ROLE OF AMH, FSH, ANDROGEN AND ESTRADIOL AS MARKER OF PCOS FOLLICULOGENESIS: NARATIVE REVIEW
DOI:
https://doi.org/10.59841/an-najat.v3i4.3451Keywords:
Folliculogenesis, marker, Polycystic Ovary SyyndromAbstract
Polycystic Ovary Syndrome (PCOS) poses a significant challenge in reproductive medicine due to its complex aetiology involving hormonal dysregulation, metabolic perturbations, and genetic predispositions. Central to PCOS pathogenesis is the disruption of folliculogenesis, the process vital for female reproductive health, characterized by the formation of numerous small antral follicles that fail to mature properly. This narrative review explores the roles of Anti-Müllerian Hormone (AMH), Follicle-Stimulating Hormone (FSH), androgens, and oestradiol as markers of PCOS folliculogenesis. AMH, prominently produced by granulosa cells, exhibits elevated levels in PCOS, contributing to excessive follicular recruitment and persistence. Dysregulation of FSH, androgen, and oestradiol further complicates follicular development, exacerbating PCOS-related abnormalities. Understanding the interplay between these markers is crucial for diagnosing and managing PCOS. However, challenges persist, including the lack of standardized serum AMH thresholds and technical limitations in testing methodologies. Further research is warranted to establish these thresholds and refine diagnostic approaches. Moreover, insights into hormonal mechanisms in PCOS folliculogenesis hold promise for developing targeted therapies to alleviate its impact on reproductive health.
References
Abdelazim, I.A., Alanwar, A., AbuFaza, M., Amer, O.O., Bekmukhambetov, Y., Zhurabekova, G., Shikanova, S., Karimova, B., 2020. Elevated and diagnostic androgens of polycystic ovary syndrome. Prz Menopauzalny 19, 1–5. https://doi.org/10.5114/pm.2020.95293
Aflatounian, A., Edwards, M.C., Paris, V.R., Bertoldo, M.J., Desai, R., Gilchrist, R.B., Ledger, W.L., Handelsman, D.J., Walters, K.A. 5, Walters, K.A., 2020. Androgen signaling pathways driving reproductive and metabolic phenotypes in a 2 PCOS mouse model Short title: Mechanism of androgenic actions in PCOS. Journal of Endocrinology 245, 381–395.
Armanini, D., Boscaro, M., Bordin, L., Sabbadin, C., 2022. Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism. Int J Mol Sci 23. https://doi.org/10.3390/IJMS23084110
Berga, S.L., 2021. The Brain Phenotype in Polycystic Ovary Syndrome (PCOS): Androgens, Anovulation, and Gender. International Society of Gynecological Endocrinology Series 1–12. https://doi.org/10.1007/978-3-030-63650-0_1/COVER
Bhattacharya, K., Saha, I., Sen, D., Bose, C., Chaudhuri, G.R., Dutta, S., Sengupta, P., Bhattacharya, S., Barman, S.S., Syamal, A.K., 2022. Role of anti-Mullerian hormone in polycystic ovary syndrome. Middle East Fertility Society Journal 2022 27:1 27, 1–10. https://doi.org/10.1186/S43043-022-00123-5
Bhide, P., Pundir, J., Gudi, A., Shah, A., Homburg, R., Acharya, G., 2019. The effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis. Acta Obstet Gynecol Scand 98, 1235–1244. https://doi.org/10.1111/aogs.13625
Bongrani, A., Plotton, I., Mellouk, N., Ramé, C., Guerif, F., Froment, P., Dupont, J., 2022. High androgen concentrations in follicular fluid of polycystic ovary syndrome women. Reproductive Biology and Endocrinology 20, 1–16. https://doi.org/10.1186/S12958-022-00959-6/FIGURES/8
Bosch, E., Labarta, E., Zuzuarregui, J., Iliodromiti, S., Nelson, S.M., 2023. Prediction of ovarian response using the automated Elecsys anti-Müllerian hormone assay in gonadotrophin-releasing hormone antagonist cycles. Reprod Biomed Online 46, 295–301. https://doi.org/10.1016/j.rbmo.2022.10.012
Cara, A.L., Burger, L.L., Beekly, B.G., Allen, S.J., Henson, E.L., Auchus, R.J., Myers, M.G., Moenter, S.M., Elias, C.F., 2023. Deletion of Androgen Receptor in LepRb Cells Improves Estrous Cycles in Prenatally Androgenized Mice. Endocrinology 164. https://doi.org/10.1210/endocr/bqad015
Chappell, N.R., Gibbons, W.E., Blesson, C.S., 2022. Pathology of hyperandrogenemia in the oocyte of polycystic ovary syndrome. Steroids 180, 108989. https://doi.org/10.1016/J.STEROIDS.2022.108989
Chauvin, S., Cohen-Tannoudji, J., Guigon, C.J., 2022. Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies. International Journal of Molecular Sciences 2022, Vol. 23, Page 512 23, 512. https://doi.org/10.3390/IJMS23010512
Chen, J., Katznelson, L., 2022. The role of growth hormone for fertility in women with hypopituitarism. Growth Hormone & IGF Research 63, 1096–6374. https://doi.org/10.1016/j.ghir.2022.101458
Chen, W., Pang, Y., 2021. Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites. Metabolites 11. https://doi.org/10.3390/METABO11120869
Crespo, R.P., Bachega, T.A.S.S., Mendonça, B.B., Gomes, L.G., 2018. An update of genetic basis of PCOS pathogenesis. Arch Endocrinol Metab 62, 352–361. https://doi.org/10.20945/2359-3997000000049
Dewailly, D., Barbotin, A.L., Dumont, A., Catteau-Jonard, S., Robin, G., 2020. Role of Anti-Müllerian Hormone in the Pathogenesis of Polycystic Ovary Syndrome. Front Endocrinol (Lausanne) 11, 577725. https://doi.org/10.3389/FENDO.2020.00641/BIBTEX
Dewailly, D., Robin, G., Peigne, M., Decanter, C., Pigny, P., Catteau-Jonard, S., 2019. Interactions between androgens, FSH, anti-mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Médecine de la Reproduction 21, 145–163. https://doi.org/10.1684/MTE.2019.0744
Dewailly, D., Robin, G., Peigne, M., Decanter, C., Pigny, P., Catteau-Jonard, S., 2016. Interactions between androgens, FSH, anti-Mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Hum Reprod Update 22, 709–724. https://doi.org/10.1093/HUMUPD/DMW027
Elsayed, A.M., Al-Kaabi, L.S., Al-Abdulla, N.M., Al-Kuwari, M.S., Al-Mulla, A.A., Al-Shamari, R.S., Alhusban, A.K., AlNajjar, A.A., Doi, S.A.R., 2023. Clinical Phenotypes of PCOS: a Cross-Sectional Study. Reproductive Sciences. https://doi.org/10.1007/s43032-023-01262-4
Fu, H., Lin, Y., Deng, X., Wu, L., 2021. Correlation between anti-Mullerian hormone levels and antral follicle counts in polycystic ovary and metabolic syndromes. Syst Biol Reprod Med 67, 112–120. https://doi.org/10.1080/19396368.2020.1860155
Geng, Y., Sui, C., Xun, Y., Lai, Q., Jin, L., 2019. MiRNA-99a can regulate proliferation and apoptosis of human granulosa cells via targeting IGF-1R in polycystic ovary syndrome. J Assist Reprod Genet 36, 211–221. https://doi.org/10.1007/S10815-018-1335-X/METRICS
Gollapalli, P., Kumari, N.S., Shetty, P., Gnanasekaran, T.S., 2022. Molecular basis of AR and STK11 genes associated pathogenesis via AMPK pathway and adipocytokine signalling pathway in the development of metabolic disorders in PCOS women. Beni Suef Univ J Basic Appl Sci 11. https://doi.org/10.1186/s43088-022-00200-8
Huang, X., Hong, L., Wu, Y., Chen, M., Kong, P., Ruan, J., Teng, X., Wei, Z., 2021. Raman Spectrum of Follicular Fluid: A Potential Biomarker for Oocyte Developmental Competence in Polycystic Ovary Syndrome. Front Cell Dev Biol 9, 777224. https://doi.org/10.3389/FCELL.2021.777224/BIBTEX
Kałużna, M., Człapka-Matyasik, M., Wachowiak-Ochmańska, K., Moczko, J., Kaczmarek, J., Janicki, A., Piątek, K., Ruchała, M., Ziemnicka, K., 2020. Effect of central obesity and hyperandrogenism on selected inflammatory markers in patients with pcos: A whtr-matched case-control study. J Clin Med 9, 1–17. https://doi.org/10.3390/JCM9093024
Kurniati, M., Suryandari, D.A., Wiweko, B., Sari, P., Yunaini, L., Panghiyangani, R., 2022. HUBUNGAN KADAR SERUM AMH DENGAN JUMLAH MUTASI PADA GEN PROMOTER AMH (ANTI-MULLERIAN HORMONE) PADA PASIEN SOPK (SINDROM OVARIUM POLIKISTIK). Jurnal Ilmu Kedokteran dan Kesehatan 9, 2549–4864.
Larsen, C.B., Kudela, E., Biringer, K., 2022. Association of FSHR and DENND1A polymorphisms with polycystic ovary syndrome: a meta-analysis. JBRA Assist Reprod. https://doi.org/10.5935/1518-0557.20220043
Laven, J.S.E., 2019. Follicle stimulating hormone receptor (FSHR) polymorphisms and polycystic ovary syndrome (PCOS). Front Endocrinol (Lausanne) 10, 418507. https://doi.org/10.3389/FENDO.2019.00023/BIBTEX
Lledó, B., Ortiz, J.A., Hortal, M., Cascales, A., Morales, R., Guerrero, J., Bernabeu, A., Bernabeu, R., 2022. FSH receptor genotype and its influence on the results of donor ovarian stimulation using corifollitropin alfa. Reprod Biomed Online 45, 943–946. https://doi.org/10.1016/J.RBMO.2022.07.013
Meena, A., Kyal, A., Mukhopadhyay, P., Sharma, P., 2021. Anti-mullerian hormone as an emerging promising marker in the prognosis of PCOS. Nepal Journal of Obstetrics and Gynaecology 16, 111–114. https://doi.org/10.3126/NJOG.V16I1.37914
Meng, L., McLuskey, A., Dunaif, A., Visser, J.A., 2023. Functional analysis of rare anti-Müllerian hormone protein-altering variants identified in women with PCOS. Mol Hum Reprod 29. https://doi.org/10.1093/molehr/gaad011
Merhi, Z., Kandaraki, E.A., Diamanti-Kandarakis, E., 2019. Implications and Future Perspectives of AGEs in PCOS Pathophysiology. Trends in Endocrinology & Metabolism 30, 150–162. https://doi.org/10.1016/J.TEM.2019.01.005
Monieum, A., Zakaria, M., Osama, A., Kamal, A., Sheashea, M.A., 2019. Anti-Mullerian Hormone as A new Marker for Diagnosis of Poly Cystic Ovary Syndrome. Egypt J Hosp Med 77, 5096–5100. https://doi.org/10.21608/EJHM.2019.50261
Moolhuijsen, L.M.E., Visser, J.A., 2020. AMH in PCOS: Controlling the ovary, placenta, or brain? Curr Opin Endocr Metab Res 12, 91–97. https://doi.org/10.1016/J.COEMR.2020.04.006
Murat Altinkilic, E., Du Toit, T., Sakin, O., Attar, R., Groessl, M., Flück, C.E., 2023. The serum steroid signature of PCOS hints at the involvement of novel pathways for excess androgen biosynthesis. Journal of Steroid Biochemistry and Molecular Biology 233, 106366. https://doi.org/10.1016/j.jsbmb.2023.106366
Naillat, F., 2022. From Ovarian Development to Folliculogenesis: Essential Networks Sustaining the Ovarian Reserve. OBM Genetics 2022, Vol. 6, 153 6, 1–17. https://doi.org/10.21926/OBM.GENET.2202153
Oduwole, O.O., Huhtaniemi, I.T., Misrahi, M., 2021. The Roles of Luteinizing Hormone, Follicle-Stimulating Hormone and Testosterone in Spermatogenesis and Folliculogenesis Revisited. International Journal of Molecular Sciences 2021, Vol. 22, Page 12735 22, 12735. https://doi.org/10.3390/IJMS222312735
Orisaka, M., Miyazaki, Y., Shirafuji, A., Tamamura, C., Tsuyoshi, H., Tsang, B.K., Yoshida, Y., 2021. The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini-review. Reprod Med Biol 20, 169–175. https://doi.org/10.1002/RMB2.12371
Rad, H.M., Javad Mowla, S., Ramazanali, F., Valojerdi, M.R., 2022. Characterization of altered microRNAs related to different phenotypes of polycystic ovarian syndrome (PCOS) in serum, follicular fluid, and cumulus cells. Taiwan J Obstet Gynecol 61, 768–779. https://doi.org/10.1016/j.tjog.2022.05.013
Rodriguez Paris, V., Bertoldo, M.J., 2019. The Mechanism of Androgen Actions in PCOS Etiology. Med Sci (Basel) 7. https://doi.org/10.3390/MEDSCI7090089
Rosenfield, R.L., Ehrmann, D.A., 2016. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev 37, 467–520. https://doi.org/10.1210/ER.2015-1104
Rudnicka, E., Kunicki, M., Calik-Ksepka, A., Suchta, K., Duszewska, A., Smolarczyk, K., Smolarczyk, R., 2021. Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS. Int J Mol Sci 22. https://doi.org/10.3390/IJMS222212507
Saadia, Z., 2020. Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS) - Obese vs. Non- Obese Women. Medical Archives 74, 289. https://doi.org/10.5455/MEDARH.2020.74.289-293
Sahmay, S., Aydogan Mathyk, B., Sofiyeva, N., Atakul, N., Azemi, A., Erel, T., 2018. Serum AMH levels and insulin resistance in women with PCOS. European Journal of Obstetrics & Gynecology and Reproductive Biology 224, 159–164. https://doi.org/10.1016/J.EJOGRB.2018.03.007
Scientific Image and Illustration Software | BioRender [WWW Document], n.d. URL https://www.biorender.com/ (accessed 2.9.24).
Shaaban, Z., Khoradmehr, A., Jafarzadeh Shirazi, M.R., Tamadon, A., 2019. Pathophysiological mechanisms of gonadotropins– and steroid hormones–related genes in etiology of polycystic ovary syndrome. Iran J Basic Med Sci 22, 3. https://doi.org/10.22038/IJBMS.2018.31776.7646
Sova, H., Unkila-Kallio, L., Tiitinen, A., Hippeläinen, M., Perheentupa, A., Tinkanen, H., Puukka, K., Bloigu, R., Piltonen, T., Tapanainen, J.S., Morin-Papunen, L., 2019. Hormone profiling, including anti-Müllerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes. Gynecological Endocrinology 35, 595–600. https://doi.org/10.1080/09513590.2018.1559807
Teede, H., Misso, M., Tassone, E.C., Dewailly, D., Ng, E.H., Azziz, R., Norman, R.J., Andersen, M., Franks, S., Hoeger, K., Hutchison, S., Oberfield, S., Shah, D., Hohmann, F., Ottey, S., Dabadghao, P., Laven, J.S.E., 2019. Anti-Müllerian Hormone in PCOS: A Review Informing International Guidelines. Trends in Endocrinology and Metabolism 30, 467–478. https://doi.org/10.1016/j.tem.2019.04.006
Tola, H., Abbas, M., Alhassan, E.A., Shrif, N.E., Rida, M., 2018. Assessment of the role of the anti-mullerian hormone, luteinizing hormone/follicle stimulating hormone ratio in the diagnosis of polycystic ovary syndrome in Sudanese women. Open Access Maced J Med Sci 6, 1244–1247. https://doi.org/10.3889/OAMJMS.2018.260
Tri Setiati, M., Dwi Santoso, S., Imam Santosa, R., Klinik Pramita Surabaya, L., 2021. Gonadotropin, Anti Mullerian Hormon dan Estradiol pada Sindrom Ovarium Polikistik. Jurnal SainHealth 5, 13–18. https://doi.org/10.51804/JSH.V5I2.1518.13-18
Walters, K.A., 2020. Polycystic ovary syndrome: Is it androgen or estrogen receptor? Curr Opin Endocr Metab Res 12, 1–7. https://doi.org/10.1016/J.COEMR.2020.01.003
Walters, K.A., Gilchrist, R.B., Ledger, W.L., Teede, H.J., Handelsman, D.J., Campbell, R.E., 2018. New Perspectives on the Pathogenesis of PCOS: Neuroendocrine Origins. Trends in Endocrinology and Metabolism 29, 841–852. https://doi.org/10.1016/J.TEM.2018.08.005
Walters, K.A., Paris, V.R., Aflatounian, A., Handelsman, D.J., 2019. Androgens and ovarian function: Translation from basic discovery research to clinical impact. Journal of Endocrinology 242, R23–R50. https://doi.org/10.1530/JOE-19-0096
Weiss, N.S., Kostova, E., Nahuis, M., Mol, B.W.J., van der Veen, F., van Wely, M., 2019. Gonadotrophins for ovulation induction in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2019. https://doi.org/10.1002/14651858.CD010290.pub3
Xu, X.L., Deng, S.L., Lian, Z.X., Yu, K., 2021. Estrogen Receptors in Polycystic Ovary Syndrome. Cells 2021, Vol. 10, Page 459 10, 459. https://doi.org/10.3390/CELLS10020459
Yadav, A., Malhotra, N., 2022. Polycystic ovarian syndrome: diagnosis and management of related infertility. Obstet Gynaecol Reprod Med 32, 197–204.
Zhou, S., Wen, S., Sheng, Y., Yang, M., Shen, X., Chen, Y., Kang, D., Xu, L., 2021. Association of Estrogen Receptor Genes Polymorphisms With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis Based on Observational Studies. Front Endocrinol (Lausanne) 12, 726184. https://doi.org/10.3389/fendo.2021.726184
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 An-Najat
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
