{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:52:41Z","timestamp":1791420761988,"version":"4.3.3"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is the expression of a complex alteration of the reproductive system. It is characterised by the increase in androgens, causing symptoms such as hirsutism, as well as infertility in many. This paper reviews whether Clomiphene Citrate, Letrozole and Inositol function better as monotherapy or combined therapy for anovulatory infertile PCOS patients. Ovulation and pregnancy rate were used as primary outcomes. PubMed and Scopus were the search engines of choice. Papers were excluded if patients were undertaking other fertility interventions, overlapping populations and non-RCT papers. It was found that co-prescribing Letrozole or Clomiphene Citrate alongside Metformin should be considered, Inositol should be examined as an alternative insulin sensitiser to Metformin and studies should be undertaken to identify the ideal dose and duration of Inositol therapy. Further large, well-designed, multi-centre studies should be conducted to solidify the claims of this review.<\/jats:p>","DOI":"10.3390\/life15060863","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T06:25:04Z","timestamp":1748499904000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Treatment Options for Managing Anovulation in Women with PCOS: An Extensive Literature Review of Evidence-Based Recommendations for Future Directions"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0908-063X","authenticated-orcid":false,"given":"Alessia","family":"Mahoney","sequence":"first","affiliation":[{"name":"School of Medicine, Cardiff University, Cardiff CF14 4YS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"School of Medicine, Cardiff University, Cardiff CF14 4YS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"33","author":"Teede","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.coemr.2020.03.004","article-title":"Polycystic ovary syndrome phenotypes and prevalence: Differential impact of diagnostic criteria and clinical versus unselected population","volume":"12","author":"Mumusoglu","year":"2020","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/cen.14050","article-title":"Effect of hyperinsulinaemia and insulin resistance on endocrine, metabolic and fertility outcomes in women with polycystic ovary syndrome undergoing ovulation induction","volume":"91","author":"Zhang","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.repbio.2015.12.006","article-title":"Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome","volume":"16","author":"Cadagan","year":"2016","journal-title":"Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100937","DOI":"10.1016\/j.molmet.2020.01.001","article-title":"Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies","volume":"35","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_6","unstructured":"Monash University (2025, April 09). International Evidence-Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2023. Available online: https:\/\/www.monash.edu\/medicine\/mchri\/pcos\/guideline."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1210\/er.2011-1034","article-title":"Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications","volume":"33","author":"Dunaif","year":"2012","journal-title":"Endocr. Rev."},{"key":"ref_8","unstructured":"Tang, T., Lord, J.M., Norman, R.J., Yasmin, E., and Balen, A.H. (2025, April 09). Insulin-Sensitising Drugs (Metformin, Rosiglitazone, Pioglitazone, D-Chiro-Inositol) for Women with Polycystic Ovary Syndrome, Oligo Amenorrhoea and Subfertility. Cochrane Database of Systematic Reviews. Available online: https:\/\/www.monash.edu\/__data\/assets\/pdf_file\/0003\/3379521\/Evidence-Based-Guidelines-2023.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gambioli, R., Forte, G., Buzzaccarini, G., Unfer, V., and Lagan\u00e0, A.S. (2021). Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060504"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2337\/diacare.29.02.06.dc05-1070","article-title":"Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome","volume":"29","author":"Baillargeon","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1056\/NEJMoa1313517","article-title":"Letrozole versus clomiphene for infertility in the polycystic ovary syndrome","volume":"371","author":"Legro","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s43032-023-01404-8","article-title":"Comparison of Letrozole and Clomiphene Citrate in Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis","volume":"31","author":"Gari","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_13","first-page":"Cd013505","article-title":"Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome","volume":"12","author":"Sharpe","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/humupd\/dms036","article-title":"Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: A systematic review and meta-analysis","volume":"19","author":"Misso","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_15","first-page":"21","article-title":"Is the Co-administration of Metformin and Clomiphene Superior to Induce Ovulation in Infertile Patients with Poly Cystic Ovary Syndrome and Confirmed Insulin-Resistance: A Double Blind Randomized Clinical Trial","volume":"17","author":"Azargoon","year":"2023","journal-title":"J. Fam. Reprod. Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1080\/09513590.2017.1332174","article-title":"Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: A prospective randomized trial","volume":"33","author":"Liu","year":"2017","journal-title":"Gynecol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.fertnstert.2017.06.026","article-title":"Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): A guideline","volume":"108","author":"Penzias","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"917","DOI":"10.3109\/09513590.2015.1096337","article-title":"Letrozole versus clomiphene citrate in polycystic ovary syndrome: Systematic review and meta-analysis","volume":"31","author":"Roque","year":"2015","journal-title":"Gynecol. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.18203\/2320-1770.ijrcog20171563","article-title":"A Randomised Clinical Trial Comparing Myoinositol and Metformin in Pcos","volume":"6","author":"Misra","year":"2017","journal-title":"Int. J. Reprod. Contracept. Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s00404-019-05064-5","article-title":"The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole","volume":"299","author":"Pourghasem","year":"2019","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3109\/09513590903366996","article-title":"Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women","volume":"26","author":"Raffone","year":"2010","journal-title":"Gynecol. Endocrinol."},{"key":"ref_22","first-page":"575","article-title":"The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone","volume":"16","author":"Nordio","year":"2012","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/1471-0528.14754","article-title":"Inositol treatment of anovulation in women with polycystic ovary syndrome: A meta-analysis of randomised trials","volume":"125","author":"Pundir","year":"2018","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1056\/NEJM199904293401703","article-title":"Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome","volume":"340","author":"Nestler","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"417","DOI":"10.4158\/EP.8.6.417","article-title":"Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome","volume":"8","author":"Iuorno","year":"2002","journal-title":"Endocr. Pract."},{"key":"ref_26","first-page":"151","article-title":"Effects of inositol on ovarian function and metabolic factors in women with PCOS: A randomized double blind placebo-controlled trial","volume":"7","author":"Gerli","year":"2003","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/oxfordjournals.humrep.a137165","article-title":"Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth","volume":"5","author":"Gonen","year":"1990","journal-title":"Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0015-0282(16)54541-5","article-title":"Cervical mucus score and in vitro sperm mucus interaction in spontaneous and clomiphene citrate cycles","volume":"56","author":"Randall","year":"1991","journal-title":"Fertil. Steril."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1093\/humupd\/dmaa055","article-title":"Risk of foetal harm with letrozole use in fertility treatment: A systematic review and meta-analysis","volume":"27","author":"Pundir","year":"2021","journal-title":"Hum. Reprod. Update"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, Y., Li, J., Yan, Z., Liu, D., Ma, J., and Tong, N. (2021). Improvement of Insulin Sensitivity Increases Pregnancy Rate in Infertile PCOS Women: A Systemic Review. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.657889"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature05185","article-title":"Phosphoinositides in cell regulation and membrane dynamics","volume":"443","year":"2006","journal-title":"Nature"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/6\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:41:10Z","timestamp":1760031670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/6\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["life15060863"],"URL":"https:\/\/doi.org\/10.3390\/life15060863","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]}}}