Discontinuous low-dose flutamide-metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: Normalizing effects on CRP, TNF-α and the neutrophil/lymphocyte ratio

Human Reproduction

Volumn 21, Issue 2, 2006, Pages 451-456

  Ibáñez, Lourdes ^a   Valls, Carme ^a   de Zegher, Francis ^b  

^a UNIVERSITY OF BARCELONA   (Spain)

^b UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Contraception; CRP; Flutamide metformin treatment; Hyperinsulinaemic hyperandrogenism; PCOS

Indexed keywords

C REACTIVE PROTEIN; CONTRACEPTIVE AGENT; DROSPIRENONE PLUS ETHINYLESTRADIOL; ETHINYLESTRADIOL PLUS NORELGESTROMIN; FLUTAMIDE; LEUPRORELIN; METFORMIN; TUMOR NECROSIS FACTOR ALPHA;

ADOLESCENT; ADULT; ARTICLE; BODY COMPOSITION; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; HORMONE DETERMINATION; HUMAN; HUMAN CELL; HYPERANDROGENISM; HYPERINSULINEMIA; LEAN BODY WEIGHT; LIPOLYSIS; LOW DRUG DOSE; LYMPHOCYTE; NEUTROPHIL; OBESITY; RANDOMIZED CONTROLLED TRIAL; SPOTTING; STATISTICAL ANALYSIS;

EID: 31544460104     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/dei329     Document Type: Article

References (41)

1. Asunción M, Calvo RM, San Millan JL, Sancho J, Avila S and Escobar-Morreale H (2000) A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 85,2434-2438.
2. Baumann EE and Rosenfield RL (2002) Polycystic ovary syndrome in adolescence. Endocrinologist 12,333-348.
3. Blum CA, Muller B, Huber P, Kraenzlin M, Schindler C, De Geyter C, Keller U and Puder JJ (2005) Low-grade inflammation and estimates of insulin resistance during the menstrual cycle in lean and overweight women. J Clin Endocrinol Metab 90,3230-3235.
4. Devriendt K, Kim AS, Mathijs G, Frints SG et al. (2001) Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia. Nat Genet 27:313-317.
5. Di Carlo C, Tommaselli GA, Sammartino A, Bifulco G, Nasti A and Nappi A (2004) Serum leptin levels and body composition in postmenopausal women: effects of hormone therapy. Menopause 11:466-473.
6. Dunaif A and Thomas A (2000) Current concepts in the polycystic ovary syndrome. Annu Rev Med 52,401-419.
7. Escobar-Morreale HF, Calvo RM, Sancho J and San Millan JL (2001) TNF-α and hyperandrogenism: A clinical, biochemical, and molecular genetic study. J Clin Endocrinol Metab 86:3671-3767.
8. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20,1183-1197.
9. González F, Thusu K, Abdel-Raman E, Prabhala A, Tomani M and Dandona P (1999) Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome. Metabolism 48,437-441.
10. Ferriman D and Gallwey JD (1961) Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 21,1440-1447.
11. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF and Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α and obesity-induced insulin resistance. Science 271,665-668.
12. Ibáñez L and de Zegher F (2003) Flutamide-metformin to reduce fat mass in hyperinsulinemic ovarian hyperandrogenism: Effects in adolescents and in women on third-generation oral contraception. J Clin Endocrinol Metab 88,4720-4724.
13. Ibáñez L and de Zegher F (2004a) Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and young women with hyperinsulinemic hyperandrogenism: Opposite effects on adipocytokines and body adiposity. J Clin Endocrinol Metab 89,1592-1597.
14. Ibáñez L and de Zegher F (2004b) Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity. Hum Reprod 19,1725-1727.
15. Ibáñez L and de Zegher F (2005) Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and anti-atherogenesis in young women with ovarian hyperandrogenism: The key role of metformin at start and after more than one year of therapy. J Clin Endocrinol Metab 90,39-43.
16. Ibáñez L, Valls C, Ferrer A, Ong K, Dunger D and de Zegher F (2002) Additive effects of insulin-sensitizing and anti-androgen treatment in young, non-obese women with hyperinsulinism, hyperandrogenism, dyslipidemia and anovulation. J Clin Endocrinol Metab 87,2870-2874.
17. Ibáñez L, Ong K, Ferrer A, Amin R, Dunger D and de Zegher F (2003a) Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in non-obese adolescents and young women with ovarian hyperandrogenism. J Clin Endocrinol Metab 88,2600-2606.
18. Ibáñez L, Ong K, de Zegher F, Marcos MV, del Rio L and Dunger D (2003b) Fat distribution in non-obese girls with and without precocious pubarche: Central adiposity related to insulinemia and androgenemia from pre-puberty to post-menarche. Clin Endocrinol 58,372-379.
19. Ibáñez L, Valls C, Cabré S and de Zegher F (2004) Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and anti-atherogenesis in young women with ovarian hyperandrogenism: The key role of early, low-dose flutamide. J Clin Endocrinol Metab 89,4716-4720.
20. Ibáñez L, Jaramillo A, Ferrer A and de Zegher F (2005a) Absence of hepatotoxicity after long-term, low-dose flutamide n hyperandrogenic girls and young women. Hum Reprod 20,1833-1836.
21. Ibáñez L, Jaramillo A, Ferrer A and de Zegher F (2005b) High neutrophil count in girls and women with hyperinsulinemic hyperandrogenism: Normalization with metformin and flutamide overcomes the aggravation by oral contraception. Hum Reprod 20,2457-2456.
22. Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM and Sattar N (2001) Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 86,2453-2455.
23. Kiebzak GM, Leamy LJ, Pierson LM, Nord RH and Zhang ZY (2000) Measurement precision of body composition variables using the Lunar DPX-L densitometer. J Clin Densitom 3,35-41.
24. Kirchengast S and Huber J (2001) Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 16,1255-1260.
25. Kraemer GR, Kraemer RR, Ogden BW, Kilpatrick RE, Gimpel TL and Castracane VD (2003) Variability of serum estrogens among postmenopausal women treated with the same transdermal estrogen therapy and the effect on androgens and sex hormone binding globulin. Fertil Steril 79,534-542.
26. Lacut K, Oger E, Le Gal G, Blouch MT, Abgrall JF, Kerlan V, Scarabin PY, Mottier D; SARAH Investigators (2003) Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein. Thromb Haemost 90,124-131.
27. Mermejo LV, Elías LLK, Marui S, Moreira AC, Mendonca BB and de Castro M (2005) Refining hormonal diagnosis of type II 3β-hydroxysteroid dehydrogenase deficiency in patients with premature pubarche and hirsutism based on HSD3B2 genotyping. J Clin Endocrinol Metab 90,1287-1293.
28. Messingham KA, Shirazi M, Duffner LA, Emanuele MA and Kovacs EJ (2001) Testosterone receptor blockade restores cellular immunity in male mice after burn injury. J Endocrinol 169,299-308.
29. Morin-Papunen L, Rautio K, Ruokonen A, Hedberg P, Puukka M and Tapanainen JS (2003a) Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88,4649-4654.
30. Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H and Tapanainen JS (2003b) Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: A randomized study. J Clin Endocrinol Metab 88,148-156.
31. New MI, Lorenzen F, Lerner AJ et al. (1983) Genotyping steroid 21-hydroxylase deficiency: Hormonal reference data. J Clin Endocrinol Metab 56,320-325.
32. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, Orazem J, Magorien RD, O'Shaughnessy C, Ganz P; Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators (2005) Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 352,29-38.
33. Puder JJ, Freda PU, Goland RS and Wardlaw SL (2002) Estrogen modulates the hypothalamic-pituitary-adrenal and inflammatory cytokine responses to endotoxin in women. J Clin Endocrinol Metab 86,2403-2408.
34. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators (2005) C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352,20-28.
35. Ropponen A, Aittomäki K, Tikkanen MJ and Ylikorkala O (2005a) Levels of serum C-reactive protein during oral and transdermal estradiol in postmenopausal women with and without a history of intrahepatic cholestasis of pregnancy. J Clin Endocrinol Metab 90,142-146.
36. Ropponen A, Aittomäki K, Vihma V, Tikkanen MJ and Ylikorkala O (2005b) Effects of oral and transdermal estradiol administration on levels of sex hormone-binding globulin in postmenopausal women with and without a history of intrahepatic cholestasis of pregnancy. J Clin Endocrinol Metab 90,3431-3434.
37. Sites CK, L'Hommedieu GD, Toth MJ, Brochu M, Cooper BC and Fairhust PA (2005) The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: A randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 90,2701-2707.
38. Taylor RW, Keil D, Gold EJ, Williams SM and Goulding A (1998) Body mass index, waist girth, and waist-to-hip ratio as indexes of total and regional adiposity in women: Evaluation using receiver operating characteristic curves. Am J Clin Nutr 67,44-49.
39. Tarkun I, Arslan BC, Canturk Z, Turemen E, Sahin T and Duman C (2004) Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab 89,5592-5596.
40. Vidal-Puig A, Moller DE (1997) Insulin resistance: Classification, prevalence, clinical manifestations, and diagnosis. In: Azziz R, Nestler JE, Dewailly D (eds) Androgen excess disorders in women. Lippincott-Raven, Philadelphia, pp. 227-236.
41. Vrbikova J, Stanicka S, Dvorakova K, Hill M, Vondra K, Bendlova B and Starka L (2004) Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyoriterone acetate in women with polycystic ovary syndrome. Eur J Endocrinol 150,215-223.