Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Aug 27:68:e230416.
doi: 10.20945/2359-4292-2023-0416. eCollection 2024.

GDF-15 levels in patients with polycystic ovary syndrome treated with metformin: a combined clinical and in silico pathway analysis

Fernanda M V Magalhães  1 , Rodrigo M C Pestana  2 , Cláudia N Ferreira  3 , Ieda F O Silva  1 , Ana L Candido  2 , Flávia R Oliveira  2 , Fernando M Reis  2 , Karina B Gomes  1
Affiliations
Randomized Controlled Trial

GDF-15 levels in patients with polycystic ovary syndrome treated with metformin: a combined clinical and in silico pathway analysis

Fernanda M V Magalhães et al. Arch Endocrinol Metab. .

Abstract

Objective: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by metabolic, reproductive, and psychological manifestations. Growth and differentiation factor 15 (GDF-15) is a cytokine associated with metabolic and inflammatory disorders. Metformin is commonly used for the treatment of PCOS. We investigated the relationship between GDF-15 levels and PCOS, the effect of metformin on GDF-15 levels, and potential biologic pathways related to GDF-15.

Subjects and methods: The study included 35 women with PCOS and 32 women without PCOS (controls). Both groups were compared in terms of GDF-15 levels. Additional analysis was conducted on samples from 22 women with PCOS who were treated with either metformin (n = 7) or placebo (n = 15), retrieved from a previous randomized, controlled trial. Levels of GDF-15 were measured using MILLIPLEX. The biologic pathways related to GDF-15 were evaluated using the databases STRING, SIGNOR, and Pathway Commons. The statistical analysis was conducted using the software SPSS.

Results: Levels of GDF-15 were higher in the PCOS group compared with the non-PCOS group (p = 0.039). Among women with PCOS, GDF-15 levels were higher in those treated with metformin compared with placebo (p = 0.007). The proteins related to GDF-15 overlapped between the databases, and a significant interaction was found between GDF-15 and proteins related to PCOS and its complications, including those related to estrogen response, oxidative stress, ovarian infertility, interleukin (IL)-18, IL-4, the ratio of advanced glycation end products to their receptor (AGE/RAGE), leptin, transforming growth factor beta (TGF-β), adipogenesis, and insulin.

Conclusion: The findings of the present study suggest a relationship between GDF-15 and PCOS and a potential increase in GDF-15 levels with metformin treatment. An additional finding was that GDF-15 could be involved in biologic pathways related to PCOS complications.

Keywords: GDF-15; biologic pathways; metformin; polycystic ovary syndrome.

PubMed Disclaimer

Conflict of interest statement

Disclosure: no potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Median levels of growth and differentiation factor 15 (GDF-15; in ng/mL) in women with polycystic ovary syndrome (PCOS group). (A) GDF-15 levels in the PCOS and non-PCOS groups. (B) GDF-15 levels in women with PCOS treated with metformin (PCOS metformin) and not treated with metformin (PCOS non-metformin).
Figure 2
Figure 2. Interactions between proteins and growth and differentiation factor 15 (GDF-15). Protein-protein interactions. Each node represents a protein, and each line refers to an interaction. Line color: blue, known interaction of selected databases; pink, known interaction determined experimentally; green, text mining; black, coexpression. There are 12 potential protein-protein interactions. Enrichment p < 0.0001.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol. 2018;182:27–36. doi: 10.1016/j.jsbmb.2018.04.008. - DOI - PubMed
    1. Goodarzi M, Dumesic D, Chazenbalk G, Azzizz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7(4):219–231. doi: 10.1038/nrendo.2010.217. - DOI - PubMed
    1. Barthelmess E, Naz R. Polycystic ovary syndrome: current status and future perspective. 104Front Biosci (Elite Ed) 2014;6 doi: 10.2741/e695. - DOI - PMC - PubMed
    1. Hoeger K, Dokras A, Piltonen T. Update on PCOS: consequences, challenges, and guiding treatment. J Clin Endocrinol Metab. 2021;106(3):e1071–e1083. doi: 10.1210/clinem/dgaa839. - DOI - PubMed
    1. Vanky E, Kjøtrød S, Salvesen K, Romundstad P, Moen M, Carlsen S. Clinical, biochemical and ultrasonographic characteristics of Scandinavian women with PCOS. Acta Obstet Gynecol Scand. 2004;83(5):482–486. doi: 10.1111/j.0001-6349.2004.00373.x. - DOI - PubMed

Publication types

LinkOut - more resources