The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome

Kisa, Ucler; GÜLİTER, Sefa; TULMAÇ, Murat; Demirci, Hüseyin; Yılmaz, Murat; unal, derya

doi:10.4274/imj.galenos.2020.75875

The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome

Derya ÜNAL, (Yedikule Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, İmmünoloji ve Alerji Hastalıkları Kliniği, İstanbul, Türkiye)

Hüseyin DEMİRCİ, (Kırıkkale Üniversitesi, Tıp Fakültesi, Endokrinoloji ve Metabolizma Hastalıkları Anabilim Dalı, Kırıkkale, Türkiye)

Murat YILMAZ, (Kırıkkale Üniversitesi, Tıp Fakültesi, Endokrinoloji ve Metabolizma Hastalıkları Anabilim Dalı, Kırıkkale, Türkiye)

Üçler KISA, (Kırıkkale Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Kırıkkale, Türkiye)

Murat TULMAÇ, (Kırıkkale Üniversitesi, Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Kırıkkale, Türkiye)

Sefa GÜLİTER (Kırıkkale Üniversitesi, Tıp Fakültesi, Gastroenteroloji Anabilim Dalı, Kırıkkale, Türkiye)

İstanbul Medical Journal

1 0

Yıl: 2020 Cilt: 21 Sayı: 1 Sayfa Aralığı: 47 - 52 Metin Dili: İngilizce DOI: 10.4274/imj.galenos.2020.75875 İndeks Tarihi: 06-10-2020

The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome

Öz:

Introduction: Patients with polycystic ovary syndrome(PCOS) are in the risk group for early-onset cardiovasculardisease. There are few studies evaluating physiological andinflammatory cardiovascular risk factors in PCOS. Our studyaimed to measure carotid intima-media thickness (IMT) inPCOS cases and to assess the effects of metformin, ethinylestradiol/cyproterone acetate (EE/CA) and metformin + EE/CA combination therapy on carotid IMT, insulin resistance,C-reactive protein (CRP), apelin and adiponectin.Methods: Basal carotid IMT, insulin resistance [Homeostasismodel assessment insulin resistance (HOMA-IR)], apelin,adiponectin, and CRP values were evaluated in 60 women withPCOS and 43 healthy volunteers between the ages of 18 and 45.After baseline evaluation, patients were divided into metformin(n=20), EE/CA (n=20) and metformin + EE/CA (n=20) treatmentgroups. Treatment regimens were administered for six months.At the end of the treatment, the same parameters were reevaluated.Results: Compared with the control group, CRP (p=0.003),HOMA-IR (p=0.004) and IMT (p=0.049) were significantlyhigher, and adiponectin (p=0.002) and apelin (p=0.031) levelswere significantly lower in patients with PCOS. At the end of thesix-month treatment, the adiponectin level in the metformin(p=0.012) and metformin + EE/CA groups (p=0.012), and theapelin level in the metformin (p=0.024), EE/CA (p=0.024) andmetformin + EE/CA groups (p=0.024) were significantly higher.There was no statistically significant change in CRP level in all treatment groups (p>0.05). There was no statistically significantchange in carotid IMT value in all treatment groups (p>0.05).Conclusion: According to these results, we can say that womenwith PCOS have subclinical atherosclerosis and that metformintreatment has a positive effect on subclinical atherosclerosis.

Anahtar Kelime:

Polikistik Over Sendromlu Olgularda Metformin, Etinil Estradiol/Siproteron Asetat ve Metformin-etinil Estradiol/Siproteron Asetat Kombinasyonu Tedavisinin Karotis Arter İntima Media Kalınlığı Üzerine Etkileri

Öz:

Amaç: Polikistik over sendromu (PKOS) erken dönemde ortaya çıkan kardiyovasküler hastalık için risk grubundadır. PKOS’de, fizyolojik ve enflamatuvar kardiyovasküler risk faktörlerini değerlendiren az sayıda çalışma vardır. Çalışmamızın amacı, PKOS olgularında karotis intima media kalınlığını (İMK) ve ayrıca metformin, etinil estradiol/siproteron asetat (EE/SA) ve metformin + EE/SA kombinasyon tedavisinin karotis İMK, insülin direnci, C-reaktif protein (CRP), apelin ve adiponektin üzerine etkilerini değerlendirmektir. Yöntemler: Çalışmamıza katılan 18-45 yaş arasındaki 60 PKOS’li kadında ve 43 sağlıklı gönüllü kadında bazal karotis İMK, insülin direnci [Homeostasis model assessment insulin resistance (HOMA-IR)], apelin, adiponektin ve CRP değerlendirmeleri yapıldı. Bazal değerlendirmeden sonra, hastalar metformin (n=20), EE/SA (n=20) ve metformin + EE/SA (n=20) tedavi gruplarına ayrıldı. Tedavi rejimleri 6 ay boyunca uygulandı. Tedavi sonunda aynı parametreler tekrar değerlendirildi. Bulgular: Kontrol grubuyla karşılaştırıldığında PKOS’li olguların CRP (p=0,003), HOMA-IR (p=0,004), İMK (p=0,049) değerleri istatistiksel olarak anlamlı derecede daha yüksek, adiponektin (p=0,002), apelin (p=0,031) düzeyleri kontrol grubundan istatistiksel olarak daha düşük saptandı. Altı aylık tedavinin sonunda adiponektin seviyesi metformin (p=0,012) ve metformin + EE/SA grubunda (p=0,012), apelin seviyesi ise metformin grubu (p=0,024), EE/SA grubu (p=0,024), ve metformin + EE/SA grubunda (p=0,024) anlamlı olarak yüksek saptandı. Üç tedavi grubunda da CRP seviyesinde istatistiksel olarak anlamlı değişim yoktu (p>0,05). Üç tedavi grubunda da karotis İMK değerinde istatistiksel olarak anlamlı değişim yoktu (p>0,05). Sonuç: Bu sonuçlara göre PKOS’de subklinik aterosklerozun varlığını ve metformin tedavisinin subklinik ateroskleroz üzerine olumlu etki gösterdiğini söyleyebiliriz.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Bellver J, Rodríguez-Tabernero L, Robles A, Muñoz E, Martínez F, Landeras J, et al. Polycystic ovary syndrome throughout a woman’s life. J Assist Reprod Genet 2018; 35: 25-39.
2. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181-91.
3. Ricardo Aziz R. Controversy in clinical endocrinology: diagnosis of Polycystic Ovarian Syndrome: The Rotterdam Criteria Are Premature. J Clin Endocrinol Metab 2006; 91: 781-5.
4. Zawadzki JK, Dunaif A. 1992 Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, eds. Polycystic ovary syndrome. Boston: Blackwell Scientific; 377-84.
5. 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 2004; 19: 41-7.
6. Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91:456-88
7. Ramezani Tehrani F, Amiri M. Polycystic Ovary Syndome in adolescents. Challenges in diagnosis and treatment. Int J Endocrinol Metab 2019; 17: e91554.
8. Hayes MG, Urbanek M, Ehrmann DA, Armstrong LL, Lee JY, Sisk R, et al. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun 2015; 6: 7502.
9. Giampaolino P, Della Corte L, De Rosa N, Mercorio A, Bruzzese D, Bifulco G et al. Ovarian volume and PCOS: A controversial issue. Gynecol Endocrinol. 2018; 34: 229-32.
10. Jayasena CN, Franks S. The Management of patients with polycystic ovary syndrome. Nat Rev Endocrinol 2014; 10: 624-36.
11. Glintborg D, Rubin KH, Nybo M, Abrahamsen B, Andersen M. Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome. Cardiovasc Diabetol 2018; 17: 37.
12. Zahary MN, Harun NS, Yahaya R, Nik Him NAS, Rohin MAK, Ridzwan NH, et al. Serum adiponectin and resistin: Correlation with metabolic syndrome and its associated criteria among temiar subtribe in Malaysia. Diabetes Metab Syndr 2019; 13: 2015-9.
13. Gourdy P, Cazals L, Thalamas C, Sommet A, Calvas F, Galitzky M, et al. Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp. Diabetes Obes Metab 2018; 20: 157- 64.
14. Blumenfeld Z. The possible practical implication of high CRP levels in PCOS. Clin Med Insights Reprod Health 2019; 22; 13.
15. Legro RS. Evaluation and treatment of polycystic ovary syndrome. In: De Groot, LJ, Chrousos, G, Dungan, K., eds. Endotext. South Dartmouth, MA: MDText.com, Inc.; 2017.
16. Teng HW, Chien YW, Hsu MI, Chen CI. The relationship between carotid intimamedia thickness and endogenous androgens in young women with polycystic ovary syndrome in Taiwan. Gynecol Endocrinol 2013; 29: 238-41.
17. Al Khalifah RA, Florez ID, Dennis B, Thabane L, Bassilious E. Metformin or oral contraceptives for adolescents with polycystic ovarian syndrome: A metaanalysis. Pediatrics 2016; 137. pii: e20154089.
18. Yuan C, Liu X, Mao Y, Diao F, Cui Y, Liu J. Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess: a prospective study. J Biomed Res 2016; 30: 197-202.
19. Talari HR, Poladchang S, Hamidian Y, Samimi M, Gilasi HR, Ebrahimi FA, et al. The Effects of Omega-3 and Vitamin E Co-supplementation on carotid intimamedia thickness and inflammatory factors in patients with polycystic ovary syndrome. Oman Med J 2018; 33: 473-9.
20. Talbott EO, Zborowski JV, Boudreaux MY, McHugh-Pemu KP, Sutton-Tyrrell K, Guzick DS. The relationship between C-reactive protein and carotid intimamedia wall thickness in middle-aged women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89: 6061-7.
21. Song DK, Hong YS, Sung YA, Lee H. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance. PLoS One 2017; 25: 12.
22. Bongrani A, Mellouk N, Rame C, Cornuau M, Guérif F, Froment P, et al. Ovarian expression of adipokines in polycystic ovary syndrome: A role for chemerin, omentin, and apelin in follicular growth arrest and ovulatory dysfunction? Int J Mol Sci 2019; 20.
23. Chang CY, Tsai YC, Lee CH, Chan TF, Wang SH, Su JH. Lower serum apelin levels in women with polycystic ovary syndrome. Fertil Steril 2011; 95: 2520-3.e1-2.
24. Demirci H, Yilmaz M, Ergun MA, Yurtcu E, Bukan N, Ayvaz G. Frequency of adiponectin gene polymorphisms in polycystic ovary syndrome and the association with serum adiponectin, androgen levels, insulin resistance and clinical parameters. Gynecol Endocrinol 2010; 26: 348-55.
25. Wang J, Zhu L, Hu K, Tang Y, Zeng X, Liu J, et al. Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: A meta-analysis A PRISMA-compliant article. Medicine (Baltimore) 2017; 96.
26. Sahin Y, Unluhizarci K, Yilmazsoy A, Yikilmaz A, Aygen E, Kelestimur F. The effects of metformin on metabolic and cardiovascular risk factors in nonobese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007; 67: 904-8.
27. Mitkov M, Pehlivanov B, Terzieva D. Combined use of metformin and ethinyl estradiol-cyproterone acetate in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2005; 118: 209-13.

APA	unal d, Demirci H, Yılmaz M, Kisa U, TULMAÇ M, GÜLİTER S (2020). The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. , 47 - 52. 10.4274/imj.galenos.2020.75875
Chicago	unal derya,Demirci Hüseyin,Yılmaz Murat,Kisa Ucler,TULMAÇ Murat,GÜLİTER Sefa The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. (2020): 47 - 52. 10.4274/imj.galenos.2020.75875
MLA	unal derya,Demirci Hüseyin,Yılmaz Murat,Kisa Ucler,TULMAÇ Murat,GÜLİTER Sefa The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. , 2020, ss.47 - 52. 10.4274/imj.galenos.2020.75875
AMA	unal d,Demirci H,Yılmaz M,Kisa U,TULMAÇ M,GÜLİTER S The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. . 2020; 47 - 52. 10.4274/imj.galenos.2020.75875
Vancouver	unal d,Demirci H,Yılmaz M,Kisa U,TULMAÇ M,GÜLİTER S The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. . 2020; 47 - 52. 10.4274/imj.galenos.2020.75875
IEEE	unal d,Demirci H,Yılmaz M,Kisa U,TULMAÇ M,GÜLİTER S "The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome." , ss.47 - 52, 2020. 10.4274/imj.galenos.2020.75875
ISNAD	unal, derya vd. "The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome". (2020), 47-52. https://doi.org/10.4274/imj.galenos.2020.75875

APA	unal d, Demirci H, Yılmaz M, Kisa U, TULMAÇ M, GÜLİTER S (2020). The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. İstanbul Medical Journal, 21(1), 47 - 52. 10.4274/imj.galenos.2020.75875
Chicago	unal derya,Demirci Hüseyin,Yılmaz Murat,Kisa Ucler,TULMAÇ Murat,GÜLİTER Sefa The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. İstanbul Medical Journal 21, no.1 (2020): 47 - 52. 10.4274/imj.galenos.2020.75875
MLA	unal derya,Demirci Hüseyin,Yılmaz Murat,Kisa Ucler,TULMAÇ Murat,GÜLİTER Sefa The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. İstanbul Medical Journal, vol.21, no.1, 2020, ss.47 - 52. 10.4274/imj.galenos.2020.75875
AMA	unal d,Demirci H,Yılmaz M,Kisa U,TULMAÇ M,GÜLİTER S The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. İstanbul Medical Journal. 2020; 21(1): 47 - 52. 10.4274/imj.galenos.2020.75875
Vancouver	unal d,Demirci H,Yılmaz M,Kisa U,TULMAÇ M,GÜLİTER S The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome. İstanbul Medical Journal. 2020; 21(1): 47 - 52. 10.4274/imj.galenos.2020.75875
IEEE	unal d,Demirci H,Yılmaz M,Kisa U,TULMAÇ M,GÜLİTER S "The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome." İstanbul Medical Journal, 21, ss.47 - 52, 2020. 10.4274/imj.galenos.2020.75875
ISNAD	unal, derya vd. "The Effects of Metformin, Ethinyl Estradiol/Cyproterone Acetate, and Metformin Ethinyl Estradiol/Cyproterone Acetate Combination Therapy on Carotid Artery Intima-media Thickness in Patients with Polycystic Ovary Syndrome". İstanbul Medical Journal 21/1 (2020), 47-52. https://doi.org/10.4274/imj.galenos.2020.75875