Öz
Giriş:
Polikistik over sendromu (PKOS), ergenlerde tanısı karmaşık olan yaygın bir endokrin problemdir. Bu nedenle ergenlerde PKOS tanısında kullanılabilecek güvenilir biyobelirteçlerin saptanması önemlidir. Polikistik over sendromlu ergenlerde Anti-Müllerian Hormon (AMH) ve İnhibin-A (INH-A) ve insulin-like peptide-3 (INSL3)’ün tanısal değerini araştırmayı, bu hormonlar ile hiperandrojenizmin klinik / laboratuvar bulguları arasındaki varsa ilişkiyi açıklamayı amaçladık.
Gereç ve Yöntem:
Çalışmaya Rotterdam kriterlerine göre Polikistik over sendromu tanısı alan 15-20 yaş arasında 55 kız dahil edildi. Kontrol grubunu en az iki yıl boyunca düzenli adet siklusu olan ve yaş ve vücut kitle indeksine (VKİ) göre çalışma grubu ile uyumlu sağlıklı ergenler oluşturdu. Hormonal profil için açlık kan örnekleri [luteinizan hormon (LH), folikül stimülan hormon (FSH), dehidroepiandrosteron-sülfat (DHEAS), androstenedion (D4-A), total testosteron (tT), serbest testosteron (sT), seks hormonu bağlayıcı globulin (SHBG), AMH, INSL3, INH-A) alındı. Transabdominal pelvik ultrasonografi sadece hasta grubuna yapıldı.
Bulgular:
AMH ve INH-A düzeyleri PKOS grubunda kontrol grubuna göre anlamlı olarak yüksek bulundu. INSL3, antropometrik veya laboratuar hiçbir parametreleriyle korelasyon göstermezken, AMH seviyesi bel çevresi (BÇ) standart deviasyon skoru (SDS), bel / kalça oranı, FAI (serbest androjen indeksi), LH, sT ve INH-A ile pozitif bir korelasyon gösterdi. Dahası, INH-A seviyesi BÇ SDS, LH, LH / FSH oranı, SHBG ve AMH ile pozitif korelasyon göstermiştir. ROC analizinde, ergenlerde PCOS tanısında AMH için cut-off değeri 5,8 ng / mL iken INH-A için cut-off değeri 9,3 pg / mL olarak hesaplandı (sırasıyla özgüllük ve duyarlılık %86 ve %70 ve %66 ve %82 idi). AMH ve INH-A birlikte kullanıldığında, özgüllük ve duyarlılık sırasıyla %74 ve %88 idi.
Sonuç:
Ergenlerde PKOS tanısında INH-A ve AMH’nın yeni biyobelirteçler olarak kullanılabileceği buna karşı INSL3’ün tanısal değerinin olmadığı gösterilmiştir.
Anahtar Kelimeler: Ergen, polikistik over sendromu, anti-müllerian hormon, inhibin-A, insulin-like peptide-3
Kaynakça
Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, et al. The polycystic ovary syndrome:a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014;171:1-29.
Isabel-Bouzas IC, Cader SA, Leao L, Maria Cristina Kuschnir, Claudia Braga. Menstrual cycle alterations during adolescence:early expression of metabolic syndrome and polycystic ovary syndrome. J Peadiatr Adolesc Gynecol 2014;27:335-41.
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). Human Reprod 2004;19:41-7.
Legro RS, Arslanian SA, Ehrmann DA, Kathleen M Hoeger, M Hassan Murad, Renato Pasquali, et al. Diagnosis and treatment of polycystic ovary syndrome:an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013;98:4565-92.
Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone:ovarian reserve testing and its potential clinical implications. Hum Reprod Update 2014;20:688-701.
Chao-Yan Yue, Lou-Kai-Yi Lu, Meng Li, Qian-Lan Zhang, Chun-Mei Ying. Threshold value of anti-Mullerian hormone for the diagnosis of polycystic ovary syndrome in Chinese women. 2018;13(8):e0203129.
Sahmay S, Atakul N, Aydogan B, Aydin Y, Imamoglu M, Seyisoglu H. Elevated serum levels of anti-Mullerian hormone can be introduced as a new diagnostic marker for polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2013;92:1369-74.
de Kretser DM, Hedger MP, Loveland KL, Phillips DJ. Inhibins, activins and follistatin in reproduction. Hum Reprod Update 2002;8:529-41.
Welt CK, Smith ZA, Pauler DK, J E Hall. Differential regulation of inhibin A and inhibin B by luteinizing hormone, folliclestimulating hormone, and stage of follicle development. J Clin Endocrinol Metab 2001;86:2531-37.
Torgac M, Kokcu A, Cetinkaya MB, Tayfun Alper, Erdal Malatyalioglu. Do basal inhibin A and inhibin B levels have value in the diagnosis of polycystic ovary syndrome? Gynecological Endocrinology 2005;20:322-6.
Anderson RA, Groome NP, Baird DT. Inhibin A and inhibin B in women with polycystic ovarian syndrome during treatment with FSH to induce mono-ovulation. Clin Endocrinol (Oxf)1998;48:577-84.
Pigny P, Cortet-Rudelli C, Decanter C, Deroubaix D, Soudan B, Duhamel A, et al. Serum levels of inhibins are differentially altered in patients with polycystic ovary syndrome:effects of being overweight and relevance to hyperandrogenism. Fertil Steril 2000;73:972-7.
Segal S, Elmadjian M, Takeshiqe T, Steven Karp, Ray Mercado, Benjamin Rivnay. Serum inhibin A concentration in women with polycystic ovarian syndrome and the correlation to ethnicity, androgens and insulin resistance. Reprod Biomed Online 2010;20:675-80.
Magoffin DA, Jakimiuk AJ. Inhibin A, inhibin B and activin A concentrations in follicular fluid from women with polycystic ovary syndrome. Hum Reprod. 1998;13:2693-8.
Foresta C, Bettella A, Vinanzi C, Paolo Dabrilli, Maria Cristina Meriggiola, et al. A novel circulating hormone of testis origin in humans. J Clin Endocrinol Metab 2004;89:5952-8.
Nichols N, Binta H, Fields PA, Maarten Drost, Shou-Mei Chang, Richard Ivell, et al. Immunohistochemical localization of relaxin-like factor/insulin-like peptide-3 in the bovine corpus luteum. Ann NY Acad Sci. 2005;1041:506-9.
Hagen CP, Mieritz MG, Nielsen JE, Anand-Ivell R, Ivell R, Juul A. Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls. Fertil Steril 2015;103:780-6.
Satchell L, Glister C, Bleach EC, Richard G Glencross, Andrew B Bicknell, Yanzhenzi Dai, et al. Ovarian expression of Insulin- Like Peptide 3 (INSL3) and its receptor (RXFP2) during development of bovine antral follicles and corpora lutea and measurement of circulating INSL3 levels during synchronized estrous cycles. Endocrinology 2013;154:1897-906.
Gambineri A, Patton L, Prontera O, F Fanelli, W Ciampaglia, GE Cognigni, et al. Basal insulin-like factor 3 levels predict functional ovarian hyperandrogenism in the polycystic ovary syndrome. J Endocrinol Invest. 2011;34:685-91.
Pelusi C, Fanelli F, Pariali M, Zanotti L, Gambineri A, Pasquali R. Parallel variations of insulin-like peptide 3 (INSL3) and antimüllerian hormone (AMH) in women with the polycystic ovary syndrome according to menstrual cycle pattern. J Clin Endocrinol Metab 2013;98:1575-82.
Pelusi C, Stancampiano M, Fanelli F, Milena Pariali, Alessandra Gambineri, Renato Pasquali. Anti-müllerian hormone and insulin-like 3 levels in healthy normal-weight ovulatory and anovulatory eumenorrheic late adolescent females:potential early biomarkers of ovarian dysfunction? Eur J Obstet Gynecol Reprod Biol. 2015;195:188-92.
World Health Organisation. Physical status: The use and interpretation of anthropometry: A report of a WHO Expert Committee. Geneva:WHO;1995.
Neyzi O, Bundak R, Gokcay G, Hülya Günöz, Andrzej Furman, Feyza Darendeliler, et al. Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children. J Clin Res Pediatr Endocrinol 2015;7:280-93.
Unalan D, Senol V, Bayat M, Mazicioglu MM, Ozturk A, Kurtoglu S, et al. Change in waist circumference over 3 years in Turkish children and adolescents. Ann Hum Biol 2013;40:419-25.
Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440-7.
Michelmore KF, Balen AH, Dunger DB, Vessey MP. Polycystic ovaries and associated clinical and biochemical features in young women. Clin Endocrinol (Oxf) 1999;51:779-86.
Yetim A, Yetim Ç, Bas F, Oğuz Bülent Erol, Gülnaz Çığ, Ahmet Uçar, et al. Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results. J Clin Res Pediatr Endocrinol 2016;8:288-97.
Cortet-Rudelli C, Pigny P, Decanter C, Leroy M, Maunoury-Lefebvre C, Thomas-Desrousseaux P, et al. Obesity and serum luteinizing hormone level have an independent and opposite effect on the serum inhibin B level in patients with polycystic ovary syndrome. Fertil Steril 2002;77:281-7.
Dursun F, Güven A, Yıldız M. Assessment of Anti-Müllerian Hormone Level in Management of Adolescents with Polycystic Ovary Syndrome. J Clin Res Pediatr Endocrinol 2016;8:55-60.
Pawelczak M, Kenigsberg L, Milla S, Ying-Hua Liu, Bina Shah. Elevated serum anti-Müllerian hormone in adolescents with polycystic ovary syndrome:relationship toultrasound features. J Pediatr Endocrinol Metab 2012;25:983-9.
Asanidze E, Kristesashvili J, Pkhaladze L, Khomasuridze A. The value of anti Mullerian hormone in the management of polycystic ovary syndrome in adolescents. Gynecol Endocrinol. 2019;35:974-7.
Hart R, Doherty DA, Norman RJ, Franks S, Dickinson JE, Hickey M, et al. Serum antimullerian hormone (AMH) levels are elevated in adolescent girls with polycystic ovaries and the polycystic ovarian syndrome (PCOS). Fertil Steril. 2010;94:1118-21.
Deveer M, Deveer R, Basaran O, Ozel Turkcu U, Akbaba E, Cullu N, et al. Serum Copeptin, Pentraxin 3, Anti-Mullerian Hormone Levels With Echocardiography and Carotid Artery Intima-Media Thickness in Adolescents With Polycystic Ovary Syndrome. J Clin Med Res. 2015;7:989-94.
Khashchenko E, Uvarova E, Vysokikh M, Ivanets T, Krechetova L, Tarasova N, et al. The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents. J Clin Med. 2020;9:1831.
Merino P.M, Villarroel C, Jesam C, López P, Codner E. New Diagnostic Criteria of Polycystic Ovarian Morphology for Adolescents:Impact on Prevalence and Hormonal Profile. Horm. Res. Paediatr. 2017;88:401-7.
Pinola P, Morin-Papunen LC, Bloiqu A, K Puukka, A Ruokonen, M-R Järvelin, et al. Anti- Müllerian hormone:correlation with testosterone and oligoor amenorrhoea in female adolescence in a populationbased cohort study. Hum Reprod 2014;29:2317-25.
Piouka A, Farmakiotis D, Katsikis I, Macut D, Gerou S, Panidis D. Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels. Am J Physiol Endocrinol Metab 2009;296:238-43.
Anand-Ivell R, Tremellen K, Dai Y, K Heng, M Yoshida, P G Knight, et al. Circulating insulin-like factor 3 (INSL3) in healthy and infertile women. Hum Reprod 2013;28:3093-102.
