The DOI matches its Crossref record; 45 of the 50 references it cites were found in a registry or an index.
Metformin Therapy in Obese Adolescents with Polycystic Ovary Syndrome and Impaired Glucose Tolerance: Amelioration of Exaggerated Adrenal Response to Adrenocorticotropin with Reduction of Insulinemia/Insulin Resistance
Abstract
Functional adrenal hyperandrogenism occurs in women with polycystic ovary syndrome (PCOS). Insulin, similar to its ovarian effect, may impact the regulation of adrenal steroidogenesis by modulating the activity of P450c17alpha, the rate-limiting enzyme in androgen biosynthesis. We previously demonstrated that obese adolescents with PCOS are severely insulin resistant and are at heightened risk for impaired glucose tolerance and type 2 diabetes. In the present study we tested the hypothesis that metformin therapy in obese adolescents with PCOS will attenuate the adrenal steroidogenic response to ACTH, with reduction of insulin resistance/insulinemia. Fifteen adolescents with PCOS and impaired glucose tolerance received 3 months of metformin (850 mg, twice daily) therapy. Pre- and posttherapy they had oral glucose tolerance testing, ACTH stimulation test, a 3-h hyperinsulinemic (80 mU/m(2).min)-euglycemic clamp to assess insulin sensitivity and a hyperglycemic clamp to assess insulin secretion. After 3 months of metformin treatment, glucose intolerance improved, with eight subjects having normal glucose tolerance. Total and free T decreased [1.5 +/- 0.2 vs. 1.0 +/- 0.1 nmol/liter (P = 0.022) and 41.3 +/- 8.3 vs. 22.2 +/- 2.1 pmol/liter (P = 0.028), respectively]. Insulin-stimulated glucose disposal increased (21.5 +/- 2.2 vs. 25.0 +/- 2.2 micromol/kg.min; P = 0.041). Fasting insulin and oral glucose tolerance test insulin and glucose area under the curve decreased significantly. ACTH-stimulated increases in androstenedione, 17-hydroxyprogesterone, and 17-hydroxypregnenelone were lower after metformin treatment [2.8 +/- 0.4 vs. 1.7 +/- 0.3 nmol/liter (P = 0.014), 7.0 +/- 0.6 vs. 5.3 +/- 0.5 nmol/liter (P = 0.011), and 30.4 +/- 3.7 vs. 25.7 +/- 4.2 nmol/liter (P = 0.054)]. Fasting insulin correlated with the 17-hydroxypregnenelone response to ACTH stimulation (r = 0.52; P = 0.008). In summary, metformin treatment of obese adolescents with PCOS and impaired glucose tolerance is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels. Moreover, metformin therapy is associated with attenuation of the adrenal steroidogenic response to ACTH. Metformin therapy was well tolerated. In conclusion, double blind, placebo-controlled studies will determine whether insulin-sensitizing therapy corrects not only ovarian hyperandrogenism but also functional adrenal hyperandrogenism in adolescents with PCOS.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Metformin clearly reduces insulin resistance in DM2and in adults and adolescents with PCOS when hyperinsulinaemic euglycaemic clamps were used (Moghetti et al. , 2000; Meyer et al. , 2007; Arslanian et al. , 2002).”
From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Arslanian et al. , 2002
Experimental — accuracy not yet measuredIn the citing paper
“A trial performed in obese adolescents with PCOS and impaired glucose tolerance [51] evaluated three months of therapy with metformin and showed an improvement in glucose tolerance in this specific population; in fact, 8 out of 15 subjects had a normalization in their oral glucose tolerance test (OGTT) with significant lower posttreatment 2-hour glucose levels (9.1 ± 0.3 vs. 7.4 ± 0.3 mmol/l; p =”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [51]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.6.0318 · Cited by 2,776
Legro, R. S. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.1.165 · Cited by 1,743
Kahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C., & Palmer, J. P. (1993) · Diabetes · doi:10.2337/diab.42.11.1663 · Cited by 1,405
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
Ehrmann, D. A., Barnes, R. B., Rosenfield, R. L., Cavaghan, M. K., & Imperial, J. (1999) · Diabetes Care · doi:10.2337/diacare.22.1.141 · Cited by 1,257 · cited 1×
“creased risk for IGT and type 2 diabetes (9, 28, 29).”
BackgroundVelazquez, E. M., Mendoza, S., Hamer, T., Sosa, F., & Glueck, C. J. (1994) · Metabolism · doi:10.1016/0026-0495(94)90209-7 · Cited by 865
Nestler, J. E., Jakubowicz, D. J., Evans, W. S., & Pasquali, R. (1998) · New England Journal of Medicine · doi:10.1056/nejm199806253382603 · Cited by 781
Nestler, J. E., & Jakubowicz, D. J. (1996) · New England Journal of Medicine · doi:10.1056/nejm199608293350902 · Cited by 743
Pasquali, R., Gambineri, A., Biscotti, D., Vicennati, V., Gagliardi, L., Colitta, D., Fiorini, S., Cognigni, G. E., Filicori, M., & Morselli-Labate, A. M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6738 · Cited by 635
Nestler, J. E., Jakubowicz, D. J., Falcon de Vargas, A., Brik, C., Quintero, N., & Medina, F. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4886 · Cited by 617
Dunaif, A. E., Scott, D., Finegood, D. T., Quintana, B., & Whitcomb, R. W. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.9.8784087 · Cited by 561
Flagged first, then by citations
5 of the 50 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The Diagnosis of Polycystic Ovary Syndrome during Adolescence
Witchel, S. F., Oberfield, S., Rosenfield, R. L., Codner, E., Bonny, A., Ibáñez, L., Pena, A., Horikawa, R., Gomez-Lobo, V., Joel, D., et al. (2015) · Hormone Research in Paediatrics · doi:10.1159/000375530 · Cited by 3,113
Self-citationDiamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947
Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., & Welt, C. K. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2350 · Cited by 1,919
Self-citationRosenfield, R. L., & Ehrmann, D. A. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1104 · Cited by 1,603
Styne, D. M., Arslanian, S. A., Connor, E. L., Farooqi, I. S., Murad, M. H., Silverstein, J. H., & Yanovski, J. A. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2573 · Cited by 1,375
Self-citation
Metadata
- Authors
- Arslanian, S. A., Lewy, V., Danadian, K., & Saad, R.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Arslanian, Silva A.
- ORCID
- Arslanian, Silva A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2002-04-01
- Volume
- 87
- Issue
- 4
- Pages
- 1555-1559
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2096929808
- Cited by
- 272
- References
- 50
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2022: 7 · 2021: 2 · 2020: 8 · 2019: 3 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 15 · 2013: 9 · 2012: 13
- FWCI
- 20.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01-RR-00084, M01RR000084)
- NIH Clinical Center
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01‐HD27503, R01HD027503, K24HD001357, K24 HD 01357)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- metformin, polycystic ovary syndrome, adolescent obesity, impaired glucose tolerance, insulin resistance, insulin levels, ACTH stimulation test, adrenal steroidogenesis, androgen production, insulin sensitivity, insulin secretion, type 2 diabetes prevention, hyperandrogenism, insulin-stimulated glucose disposal, androstenedione, 17-hydroxyprogesterone
- MeSH terms
- Insulin Secretion, Adolescent, Adrenal Glands, Adrenocorticotropic Hormone, Androgens, Body Composition, Female, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Metformin, Obesity, Polycystic Ovary Syndrome, Glucose Intolerance
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.
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
