Elsevier

Metabolism

Volume 43, Issue 5, May 1994, Pages 647-654
Metabolism

Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy

https://doi.org/10.1016/0026-0495(94)90209-7Get rights and content

Abstract

Using polycystic ovary syndrome (PCOS) as a model of insulin resistance and hyperandrogenism, our specific aim was to assess the effect of Metformin on lipoproteins, sex hormones, gonadotropins, and blood pressure in 26 women with PCOS who were studied at baseline, received Metformin 1.5 g/d for 8 weeks, and were then restudied. None of the women had normal menstrual cycles, 100% had multiple subcapsular follicules by pelvic ultrasound, 90% were hirsute, and 85% had high free testosterone. Comparing post-Metformin versus baseline levels, the Quetelet Index (QI) decreased 1.5% (P = .04) and the waist to hip ratio (WHR) decreased 2.8% (P = .003). After covariance adjusting for changes in the QI and WHR, on Metformin the area under the insulin curve (IA) during oral glucose tolerance testing decreased 35% (P = .04), and the insulin area to glucose area ratio decreased 31% (P = .03). On Metformin, covariance-adjusted systolic blood pressure (SBP) decreased (P = .04) and apo A-1 increased (P = .05). On Metformin, with improvement in insulin sensitivity, there were sharp reductions in covariance-adjusted luteinizing hormone ([LH] P = .0007), total testosterone ([T] P = .0004), free T (P = .0001), androstenedione (P = .002), dehydroepiandrosterone sulfate ([DHEAS] P = .006), and the free androgen index ([FAI] P = .0005), with increments in follicle-stimulating hormone ([FSH] P = .04) and sex hormone-binding globulin ([SHBG] P = .04). The change (decrease) in IA on Metformin was a significant independent positive determinant of the reduction in total T (R2 = 22%, P = .03), free T (R2 = 30%, P = .01), and FAI (R2 = 29%, P = .01). Three spontaneous pregnancies occurred during treatment. Those seven patients who continued Metformin therapy all resumed normal menstrual cycles. In PCOS, hyperinsulinemia favors hyperproduction of androgens with subsequent alterations in secretion of gonadotropins, depression of apo A-1, and elevation of SBP, metabolic changes that increase coronary heart disease risk. Most of the metabolic abnormalities of PCOS can be reversed by Metformin, with the additional benefit of enough normalization of the endocrine milieu to allow regular menstrual cycles, reversal of infertility, and spontaneous pregnancy.

References (63)

  • RA Wild et al.

    Clinical signs of androgen excess risk factors for coronary artery disease

    Fertil Steril

    (1990)
  • JE Nestler et al.

    Insulin as an effector of human ovarian and adrenal steroid metabolism

    Endocrinol Metab Clin North Am

    (1991)
  • P Ducimetiere et al.

    Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population

    Diabetologia

    (1980)
  • K Pyörälä et al.

    Plasma insulin as coronary heart disease risk factor: Relationship to other risk factors and predictive value during 912years follow-up of the Helsinki policemen study population

    Acta Med Scand

    (1985)
  • M Modan et al.

    Hyperinsulinemia, sex, and risk of atherosclerotic vascular disease

    Circulation

    (1991)
  • J Slowinski-Srzendnicka et al.

    The role of hyperinsulinemia in the development of lipid disturbances in non-obese and obese women with the polycystic ovary syndrome

    J Endocrinol Invest

    (1991)
  • A Laws et al.

    Evidence for an independent relationship between insulin resistance and fasting plasma HDL cholesterol, triglyceride and insulin concentrations

    J Intern Med

    (1992)
  • GM Reaven

    Role of insulin resistance in human disease

    Diabetes

    (1988)
  • LA Mattson et al.

    Lipid metabolism in women with polycystic ovary syndrome: Possible implications for an increased risk of coronary heart disease

    Fertil Steril

    (1984)
  • RA Wild et al.

    Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome

    J Clin Endocrinol Metab

    (1985)
  • E Ferrannini et al.

    Insulin resistance in essential hypertension

    N Engl J Med

    (1987)
  • S Zimmermann et al.

    Polycystic ovary syndrome: Lack of hypertension despite profound insulin resistance

    J Clin Endocrinol Metab

    (1992)
  • GM Reaven et al.

    Hypertension as a disease of carbohydrate and lipoprotein metabolism

    Am J Med

    (1989)
  • GM Reaven

    Role of abnormalities of carbohydrate and lipoprotein metabolism in the pathogenesis and clinical course of hypertension

    J Cardovasc Pharmacol

    (1990)
  • K Landin et al.

    Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors

    J Intern Med

    (1991)
  • V Scelles et al.

    Plasminogen activator inhibitor-1 and insulin levels in various insulin resistance states

    Diabetes Metab

    (1992)
  • GA Burghen et al.

    Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease

    J Clin Endocrinol Metab

    (1980)
  • A Dunaif et al.

    Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome

    Diabetes

    (1989)
  • Velazquez ME, Mendoza GS: Lipoproteinas, respuesta insulinicy y hormonas sexules en el sindrome de ovarios...
  • DR Shelley et al.

    Polycystic ovary syndrome

    Compr Ther

    (1990)
  • S Franks

    Polycystic ovary syndrome: A changing perspective

    Clin Endocrinol

    (1989)
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    Supported in part by Grant No. M-392-91, Merida, Venezuela, M-402, and by Grants No. 757 and 2–728 from the Jewish Hospital Medical Research Council, Jewish Hospital of Cincinnati.

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