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Cited by 272Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsAdrenal Hormones and Disorders

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

Arslanian, Silva A., Lewy, Vered, Danadian, Kapriel, Saad, Rola·2002·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.87.4.8398
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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.

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  • Metformin reduces insulin resistance in type 2 diabetes and in adults and adolescents with PCOS when hyperinsulinaemic euglycaemic clamps are used.

    “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

    The Results (p. 3) report significantly higher insulin-stimulated glucose disposal after metformin treatment, measured with a hyperinsulinemic-euglycemic clamp in obese adolescents with PCOS and impaired glucose tolerance. This study did not test adults with PCOS or people with type 2 diabetes. The Discussion (p. 4) also cautions that, because the trial was open-label, the observed effects cannot be attributed to metformin with certainty. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In obese adolescents with PCOS and impaired glucose tolerance, three months of metformin improved glucose tolerance, with 8 out of 15 subjects normalizing oral glucose tolerance test and lower posttreatment 2-hour glucose levels (9.1 ± 0.3 vs. 7.4 ± 0.3 mmol/l; p = 0.005).

    “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]

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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
DOI
10.1210/jcem.87.4.8398
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

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