Generic placeholder image

Current Pharmacogenomics and Personalized Medicine

Author(s): Alma Trisa Sunil, Caroline Jo, Sanigha P. S., Aparna Eledath Kolasseri, Ramasamy Tamizhselvi and Sivaraman Jayanthi*

DOI: 10.2174/0118756921331801240820115132

DownloadDownload PDF Flyer Cite As
Navigating the Future of PCOS Treatment: The Precision Medicine Paradigm

Article ID: e18756921331801 Pages: 11

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Polycystic Ovary Syndrome (PCOS) is a condition affecting women of reproductive age, characterized by a heterogeneous array of symptoms. This study aims to examine the role of Precision and Personalized Medicine (PPM) in managing PCOS, given the diverse manifestations of the disease and any genetic factors involved. In this review, we have analyzed the existing literature on the heterogeneity in PCOS symptoms, efforts to acquire PPM data for the characterization of molecular changes in PCOS, and the impact of advances in artificial intelligence on precision medicine. PCOS symptoms present differently in each individual, making traditional therapies ineffective. By tailoring treatment to each individual's genetic and molecular profile, PPM offers a promising approach to address the complex nature of PCOS. Understanding PCOS molecular underpinnings requires continuous acquisition of PPM data. Advances in artificial intelligence have greatly enhanced precision medicine's potential applications. Precision medicine could become a standard component of PCOS care, similar to its application in treating serious conditions like cancer and heart disease, due to its ability to address the condition's complexity through individualized treatment approaches.

Keywords: Precision medicine, PCOS, AI, ML, epigenetics, management.

Graphical Abstract

[1]
Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article. Eur J Obstet Gynecol Reprod Biol X 2019; 3: 100060.
[http://dx.doi.org/10.1016/j.eurox.2019.100060] [PMID: 31403134]
[2]
Bulsara J, Patel P, Soni A, Acharya S. A review: Brief insight into polycystic ovarian syndrome. Endocr Metab Sci 2021; 3: 100085.
[http://dx.doi.org/10.1016/j.endmts.2021.100085]
[3]
Pundir CS, Deswal R, Narwal V, Dang A. The prevalence of polycystic ovary syndrome: A brief systematic review. J Hum Reprod Sci 2020; 13(4): 261-71.
[http://dx.doi.org/10.4103/jhrs.JHRS_95_18] [PMID: 33627974]
[4]
Carey AH, Chan KL, Short F, White D, Williamson R, Franks S. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf) 1993; 38(6): 653-8.
[http://dx.doi.org/10.1111/j.1365-2265.1993.tb02150.x] [PMID: 8334753]
[5]
Prapas N, Karkanaki A, Prapas I, Kalogiannidis I, Katsikis I, Panidis D. Genetics of polycystic ovary syndrome. Hippokratia 2009; 13(4): 216-23.
[PMID: 20011085]
[6]
Parker J, O’Brien C, Hawrelak J, Gersh FL. Polycystic ovary syndrome: An evolutionary adaptation to lifestyle and the environment. Int J Environ Res Public Health 2022; 19(3): 1336.
[http://dx.doi.org/10.3390/ijerph19031336] [PMID: 35162359]
[7]
Khan MJ, Ullah A, Basit S. Genetic basis of polycystic ovary syndrome (PCOS): Current perspectives. Appl Clin Genet 2019; 12: 249-60.
[http://dx.doi.org/10.2147/TACG.S200341]
[8]
Halpern A, Mancini MC, Magalhães MEC, et al. Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: From diagnosis to treatment. Diabetol Metab Syndr 2010; 2(1): 55.
[http://dx.doi.org/10.1186/1758-5996-2-55] [PMID: 20718958]
[9]
Lo ACQ, Lo CCW, Oliver-Williams C. Cardiovascular disease risk in women with hyperandrogenism, oligomenorrhea/ menstrual irregularity or polycystic ovaries(components of polycystic ovary syndrome): A systematic review and meta-analysis. EuroHeart J Open 2023; 3(4): oead061.
[http://dx.doi.org/10.1093/ehjopen/oead061] [PMID: 37404840]
[10]
Rosenfield RL, Ehrmann DA. The pathogenesis of Polycystic Ovary Syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev 2016; 37(5): 467-520.
[http://dx.doi.org/10.1210/er.2015-1104] [PMID: 27459230]
[11]
Mihailidis J, Dermesropian R, Taxel P, Luthra P, Grant-Kels JM. Endocrine evaluation of hirsutism. Int J Womens Dermatol 2017; 3(1) (Suppl. 1): S6-S10.
[http://dx.doi.org/10.1016/j.ijwd.2017.02.007] [PMID: 28492032]
[12]
Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: Biobehavioral mechanisms and interventions. Fertil Steril 2010; 94(5): 1565-74.
[http://dx.doi.org/10.1016/j.fertnstert.2010.03.081] [PMID: 20471009]
[13]
Baig M, Rehman R, Tariq S, Fatima SS. Serum leptin levels in polycystic ovary syndrome and its relationship with metabolic and hormonal profile in pakistani females. Int J Endocrinol 2014; 2014: 1-5.
[http://dx.doi.org/10.1155/2014/132908] [PMID: 25587271]
[14]
Unluturk U, Harmanci A, Kocaefe C, Yildiz BO. The genetic basis of the polycystic ovary syndrome: A literature review including discussion of PPAR-γ. PPAR Res 2007; 2007: 1-23.
[http://dx.doi.org/10.1155/2007/49109] [PMID: 17389770]
[15]
Wickenheisser JK, Biegler JM, Nelson-DeGrave VL, Legro RS, Strauss JF III, McAllister JM. Cholesterol side-chain cleavage gene expression in theca cells: Augmented transcriptional regulation and mRNA stability in polycystic ovary syndrome. PLoS One 2012; 7(11): e48963.
[http://dx.doi.org/10.1371/journal.pone.0048963] [PMID: 23155436]
[16]
Shen W, Li T, Hu Y, Liu H, Song M. Common polymorphisms in the CYP1A1 and CYP11A1 genes and polycystic ovary syndrome risk: A meta-analysis and meta-regression. Arch Gynecol Obstet 2014; 289(1): 107-18.
[http://dx.doi.org/10.1007/s00404-013-2939-0] [PMID: 23852617]
[17]
Pusalkar M, Meherji P, Gokral J, Chinnaraj S, Maitra A. CYP11A1 and CYP17 promoter polymorphisms associate with hyperandrogenemia in polycystic ovary syndrome. Fertil Steril 2009; 92(2): 653-9.
[http://dx.doi.org/10.1016/j.fertnstert.2008.07.016] [PMID: 18725155]
[18]
Techatraisak K, Chayachinda C, Wongwananuruk T, et al. No association between CYP17 ‐34T/C polymorphism and insulin resistance in Thai polycystic ovary syndrome. J Obstet Gynaecol Res 2015; 41(9): 1412-7.
[http://dx.doi.org/10.1111/jog.12733] [PMID: 26096606]
[19]
Chen J, Shen S, Tan Y, et al. The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome. J Ovarian Res 2015; 8(1): 11.
[http://dx.doi.org/10.1186/s13048-015-0139-1] [PMID: 25881575]
[20]
Dawood AS, Goyal M. Debates regarding lean patients with polycystic ovary syndrome: A narrative review. J Hum Reprod Sci 2017; 10(3): 154-61.
[http://dx.doi.org/10.4103/jhrs.JHRS_77_17] [PMID: 29142442]
[21]
Chua AK, Azziz R, Goodarzi MO. Association study of CYP17 and HSD11B1 in polycystic ovary syndrome utilizing comprehensive gene coverage. Mol Hum Reprod 2012; 18(6): 320-4.
[http://dx.doi.org/10.1093/molehr/gas002] [PMID: 22238371]
[22]
Xing C, Zhang J, Zhao H, He B. Effect of sex hormone-binding globulin on polycystic ovary syndrome: Mechanisms, manifestations, genetics, and treatment. Int J Womens Health 2022; 14: 91-105.
[http://dx.doi.org/10.2147/IJWH.S344542]
[23]
Ferk P, Teran N, Gersak K. The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome. Hum Reprod 2007; 22(4): 1031-6.
[http://dx.doi.org/10.1093/humrep/del457] [PMID: 17189294]
[24]
De Leo V, Musacchio MC, Cappelli V, Massaro MG, Morgante G, Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: An update. Reprod Biol Endocrinol 2016; 14(1): 38.
[http://dx.doi.org/10.1186/s12958-016-0173-x] [PMID: 27423183]
[25]
Blomquist CH. Kinetic analysis of enzymic activities: Prediction of multiple forms of 17β-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 1995; 55(5-6): 515-24.
[http://dx.doi.org/10.1016/0960-0760(95)00200-6] [PMID: 8547176]
[26]
Carbunaru G, Prasad P, Scoccia B, et al. The hormonal phenotype of Nonclassic 3 β-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency. J Clin Endocrinol Metab 2004; 89(2): 783-94.
[http://dx.doi.org/10.1210/jc.2003-030934] [PMID: 14764797]
[27]
Waterworth DM, Bennett ST, Gharani N, et al. Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet 1997; 349(9057): 986-90.
[http://dx.doi.org/10.1016/S0140-6736(96)08368-7] [PMID: 9100625]
[28]
Diamanti-Kandarakis E, Piperi C. Genetics of polycystic ovary syndrome: Searching for the way out of the labyrinth. Hum Reprod Update 2005; 11(6): 631-43.
[http://dx.doi.org/10.1093/humupd/dmi025] [PMID: 15994846]
[29]
Bhimwal T. Puneet, Priyadarshani A. Understanding polycystic ovary syndrome in light of associated key genes. Egypt J Med Hum Genet 2023; 24(1): 38.
[http://dx.doi.org/10.1186/s43042-023-00418-w]
[30]
Hiam D, Moreno-Asso A, Teede HJ, et al. The genetics of polycystic ovary syndrome: An overview of candidate gene systematic reviews and genome-wide association studies. J Clin Med 2019; 8(10): 1606.
[http://dx.doi.org/10.3390/jcm8101606] [PMID: 31623391]
[31]
Benrick A, Chanclón B, Micallef P, et al. Adiponectin protects against development of metabolic disturbances in a PCOS mouse model. Proc Natl Acad Sci USA 2017; 114(34): E7187-96.
[http://dx.doi.org/10.1073/pnas.1708854114] [PMID: 28790184]
[32]
Groth SW. Adiponectin and polycystic ovary syndrome. Biol Res Nurs 2010; 12(1): 62-72.
[http://dx.doi.org/10.1177/1099800410371824] [PMID: 20498127]
[33]
Teede H, Deeks A, Moran L. Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010; 8(1): 41.
[http://dx.doi.org/10.1186/1741-7015-8-41] [PMID: 20591140]
[34]
Bickerton AST, Clark N, Meeking D, et al. Cardiovascular risk in women with polycystic ovarian syndrome (PCOS). J Clin Pathol 2005; 58(2): 151-4.
[http://dx.doi.org/10.1136/jcp.2003.015271] [PMID: 15677534]
[35]
Shah AK, Yadav BK, Shah AK, Suri A, Deo SK. Cardiovascular risk predictors high sensitivity c-reactive protein and plasminogen activator inhibitor-1 in women with lean phenotype of polycystic ovarian syndrome: A prospective case-control study. J Lab Physicians 2023; 15(1): 31-7.
[http://dx.doi.org/10.1055/s-0042-1750066]
[36]
Shaaban Z, Khoradmehr A, Amiri-Yekta A, Jafarzadeh Shirazi MR, Tamadon A. Pathophysiologic mechanisms of obesity- and chronic inflammation-related genes in etiology of polycystic ovary syndrome. Iran J Basic Med Sci 2019; 22(12): 1378-86.
[http://dx.doi.org/10.22038/IJBMS.2019.14029] [PMID: 32133054]
[37]
Welt CK. Genetics of polycystic ovary syndrome. Endocrinol Metab Clin North Am 2021; 50(1): 71-82.
[http://dx.doi.org/10.1016/j.ecl.2020.10.006] [PMID: 33518187]
[38]
Castro V, Shen Y, Yu S, et al. Identification of subjects with polycystic ovary syndrome using electronic health records. Reprod Biol Endocrinol 2015; 13(1): 116.
[http://dx.doi.org/10.1186/s12958-015-0115-z] [PMID: 26510685]
[39]
Xu N, Azziz R, Goodarzi MO. Epigenetics in polycystic ovary syndrome: A pilot study of global DNA methylation. Fertil Steril 2010; 94(2): 781-783.e1.
[http://dx.doi.org/10.1016/j.fertnstert.2009.10.020] [PMID: 19939367]
[40]
Mukherjee S. Pathomechanisms of polycystic ovary syndrome multidimensional approaches. Front Biosci (Elite Ed) 2018; 10(3): 384-422.
[http://dx.doi.org/10.2741/e829]
[41]
Narayan P. Genetic Models for the Study of Luteinizing Hormone Receptor Function. Front Endocrinol (Lausanne) 2015; 6: 152.
[http://dx.doi.org/10.3389/fendo.2015.00152] [PMID: 26483755]
[42]
McAllister JM, Modi B, Miller BA, et al. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci USA 2014; 111(15): E1519-27.
[http://dx.doi.org/10.1073/pnas.1400574111] [PMID: 24706793]
[43]
Dumesic DA, Hoyos LR, Chazenbalk GD, Naik R, Padmanabhan V, Abbott DH. Mechanisms of intergenerational transmission of polycystic ovary syndrome. Reproduction 2020; 159(1): R1-R13.
[http://dx.doi.org/10.1530/REP-19-0197] [PMID: 31376813]
[44]
Barker DJ. The fetal and infant origins of adult disease. BMJ 1990; 301(6761): 1111-1.
[http://dx.doi.org/10.1136/bmj.301.6761.1111] [PMID: 2252919]
[45]
Filippou P, Homburg R. Is foetal hyperexposure to androgens a cause of PCOS? Hum Reprod Update 2017; 23(4): 421-32.
[http://dx.doi.org/10.1093/humupd/dmx013] [PMID: 28531286]
[46]
Barker DJP. The origins of the developmental origins theory. J Intern Med 2007; 261(5): 412-7.
[http://dx.doi.org/10.1111/j.1365-2796.2007.01809.x] [PMID: 17444880]
[47]
Piltonen TT, Giacobini P, Edvinsson Å, et al. Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term. Fertil Steril 2019; 111(3): 588-596.e1.
[http://dx.doi.org/10.1016/j.fertnstert.2018.11.028] [PMID: 30630591]
[48]
Nilsson EE, Sadler-Riggleman I, Skinner MK. Environmentally induced epigenetic transgenerational inheritance of disease. Environ Epigenet 2018; 4(2): dvy016.
[http://dx.doi.org/10.1093/eep/dvy016] [PMID: 30038800]
[49]
Stueve TR, Wolff MS, Pajak A, Teitelbaum SL, Chen J. CYP19A1 promoter methylation in saliva associated with milestones of pubertal timing in urban girls. BMC Pediatr 2014; 14(1): 78.
[http://dx.doi.org/10.1186/1471-2431-14-78] [PMID: 24649863]
[50]
Vázquez-Martínez ER, Gómez-Viais YI, García-Gómez E, et al. DNA methylation in the pathogenesis of polycystic ovary syndrome. Reproduction 2019; 158(1): R27-40.
[http://dx.doi.org/10.1530/REP-18-0449] [PMID: 30959484]
[51]
Hoeger KM, Dokras A, Piltonen T. Update on PCOS: Consequences, challenges, and guiding treatment. J Clin Endocrinol Metab 2021; 106(3): e1071-83.
[http://dx.doi.org/10.1210/clinem/dgaa839] [PMID: 33211867]
[52]
Checa MA, Prat MO, Checa MA, Carreras RC. Current trends in the treatment of polycystic ovary syndrome with desire for children. Ther Clin Risk Manag 2009; 5(2): 353-60.
[http://dx.doi.org/10.2147/TCRM.S3779] [PMID: 19536311]
[53]
Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2013; 98(12): 4565-92.
[http://dx.doi.org/10.1210/jc.2013-2350] [PMID: 24151290]
[54]
Lesko LJ. Personalized medicine: Elusive dream or imminent reality? Clin Pharmacol Ther 2007; 81(6): 807-16.
[http://dx.doi.org/10.1038/sj.clpt.6100204] [PMID: 17505496]
[55]
Ginsburg GS, Willard HF. Genomic and personalized medicine: Foundations and applications. Transl Res 2009; 154(6): 277-87.
[http://dx.doi.org/10.1016/j.trsl.2009.09.005] [PMID: 19931193]
[56]
Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol 2010; 28(10): 1069-78.
[http://dx.doi.org/10.1038/nbt.1678] [PMID: 20944599]
[57]
García-Giménez JL, Seco-Cervera M, Tollefsbol TO, et al. Epigenetic biomarkers: Current strategies and future challenges for their use in the clinical laboratory. Crit Rev Clin Lab Sci 2017; 54(7-8): 529-50.
[http://dx.doi.org/10.1080/10408363.2017.1410520] [PMID: 29226748]
[58]
Szyf M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol 2009; 49(1): 243-63.
[http://dx.doi.org/10.1146/annurev-pharmtox-061008-103102] [PMID: 18851683]
[59]
Hunter P. The second coming of epigenetic drugs. EMBO Rep 2015; 16(3): 276-9.
[http://dx.doi.org/10.15252/embr.201540121] [PMID: 25662153]
[60]
DeWoskin VA, Million RP. The epigenetics pipeline. Nat Rev Drug Discov 2013; 12(9): 661-2.
[http://dx.doi.org/10.1038/nrd4091] [PMID: 23989788]
[61]
Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 2000; 343(19): 1350-4.
[http://dx.doi.org/10.1056/NEJM200011093431901] [PMID: 11070098]
[62]
Wang Y, Krishnan HR, Ghezzi A, Yin JCP, Atkinson NS. Drug-induced epigenetic changes produce drug tolerance. PLoS Biol 2007; 5(10): e265.
[http://dx.doi.org/10.1371/journal.pbio.0050265] [PMID: 17941717]
[63]
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol 2013; 14(10): R115.
[http://dx.doi.org/10.1186/gb-2013-14-10-r115] [PMID: 24138928]
[64]
Johnson KB, Wei WQ, Weeraratne D, et al. Precision medicine, AI, and the future of personalized health care. Clin Transl Sci 2021; 14(1): 86-93.
[http://dx.doi.org/10.1111/cts.12884] [PMID: 32961010]
[65]
Subramanian M, Wojtusciszyn A, Favre L, et al. Precision medicine in the era of artificial intelligence: Implications in chronic disease management. J Transl Med 2020; 18(1): 472.
[http://dx.doi.org/10.1186/s12967-020-02658-5] [PMID: 33298113]
[66]
Quazi S. Artificial intelligence and machine learning in precision and genomic medicine. Med Oncol 2022; 39(8): 120.
[http://dx.doi.org/10.1007/s12032-022-01711-1] [PMID: 35704152]
[67]
Barrera FJ, Brown EDL, Rojo A, et al. Application of machine learning and artificial intelligence in the diagnosis and classification of polycystic ovarian syndrome: A systematic review. Front Endocrinol (Lausanne) 2023; 14: 1106625.
[http://dx.doi.org/10.3389/fendo.2023.1106625] [PMID: 37790605]
[68]
Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2016; 2016: 2016-963.
[http://dx.doi.org/10.1210/jc.2016-2963]
[69]
Khanna VV, Chadaga K, Sampathila N, Prabhu S, Bhandage V, Hegde GK. A distinctive explainable machine learning framework for detection of polycystic ovary syndrome. Appl Syst Innov 2023; 6(2): 32.
[http://dx.doi.org/10.3390/asi6020032]
[70]
Elmannai H, El-Rashidy N, Mashal I, et al. Polycystic ovary syndrome detection machine learning model based on optimized feature selection and explainable artificial intelligence. Diagnostics (Basel) 2023; 13(8): 1506.
[http://dx.doi.org/10.3390/diagnostics13081506] [PMID: 37189606]
[71]
Nave OP. Modification of semi-analytical method applied system of ODE. Mod Appl Sci 2020; 14(6): 75.
[http://dx.doi.org/10.5539/mas.v14n6p75]
[72]
Verma P, Maan P, Gautam R, Arora T. Unveiling the role of artificial intelligence (AI) in polycystic ovary syndrome (PCOS) diagnosis: A comprehensive review. Reprod Sci 2024; (Jun):
[http://dx.doi.org/10.1007/s43032-024-01615-7] [PMID: 38907128]
[73]
Yan SK, Liu RH, Jin HZ, et al. Omics in pharmaceutical research: Overview, applications, challenges, and future perspectives. Chin J Nat Med 2015; 13(1): 3-21.
[http://dx.doi.org/10.1016/S1875-5364(15)60002-4] [PMID: 25660284]
[74]
D’Adamo GL, Widdop JT, Giles EM. The future is now? Clinical and translational aspects of Omics technologies. Immunol Cell Biol 2021; 99(2): 168-76.
[http://dx.doi.org/10.1111/imcb.12404] [PMID: 32924178]
[75]
Hartl D, de Luca V, Kostikova A, et al. Translational precision medicine: An industry perspective. J Transl Med 2021; 19(1): 245.
[http://dx.doi.org/10.1186/s12967-021-02910-6] [PMID: 34090480]
[76]
Hasin Y, Seldin M, Lusis A. Multi-omics approaches to disease. Genome Biol 2017; 18(1): 83.
[http://dx.doi.org/10.1186/s13059-017-1215-1] [PMID: 28476144]
[77]
Khodadadian A. Genomics and transcriptomics: The powerful technologies in precision medicine. Int J Gen Med 2020; 13: 627-40.
[http://dx.doi.org/10.2147/IJGM.S249970]
[78]
Horgan RP, Kenny LC. Omic technologies: Genomics, transcriptomics, proteomics and metabolomics. Obstet Gynaecol 2011; 13(3): 189-95.
[http://dx.doi.org/10.1576/toag.13.3.189.27672]
[79]
Holmes C, Carlson SM, McDonald F, Jones M, Graham J. Exploring the post-genomic world: Differing explanatory and manipulatory functions of post-genomic sciences. New Genet Soc 2016; 35(1): 49-68.
[http://dx.doi.org/10.1080/14636778.2015.1133280] [PMID: 27134568]
[80]
Hasanzad M, Sarhangi N, Ehsani Chimeh S, et al. Precision medicine journey through omics approach. J Diabetes Metab Disord 2021; 21(1): 881-8.
[http://dx.doi.org/10.1007/s40200-021-00913-0] [PMID: 35673436]
[81]
Clish CB. Metabolomics: An emerging but powerful tool for precision medicine. Molecular Case Studies 2015; 1(1): a000588.
[http://dx.doi.org/10.1101/mcs.a000588] [PMID: 27148576]
[82]
Puchades-Carrasco L. Pineda- Lucena A. Metabolomics applications in precision medicine: An oncological perspective. Curr Top Med Chem 2017; 17(24): 2740-51.
[http://dx.doi.org/10.2174/1568026617666170707120034] [PMID: 28685691]
[83]
Bekri S. The role of metabolomics in precision medicine. Expert Rev Precis Med Drug Dev 2016; 1(6): 517-32.
[http://dx.doi.org/10.1080/23808993.2016.1273067]
[84]
Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab 2005; 90(8): 4650-8.
[http://dx.doi.org/10.1210/jc.2005-0628] [PMID: 15944216]