The Role of the AMH, SHBG, Free Androgen Index and LH/FSH Ratio in the Diagnosis of Polycystic Ovary Syndrome in Adolescent

Yıl 2024, Cilt: 18 Sayı: 1, 34 - 40, 10.01.2024

Gönül Büyükyılmaz , Serkan Bilge Koca , Keziban Toksoy Adıgüzel , Mehmet Boyraz , Fatih Gurbuz

https://doi.org/10.12956/tchd.1347807

Öz

Objective: Polycystic ovary syndrome (PCOS) diagnosis is controversial in adolescents. Therefore, auxiliary markers are required for the diagnosis of PCOS. We aimed to evaluate whether luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), anti-Mullerian hormone (AMH), and sex hormone-binding globulin (SHBG) levels are a useful test to screen adolescents with PCOS and to investigate which of them has more diagnostic value in the PCOS diagnosis.
Material and Methods: A total of 56 girls with PCOS and 70 healthy girls consisted in this study. Pediatric Endocrine Society criteria were used to diagnose PCOS. Clinical examinations and hormonal assays were performed.
Results: The LH/FSH ratio, and FAI levels were detected significantly higher, and SHBG levels were detected significantly lower in the PCOS group than in the control group (p<0.001). The best marker for PCOS diagnosis was found as AMH. In all adolescents with PCOS, irrespective of obesity/overweight, significantly higher AMH levels were observed compared to the control subjects (p<0.001). Also, we measured a LH/FSH ratio cut-off value of 1.48 ng/ml with 77% sensitivity and 77% specificity to differentiate cases with PCOS from healthy controls.
Conclusion: AMH, FAI, and LH/FSH ratio could be usefull and valuable tests for the PCOS diagnosis in the presence of the PCOS criteria. AMH was found to be the strongest diagnostic marker in patients with PCOS.

Anahtar Kelimeler

Anti-Mullerian hormone, Free androgen index, LH/FSH ratio, Polycystic ovary syndrome, Sex hormone-binding globulin

Adölesanlarda Polikistik Over Sendromu Tanısında AMH, SHBG ve LH/FSH Oranının Rolü

Öz

Amaç: Adölesanlarda polikistik over sendromu (PKOS) tanısı tartışmalıdır. Bu nedenle PKOS tanısı için yardımcı belirteçlere ihtiyaç vardır. PKOS’lu adölesanları taramak ve PKOS tanısında hangisinin tanısal değerinin daha fazla olduğunu araştırmak için Luteinizan hormon (LH)/folikül uyarıcı hormon (FSH) oranı, serbest androjen indeksi (SAI), anti-müllerian hormon (AMH) ve seks hormon bağlayıcı globulin (SHBG) düzeylerinin yararlı ve değerli bir test olup olmadığını değerlendirmeyi amaçladık.
Gereç ve Yöntemler: Bu çalışmaya PKOS tanılı 56 ve sağlıklı 70 kız dahil edildi. PKOS’u teşhis etmek için Pediatrik Endokrin Derneği kriterleri kullanıldı. Klinik muayeneleri ve hormon tahlilleri yapıldı.
Bulgular: PKOS grubunda kontrol grubuna göre LH/FSH oranı ve SAI düzeyleri anlamlı olarak yüksek, SHBG düzeyleri anlamlı olarak düşük saptandı (p<0.001). PKOS tanısı için en iyi belirteç AMH olarak bulundu. PKOS’lu tüm adölesanlarda, obezite/fazla kilodan bağımsız olarak, kontrol grubu ile karşılaştırıldığında anlamlı olarak daha yüksek AMH seviyeleri gözlendi (p<0.001). PKOS’lu vakaları sağlıklı kontrollerden ayırt etmek için LH/FSH oranı eşik değeri %77 duyarlılık ve %77 özgüllük ile 1.48 ng/ml ölçüldü.
Sonuç: AMH, SAI ve LH/FSH oranı, PKOS kriterlerinin varlığında PKOS tanısında yararlı ve değerli testler olabilir. AMH PKOS’lu hastalarda en güçlü tanısal belirteç olarak bulundu.

Anahtar Kelimeler

Anti müllerian hormon, Seks hormon bağlayıcı globülin, LH/FSH oranı, Polikistik over sendromu, Serbest androjen indeks

Kaynakça

• Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2016;2:16057.
• Dabadghao P. Polycystic ovary syndrome in adolescents. Best Pract Res Clin Endocrinol Metab 2019;33:101272.
• Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev 2016;37:467-520.
• Ramezani Tehrani F, Amiri M. Polycystic Ovary Syndrome in Adolescents: Challenges in Diagnosis and Treatment. Int J Endocrinol Metab 2019;17:e91554.
• Martin KA, Anderson RR, Chang RJ, Ehrmann DA, Lobo RA, Murad MH, et al. Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018;103:1233-57.
• Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012;97:28-38.e25.
• Ibáñez L, Oberfield SE, Witchel S, Auchus RJ, Chang RJ, Codner E, et al. An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence. Horm Res Paediatr 2017;88:371-95.
• Yildiz BO, Bolour S, Woods K, Moore A, Azziz R. Visually scoring hirsutism. Hum Reprod Update 2010;16:51-64.
• Ożga K, Krzyczkowska-Sendrakowska M, Hubalewska-Dydejczyk A, Gilis-Januszewska A, Ratajczak M, Ratajczak M, et al. The value of the free androgen index depends on the phenotype of polycystic ovary syndrome - a single-centre experience. Endokrynol Pol 2019;70:330-5.
• Rosenfield RL. The Diagnosis of Polycystic Ovary Syndrome in Adolescents. Pediatrics 2015;136:1154-65.
• Rothenberg SS, Beverley R, Barnard E, Baradaran-Shoraka M, Sanfilippo JS. Polycystic ovary syndrome in adolescents. Best Pract Res Clin Obstet Gynaecol 2018;48:103-14.
• Le MT, Le VNS, Le DD, Nguyen VQH, Chen C, Cao NT. Exploration of the role of anti-Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2019;90:579-85.
• Casadei L, Madrigale A, Puca F, Manicuti C, Emidi E, Piccione E, et al. The role of serum anti-Müllerian hormone (AMH) in the hormonal diagnosis of polycystic ovary syndrome. Gynecol Endocrinol 2013;29:545-50.
• Wongwananuruk T, Panichyawat N, Indhavivadhana S, Rattanachaiyanont M, Angsuwathana S, Techatraisak K, et al. Accuracy of anti-Müllerian hormone and total follicles count to diagnose polycystic ovary syndrome in reproductive women. Taiwan J Obstet Gynecol 2018;57:499-506.
• Qu X, Donnelly R. Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome. Int J Mol Sci 2020;21:8191.
• Dunn JF, Nisula BC, Rodbard D. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab 1981;53:58-68.
• Moran LJ, Teede HJ, Noakes M, Clifton PM, Norman RJ, Wittert GA. Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome. J Endocrinol Invest 2013;36:1004-10.
• Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril 2018;110:364-79.
• Sahmay S, Atakul N, Aydogan B, Aydin Y, Imamoglu M, Seyisoglu H. Elevated serum levels of anti-Müllerian hormone can be introduced as a new diagnostic marker for polycystic ovary syndrome. Acta Obstet Gynecol Scand 2013;92:1369-74.
• Yue CY, Lu LK, Li M, Zhang QL, Ying CM. Threshold value of anti-Mullerian hormone for the diagnosis of polycystic ovary syndrome in Chinese women. PLoS One 2018;13:e0203129.
• Sopher AB, Grigoriev G, Laura D, Cameo T, Lerner JP, Chang RJ, et al. Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents. J Pediatr Endocrinol Metab 2014;27:1175-9.
• Reinehr T, Kulle A, Rothermel J, Knop C, Lass N, Bosse C, et al. Weight loss in obese girls with polycystic ovarian syndrome is associated with a decrease in Anti-Muellerian Hormone concentrations. Clin Endocrinol (Oxf) 2017;87:185-93.
• 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:E238-43.
• Freeman EW, Gracia CR, Sammel MD, Lin H, Lim LC, Strauss JF, 3rd. Association of anti-mullerian hormone levels with obesity in late reproductive-age women. Fertil Steril 2007;87:101-6.
• Woo HY, Kim KH, Rhee EJ, Park H, Lee MK. Differences of the association of anti-Müllerian hormone with clinical or biochemical characteristics between women with and without polycystic ovary syndrome. Endocr J 2012;59:781-90.
• Iliodromiti S, Kelsey TW, Anderson RA, Nelson SM. Can anti-Mullerian hormone predict the diagnosis of polycystic ovary syndrome? A systematic review and meta-analysis of extracted data. J Clin Endocrinol Metab 2013;98:3332-40.
• 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.
• Peña AS, Witchel SF, Hoeger KM, Oberfield SE, Vogiatzi MG, Misso M, et al. Adolescent polycystic ovary syndrome according to the international evidence-based guideline. BMC Med 2020;18:72.
• Saadia Z. Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS) - Obese vs. Non- Obese Women. Med Arch 2020;74:289-93.
• Anderson AD, Solorzano CM, McCartney CR. Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med 2014;32:202-13.
• Deswal R, Yadav A, Dang AS. Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis. Syst Biol Reprod Med 2018;64:12-24.
• Yetim A, Yetim Ç, Baş F, Erol OB, Çığ G, Uçar A, 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.
• Calzada M, López N, Noguera JA, Mendiola J, Hernández AI, Corbalán S, et al. AMH in combination with SHBG for the diagnosis of polycystic ovary syndrome. J Obstet Gynaecol 2019;39:1130-6.
• Wang L, Li J. The value of serum-free androgen index in the diagnosis of polycystic ovary syndrome: A systematic review and meta-analysis. J Obstet Gynaecol Res 2021;47:1221-31.
• Jamil AS, Alalaf SK, Al-Tawil NG, Al-Shawaf T. Comparison of clinical and hormonal characteristics among four phenotypes of polycystic ovary syndrome based on the Rotterdam criteria. Arch Gynecol Obstet 2016;293:447-56.