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

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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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Background
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Self-citation

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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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

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