Exp Clin Endocrinol Diabetes 2002; 110(2): 74-76
DOI: 10.1055/s-2002-23489
Articles

© Johann Ambrosius Barth

Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome

J. Vrbíková 1 , M. Bičíková 1 , J. Tallová 2 , M. Hill 1 , L. Stárka 1
  • 1 Institute of Endocrinology Prague 1, Czech Republic
  • 2 Masaryk University, Brno, Czech Republic
Further Information

Publication History

received 22 February 2001 first decision 25 April 2001

accepted 07 June 2001

Publication Date:
27 March 2002 (online)

Summary

Risk for atherosclerosis is increased in women with polycystic ovary syndrome (PCOS). Homocysteine (Hcy) is one of the independent risk factors for ischemic heart disease. We examined the effect of metformin (M) treatment on Hcy levels, steroids and glycide tolerance in PCOS. Material and methods: 9 women with PCOS (defined as hyperandrogenemia and chronic anovulation); age 20 ± 3.8 yrs, BMI 28.1 ± 6.5 kg/m2; examined in the follicular phase of spontaneous menstrual cycle before and after 27 ± 4 weeks of treatment with M 1000 mg/day. The plasma concentrations of Hcy, DHEA, DHEA-S, cortisol (F), allopregnanolone (HPO), 17OHpregnenolone (17OHPl), insulin (I) and blood glucose (G) before and after the course of M were measured. Results: After the course of M, Hcy significantly increased (10.1 ± 2.6 to 13.4 ± 5.1 μmol/l, p < 0.05.). There was no significant change in levels of I, HPO, F, DHEA-S and 17OHPl. DHEA levels increased significantly (from 26.9 ± 15.7 to 44.4 ± 24.6 nmol/l, p < 0.05). A borderline significant trend towards reduction in waist-hip ratio was seen (from 0.986 ± 0.042 to 0.951 ± 0.085; p < 0.06). Conclusions: Treatment with metformin in women with PCOS can lead to the increase in homocysteine levels - a risk factor for atherosclerosis.

References

  • 1 Aarsand A K, Carlsen S M. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment.  J Intern Med. 1998;  244 169-174
  • 2 Barrett-Connor E, Ferrara A. Dehydroepiandrosterone, dehydroepiandrosterone sulfate, obesity, waist- hip ratio, and noninsulin-dependent diabetes in postmenopausal women: the Rancho Bernardo Study.  J Clin Endocrinol Metab. 1996;  81 59-64
  • 3 Bicikova M, Lapcik O, Hampl R, Starka L, Knuppen R, Haupt O, Dibbelt L. A novel radioimmunoassay of allopregnanolone.  Steroids. 1995;  60 210-213
  • 4 Carlsen S M, Folling I, Grill V, Bjerve K S, Schneede J, Refsum H. Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease.  Scand J Clin Lab Invest. 1997;  57 521-527
  • 5 Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome [see comments].  Eur J Endocrinol. 1998;  138 269-274
  • 6 Glueck C J, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome.  Metabolism. 1999;  48 511-519
  • 7 Hill M, Lukac D, Lapcik O, Sulcova J, Hampl R, Pouzar V, Starka L. Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects.  Clin Chem Lab Med. 1999;  37 439-447
  • 8 Hoogeveen E K, Kostense P J, Jakobs C, Bouter L M, Heine R J, Stehouwer C D. Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus?.  J Intern Med. 1997;  242 389-394
  • 9 Kolodziejczyk B, Duleba A J, Spaczynski R Z, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome.  Fertil Steril. 2000;  73 1149-1154
  • 10 Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolin E, Muggeo M. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.  J Clin Endocrinol Metab. 2000;  85 139-146
  • 11 Morin-Papunen L, Koivunen R M, Ruokonen A, Martikainen H K. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome.  Fertil Steril. 1998;  69 691-696
  • 12 Nestler J E, Clore J N, Blackard W G. Metabolism and actions of dehydroepiandrosterone in humans.  J Steroid Biochem Mol Biol. 1991;  40 599-605
  • 13 Nestler J E, Jakubowicz D J. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome [see comments].  N Engl J Med. 1996;  335 617-623
  • 14 Nestler J E, Jakubowicz D J. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens.  J Clin Endocrinol Metab. 1997;  82 4075-4079
  • 15 Suzuki M, Kanazawa A, Hasegawa M, Hattori Y, Harano Y. A close association between insulin resistance and dehydroepiandrosterone sulfate in subjects with essential hypertension.  Endocr J. 1999;  46 521-528
  • 16 Tallova J, Tomandl J, Bicikova M, Hill M. Changes of plasma total homocysteine levels during the menstrual cycle.  Eur J Clin Invest. 1999;  29 1041-1044
  • 17 Velazquez E, Acosta A, Mendoza S G. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.  Obstet Gynecol. 1997;  90 392-395
  • 18 Velazquez E M, Mendoza S, Hamer T, Sosa F, Glueck C J. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy.  Metabolism. 1994;  43 647-654

M.D. Jana Vrbíková

Institute of Endocrinology

Národní 8

116 94 Prague 1

Czech Republic

Phone: +420-2-24905111

Email: jvrbikova@endo.cz

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