Subscribe to RSS
DOI: 10.1055/s-0029-1237705
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
The Effect of Metformin Treatment for 2 Years without Caloric Restriction on Endocrine and Metabolic Parameters in Women with Polycystic Ovary Syndrome
Publication History
received 19.05.2009
first decision 08.06.2009
accepted 30.07.2009
Publication Date:
08 December 2009 (online)

Abstract
Introduction: The aim of this study was to evaluate long-term changes in endocrine and metabolic parameters and body mass index in women with polycystic ovary syndrome (PCOS) who were treated with metformin over 2 years without caloric restriction.
Material and Methods: Twenty-six obese women with PCOS were treated with metformin over 2 years without caloric restriction. Clinical, metabolic and endocrine parameters and the body mass index were measured and an oral glucose tolerance test was carried out to calculate insulin resistance indices at the beginning and at the follow-up after 2 years. The Homeostatic Model for Assessment of Insulin Resistance (HOMA-IR) was calculated.
Results: No significant changes in body mass index or HOMA-IR were observed. However, a significant decrease in fasting and 2-h insulin levels was observed. Women showed a significant increase in sex hormone–binding globulin (SHBG) levels, while total testosterone (TT) levels and the free androgen index decreased significantly. Furthermore a significant decrease in Hirsutism was observed. There was a decrease in cholesterol and an increase in high-density lipoprotein.
Conclusions: Long-term treatment with metformin in women with PCOS appears to reduce androgen excess due to increased SHBG and decreased TT levels resulting in improvement of Hirsutism as a clinical sign of androgen excess. Furthermore a significant decrease in fasting and 2-h insulin levels and slightly improved insulin resistance indices were observed.
Key words
insulin resistance - hyperandrogenemia - hormones - polycystic - ovary syndrome - obesity
References
- 1
Alberti KG.
The costs of non-insulin-dependent diabetes mellitus.
Diabetic Medicine.
1997;
14
7-9
MissingFormLabel
- 2
American Diabetes Association
.
Economic consequences of diabetes mellitus in the U.S. in 1997.
Diabetes Care.
1998;
21
296-309
MissingFormLabel
- 3
Archer JS, Chang RJ.
Hirsutism and acne in polycystic ovary syndrome. Best Practice & Research.
Clinical Obstetrics & Gynaecology.
2004;
18
737-754
MissingFormLabel
- 4
Azziz R, Carmina E, Dewailly D. et al. .
Androgen Excess Society
Position statement: criteria for defining polycystic ovary syndrome as a predominantly
hyperandrogenic syndrome: an Androgen Excess Society guideline.
Journal of Clinical Endocrinology and Metabolism.
2006;
91
4237-4245
MissingFormLabel
- 5
Chen MJ, Yang WS, Yang JH. et al .
Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol
and metabolic syndrome in women with PCOS.
Human Reproduction.
2006;
21
2261-2271
MissingFormLabel
- 6
Cho LW, Kilpatrick ES, Keevil BG. et al .
Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance
and its biological variability in polycystic ovary syndrome.
Clinical Endocrinology (Oxford).
2009;
70
233-237
MissingFormLabel
- 7
Cupisti S, Kajaia N, Dittrich R. et al .
Body mass index and ovarian function are associated with endocrine and metabolic abnormalities
in women with hyperandrogenic syndrome.
European Journal of Endocrinology.
2008;
158
711-719
MissingFormLabel
- 8
Dahlgren E, Johansson S, Lindstedt G. et al .
Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up
focusing on natural history and circulating hormones.
Fertility and Sterility.
1992;
57
505-513
MissingFormLabel
- 9
De Leo V, Musacchino MC, Morgante G. et al .
Metformin treatment is effective in obese teenage girls with PCOS.
Human Reproduction.
2006;
21
2252-2256
MissingFormLabel
- 10
Dunaif A.
Insulin resistance and the polycystic ovary syndrome: mechanism and implications for
pathogenesis.
Endocrine Reviews.
1997;
18
774-800
MissingFormLabel
- 11
Ehrmann DA, Barnes RB, Rosenfield RL. et al .
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary
syndrome.
Diabetes Care.
1999;
22
141-146
MissingFormLabel
- 12
Eckel RH, Grundy SM, Zimmet PZ.
The metabolic syndrome.
Lancet.
2005;
365
1415-1428
MissingFormLabel
- 13
Fleming R, Hopkinson ZE, Wallace AM. et al .
Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin
in a randomized double blind placebo-controlled trial.
Journal of Clinical Endocrinology and Metabolism.
2002;
87
569-574
MissingFormLabel
- 14
Guzick DS.
Do cardiovascular risk factors in polycystic ovarian syndrome result in more cardiovascular
events?.
Journal of Clinical Endocrinology and Metabolism.
2008;
93
1170-1171
MissingFormLabel
- 15
Hoeger K, Davidson K, Kochman L. et al .
The impact of metformin, oral contraceptives and lifestyle modification on polycystic
ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical
trials.
Journal of Clinical Endocrinology and Metabolism.
2008;
93
4299-4306
MissingFormLabel
- 16
Ibáñez L, López-Bermejo A, Díaz M. et al .
Metformin treatment for four years to reduce total and visceral fat in low birth weight
girls with precocious pubarche.
Journal of Clinical Endocrinology and Metabolism.
2008;
93
1841-1845
MissingFormLabel
- 17
Isomaa B, Almgren P, Tuomi T. et al .
Cardiovascular morbidity and mortality associated with the metabolic syndrome.
Diabetes Care.
2001;
24
683-689
MissingFormLabel
- 18
Kajaia N, Binder H, Dittrich R. et al .
Low sex hormone-binding globulin as a predictive marker for insulin resistance in
women with hyperandrogenic syndrome.
European Journal of Endocrinology.
2007;
157
499-507
MissingFormLabel
- 19
Katz A, Nambi SS, Mather K. et al .
Quantitative insulin sensitivity check index: a simple, accurate method for assessing
insulin sensitivity in humans.
Journal of Clinical Endocrinology and Metabolism.
2000;
85
2402-2410
MissingFormLabel
- 20
Kocak M, Caliskan E, Simsir C. et al .
Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in
clomiphene citrate-resistant women with polycystic ovary syndrome.
Fertility and Sterility.
2002;
77
101-106
MissingFormLabel
- 21
Korytkowski MT, Krug EL, Daly MA. et al .
Does androgen excess contribute to the cardiovascular risk profile in postmenopausal
women with type 2 diabetes?.
Metabolism.
2005;
54
1626-1631
MissingFormLabel
- 22
Luque-Ramírez M, Alvarez-Blasco F, Uriol Rivera MG. et al .
Serum uric acid concentration as non-classic cardiovascular risk factor in women with
polycystic ovary syndrome: effect of treatment with ethinyl-estradiol plus cyproterone
acetate versus metformin.
Human Reproduction.
2008;
23
1594-1601
MissingFormLabel
- 23
Maciel GA, Soares Junior JM, Alves da Motta EL. et al .
Nonobese women with polycystic ovary syndrome respond better than obese women to treatment
with metformin.
Fertility and Sterility.
2004;
81
355-360
MissingFormLabel
- 24
Matsuda M, DeFronzo RA.
Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison
with the euglycemic insulin clamp.
Diabetes Care.
1999;
22
1462-1470
MissingFormLabel
- 25
Matthews DR, Hosker JP, Rudenski AS. et al .
Homeostasis model assessment: insulin resistance and beta-cell function from fasting
plasma glucose and insulin concentrations in man.
Diabetologia.
1985;
28
412-419
MissingFormLabel
- 26
Meigs JB, Rutter MK, Sullivan LM. et al .
Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease
in people with metabolic syndrome.
Diabetes Care.
2007;
30
1219-1225
MissingFormLabel
- 27
Moghetti P, Castello R, Negri C. et al .
Metformin effects on clinical features, endocrine and metabolic profile, and insulin
sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-con-trolled
6-month trial, followed by open, long-term clinical evaluation.
Journal of Clinical Endocrinology and Metabolism.
2000;
85
139-146
MissingFormLabel
- 28
Morin-Papunen LC, Vauhkonen I, Koivunen RM. et al .
Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone
acetate in obese women with polycystic ovary syndrome: a randomized study.
Journal of Clinical Endocrinology and Metabolism.
2000;
85
3161-3168
MissingFormLabel
- 29
Nestler JE, Powers LP, Matt DW. et al .
A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in
obese women with the polycystic ovary syndrome.
Journal of Clinical Endocrinology and Metabolism.
1991;
72
83-89
MissingFormLabel
- 30
Nestler JE.
Metformin for the treatment of the polycystic ovary syndrome.
New England Journal of Medicine.
2008;
358
47-54
MissingFormLabel
- 31
Ng EH, Wat NM, Ho PC.
Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with
clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled
trial.
Human Reproduction.
2001;
16
1625-1631
MissingFormLabel
- 32
Norman RJ, Dewailly D, Legro RS. et al .
Polycystic ovary syndrome.
Lancet.
2007;
370
685-697
MissingFormLabel
- 33
Pasquali R, Gambineri A, Biscotti D. et al .
Effect of long-term treatment with metformin added to hypocaloric diet on body composition,
fat distribution, and androgen and insulin levels in abdominally obese women with
and without the polycystic ovary syndrome.
Journal of Clinical Endocrinology and Metabolism.
2000;
85
2767-2774
MissingFormLabel
- 34
Petra PH.
The plasma sex steroid binding protein (SBP or SHBG). A critical review of recent
developments on the structure, molecular biology and function.
Journal of Steroid Biochemistry and Molecular Biology.
1991;
40
735-753
MissingFormLabel
- 35
Ovalle F, Azziz R.
Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus.
Fertility and Sterility.
2002;
77
1095-1105
MissingFormLabel
- 36
Reaven GM.
Banting lecture 1988. Role of insulin resistance in human disease.
Diabetes.
1988;
37
1595-1607
MissingFormLabel
- 37
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
.
Revised 2003 consensus on diagnostic criteria and long-term health risks related to
polycystic ovary syndrome.
Fertility and Sterility.
2004;
81
19-25
MissingFormLabel
- 38
Shaw LJ, Bairey Merz CN, Azziz R. et al .
Postmenopausal women with a history of irregular menses and elevated androgen measurements
at high risk for worsening cardiovascular event-free survival: results from the National
Institutes of Health – National Heart, Lung, and Blood Institute sponsored Women's
Ischemia Syndrome Evaluation.
Journal of Clinical Endocrinology and Metabolism.
2008;
93
1276-1284
MissingFormLabel
- 39
Trolle B, Flyvbjerg A, Kesmodel U. et al .
Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome:
a randomized, double-blinded, placebo-controlled cross-over trial.
Human Reproduction.
2007;
22
2967-2973
MissingFormLabel
- 40
Velazquez EM, Mendoza S, Hamer T. et al .
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
MissingFormLabel
- 41 Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach.. In:, Dunaif A, Givens JR, Haseltine FP, &Merriam, Eds Polycystic Ovary Syndrome. GR. Boston: Blackwell Scientific; 1992: pp 377-384
MissingFormLabel
1 Both authors contributed equally.
Correspondence
Dr. A. Mueller
Department of Obstetrics and Gynecology
Erlangen University Hospital
Universitätsstraße 21–23
D-91054 Erlangen
Germany
Phone: +49/9131/853 35 53
Fax: +49/9131/853 35 52
Email: andreas.mueller@uk-erlangen.de