Possible metformin effect on adrenal androgens during pretreatment and IVF cycle in women with polycystic ovary syndrome

Fertility and Sterility

Volumn 91, Issue 2, 2009, Pages 500-508

  Kjøtrød, Sigrun B ^a   Sunde, Arne ^a,b   von Düring, Vidar ^a   Carlsen, Sven M ^a,b  

^a TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^b NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

Author keywords

dehydroepiandrosterone sulphate; free testosterone index; hyperandrogenemia; metformin; Polycystic ovary syndrome

Indexed keywords

5 ALPHA ANDROSTAN 3 ALPHA,17 BETA DIOL GLUCURONIDE; ANDROGEN; ANDROSTANEDIOL; ANDROSTANOLONE; ANDROSTENEDIONE; CHORIONIC GONADOTROPIN; METFORMIN; PLACEBO; PRASTERONE; PRASTERONE SULFATE; TESTOSTERONE; UNCLASSIFIED DRUG;

ADULT; ANDROGEN BLOOD LEVEL; ANDROSTENEDIONE BLOOD LEVEL; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; FEMALE INFERTILITY; FERTILIZATION IN VITRO; FOLLICULAR ASPIRATION; HUMAN; MAJOR CLINICAL STUDY; OOCYTE RETRIEVAL; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; REBOUND; TESTOSTERONE BLOOD LEVEL; UNIVERSITY HOSPITAL;

ADRENAL GLANDS; ADULT; ANDROGENS; BODY MASS INDEX; CHORIONIC GONADOTROPIN; DEHYDROEPIANDROSTERONE SULFATE; DOUBLE-BLIND METHOD; FEMALE; FERTILITY AGENTS, FEMALE; FERTILIZATION IN VITRO; HUMANS; INFERTILITY, FEMALE; INSULIN; INSULIN RESISTANCE; METFORMIN; POLYCYSTIC OVARY SYNDROME; PROSPECTIVE STUDIES; TIME FACTORS; TREATMENT OUTCOME;

EID: 59249087603     PISSN: 00150282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fertnstert.2007.11.069     Document Type: Article

References (49)

1. The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19 (2004) 411-417
2. Velazquez E.M., Mendoza S., Hamer T., Sosa F., and Gluck C.J. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 43 (1994) 647-654
3. Baillargeon J.P., Jakubowicz D.J., Iuorno M.J., Jakubowicz S., and Nestler J.E. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril 82 (2004) 893-902
4. Elter K., Imir G., and Durmusoglu F. 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 17 (2002) 1729-1737
5. Moghetti P., Castello R., Negri C., Tosi F., Perrone F., Muggeo M., et al. 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 851 (2000) 139-146
6. Hung Yu Ng E., Ming Sun Wat N., and Chung Ho P. 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 16 (2001) 1625-1631
7. Pasquali R., Gambineri A., Biscotti D., Vicennati V., Gagliardi L., Morselli-Labate A.M., 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. J Clin Endocrinol Metab 85 (2000) 2767-2774
8. Kocak I., and Ustun C. Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling. J Obstet Gynaecol 32 (2006) 292-298
9. Tang T., Glanville J., Orsi N., Barth J., and Balen A.H. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod 21 (2006) 1416-1425
10. Legro R.S., Barnhart H.X., Schlaff W.D., Carr B.R., Diamond M.P., Myers E.R., et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 356 (2007) 551-566
11. Ehrmann D.A., Cavagham M.K., Imperial J., Sturis J., Rosenfeld R.L., and Polonsky K.S. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 82 (1997) 524-530
12. Acbay O., and Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome?. Fertil Steril 65 (1996) 946-949
13. Crave J.C., Fimbel S., Lejune H., Cugnardey N., Dechaud H., and Pugeat. Effects of diet and metformin administration on sex-hormone binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab 80 (1995) 2057-2062
14. Fleming R., Hopkinson Z.E., Wallace A.M., Greer I.A., and Sattar N. Ovarian function and metabolic factors in women with oligoamenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab 87 (2002) 569-574
15. Aruna J., Mittal S., Kumar S., Misra R., Dadhwal V., and Vimala N. Metformin therapy in women with polycystic ovary syndrome. Int J Gynecol Obstet 87 (2004) 237-241
16. Hoeger K.M., Kochman L., Wixom N., Craig K., Miller R.K., and GuzickA randomized D.S. 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril 82 (2004) 421-429
17. Sturrock N.D.C., Lannon B., and Fay T.N. Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice. Br J Clin Pharmacol 53 (2001) 469-473
18. Vandermolen D.T., Ratts V.S., Evans W.S., Stovall D.W., Kauma, and Nestler J.E. Metformin increases the ovulatory rate and pregnancy rate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril 75 2 (2001) 310-315
19. Vanky E., Salvesen K.A., Heimstad R., Fougner K.J., Romundstad P., and Carlsen S.M. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum Reprod 19 (2004) 1734-1740
20. Labrie F., Luu-The V., Labrie C., Belanger A., Simard J., Pelletier G., et al. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 24 (2003) 152-182
21. Labrie F., Luu-The V., Lin S.X., Simard J., Labrie C., Belanger A., et al. Intracrinology: the role of the family of 17β-hydroxysteroid dehydrogenases in human physiology and disease. J Mol Endocrinol 25 (2000) 1-16
22. Lobo R.A., Paul W.L., and Goebelsman U. Dehydroepiandrosterone sulphate as an indicator of adrenal androgen function. Obstet Gynecol 57 (1981) 69
23. Abraham G.E. Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle. J Clin Endocrinol Metab 39 (1974) 340-346
24. Mikulecky M., Kreze A., Putz Z., and Moravcik M. Daily variation of serum cortisol 17-hydroxyprogesterone and five androgens in healthy women. Braz J Med Biol Res 28 (1995) 485-490
25. Longcope C. Dehydroepiandrosterone metabolism. J Endocrinol 150 (1996) 125-127
26. Hoffmann D.I., Klove K., and Lobo R.A. The prevalence and significance of elevated dehydroepiandrosterone sulfate levels in anovulatory women. Fertil Steril 42 (1984) 76-81
27. Kumar A., Woods K.S., Bartolucci A.A., and Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). J Clin Endocrinol (Oxf) 62 (2005) 644-649
28. Haning R.V., Flood C.A., Hackett R.J., Loughlin J.S., McClure N., and Longscope C. Metabolic clearance rate of dehydroepiandrosterone sulphate, its metabolism to testosterone, and its intrafolllicular metabolism to dehydrotestosterone, androsterone, testosterone, and dihydrotestosterone in vivo. J Clin Endocrinol Metab 72 (1991) 1088-1095
29. Bonser J., Walker J., Purohit A., Reed M.J., Potter B.V.L., Mason H.D., et al. Human granulosa cells are a site of sulphatase activity and are able to utilize dehydroepiandrosterone sulphate as a precursor for oestradiol production. J Endocrinol 167 (2000) 465-471
30. Fassnacht M., Schlenz N., Schneider S.B., Wudy S.A., Allolio B., and Arlt W. Beyond adrenal and ovarian androgen generation: increased peripheral 5α-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88 (2003) 2760-2766
31. Jakimiuk A.J., Weitsman S.R., and Magoffin D.A. 5α-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 847 (1999) 2414-2418
32. Agarwal S.K., Judd H.L., and Magoffin D.A. A mechanism for the suppression of estrogen production in polycystic ovary syndrome. J Clin Endocrinol Metab 81 (1996) 3686-3691
33. Lobo R.A., Paul W.L., Gentzschein E., Serafini P.C., Catalino J.A., Horton R., et al. Production of 3 alpha-androstanediol glucuronide in human genital skin. J Clin Endocrinol Metab 65 (1987) 711-714
34. Kjøtrød S.B., von During V., and Carlsen S.M. Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Hum Reprod 19 (2004) 1-8
35. Adams J., Polson D.W., and Franks S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J 293 (1986) 355-359
36. Dehenin L., Jondet M., and Scholler R. Androgen and 19-nonstereoid profiles in human preovulatory follicles from stimulated cycles: an isotope dilution mass spectrometric study. J Stereoid Biochem 26 (1987) 399-405
37. Moran C., Knochenhauer E., Boots L.R., and Azziz R. Adrenal androgen excess in hyperandrogenism: relation to age and body mass. Fertil Steril 71 (1999) 671-674
38. Shimokata H., Muller D.C., Fleg J.L., Sorkin J., Ziemba A.W., and Andres R. Age as an independent determinant of glucose tolerance. Diabetes 40 (1991) 44-51
39. Kreisberg R.A. Aging, glucose metabolism, and diabetes: current concepts. Geriatrics 42 (1987) 67-72
40. Wild R.A., Umstot E.S., Andersen R.N., Ranney G.B., and Givens J.R. Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol 146 (1983) 602-606
41. Carmina E., and Lobo R.A. Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes. J Endocrinol Invest 30 (2007) 111-116
42. Carmina E. Ovarian and adrenal hyperandrogenism. Ann N Y Acad Sci 1092 (2006) 130-137
43. Schriock E.D., Buffington C.K., and Hubert G.D. Divergent correlations of circulating dehydroepiandrosterone sulphate and testosterone with insulin levels and insulin receptor binding. J Clin Endocrinol Metab 66 (1990) 1329-1331
44. Diamond M.P., Grainger D.A., Laudano A.J., Starick-Zych K., and DeFronzo R.A. Effect of acute physiological elevations of insulin on circulating androgen levels in nonobese women. J Clin Endocrinol Metab 72 (1991) 883-887
45. Buyalos R.P., Geffner M.E., Azziz R., and Judd H.L. Impact of overnight dexamethasone suppression on the adrenal androgen response to an oral glucose tolerance test in women with and without polycystic ovary syndrome. Hum Reprod 12 (1997) 1138-1141
46. Nestler J.E., Beer N.A., Jakubowicz D.J., and Beer R.M. Effects of a reduction in circulating insulin by metformin on serum dehydroepiandrosterone sulfate in nondiabetic men. J Clin Endocrinol Metab 78 (1994) 549-554
47. Nestler J.E., Beer N.A., Jackubowicz D.J., Colombo C., and Beer R.M. Effects of insulin reduction with benfluorex on serum dehydroepiandrosterone (DHEA), DHEA sulphate, and blood pressure in hypertensive middle-aged and elderly men. J Clin Endocrinol Metab 80 (1995) 700-706
48. Glueck C.J., Moreira A., Goldenberg N., Sieve L., and Wang P. Pioglitazone and metformin in obese women with polycystic ovary syndrome not optimally responsive to metformin. Hum Reprod 18 (2003) 1618-1625
49. Greisen S., Ledet T., and Ovesen P. Effects of androstenedione, insulin and luteinizing hormone on stereoidogenesis in human granulosa luteal cells. Hum Reprod 16 (2001) 2061-2065