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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2014

Open Access 01-12-2014 | Research

Metformin induces a prompt decrease in LH-stimulated testosterone response in women with PCOS independent of its insulin-sensitizing effects

Authors: Dorothea Kurzthaler, Dijana Hadziomerovic-Pekic, Ludwig Wildt, Beata E Seeber

Published in: Reproductive Biology and Endocrinology | Issue 1/2014

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Abstract

Background

The use of insulin-sensitizing drugs has been shown to improve both the reproductive and the metabolic aspects of PCOS. However, the mechanisms by which metformin exerts its effects in PCOS are still not completely understood. There is growing evidence of a direct effect of metformin on ovarian steroidogenesis, independent of its effects on insulin sensitivity.

Methods

We evaluated the short-term effects of metformin compared to placebo on basal and LH- stimulated androgen secretion as well as on hormonal and metabolic parameters in 19 women with PCOS during a four-day randomized, double-blinded placebo-controlled clinical trial. In a three month follow-up evaluation, we investigated the longer-term therapeutic effects of metformin on ovulation, metabolic and endocrine parameters.

Results

Compared to placebo, 2 days of metformin was associated with a borderline significant reduction in the free androgen index (FAI) (p = 0.05) and with a reduction in the serum concentration of LH-stimulated testosterone (T) (p = 0.03). Following three months of use, a decline in serum T was observed, independent of changes in weight, metabolic parameters, or insulin sensitivity.

Conclusions

In women with PCOS, Metformin induces a prompt decrease in LH-stimulated T secretion after only several days of use. This action precedes the medication’s effects on insulin sensitivity or weight loss.
Literature
1.
Rotterdam E: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004, 19: 41-CrossRef
2.
Dunaif A, Segal KR, Futterweit W, Dobrjansky A: Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989, 38: 1165-1174. 10.2337/diab.38.9.1165.CrossRefPubMed
3.
Dunaif A, Finegood DT: Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996, 81: 942-947.PubMed
4.
Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ: 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. 10.1016/0026-0495(94)90209-7.CrossRefPubMed
5.
Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L: Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril. 2000, 73: 1149-1154. 10.1016/S0015-0282(00)00501-X.CrossRefPubMed
6.
Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A: Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrin. 1998, 138: 269-274. 10.1530/eje.0.1380269.CrossRef
7.
Chou KH, von Eye Corleta H, Capp E, Spritzer PM: Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial. Horm Metab Res. 2003, 35: 86-91. 10.1055/s-2003-39056.CrossRefPubMed
8.
Ehrmann DA, Cavaghan MK, Imperial J, Sturis J, Rosenfield RL, Polonsky KS: Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1997, 82: 524-530.PubMed
9.
Mansfield R, Galea R, Brincat M, Hole D, Mason H: Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril. 2003, 79: 956-962. 10.1016/S0015-0282(02)04925-7.CrossRefPubMed
10.
la Marca A, Morgante G, Paglia T, Ciotta L, Cianci A, De Leo V: Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome. Fertil Steril. 1999, 72: 985-989. 10.1016/S0015-0282(99)00407-0.CrossRefPubMed
11.
Unluhizarci K, Kelestimur F, Sahin Y, Bayram F: The treatment of insulin resistance does not improve adrenal cytochrome P450c17alpha enzyme dysregulation in polycystic ovary syndrome. Eur J Endocrin. 1999, 140: 56-61. 10.1530/eje.0.1400056.CrossRef
12.
Wickenheisser JK, Nelson-Degrave VL, McAllister JM: Dysregulation of cytochrome P450 17alpha-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005, 90: 1720-1727. 10.1210/jc.2004-1860.CrossRefPubMed
13.
Zhang LH, Rodriguez H, Ohno S, Miller WL: Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc Natl Acad Sci U S A. 1995, 92: 10619-10623. 10.1073/pnas.92.23.10619.PubMedCentralCrossRefPubMed
14.
Poretsky L, Smith D, Seibel M, Pazianos A, Moses AC, Flier JS: Specific insulin binding sites in human ovary. J Clin Endocrinol Metab. 1984, 59: 809-811. 10.1210/jcem-59-4-809.CrossRefPubMed
15.
Nestler JE, Jakubowicz DJ: Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med. 1996, 335: 617-623. 10.1056/NEJM199608293350902.CrossRefPubMed
16.
Diamanti-Kandarakis E, Papavassiliou AG: Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med. 2006, 12: 324-332. 10.1016/j.molmed.2006.05.006.CrossRefPubMed
17.
Seto-Young D, Paliou M, Schlosser J, Avtanski D, Park A, Patel P, Holcomb K, Chang P, Poretsky L: Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J Clin Endocrinol Metab. 2005, 90: 6099-6105. 10.1210/jc.2005-0469.CrossRefPubMed
18.
Pirwany IR, Yates RW, Cameron IT, Fleming R: Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea. Hum Reprod. 1999, 14: 2963-2968. 10.1093/humrep/14.12.2963.CrossRefPubMed
19.
Hadziomerovic D, Rabenbauer B, Wildt L: Normalizaion of hyperinsulinemia by chronic opioid receptor blockade in hyperandrogenemic women. Fertil Steril. 2006, 86: 651-657. 10.1016/j.fertnstert.2006.01.039.CrossRefPubMed
20.
Lunger F, Wildt L, Seeber B: Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations. Gynecol Endocrinol. 2013, 29 (6): 541-544. 10.3109/09513590.2013.774362.CrossRefPubMed
21.
Morin-Papunen LC, Koivunen RM, Ruokonen A, Martikainen HK: Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil Steril. 1998, 69 (4): 691-694. 10.1016/S0015-0282(98)00011-9.CrossRefPubMed
22.
Nestler JE: Metformin in the treatment of infertility in polycystic ovary syndrome: an alternative perspective. Fertil Steril. 2008, 90: 14-16. 10.1016/j.fertnstert.2008.04.073.PubMedCentralCrossRefPubMed
23.
Hadziomerovic-Pekic D, Wildt L, Weiss JM, Moeller K, Mattle V, Seeber BE: Metformin, naltrexone, or the combination of prednisolone and antiandrogenic oral contraceptives as first-line therapy in hyperinsulinemic women with polycystic ovary syndrome. Fertil Steril. 2010, 94 (6): 2385-2388. 10.1016/j.fertnstert.2010.02.041.CrossRefPubMed
Metadata
Title
Metformin induces a prompt decrease in LH-stimulated testosterone response in women with PCOS independent of its insulin-sensitizing effects
Authors
Dorothea Kurzthaler
Dijana Hadziomerovic-Pekic
Ludwig Wildt
Beata E Seeber
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2014
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-12-98

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