Recent Genetic Study Found Distinct Subtypes of Polycystic Ovary Syndrome

As written by Sascha Gallardo, Ben’s Friends Resident Writer

Results of a genetic study published on June 23 in PLoS Med showed two polycystic ovary syndrome subtypes.

“Using an unsupervised clustering approach featuring quantitative hormonal and anthropometric data, we identified reproductive and metabolic subtypes of PCOS that appeared to have distinct genetic architecture,” the study states. [1]

Based on an initial observation that PCOS could possibly be genetically heterogeneous, the researchers used cluster analysis to examine 893 PCOS cases to find out whether subtypes of this condition exist.

After this, the team reproduced the same results in another set, this time involving 263 cases.

Two subtypes were observed in their analysis. One subtype, which the authors call ‘metabolic’ subtype, exhibits an elevated insulin levels and body mass index but shows low levels of luteinizing hormone (LH) and sex hormone binding globulin (SHBG).

The other group, which the team calls ‘reproductive,’ exhibits the inverse of the metabolic subtype characteristics. The reproductive subtype shows elevated levels of SHBG and LH but low insulin levels and body mass index.

How important are these findings to patients suffering from PCOS?

Relevance of this research to patients

The authors explained that “[w]omen with PCOS may be poorly served by being grouped under a single diagnosis because PCOS subtypes may differ in responses to therapy and in long-term outcomes.”

As stated by the authors, the findings are very important because this justifies the conduct of additional research on the genetic heterogeneity of PCOS. This could then change the process of analyzing, classifying and treating PCOS.

The research team also acknowledges that the diagnostic benchmarks of PCOS is mired in controversy considering that they are basically dependent on expert opinion.

Some Issues concerning PCOS diagnostic system

In a different study published in 2019 in the journal Human Reproduction Open, Tessa Copp and her colleagues analyzed the impact, both positive and negative, of a PCOS diagnosis to patients. They found out that many of these patients benefited from the information such as the relief of finally knowing the cause of their symptoms and learning ways to care for themselves.

For those patients whose symptoms are considered very mild, however, the diagnosis has caused them anxiety because of possible infertility. Considering their findings, the authors suggest that “[a]t the minimum, accurate information and personalized counselling regarding long-term risks in women with milder phenotypes and minimal symptoms is needed to help alleviate anxiety and fear in this expanding patient group.” [2]

Another issue with regards to PCOS concerns the name of the syndrome itself. In a study published in 2014 that was conducted by Prof Helena Teede and her team, 84% of the physicians surveyed agree that its name should be changed.

The researchers assert that “the name of a condition should reflect pathology, should promote both recognition and understanding by health professionals and consumers, and should not be inaccurate.” [3] They explain that “the ‘cysts’ noted in PCOS are in fact antral follicles whose growth and maturation have been inhibited and are not true epithelial-lined cysts.” [3]

In a separate study also led by Teede, they cautioned about the possibility of “overdiagnosis, including when isolated polycystic ovarian morphology on ultrasound is incorrectly equated with PCOS.” [4]

Conclusion

This recent genetic study showing subtypes of polycystic ovary syndrome is a positive development in PCOS research. Considering the controversies associated with PCOS diagnosis, results of this study shows promise for the further improvement of diagnostic procedures and treatment of patients with PCOS.

Notes

[1] Dapas M., Lin FTJ., Nadkarni GN., Sisk R., Legro RS., Urbanek M., et al. (2020) Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. PLoS Med 17(6): e1003132. https://doi.org/10.1371/journal.pmed.1003132

[2] Copp T., Hersch J., Muscat D.M., McCaffery K.J., Doust J., Dokras A., Mol B.W., Jansen J. (2019). The benefits and harms of receiving a polycystic ovary syndrome diagnosis: a qualitative study of women’s experiences, Human Reproduction Open, Volume 2019, Issue 4, 2019, hoz026, https://doi.org/10.1093/hropen/hoz026

[3] Teede H., Gibson-Helm M., Norman R., Boyle J. (2014). Polycystic Ovary Syndrome: Perceptions and Attitudes of Women and Primary Health Care Physicians on Features of PCOS and Renaming the Syndrome, The Journal of Clinical Endocrinology & Metabolism , Volume 99, Issue 1, 1 January 2014, Pages E107–E111, https://doi.org/10.1210/jc.2013-2978

[4] Teede, H., Misso M., Boyle, J., Garad, R., McAllister V., Downes L., Gibson-Helm M., Hart R., Rombauts L., Moran L., Dokras A., Laven J., Piltonen T., Rodgers R., Thondan M., Costello M., and Norman, R., on behalf of the International PCOS Network (2018). Translation and implementation of the Australian-led PCOS guideline: clinical summary and translation resources from the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Med J Aust 2018; 209 (7): S3-S8. || doi: 10.5694/mja18.00656

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