Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea

Human Reproduction

Volumn 14, Issue 12, 1999, Pages 2963-2968

  Pirwany, I R ^a,b   Yates, R W S ^a   Cameron, I T ^a   Fleming, R ^a  

^a GLASGOW ROYAL INFIRMARY   (United Kingdom)

^b NHS LANARKSHIRE   (United Kingdom)

Author keywords

Hyperandrogenism; Metformin; Ovulation; Polycystic ovarian syndrome

Indexed keywords

ANDROGEN; INSULIN; LUTEINIZING HORMONE; METFORMIN; TESTOSTERONE;

ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIET RESTRICTION; FEMALE; HORMONE BLOOD LEVEL; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; MENSTRUATION DISORDER; OBESITY; OLIGOMENORRHEA; OVARY FOLLICLE DEVELOPMENT; OVARY FUNCTION; OVARY POLYCYSTIC DISEASE; OVULATION; STEROID METABOLISM;

EID: 0032759616     PISSN: 02681161     EISSN: None     Source Type: Journal    
DOI: 10.1093/humrep/14.12.2963     Document Type: Article

References (37)

1. Acbay, O. and Gundogdu, S. (1996) Can metformin reduce insulin resistance in polycyslic ovary syndrome? Fertil. Steril., 65, 946-949.
2. Adams, J., Polson, D.W. and Franks, S. (1986) Prevalence of polycystic ovaries in women with anovulalion and idiopathic hirsutism. Br. Med. J. Clin. Res. Ed., 293, 355-359.
3. Barbieri, R.L., Makris, A., Randall, R.W. et al. (1986) Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J. Clin. Endocrinol. Metab., 62, 904-910.
4. Barbieri, R.L., Smith, S. and Ryan, K.J. (1988) The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil. Steril., 50, 197-212.
5. Bergh, C., Carlsson, B., Olsson. J.H. et al. (1993) Regulation of androgen production in cultured human thecal cells by insulin-like growth factor 1 and insulin. Fertil. Steril., 59, 323-331.
6. Cara, J.F. and Rosenfield, R.L. (1988) Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology, 123, 733-739.
7. Chang. R.J., Nakamura, R.M., Judd, H.L. et al. (1983) Insulin resistance in nonobese patients with polycystic ovarian disease. J. Clin. Endocrinol. Metab., 57, 356-359.
8. Cigolini, M., Seidell, J.C., Charzewska, J. et al. (1991) Fasting serum insulin in relation to fat distribution, serum lipid profile, and blood pressure in European women: the European Fat Distribution Study. Metab. Clin. Exp., 40, 781-787.
9. Crave, J.C., Fimbel, S., Lejeune, H. et al. (1995) Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J. Clin. Endocrinol. Metab., 80, 2057-2062.
10. DeVane, G.W., Czekala, N.M., Judd, H.L. et al. (1975) Circulating gonadotropins, estrogens, and androgens in polycystic ovarian disease. Am. J. Obstet. Gynecol., 121, 496-500.
11. Dunaif, A., Segal, K.R., Futterweit, W. et al. (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes, 38, 1165-1174.
12. Dunaif, A., Scott, D., Finegood, D. et al. (1996) The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 81, 3299-3306.
13. Edwards, K.L., Austin, M.A., Newman, B. et al. (1994) Multivariate analysis of the insulin resistance syndrome in women. Arterioscler. Thromb., 14, 1940-1945.
14. Ehrmann, D.A., Schneider, D.J., Sobel, B.E. et al. (1997a) Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 82, 2108-2116.
15. Ehrmann, D.A., Cavaghan, M.K., Imperial, J. et at. (2997b) Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 82, 524-530.
16. Franks, S. (1995) Polycystic ovary syndrome. N. Engl. J. Med., 333, 853-861.
17. Franks, S., Gharani, N., Waterworth, D. et al. (1997) The genetic basis of polycystic ovary syndrome. Hum. Reprod., 12, 2641-2648.
18. Gilling-Smith, C., Willis, D.S., Beard, R.W. et al. (1994) Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J. Clin. Endocrinol. Metab., 79, 1158-1165.
19. Gilling-Smith, C., Story, H., Rogers, V. et al. (1997) Evidence for a primary abnormality of thecal cell steroidogenesis in polycystic ovary syndrome. Clin. Endocrinol., 47, 93-99.
20. Kiddy, D.S., Hamilton-Fairley, D., Bush, A. et al. (1992) Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin. Endocrinol., 36, 105-111.
21. Kyei-Mensah, A.A., LinTan, S., Zaidi, J. et al (1998) Relationship of ovarian stromal volume to serum androgen concentrations in patients with polycystic ovary syndrome. Hum. Reprod., 13, 1437-1441.
22. Morin-Papunen, L.C., Koivunen, R.M., Ruokonen, A. et al. (1998) Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil. Steril., 69, 691-696.
23. Nahum, R., Thong, K.J., and Hillier, S.G. (1995) Metabolic regulation of androgen production by human thecal cells in vitro. Hum. Reprod., 10, 75-81.
24. Nestler, J.E. and Jakubowicz, D.J. (1996) Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N. Engl. J. Med., 335, 617-623.
25. Nestler, J.E., Barlascini, C.O., Matt, D.W. et al. (1989) Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 68, 1027-1032.
26. Nestler, J.E., Jakubowicz, D.J., Evans, W.S. et al. (1998) Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N. Engl. J. Med., 338, 1876-1880.
27. Pasquali, R., Casimiri, F., Cantobelli, S. et al. (1993) Insulin and androgen relationships with abdominal body fat distribution in women with and without hyperandrogenism. Horm. Res., 39, 179-187.
28. Poretsky, L. and Kalin, M.F. (1987) The gonadotropic function of insulin. Endocr. Rev., 8, 132-141.
29. Rebar, R., Judd, H.L., Yen, S.S. et al. (1976) Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J. Clin. Invest., 57, 1320-1329.
30. Robinson, S., Rodin, D.A., Deacon, A. et al. (1992) Which hormone tests for the diagnosis of polycystic ovary syndrome? Br. J. Obstel. Gynaecol., 99, 232-238.
31. Schoemaker, J. (1991) Neuroendocrine control in polycystic ovary-like syndrome. Gynecol. Endocrinol., 5, 277-288.
32. Velazquez, E.M., Mendoza, S., Hamer, T. et al. (1994) Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metab. Clin. Exp., 43, 647-654.
33. Velazquez, E.M., Mendoza, S.G., Wang, P. et al. (1997a) Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metab. Clin. Exp., 46, 454-157.
34. Velazquez, E.M., Acosta, A. and Mendoza, S.G. (1997b) Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet. Gynecol., 90, 392-395.
35. Willis, D. and Franks, S. (1995) Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the type-I insulin-like growth factor receptor. J. Clin. Endocrinol. Metab., 80, 3788-3790.
36. Willis, D., Mason, H., Gilling-Smith, C. et al. (1996) Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J. Clin. Endocrinol. Metab., 81, 302-309.
37. Yen, S.S., Vela, P., and Rankin, J. (1970) Inappropriate secretion of follicle stimulating hormone and luteinizing hormone in polycystic ovarian disease. J. Clin. Endocrinol. Metab., 30, 435-442.