opportunities
Dong, J., & Rees, D. A. (2023) · BMJ Medicine · doi:10.1136/bmjmed-2023-000548 · Cited by 123
Li, H., Huang, X. Y., Chang, X., Yao, J., He, Q., Shen, Z., Ji, Y., & Wang, K. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14642 · Cited by 115
Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment
parker, J., O'Brien, C., Hawrelak, J., & Gersh, F. (2021) · doi:10.20944/preprints202112.0088.v1 · Cited by 113
Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment
Parker, J., O’Brien, C., Hawrelak, J., & Gersh, F. L. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19031336 · Cited by 114
“A systematic review and meta-analysis of euglycemic-hyperinsulinaemic clamp studies found that women with PCOS have a 27% reduction in insulin sensitivity compared to body mass index (BMI) and age-matched controls (154).”
BackgroundAndrogen excess and metabolic disorders in women with PCOS: beyond the body mass index
Condorelli, R. A., Calogero, A. E., Mauro, M. D., Mongioì, L. M., Cannarella, R., Rosta, G., & Vignera, S. L. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0762-3 · Cited by 104
Semaglutide delays 4‐hour gastric emptying in women with polycystic ovary syndrome and obesity
Jensterle, M., Ferjan, S., Ležaič, L., Sočan, A., Goričar, K., Zaletel, K., & Janez, A. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14944 · Cited by 102
“An increase in SHBG has been linked with improvement of hyperandrogenism via reduced bioavailability of testosterone.(41) Similar to our finding, treatment with liraglutide increased SHBG and reduced free androgen index.”
BackgroundPolycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review
Livadas, S., Anagnostis, P. G., Bosdou, J. Κ., Bantouna, D., & Paparodis, R. D. (2022) · World Journal of Diabetes · doi:10.4239/wjd.v13.i1.5 · Cited by 111
The effect of excess body fat on female and male reproduction
Mintziori, G., Nigdelis, M. P., Mathew, H., Mousiolis, A. C., Goulis, D. G., & Mantzoros, C. S. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154193 · Cited by 97
Tay, C. T., Mousa, A., Vyas, A., Pattuwage, L., Tehrani, F. R., & Teede, H. J. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.033572 · Cited by 104
“47 In terms of mechanisms, evidence has consistently demonstrated increased CVRFs in PCOS, including insulin resistance, 48 obesity, 49 diabetes, 3 metabolic syndrome, 3 dyslipidemia, 5,11 and hypertension.”
Self-citationInsulin Resistance is Associated with Depression Risk in Polycystic Ovary Syndrome
Greenwood, E. A., Pasch, L. A., Cedars, M. I., Legro, R. S., Eisenberg, E., & Huddleston, H. G. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.03.009 · Cited by 88
“Additionally, systemic insulin resistance is core to the pathophysiology of the disorder (3).”
BackgroundMoran, L. J., Tassone, E. C., Boyle, J., Brennan, L., Harrison, C. L., Hirschberg, A. L., Lim, S., Marsh, K., Misso, M. L., Redman, L., et al. (2020) · Obesity Reviews · doi:10.1111/obr.13046 · Cited by 84
Self-citationUric acid participating in female reproductive disorders: a review
Hu, J., Xu, W., Yang, H., & Mu, L. (2021) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-021-00748-7 · Cited by 82
“obesity, which can also be observed in many patients with hyperuricaemia [53].”
BackgroundHuang, Y., & Zhang, X. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00034.2021 · Cited by 81
Stepto, N. K., Moreno‐Asso, A., McIlvenna, L. C., Walters, K. A., & Rodgers, R. J. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00167 · Cited by 81
Self-citationWang, M., Yin, Q., & Xu, X. J. (2020) · Medical Science Monitor · doi:10.12659/msm.922136 · Cited by 84
“Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder in gynecology, characterized by persistent anovulation, high androgen, ovarian polycystic changes, and always combined with insulin resistance (IR) and obesity, with an incidence of 15% to 20% [1].”
BackgroundMelin, J., Forslund, M., Alesi, S., Piltonen, T., Romualdi, D., Spritzer, P. M., Tay, C. T., Pena, A., Witchel, S. F., Mousa, A., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad465 · Cited by 78
Self-citationHansen, S., Svendsen, P., Jeppesen, J., Høeg, L. D., Andersen, N. R., Kristensen, J. M., Nilas, L., Lundsgaard, A., Wojtaszewski, J., Madsbad, S., et al. (2018) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2018-01771 · Cited by 69
Shpakov, A. O. (2021) · Pharmaceuticals · doi:10.3390/ph14010042 · Cited by 83
Wu, Y., Tu, M., Huang, Y., Liu, Y., & Zhang, D. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.11995 · Cited by 72
Aerobic Training Improves Quality of Life in Women with Polycystic Ovary Syndrome
COSTA, E. C., DE SÁ, J. C. F., STEPTO, N. K., COSTA, I. B. B., FARIAS-JUNIOR, L. F., MOREIRA, S. D. N. T., SOARES, E. M. M., LEMOS, T. M. A. M., BROWNE, R. A. V., & AZEVEDO, G. D. (2018) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001579 · Cited by 71
Self-citationIslam, H., Masud, J., Islam, Y. N., & Haque, F. K. M. (2022) · Women s Health · doi:10.1177/17455057221117966 · Cited by 98
The role of gonadotropin‐releasing hormone neurons in polycystic ovary syndrome
McCartney, C. R., Campbell, R. E., Marshall, J. C., & Moenter, S. M. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13093 · Cited by 77
Melin, J., Forslund, M., Alesi, S., Piltonen, T., Romualdi, D., Spritzer, P. M., Tay, C. T., Pena, A., Witchel, S. F., Mousa, A., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad098 · Cited by 72
Self-citationAustregésilo de Athayde De Hollanda Morais, B., Martins Prizão, V., de Moura de Souza, M., Ximenes Mendes, B., Rodrigues Defante, M. L., Cosendey Martins, O., & Rodrigues, A. M. (2024) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2024.108834 · Cited by 68
A review on critical appraisal and pathogenesis of polycystic ovarian syndrome
Hajam, Y. A., Rather, H., Neelam, N., Kumar, R., Basheer, M., & Reshi, M. S. (2024) · Endocrine and Metabolic Science · doi:10.1016/j.endmts.2024.100162 · Cited by 86
Arentz, S., Smith, C. A., Abbott, J. A., & Bensoussan, A. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-2011-x · Cited by 73
“The pathogenesis is underpinned by insulin resistance [7] which affects up to 75% of lean women and up to 95% of obese women (compared to 62% in BMI matched non-POCS controls) [8].”
BackgroundCardiometabolic Risk in PCOS: More than a Reproductive Disorder
Torchen, L. C. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0956-2 · Cited by 65
Nutritional guidelines for the management of insulin resistance
Muscogiuri, G., Barrea, L., Caprio, M., Ceriani, F., Chavez, A. O., El Ghoch, M., Frias-Toral, E., Mehta, R. J., Mendez, V., Paschou, S. A., et al. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1908223 · Cited by 63
“%) was found in women with PCOS when compared with controls by using a euglycemic-hyperinsulinemic clamp, independent of BMI, lower levels of sex hormone-binding globulin (SHBG) is related to a reduced IS and increased availability of free androgens (Cassar et al. 2016).”
ResultGreenwood, E. A., Yaffe, K. S., Wellons, M., Cedars, M. I., & Huddleston, H. G. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00234 · Cited by 64
Cardiometabolic risks in PCOS: a review of the current state of knowledge
Kakoly, N. S., Moran, L., Teede, H. J., & Joham, A. E. (2018) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2019.1556094 · Cited by 71
“The vast majority of individual studies that evaluated the relationship between PCOS, BMI, and DM2 note that both PCOS and BMI are independent contributors to DM2 [14,29,42].”
MethodInfluentialSelf-citationLuque-Ramírez, M., Nattero-Chávez, L., Ortiz Flores, A. E., & Escobar-Morreale, H. F. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmx039 · Cited by 62
Long‐term health outcomes in young women with polycystic ovary syndrome: A narrative review
Allen, L. A., Shrikrishnapalasuriyar, N., & Rees, A. (2021) · Clinical Endocrinology · doi:10.1111/cen.14609 · Cited by 75
“However, the increased risk of symptoms persists even when women with PCOS are matched by BMI with controls.77 The cutaneous manifestations of PCOS (hirsutism, acne and scalp hair loss) are emotionally distressing, while fertility may be another major concern, albeit that depression and anxiety scores remain higher th…”
BackgroundMethodInfluentialTestosterone a key factor in gender related metabolic syndrome
Bianchi, V. E., & Locatelli, V. (2018) · Obesity Reviews · doi:10.1111/obr.12633 · Cited by 65
Complex diseases and co-morbidities: polycystic ovary syndrome and type 2 diabetes mellitus
Rodgers, R. J., Avery, J. C., Moore, V. M., Davies, M. J., Azziz, R., Stener-Victorin, E., Moran, L. J., Robertson, S. A., Stepto, N. K., Norman, R. J., et al. (2019) · Endocrine Connections · doi:10.1530/ec-18-0502 · Cited by 60
Self-citationFitz, V., Graca, S., Mahalingaiah, S., Liu, J., Lai, L., Butt, A., Armour, M., Rao, V., Naidoo, D., Maunder, A., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad762 · Cited by 70
Self-citationXiang, S., Xia, M., Song, J., Liu, D., & Lian, F. (2020) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-020-3219-z · Cited by 60
van der Ham, K., Laven, J. S. E., Tay, C. T., Mousa, A., Teede, H. J., & Louwers, Y. V. (2024) · Fertility and Sterility · doi:10.1016/j.fertnstert.2024.05.163 · Cited by 79
Self-citationTao, X., Cai, L., Chen, L., Ge, S., & Deng, X. (2019) · Journal of Ovarian Research · doi:10.1186/s13048-019-0555-8 · Cited by 60
Nutritional Supplements and Complementary Therapies in Polycystic Ovary Syndrome
Alesi, S., Ee, C., Moran, L., Rao, V. S., & Mousa, A. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab141 · Cited by 191
Higher risk of type 2 diabetes in women with hyperandrogenic polycystic ovary syndrome
Persson, S., Elenis, E., Türkmen, Ş., Kramer, M. S., Yong, E., & Poromaa, I. S. (2021) · Fertility and Sterility · doi:10.1016/j.fertnstert.2021.04.018 · Cited by 57
Liu, Q., Tang, B., Zhu, Z., Kraft, P. L., Deng, Q., Stener‐Victorin, E., & Jiang, X. (2022) · Diabetologia · doi:10.1007/s00125-022-05746-x · Cited by 55
Urgatz, B., & Razvi, S. (2023) · Current Medical Research and Opinion · doi:10.1080/03007995.2023.2165811 · Cited by 72
Patten, R. K., McIlvenna, L. C., Levinger, I., GARNHAM, A. P., Shorakae, S., Parker, A. G., McAinch, A. J., Rodgers, R. J., Hiam, D., Moreno‐Asso, A., et al. (2022) · Human Reproduction · doi:10.1093/humrep/deac047 · Cited by 63
Self-citationExercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis
Stepto, N. K., Hiam, D., Gibson‐Helm, M. E., Cassar, S., Harrison, C. L., Hutchison, S. K., Joham, A. E., Canny, B. J., Moreno‐Asso, A., Strauss, B. J., et al. (2020) · Endocrine Connections · doi:10.1530/ec-19-0551 · Cited by 53
“This insulin resistance is exacerbated by obesity (extrinsic insulin resistance (9, 10, 13)).”
BackgroundMethodInfluentialSelf-citationShirazi, F. K. H., Khodamoradi, Z., & Jeddi, M. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00710-z · Cited by 58
Parker, L., Shaw, C. S., Banting, L., Levinger, I., Hill, K. M., McAinch, A. J., & Stepto, N. K. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2016.00661 · Cited by 53
“Females diagnosed with polycystic ovary syndrome (PCOS) were included in the study as they have an intrinsic insulin resistance and are at a 4-fold greater risk of developing type 2 diabetes (Stepto et al., 2013; Cassar et al., 2016).”
BackgroundSelf-citationHuang, J., Zhao, J., Geng, X., Chu, W., Li, S., Chen, Z., & Du, Y. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.12.008 · Cited by 51
“For example, insulin resistance and compensatory hyperinsulinemia in PCOS contribute to hyperandrogenemia and ovulatory disturbances.(67) In PCOS, a post-binding defect is observed in receptor signaling, likely owing to inactivated IRS1 that selectively affects metabolic action in classic insulin target tissues and in…”
BackgroundUnfer, V., Kandaraki, E., Pkhaladze, L., Roseff, S., Vazquez-Levin, M. H., Laganà, A. S., Chan, S. Y., Yap‐Garcia, M. I. M., Greene, N. D. E., Soulage, C. O., et al. (2024) · Endocrine and Metabolic Science · doi:10.1016/j.endmts.2024.100159 · Cited by 58
“The EGOI suggested the consideration of the inclusion of IR, as a diagnostic marker, since IR affects around 75 % of PCOS patients and can cause hyperandrogenism (Cassar et al., 2016; Tosi et al., 2021).”
BackgroundMukherjee, A. G., Wanjari, U. R., Kannampuzha, S., Murali, R., Namachivayam, A., Ganesan, R., Dey, A., Babu, A., Renu, K., Vellingiri, B., et al. (2023) · Metabolites · doi:10.3390/metabo13010129 · Cited by 56
Polycystic ovary syndrome: A metabolic disorder with therapeutic opportunities
Zhang, Y., Chen, Z., & Zhao, H. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.08.002 · Cited by 62
Exercise Recommendations for Women with Polycystic Ovary Syndrome: Is the Evidence Enough?
Stepto, N. K., Patten, R. K., Tassone, E. C., Misso, M. L., Brennan, L., Boyle, J. A., Boyle, R. A., Harrison, C. L., Hirschberg, A. L., Marsh, K. A., et al. (2019) · Sports Medicine · doi:10.1007/s40279-019-01133-6 · Cited by 51
Self-citationPatten, R. K., Pascoe, M. C., Moreno‐Asso, A., Boyle, R. A., Stepto, N. K., & Parker, A. G. (2021) · BMC Public Health · doi:10.1186/s12889-021-12280-9 · Cited by 57
Self-citationPolycystic ovary syndrome and aging: Health implications after menopause
Helvacı, N., & Yıldız, B. O. (2020) · Maturitas · doi:10.1016/j.maturitas.2020.05.013 · Cited by 49
Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS
Halama, A., Aye, M. M., Dargham, S. R., Kuliński, M., Suhre, K., & Atkin, S. L. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00116 · Cited by 45
“However, by any of the diagnostic criteria, PCOS is associated with metabolic features commonly related to lower insulin sensitivity (IS) that is contributed to by an increased BMI in women with PCOS compared to those without PCOS (6); PCOS subjects that were overweight showed moderately lower IS compared with lean PC…”
BackgroundRecent advances in emerging PCOS therapies
Glendining, K. A., & Campbell, R. E. (2023) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2022.102345 · Cited by 45
Mo, L., Mansfield, D. R., Joham, A., Cain, S. W., Bennett, C., Blumfield, M., Teede, H., & Moran, L. J. (2019) · Clinical Endocrinology · doi:10.1111/cen.13922 · Cited by 42
Self-citationWhy does Polycystic Ovary Syndrome (PCOS) Need Long-term Management?
Ruan, X., Li, M., & Mueck, A. O. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190130104922 · Cited by 44
Anagnostis, P. G., Paparodis, R. D., Bosdou, J. Κ., Bothou, C., Μacut, D., Goulis, D. G., & Livadas, S. (2021) · Endocrine · doi:10.1007/s12020-021-02801-2 · Cited by 45
Cai, M., Shao, X., Xing, F., Zhang, Y., Gao, X., Zeng, Q., Dilimulati, D., Qu, S., & Zhang, M. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14583 · Cited by 44
“Insulin resistance affects 50% to 80% of women with PCOS, depending on the population and diagnostic method used,(2,3) and plays an intrinsic role in the pathogenesis of PCOS, independently of obesity.(6,7) Previous studies have demonstrated that IR may bring about hyperandrogenaemia by disrupting the hypothalamic-pit…”
BackgroundParker, J. (2023) · Life · doi:10.3390/life13041056 · Cited by 43
Blackshaw, L. C. D., Chhour, I., Stepto, N. K., & Lim, S. S. (2019) · Medical Sciences · doi:10.3390/medsci7070076 · Cited by 40
“The degree of insulin resistance experienced by women with PCOS has also been shown to be above what would be expected given their BMI [2,5].”
BackgroundInfluentialSelf-citationRisk and incidence of cardiovascular disease associated with polycystic ovary syndrome
Wan, Z., Zhao, J., Ye, Y., Sun, Z., Li, K., Chen, Y., Fang, Y., Zhang, Y., Lin, J., Sun, P., et al. (2024) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwae066 · Cited by 43
Lin, H., Xing, W., Li, Y., Xie, Y., Tang, X., & Zhang, Q. (2018) · Gynecological Endocrinology · doi:10.1080/09513590.2018.1459548 · Cited by 41
“It is believed that the dysfunction of gene regulation should take responsibility for the development of PCOS [8].”
BackgroundHyperandrogenism and Cardiometabolic Risk in Pre- and Postmenopausal Women—What Is the Evidence?
Hirschberg, A. L. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad590 · Cited by 44
Li, W., Chen, Q., Xie, Y., Hu, J., Yang, S., & Lin, M. (2018) · Clinical Endocrinology · doi:10.1111/cen.13860 · Cited by 39
Lipids and insulin regulate mitochondrial‐derived peptide (MOTS‐c) in PCOS and healthy subjects
Ramanjaneya, M., Jerobin, J., Bettahi, I., Bensila, M., Aye, M., Siveen, K. S., Sathyapalan, T., Skarulis, M. C., Abou‐Samra, A., & Atkin, S. L. (2019) · Clinical Endocrinology · doi:10.1111/cen.14007 · Cited by 38
Racial and ethnic differences in the metabolic response of polycystic ovary syndrome
Ezeh, U. I., Chen, Y.-D. I., & Azziz, R. (2020) · Clinical Endocrinology · doi:10.1111/cen.14193 · Cited by 40
Metadata
- Authors
- Cassar, S., Misso, M. L., Hopkins, W. G., Shaw, C. S., Teede, H. J., & Stepto, N. K.
- Affiliations
- Monash Health (AU)
- Deakin University (AU)
- Corresponding author
- Stepto, Nigel K.
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-10-07
- Volume
- 31
- Issue
- 11
- Pages
- 2619-2631
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2528179062
- Semantic Scholar
- 7bd1e54cb161a47c607c26284f2c1061e768c318
- Cited by
- 415
- References
- 79
- Citations by year
- 2026: 54 · 2025: 51 · 2024: 59 · 2023: 54 · 2022: 46 · 2021: 42 · 2020: 36 · 2019: 30 · 2018: 22 · 2017: 20 · 2016: 1
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Australian Government
- Monash University
- Medical Research Council
- National Health and Medical Research Council (606553)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, insulin resistance, insulin sensitivity, body mass index, hyperinsulinemic-euglycemic clamp, PCOS diagnostic criteria, NIH criteria, Rotterdam criteria, sex hormone-binding globulin, hyperandrogenism, hyperinsulinemia, hypertriglyceridemia, hyperlipidemia, hyperuricemia, hyperoestrogenism
- MeSH terms
- Female, Humans, Insulin Resistance, Polycystic Ovary Syndrome, Glucose Clamp Technique, Body Mass Index
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 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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
