help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ehrmann, D. A.
Right arrow Articles by Polonsky, K. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ehrmann, D. A.
Right arrow Articles by Polonsky, K. S.
The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 2 524-530
Copyright © 1997 by The Endocrine Society

Clinical Research Center Studies

Effects of Metformin on Insulin Secretion, Insulin Action, and Ovarian Steroidogenesis in Women with Polycystic Ovary Syndrome1

David A. Ehrmann, Melissa K. Cavaghan, Jacqueline Imperial, Jeppe Sturis2, Robert L. Rosenfield and Kenneth S. Polonsky

Departments of Medicine (D.A.E., M.K.C., J.I., J.S., R.L.R., K.S.P.) and Pediatrics (R.L.R.), University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: David A. Ehrmann, M.D., Department of Medicine, Section of Endocrinology, University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637. E-mail: dehrmann{at}medicine.bsd.uchicago.edu

Abstract

Hyperinsulinemia contributes to the ovarian androgen overproduction and glucose intolerance of polycystic ovary syndrome (PCOS). We sought to determine whether metformin would reduce insulin levels in obese, nondiabetic women with PCOS during a period of weight maintenance and thus attenuate the ovarian steroidogenic response to the GnRH agonist leuprolide. All subjects (n = 14) had an oral glucose tolerance test, a GnRH agonist (leuprolide) test, a frequently sampled iv glucose tolerance test, graded and oscillatory glucose infusions, and a dual energy x-ray absorptiometry scan before and after treatment with metformin (850 mg, orally, three times daily for 12 weeks).

With weight maintenance (body mass index: pretreatment, 39.0 ± 7.7 kg/m2; posttreatment, 39.1 ± 7.9 kg/m2), oral glucose tolerance, insulin sensitivity (Si; 0.87 ± 0.82 vs. 0.74 ± 0.63 x 10-5 min-1/pmol·L), and the relationship between Si and first phase insulin secretion (AIRg vs. Si) were not improved by metformin. The insulin secretory response to glucose, administered in both graded and oscillatory fashions, was likewise unaltered in response to metformin. Free testosterone levels remained about 2-fold elevated (pretreatment, 26.6 ± 12.7 pg/mL; posttreatment, 22.4 ± 9.8 pg/mL). Both basal and stimulated LH and FSH levels were unaffected by metformin. The mean responses to leuprolide of 17-hydroxyprogesterone (pretreatment, 387 ± 158 ng/dL; posttreatment, 329 ± 116 ng/dL) as well as those of the other ovarian secretory products (androstenedione, dehydroepiandrosterone, progesterone, and estradiol) were not attenuated by metformin.

We conclude that hyperinsulinemia and androgen excess in obese nondiabetic women with PCOS are not improved by the administration of metformin.




This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
K. Elkind-Hirsch, O. Marrioneaux, M. Bhushan, D. Vernor, and R. Bhushan
Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2670 - 2678.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
T. Tang, J. Glanville, C. J. Hayden, D. White, J. H. Barth, and A. H. Balen
Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study
Hum. Reprod., January 1, 2006; 21(1): 80 - 89.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
N. A. Cataldo, F. Abbasi, T. L. McLaughlin, M. Basina, P. Y. Fechner, L. C. Giudice, and G. M. Reaven
Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome
Hum. Reprod., January 1, 2006; 21(1): 109 - 120.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. R. Harborne, N. Sattar, J. E. Norman, and R. Fleming
Metformin and Weight Loss in Obese Women with Polycystic Ovary Syndrome: Comparison of Doses
J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4593 - 4598.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
M.A. Checa, A. Requena, C. Salvador, R. Tur, J. Callejo, J.J. Espinos, F. Fabregues, J. Herrero, and (Reproductive Endocrinology Interest Group of the
Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome
Hum. Reprod. Update, July 1, 2005; 11(4): 375 - 390.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. Ortega-Gonzalez, S. Luna, L. Hernandez, G. Crespo, P. Aguayo, G. Arteaga-Troncoso, and A. Parra
Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1360 - 1365.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
K Rautio, J S Tapanainen, A Ruokonen, and L C Morin-Papunen
Effects of metformin and ethinyl estradiol-cyproterone acetate on lipid levels in obese and non-obese women with polycystic ovary syndrome
Eur. J. Endocrinol., February 1, 2005; 152(2): 269 - 275.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C Ortega-Gonzalez, L Cardoza, B Coutino, R Hidalgo, G Arteaga-Troncoso, and A Parra
Insulin sensitizing drugs increase the endogenous dopaminergic tone in obese insulin-resistant women with polycystic ovary syndrome
J. Endocrinol., January 1, 2005; 184(1): 233 - 239.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
V. Sepilian and M. Nagamani
Effects of Rosiglitazone in Obese Women with Polycystic Ovary Syndrome and Severe Insulin Resistance
J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 60 - 65.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A.S. Sonmez, L. Yasar, K. Savan, S. Koc, J. Ozcan, A. Toklar, F. Yazicioglu, A. Akgun, and N. Sut
Comparison of the effects of acarbose and metformin use on ovulation rates in clomiphene citrate-resistant polycystic ovary syndrome
Hum. Reprod., January 1, 2005; 20(1): 175 - 179.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
S. Muth, J. Norman, N. Sattar, and R. Fleming
Women with polycystic ovary syndrome (PCOS) often undergo protracted treatment with metformin and are disinclined to stop: indications for a change in licensing arrangements?
Hum. Reprod., December 1, 2004; 19(12): 2718 - 2720.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Palomba, F. Orio Jr., L. G. Nardo, A. Falbo, T. Russo, D. Corea, P. Doldo, G. Lombardi, A. Tolino, A. Colao, et al.
Metformin Administration Versus Laparoscopic Ovarian Diathermy in Clomiphene Citrate-Resistant Women with Polycystic Ovary Syndrome: A Prospective Parallel Randomized Double-Blind Placebo-Controlled Trial
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4801 - 4809.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
R. J. Norman, M. Noakes, R. Wu, M. J. Davies, L. Moran, and J. X. Wang
Improving reproductive performance in overweight/obese women with effective weight management
Hum. Reprod. Update, May 1, 2004; 10(3): 267 - 280.
[Abstract] [Full Text] [PDF]

Home page
 Clin Med ResHome page
M. T. Sheehan
Polycystic Ovarian Syndrome: Diagnosis and Management
Clin. Med. Res., February 1, 2004; 2(1): 13 - 27.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
V. De Leo, A. la Marca, and F. Petraglia
Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome
Endocr. Rev., October 1, 2003; 24(5): 633 - 667.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C. J. Glueck, A. Moreira, N. Goldenberg, L. Sieve, and P. Wang
Pioglitazone and metformin in obese women with polycystic ovary syndrome not optimally responsive to metformin
Hum. Reprod., August 1, 2003; 18(8): 1618 - 1625.
[Abstract] [Full Text] [PDF]

Home page
 The Journal of the Royal Society for the Promotion of HealthHome page
A. S. M Ahmed
Polycystic ovaries: the role of insulin
The Journal of the Royal Society for the Promotion of Health, June 1, 2003; 123(2): 78 - 79.
[PDF]

Home page
 Endocr. Rev.Home page
F. C. W. Wu and A. von Eckardstein
Androgens and Coronary Artery Disease
Endocr. Rev., April 1, 2003; 24(2): 183 - 217.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
S. S. George, K. George, C. Irwin, V. Job, R. Selvakumar, V. Jeyaseelan, and M.S. Seshadri
Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial
Hum. Reprod., February 1, 2003; 18(2): 299 - 304.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J.G. Dolfing, K.E. Tucker, C.M. Lem, J. Uittenbogaart, J.C. Verzijl, and D.H. Schweitzer
Low 11-deoxycortisol to cortisol conversion reflects extra-adrenal factors in the majority of women with normo-gonadotrophic normo-estrogenic infertility
Hum. Reprod., February 1, 2003; 18(2): 333 - 337.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Morin-Papunen, I. Vauhkonen, R. Koivunen, A. Ruokonen, H. Martikainen, and J. S. Tapanainen
Metformin Versus Ethinyl Estradiol-Cyproterone Acetate in the Treatment of Nonobese Women with Polycystic Ovary Syndrome: A Randomized Study
J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 148 - 156.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
L. A. Stadtmauer, B. C. Wong, and S. Oehninger
Should patients with polycystic ovary syndrome be treated with metformin?: Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction
Hum. Reprod., December 1, 2002; 17(12): 3016 - 3026.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes Spectr.Home page
R. Murray
Recognizing the Signs of Metabolic Syndrome and Polycystic Ovary Syndrome in a Caucasian Adolescent Girl: Differentiating Type 2 From Type 1 Diabetes
Diabetes Spectr, October 1, 2002; 15(4): 227 - 231.
[Full Text] [PDF]

Home page
 Hum ReprodHome page
E. Seli and A. J. Duleba
Should patients with polycystic ovarian syndrome be treated with metformin?
Hum. Reprod., September 1, 2002; 17(9): 2230 - 2236.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
V. De Leo and A. la Marca
Metformin and FSH for induction of ovulation in women with polycystic ovarian syndrome
Hum. Reprod., September 1, 2002; 17(9): 2481 - 2482.
[Full Text] [PDF]

Home page
 Hum ReprodHome page
K. Elter, G. Imir, and F. Durmusoglu
Clinical, endocrine and metabolic effects of metformin added to ethinyl estradiol-cyproterone acetate in non-obese women with polycystic ovarian syndrome: a randomized controlled study
Hum. Reprod., July 1, 2002; 17(7): 1729 - 1737.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. A. Arslanian, V. Lewy, K. Danadian, and R. Saad
Metformin Therapy in Obese Adolescents with Polycystic Ovary Syndrome and Impaired Glucose Tolerance: Amelioration of Exaggerated Adrenal Response to Adrenocorticotropin with Reduction of Insulinemia/Insulin Resistance
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1555 - 1559.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R. Homburg
Should patients with polycystic ovarian syndrome be treated with metformin?: A note of cautious optimism
Hum. Reprod., April 1, 2002; 17(4): 853 - 856.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Fleming, Z. E. Hopkinson, A. M. Wallace, I. A. Greer, and N. Sattar
Ovarian Function and Metabolic Factors in Women with Oligomenorrhea Treated with Metformin in a Randomized Double Blind Placebo-Controlled Trial
J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 569 - 574.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R. M. Koivunen, L. C. Morin-Papunen, A. Ruokonen, J. S. Tapanainen, and H. K. Martikainen
Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin
Hum. Reprod., December 1, 2001; 16(12): 2546 - 2551.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E. H. Y. Ng, N. M. S. Wat, and P. C. Ho
Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial
Hum. Reprod., August 1, 2001; 16(8): 1625 - 1631.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. E. Oberfield
Metabolic Lessons from the Study of Young Adolescents with Polycystic Ovary Syndrome--Is Insulin, Indeed, the Culprit?
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3520 - 3525.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Ibáñez, C. Valls, N. Potau, M. V. Marcos, and F. de Zegher
Sensitization to Insulin in Adolescent Girls to Normalize Hirsutism, Hyperandrogenism, Oligomenorrhea, Dyslipidemia, and Hyperinsulinism after Precocious Pubarche
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3526 - 3530.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. C. Morin-Papunen, I. Vauhkonen, R. M. Koivunen, A. Ruokonen, H. K. Martikainen, and J. S. Tapanainen
Endocrine and Metabolic Effects of Metformin Versus Ethinyl Estradiol-Cyproterone Acetate in Obese Women with Polycystic Ovary Syndrome: A Randomized Study
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3161 - 3168.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
D. Deplewski and R. L. Rosenfield
Role of Hormones in Pilosebaceous Unit Development
Endocr. Rev., August 1, 2000; 21(4): 363 - 392.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Pasquali, A. Gambineri, D. Biscotti, V. Vicennati, L. Gagliardi, D. Colitta, S. Fiorini, G. E. Cognigni, M. Filicori, and A. M. Morselli-Labate
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
J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2767 - 2774.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. Moghetti, R. Castello, C. Negri, F. Tosi, F. Perrone, M. Caputo, E. Zanolin, and M. Muggeo
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., January 1, 2000; 85(1): 139 - 146.
[Abstract] [Full Text]

Home page
 Hum ReprodHome page
A. la Marca, T. O. Egbe, G. Morgante, T. Paglia, A. Ciani, and V. De Leo
Metformin treatment reduces ovarian cytochrome P-450c17{alpha} response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome
Hum. Reprod., January 1, 2000; 15(1): 21 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
I.R. Pirwany, R.W.S. Yates, I.T. Cameron, and R. Fleming
Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea
Hum. Reprod., December 1, 1999; 14(12): 2963 - 2968.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M.F.M. Mitwally, N.K. Kuscu, and T.M. Yalcinkaya
High ovulatory rates with use of troglitazone in clomiphene-resistant women with polycystic ovary syndrome
Hum. Reprod., November 1, 1999; 14(11): 2700 - 2703.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice
The Insulin-Related Ovarian Regulatory System in Health and Disease
Endocr. Rev., August 1, 1999; 20(4): 535 - 582.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. J. Sarlis, S. J. Weil, and L. M. Nelson
Administration of Metformin to a Diabetic Woman with Extreme Hyperandrogenemia of Nontumoral Origin: Management of Infertility and Prevention of Inadvertent Masculinization of a Female Fetus
J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1510 - 1512.
[Full Text]

Home page
 BMJHome page
Z. E C Hopkinson, N. Sattar, R. Fleming, and I. A Greer
Fortnightly Review: Polycystic ovarian syndrome: the metabolic syndrome comes to gynaecology
BMJ, August 1, 1998; 317(7154): 329 - 332.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. C. Morin-Papunen, R. M. Koivunen, C. Tomás, A. Ruokonen, and H. K. Martikainen
Decreased Serum Leptin Concentrations during Metformin Therapy in Obese Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2566 - 2568.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. L. Pastor, M. L. Griffin-Korf, J. A. Aloi, W. S. Evans, and J. C. Marshall
Polycystic Ovary Syndrome: Evidence for Reduced Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone
J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 582 - 590.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
A. Dunaif
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Endocr. Rev., December 1, 1997; 18(6): 774 - 800.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. L. Daniels and S. L. Berga
Resistance of Gonadotropin Releasing Hormone Drive to Sex Steroid-Induced Suppression in Hyperandrogenic Anovulation
J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4179 - 4183.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. A. Ehrmann, D. J. Schneider, B. E. Sobel, M. K. Cavaghan, J. Imperial, R. L. Rosenfield, and K. S. Polonsky
Troglitazone Improves Defects in Insulin Action, Insulin Secretion, Ovarian Steroidogenesis, and Fibrinolysis in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2108 - 2116.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society