LEAN PCOS AS A DISTINCT PHENOTYPE: METABOLIC DYSFUNCTION, DIAGNOSTIC IMPLICATIONS, AND THE EMERGING ROLE OF GLP-1–BASED THERAPIES

Kaja Stolarska; Antonina Gaj-Hunter; Patrycja Rędziniak; Alicja Ruzik; Monika Rajs; Patrycja Przebieradło; Sandra Żak; Monika Kowalska; Katarzyna Żurek; Sandra Terpiłowska

doi:10.31435/ijitss.2(50).2026.5971

Authors

Kaja Stolarska Jan Kochanowski University in Kielce Faculty of Medicine, Kielce, Poland https://orcid.org/0009-0002-8849-1141
Antonina Gaj-Hunter Jan Kochanowski University in Kielce Faculty of Medicine, Kielce, Poland https://orcid.org/0009-0009-6916-1391
Patrycja Rędziniak University of Rzeszow Faculty of Medicine, Rzeszow, Poland https://orcid.org/0000-0002-2301-3192
Alicja Ruzik Jan Kochanowski University in Kielce Faculty of Medicine, Kielce, Poland https://orcid.org/0009-0006-6072-5005
Monika Rajs University of Rzeszow Faculty of Medicine, Rzeszow, Poland https://orcid.org/0009-0004-3368-0847
Patrycja Przebieradło University of Rzeszow Faculty of Medicine, Rzeszow, Poland https://orcid.org/0009-0005-7583-1890
Sandra Żak Jan Kochanowski University in Kielce Faculty of Medicine, Kielce, Poland https://orcid.org/0009-0009-0227-6899
Monika Kowalska Medical University of Lodz Faculty of Medicine, Lodz, Poland https://orcid.org/0009-0004-8465-2133
Katarzyna Żurek Jan Kochanowski University in Kielce Faculty of Medicine, Kielce, Poland https://orcid.org/0000-0002-7073-4160
Sandra Terpiłowska Medical University of Warsaw Faculty of Medicine, Warsaw, Poland https://orcid.org/0009-0007-7531-6594

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5971

Keywords:

Lean PCOS, Polycystic Ovary Syndrome, Metabolic Dysfunction, Endocrine Phenotypes, Incretin Therapy

Abstract

Background: Polycystic Ovary Syndrome (PCOS) affects 5–26% of reproductive-age women, yet current diagnostic frameworks insufficiently distinguish metabolically distinct phenotypes, particularly lean PCOS (BMI ≤25 kg/m²).

Objective: This narrative review evaluates lean PCOS as a distinct pathophysiological entity and discusses its neuroendocrine and metabolic features, diagnostic challenges, and weight-stratified classification approaches.

Methods: A literature search of PubMed, Google Scholar, and clinical guidelines (2015–2026) was conducted, including meta-analyses and comparative studies of lean and obese PCOS phenotypes.

Results: Lean PCOS is characterized by neuroendocrine predominance (elevated LH/FSH ratio, adrenal androgen excess), intrinsic insulin resistance independent of BMI, and altered adipokine signaling reflecting adipose tissue dysfunction. Despite relatively favorable cardiometabolic profiles, patients exhibit subclinical hepatic and vascular risk. Genetic studies confirm distinct metabolic and insulin-signaling pathway involvement.

Conclusions: Lean PCOS represents a biologically distinct phenotype requiring weight-stratified diagnostic strategies and phenotype-specific therapeutic approaches, including investigation of incretin-based therapies.

References

Zheng, C., Lin, Y., Zhang, Z., Ye, J., Lin, Y., & Tian, J. (2025). Analyzing and evaluating the metabolic and endocrine characteristics between lean and obese patients with polycystic ovary syndrome: A systemic review and meta-analysis. Frontiers in Endocrinology, 16, 1680685. https://doi.org/10.3389/fendo.2025.1680685

Teede, H., Misso, M., Costello, M., et al. (2018). Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction, 33(9), 1602–1618. https://doi.org/10.1093/humrep/dey256

Teede, H. J., Bahri Khomami, M., Morman, R., et al. (2026). Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: A multistep global consensus process. The Lancet, 407(10531), S0140-6736(26)00717-8. https://doi.org/10.1016/S0140-6736(26)00717-8

Teede, H. J., Moran, L. J., Morman, R., et al. (2025). Polycystic ovary syndrome perspectives from patients and health professionals on clinical features, current name, and renaming: A longitudinal international online survey. EClinicalMedicine, 84, 103287. https://doi.org/10.1016/j.eclinm.2025.103287

Rimmer, A. (2026). PCOS name change to PMOS must be managed to avoid confusing patients, says expert. BMJ, 42140653.

Wu, P., Chew-Graham, C. A., Heera-Shergill, N., & Heald, A. H. (2026). Improving awareness and care in polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome). BMJ. PMID: 42140655

Morman, R. (2026). PMOS: What’s in a name? Everything. BMJ. PMID: 42161406

Barrea, L., Frias-Toral, E., Verde, L., et al. (2021). PCOS and nutritional approaches: Differences between lean and obese phenotype. Metabolism Open, 12, 100123. https://doi.org/10.1016/j.metop.2021.100123

Carmina, E., & Lobo, R. (2022). Comparing lean and obese PCOS in different PCOS phenotypes: Evidence that the body weight is more important than the Rotterdam phenotype in influencing the metabolic status. Diagnostics, 12(10), 2313. https://doi.org/10.3390/diagnostics12102313

Pratama, G., Wiweko, B., Asmarinah, et al. (2024). Mechanism of elevated LH/FSH ratio in lean PCOS revisited: A path analysis. Scientific Reports, 14(1), 8229. https://doi.org/10.1038/s41598-024-58064-0

Herman, R., Šikonja, J., Jensterle, M., et al. (2023). Insulin metabolism in polycystic ovary syndrome: Secretion, signaling, and clearance. International Journal of Molecular Sciences, 24(4), 3140. https://doi.org/10.3390/ijms24043140

Pugliese, G., de Alteriis, G., Muscogiuri, G., et al. (2023). Liraglutide and polycystic ovary syndrome: Is it only a matter of body weight? Journal of Endocrinological Investigation, 46(9), 1761–1774. https://doi.org/10.1007/s40618-023-02084-6

Sridharan, K., & Sivaramakrishnan, G. (2025). Expanding therapeutic horizons: Glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors in polycystic ovarian syndrome: A comprehensive review including systematic review and network meta-analysis of randomized clinical trials. Diabetology & Metabolic Syndrome, 17, 197. https://doi.org/10.1186/s13098-025-01730-8

Szczęsnowicz, A., Szeliga, A., Niwczyk, O., Bala, G., & Męczekalski, B. (2023). Do GLP-1 analogs have a place in the treatment of PCOS? New insights and promising therapies. Journal of Clinical Medicine, 12(18), 5915. https://doi.org/10.3390/jcm12185915

Goldberg, A. S., Graca, S., Liu, J., et al. (2024). Anti-obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta-analysis to inform the 2023 international evidence-based guideline. Obesity Reviews, 25(4), e13704. https://doi.org/10.1111/obr.13704

Carmina, E., & Longo, R. A. (2023). Semaglutide treatment of excessive body weight in obese PCOS patients unresponsive to lifestyle programs. Journal of Clinical Medicine, 12(18), 5921. https://doi.org/10.3390/jcm12185921

Whooten, R., Rifas-Shiman, S., Aris, I., et al. (2025). Adolescent “lean PCOS” is characterized by higher insulin resistance and adverse adipokine profile. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgaf606

Fighera, T., Santos, B. R., & Spritzer, P. (2023). Lean mass and associated factors in women with PCOS with different phenotypes. PLOS ONE, 18(10), e0292623. https://doi.org/10.1371/journal.pone.0292623

Liu, C., Liu, K., Zhao, X., et al. (2022). The associations between alanine aminotransferase and other biochemical parameters in lean PCOS. Reproductive Sciences, 30(2), 633–641. https://doi.org/10.1007/s43032-022-01030-w

Elnashar, A. (2024). Lean polycystic ovary syndrome: A narrative review. Clinical and Experimental Obstetrics & Gynecology, 51(6). https://doi.org/10.31083/j.ceog5106142

Cardozo, L. L., Romero, D., & Reckelhoff, J. (2017). Cardiometabolic features of polycystic ovary syndrome: Role of androgens. Physiology, 32(5), 357–366. https://doi.org/10.1152/physiol.00030.2016

Chen-Patterson, A., Bernier, A., Burgert, T., et al. (2024). Distinct reproductive phenotypes segregate with differences in body weight in adolescent polycystic ovary syndrome. Journal of the Endocrine Society, 8(2). https://doi.org/10.1210/jendso/bvad169

Darmon, S., Molinari, E., Albertini, D., Patrizio, P., Barad, D., & Gleicher, N. (2021). P-666 Validating the hypo-androgenic PCOS-like phenotype (H-PCOS), derived from the “lean” PCOS phenotype at younger ages. Human Reproduction, 36(Suppl. 1), P-666. https://doi.org/10.1093/humrep/deab130.665

Dhar, S., & Bhattacharjee, P. (2024). Clinical-exome sequencing unveils the genetic landscape of polycystic ovarian syndrome (PCOS) focusing on lean and obese phenotypes. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-024-75719-0

Misra, S., Gada, J. V., Chauhan, Y. V., et al. (2025). Comparative study of anti-Mullerian hormone and its correlation with androgens and insulin resistance in lean and obese women with polycystic ovary syndrome. Indian Journal of Endocrinology and Metabolism, 29(3), 319–324. https://doi.org/10.4103/ijem.ijem_491_24

Toosy, S., Sodi, R., & Pappachan, J. (2018). Lean polycystic ovary syndrome (PCOS): An evidence-based practical approach. Journal of Diabetes & Metabolic Disorders, 17(2), 277–285. https://doi.org/10.1007/s40200-018-0371-5

Chaker, W., Adi, R., Madkour, M., et al. (2025). Characterizing genetic, epigenetic, nutritional, and clinico-biochemical profile of women with polycystic ovary syndrome: A case-control study. Journal of Nutrition and Metabolism, 2025(1), 8817919. https://doi.org/10.1155/jnme/8817919

Masters, M., Dropping, K., Parry-Jones, A., & Sinley, R. (2024). Diagnosis experiences in individuals with lean polycystic ovary syndrome. Nursing for Women’s Health. PMID: 39343418

Burns, K., Mullin, B. H., Moolhuijsen, L. M. E., et al. (2024). Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry. BMC Genomics, 25, 208. https://doi.org/10.1186/s12864-024-09990-w

Fouks, Y., Neuhausser, W., Ryley, D., et al. (2023). ART outcomes in lean compared to obese phenotypes of polycystic ovarian syndrome. Journal of Assisted Reproduction and Genetics, 40, 1437–1445. https://doi.org/10.1007/s10815-023-02804-0

Sánchez-Garrido, M. A., & Tena-Sempere, M. (2020). Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Molecular Metabolism, 35, 100937. https://doi.org/10.1016/j.molmet.2020.01.001

Parker, J., O’Brien, C., Hawrelak, J., & Gersh, F. L. (2022). Polycystic ovary syndrome: An evolutionary adaptation to lifestyle and the environment. International Journal of Environmental Research and Public Health, 19(3), 1336. https://doi.org/10.3390/ijerph19031336

Bashir, R., Asrar, M., Kamboj, S., et al. (2026). Metabolic-endocrine correlates of gut-brain axis mediators in polycystic ovary syndrome: A case-control study. Journal of Neuroendocrinology, 38(5). https://doi.org/10.1111/jne.70180