Low-dose pioglitazone, flutamide, metformin plus an estro-progestagen for non-obese young women with polycystic ovary syndrome: Increasing efficacy and persistent safety over 30 months

Gynecological Endocrinology

Volumn 26, Issue 12, 2010, Pages 869-873

  IbáÑez, Lourdes ^a,b   López Bermejo, Abel ^c   Díaz, Marta ^a,b   Enríquez, Goya ^d   Del Río, Luis ^e   De Zegher, Francis ^f  

^a UNIVERSITY OF BARCELONA   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c HOSPITAL JOSEP TRUETA   (Spain)

^d UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^e CETIR   (Spain)

^f UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

acne; adiposity; androgen excess; BMD; BMI; carotid intima media thickness; DHEAS; drospirenone; flutamide; HDL cholesterol; hirsutism; IGF I; lymphocytes; metformin; neutrophils; PCOS; pioglitazone; Visceral fat; waist hip ratio; weight

Indexed keywords

ANDROGEN; ASPARTATE AMINOTRANSFERASE; C REACTIVE PROTEIN; DROSPIRENONE PLUS ETHINYLESTRADIOL; FLUTAMIDE; GAMMA GLUTAMYLTRANSFERASE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LACTATE DEHYDROGENASE; METFORMIN; PIOGLITAZONE; PLACEBO;

ADD ON THERAPY; ADULT; ARTICLE; BODY MASS; BODY WEIGHT; BONE DENSITY; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; GLUCOSE BLOOD LEVEL; HIRSUTISM; HUMAN; HYPERINSULINEMIA; INSULIN SENSITIVITY; INTRAABDOMINAL FAT; LOW DRUG DOSE; OBESITY; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TREATMENT OUTCOME;

ADOLESCENT; ALANINE TRANSAMINASE; ANDROGENS; ANDROSTENES; ASPARTATE AMINOTRANSFERASES; BLOOD GLUCOSE; BODY COMPOSITION; C-REACTIVE PROTEIN; CHOLESTEROL; CROSS-OVER STUDIES; DRUG THERAPY, COMBINATION; ETHINYL ESTRADIOL; FEMALE; FLUTAMIDE; GAMMA-GLUTAMYLTRANSFERASE; HUMANS; HYDRO-LYASES; INSULIN; LONGITUDINAL STUDIES; METFORMIN; POLYCYSTIC OVARY SYNDROME; THIAZOLIDINEDIONES; TUNICA INTIMA; YOUNG ADULT;

EID: 78149462550     PISSN: 09513590     EISSN: 14730766     Source Type: Journal    
DOI: 10.3109/09513590.2010.487589     Document Type: Article

References (22)

1. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 8:1165-1174. (Pubitemid 19250404)
2. Velazquez EM, Mendoza S, Hamer T, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandro-genemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994;43:647-654. (Pubitemid 24145474)
3. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab 1997;82:4075-4079.
4. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. New Engl J Med 1998; 338:1876-1880. (Pubitemid 28287859)
5. Ibáñez L, Valls C, Potau N, Marcos MV, de Zegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000;85:3526-3530.
6. Ibáñez L, Valls C, Ferrer A, Marcos MV, Rodriguez-Hierro F, de Zegher F. Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism. J Clin Endocrinol Metab 2001;86:3595-3598. (Pubitemid 32755948)
7. Ibáñez L, Jaramillo AM, Ferrer A, de Zegher F. High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and fluta-mide overcomes the aggravation by oral contraception. Hum Reprod 2005;20:2457-2462. (Pubitemid 41226405)
8. Ehrmann DA. Polycystic ovary syndrome. New Engl J Med 2005;352:1223-1236.
9. Rosenfield RL. Clinical review: identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92:787-796. (Pubitemid 46465641)
10. Ibáñez L, Valls C, Cabré S, de Zegher F. Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperan-drogenism: the key role of early, low-dose flutamide. J Clin Endocrinol Metab 2004;89:4716-4720. (Pubitemid 39244493)
11. Ibáñez L, de Zegher F. Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women. Hum Reprod Update 2006;12:243-252. (Pubitemid 43913770)
12. Ibáñez L, López-Bermejo A, del Rio L, Enŕiquez G, Valls C, de Zegher F. Combined low-dose pioglitazone, flutamide, and metformin for women with androgen excess. J Clin Endocri-nol Metab 2007;92:1710-1714. (Pubitemid 46997176)
13. Ibáñez L, López-Bermejo A, D́iaz M, Enŕiquez G, Valls C, de Zegher F. Pioglitazone (7.5 mg/d) added to flutamide-metformin in women with androgen excess: additional increments of visfatin and high-molecular-weight adiponectin. Clin Endocrinol (Oxf) 2008;68:317-320.
14. Ibáñez L, López-Bermejo A, D́iaz M, Enŕiquez G, del Rio L, de Zegher F. Low-dose pioglitazone and low-dose flutamide added to metformin and estro-progestagens for hyperinsuli-nemic women with androgen excess: add-on benefits disclosed by a randomized double-placebo study over 24 months. Clin Endocrinol (Oxf) 2009;71:351-357.
15. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, editors. Polycystic ovary syndrome, Boston: Blackwell Scientific; 1992. pp 377-384.
16. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19-25. (Pubitemid 38058321)
17. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, et al. Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006;91:4237-4245. (Pubitemid 44833391)
18. Ibáñez L, Sebastiani G, Diaz M, López-Bermejo A, Gómez-Roig MD, de Zegher F. Gender specificity ofbody adiposity and circulating adiponectin, visfatin, insulin and IGF-I at term birth: relation to prenatal growth. J Clin Endocrinol Metab 2008;93:2774-2778. (Pubitemid 352008550)
19. Ibáñez L, Jaramillo A;Ferrer A, de Zegher F. Absence of hepatotoxicity after long-term, low-dose flutamide in hyper-androgenic girls and young women. Hum Reprod 2005;20: 1833-1836. (Pubitemid 40932364)
20. Dikensoy E, Balat O, Pence S, Akcali C, Cicek H. The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism. Arch Gynecol Obstet 2009;279:321-327.
21. de Zegher F, Ibáñez L. Low-dose flutamide for women with androgen excess: anti-androgenic efficacy and hepatic safety. J Endocrinol Invest 2009;32:83-84.
22. Setji TL, Holland ND, Sanders LL, Pereira KC, Diehl AM, Brown AJ. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1741-1747.