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Published in: Archives of Gynecology and Obstetrics 1/2010

01-01-2010 | Original Article

Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome

Authors: Levent Kebapcilar, Cuneyt Eftal Taner, Ayse Gul Kebapcilar, Ahmet Alacacioglu, Ismail Sari

Published in: Archives of Gynecology and Obstetrics | Issue 1/2010

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Abstract

Objective

To determine the effects of different treatment regimens on the hormonal features, metabolic parameters, and hematologic variables in women with polycystic ovary syndrome (PCOS).

Methods

Forty-eight women with PCOS were randomized into four treatment protocols: ethinyl estradiol/cyproterone acetate (EE/CA; n = 12), EE/CA–metformin (n = 12), metformin alone (n = 12) and EE/CA–spironolactone (n = 12). These treatment protocols were given for 3 months and pre- and post-treatment variables were compared.

Results

Activated partial thromboplastin time (APTT) and prothrombin time (PT) levels, D-dimer, HOMA-IR, insulin, WBC, MPV as well as androgen levels decreased in all treatment groups. EE/CA–metformin and metformin alone groups resulted in a higher proportional reduction of D-dimer levels than the other protocols, while no significant different proportional reduction was observed in all the four groups for MPV, WBC, APTT, PT values. EE/CA–metformin group showed higher proportional reduction fasting insulin concentrations, HOMA-IR and free testosterone levels than metformin alone and EE/CA–spironolactone groups. DHEAs levels significantly decreased in group EE/CA–metformin than EE/CA alone and EE/CA–spironolactone groups. In multiple stepwise regression analyses, reduction in proportional insulin levels was independently and positively associated with decrease of MPV, D-dimer, free testosterone levels.

Conclusions

In all treatment groups, we observed reduced levels of coagulation parameters, improvement of hormonal, hematological and metabolical variables by most probably reducing insulin levels. Among the treatment groups, EE/CA–metformin may be a more effective therapeutic option than the other protocols and this may be due to the beneficial effect of EE/CA–metformin on insulin resistance.
Literature
2.
go back to reference von Eckardstein S, von Eckardstein A, Bender HG, Schulte H, Assmann G (1996) Elevated low-density lipoprotein-cholesterol in women with polycystic ovary syndrome. Gynecol Endocrinol 10:311–318. doi:10.3109/09513599609012817 CrossRef von Eckardstein S, von Eckardstein A, Bender HG, Schulte H, Assmann G (1996) Elevated low-density lipoprotein-cholesterol in women with polycystic ovary syndrome. Gynecol Endocrinol 10:311–318. doi:10.​3109/​0951359960901281​7 CrossRef
5.
go back to reference Kebapcilar L, Taner CE, Kebapcilar AG, Sari I (2008) High mean platelet volume, low-grade systemic coagulation and fibrinolytic activation are associated with androgen and insulin levels in polycystic ovary syndrome. Arch Gynecol Obstet [Epub ahead of print] Kebapcilar L, Taner CE, Kebapcilar AG, Sari I (2008) High mean platelet volume, low-grade systemic coagulation and fibrinolytic activation are associated with androgen and insulin levels in polycystic ovary syndrome. Arch Gynecol Obstet [Epub ahead of print]
6.
go back to reference Derosa G, Dangelo A, Ragonesi PD, Ciccarelli L, Piccinni MN, Pricolo F, Salvadeo S, Montagna L, Gravina A, Ferrari I, Galli S, Paniga S, Cicero AF (2006) Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome. J Int Med Res 34:545–555PubMed Derosa G, Dangelo A, Ragonesi PD, Ciccarelli L, Piccinni MN, Pricolo F, Salvadeo S, Montagna L, Gravina A, Ferrari I, Galli S, Paniga S, Cicero AF (2006) Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome. J Int Med Res 34:545–555PubMed
7.
go back to reference The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome PCOS. Hum Reprod 19:41–47. doi:10.1093/humrep/deh098 CrossRef The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome PCOS. Hum Reprod 19:41–47. doi:10.​1093/​humrep/​deh098 CrossRef
8.
go back to reference Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H, Tapanainen JS (2003) 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. doi:10.1210/jc.2002-020997 CrossRefPubMed Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H, Tapanainen JS (2003) 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. doi:10.​1210/​jc.​2002-020997 CrossRefPubMed
9.
go back to reference Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Martínez-Bermejo E, Lasunción MA, Escobar-Morreale HF (2007) Comparison of ethinyl-estradiol plus cyproterone acetate versus metformin effects on classic metabolic cardiovascular risk factors in women with the polycystic ovary syndrome. J Clin Endocrinol Metab 92:2453–2461. doi:10.1210/jc.2007-0282 CrossRefPubMed Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Martínez-Bermejo E, Lasunción MA, Escobar-Morreale HF (2007) Comparison of ethinyl-estradiol plus cyproterone acetate versus metformin effects on classic metabolic cardiovascular risk factors in women with the polycystic ovary syndrome. J Clin Endocrinol Metab 92:2453–2461. doi:10.​1210/​jc.​2007-0282 CrossRefPubMed
10.
go back to reference Karakurt F, Gumus II, Bavbek N, Kargili A, Koca C, Selcoki Y, Ozbek M, Kosar A, Akcay A (2008) Increased thrombin-activatable fibrinolysis inhibitor antigen levels as a clue for prothrombotic state in polycystic ovary syndrome. Gynecol Endocrinol 24:491–497. doi:10.1080/09513590802291824 CrossRefPubMed Karakurt F, Gumus II, Bavbek N, Kargili A, Koca C, Selcoki Y, Ozbek M, Kosar A, Akcay A (2008) Increased thrombin-activatable fibrinolysis inhibitor antigen levels as a clue for prothrombotic state in polycystic ovary syndrome. Gynecol Endocrinol 24:491–497. doi:10.​1080/​0951359080229182​4 CrossRefPubMed
11.
go back to reference Luque-Ramírez M, Mendieta-Azcona C, del Rey Sánchez JM, Matíes M, Escobar-Morreale HF (2009) Effects of an antiandrogenic oral contraceptive pill compared with metformin on blood coagulation tests and endothelial function in women with the polycystic ovary syndrome: influence of obesity and smoking. Eur J Endocrinol 160:469–480. doi:10.1530/EJE-08-0725 CrossRefPubMed Luque-Ramírez M, Mendieta-Azcona C, del Rey Sánchez JM, Matíes M, Escobar-Morreale HF (2009) Effects of an antiandrogenic oral contraceptive pill compared with metformin on blood coagulation tests and endothelial function in women with the polycystic ovary syndrome: influence of obesity and smoking. Eur J Endocrinol 160:469–480. doi:10.​1530/​EJE-08-0725 CrossRefPubMed
12.
go back to reference Kiliçli-Camur N, Demirtunç R, Konuralp C, Eskiser A, Başaran Y (2005) Could mean platelet volume be a predictive marker for acute myocardial infarction? Med Sci Monit 11:CR387–CR392PubMed Kiliçli-Camur N, Demirtunç R, Konuralp C, Eskiser A, Başaran Y (2005) Could mean platelet volume be a predictive marker for acute myocardial infarction? Med Sci Monit 11:CR387–CR392PubMed
14.
go back to reference Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolin E, Muggeo M (2000) 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 85:139–146. doi:10.1210/jc.85.1.139 CrossRefPubMed Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolin E, Muggeo M (2000) 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 85:139–146. doi:10.​1210/​jc.​85.​1.​139 CrossRefPubMed
15.
go back to reference Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N (2002) Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab 87:569–574. doi:10.1210/jc.87.2.569 CrossRefPubMed Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N (2002) Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab 87:569–574. doi:10.​1210/​jc.​87.​2.​569 CrossRefPubMed
16.
go back to reference Elter K, Imir G, Durmusoglu F (2002) 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 17:1729–1737. doi:10.1093/humrep/17.7.1729 CrossRefPubMed Elter K, Imir G, Durmusoglu F (2002) 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 17:1729–1737. doi:10.​1093/​humrep/​17.​7.​1729 CrossRefPubMed
18.
go back to reference Wu J, Zhu Y, Jiang Y, Cao Y (2008) Effects of metformin and ethinyl estradiol–cyproterone acetate on clinical, endocrine and metabolic factors in women with polycystic ovary syndrome. Gynecol Endocrinol 24:392–398. doi:10.1080/09513590802217027 CrossRefPubMed Wu J, Zhu Y, Jiang Y, Cao Y (2008) Effects of metformin and ethinyl estradiol–cyproterone acetate on clinical, endocrine and metabolic factors in women with polycystic ovary syndrome. Gynecol Endocrinol 24:392–398. doi:10.​1080/​0951359080221702​7 CrossRefPubMed
19.
go back to reference Pasquali R, Gambineri A, Anconetani B, Vicennati V, Colitta D, Caramelli E, Casimirri F, Morselli-Labate AM (1999) The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen–progestogen treatment. Clin Endocrinol (Oxf) 50:517–527. doi:10.1046/j.1365-2265.1999.00701.x CrossRef Pasquali R, Gambineri A, Anconetani B, Vicennati V, Colitta D, Caramelli E, Casimirri F, Morselli-Labate AM (1999) The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen–progestogen treatment. Clin Endocrinol (Oxf) 50:517–527. doi:10.​1046/​j.​1365-2265.​1999.​00701.​x CrossRef
20.
go back to reference Cagnacci A, Paoletti AM, Renzi A, Orrù M, Pilloni M, Melis GB, Volpe A (2003) Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel. J Clin Endocrinol Metab 88:3621–3625. doi:10.1210/jc.2003-030328 CrossRefPubMed Cagnacci A, Paoletti AM, Renzi A, Orrù M, Pilloni M, Melis GB, Volpe A (2003) Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel. J Clin Endocrinol Metab 88:3621–3625. doi:10.​1210/​jc.​2003-030328 CrossRefPubMed
21.
go back to reference Cibula D, Fanta M, Vrbikova J, Stanicka S, Dvorakova K, Hill M, Skrha J, Zivny J, Skrenkova J (2005) The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. Hum Reprod 20:180–184. doi:10.1093/humrep/deh588 CrossRefPubMed Cibula D, Fanta M, Vrbikova J, Stanicka S, Dvorakova K, Hill M, Skrha J, Zivny J, Skrenkova J (2005) The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. Hum Reprod 20:180–184. doi:10.​1093/​humrep/​deh588 CrossRefPubMed
22.
go back to reference Vrbíková J, Stanická S, Dvoráková K, Hill M, Vondra K, Bendlová B, Stárka L (2004) Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome. Eur J Endocrinol 150:215–223. doi:10.1530/eje.0.1500215 CrossRefPubMed Vrbíková J, Stanická S, Dvoráková K, Hill M, Vondra K, Bendlová B, Stárka L (2004) Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome. Eur J Endocrinol 150:215–223. doi:10.​1530/​eje.​0.​1500215 CrossRefPubMed
23.
go back to reference Holmang A, Larsson BM, Brzezinska Z, Bjorntorp P (1992) Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats. Am J Physiol 262:E851–E855PubMed Holmang A, Larsson BM, Brzezinska Z, Bjorntorp P (1992) Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats. Am J Physiol 262:E851–E855PubMed
24.
go back to reference Rincon J, Holmang A, Wahlstrom EO, Lonnroth P, Bjorntorp P, Zierath JR, Wallberg-Henriksson H (1996) Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes 45:615–621. doi:10.2337/diabetes.45.5.615 CrossRefPubMed Rincon J, Holmang A, Wahlstrom EO, Lonnroth P, Bjorntorp P, Zierath JR, Wallberg-Henriksson H (1996) Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes 45:615–621. doi:10.​2337/​diabetes.​45.​5.​615 CrossRefPubMed
26.
go back to reference Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ (2003) Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 88:812–819. doi:10.1210/jc.2002-020815 CrossRefPubMed Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ (2003) Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 88:812–819. doi:10.​1210/​jc.​2002-020815 CrossRefPubMed
27.
go back to reference Hoeger KM (2006) Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 20:293–310 Hoeger KM (2006) Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 20:293–310
Metadata
Title
Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome
Authors
Levent Kebapcilar
Cuneyt Eftal Taner
Ayse Gul Kebapcilar
Ahmet Alacacioglu
Ismail Sari
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 1/2010
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-009-1051-y

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