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.
Key words:
Polycystic ovary syndrome - Metformin - Homocysteine
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