Analysis of the association between mitochondrial dysfunction and common female reproductive endocrinological disorders in a Hungarian cohort
Várhegyi Vera
János Szentágothai Neurosciences
Dr. Bereczki Dániel
Semmelweis Egyetem II.sz. Szülészeti és Nőgyógyászati Klinika előadóterme
2026-05-28 09:30:00
Klinikai idegtudományok
Dr.Gál Anikó,Dr.Várbíró Szabolcs
Dr. Valent Sándor
Dr. Juhász Szilvia
Dr. Buzás Edit
Dr. Visnovitz Tamás
Vellainé Dr. Takács Krisztina
Aims/hypothesis: This thesis investigated the role of mitochondrial dysfunction in insulin resistance (IR) and its associated female reproductive endocrine disorders, with a particular focus on polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). It was hypothesised that GDF-15 and mtDNA deletions act as complementary biomarkers of mitonuclear stress, reflecting metabolic burden and contributing to accelerated reproductive and systemic aging.
Methods: Two observational studies were conducted, including 81 insulin-resistant women with or without PCOS or POI, as well as healthy controls. The participants were divided into three subgroups: IR-only, IR-PCOS, and IR-POI. Insulin resistance was defined using oral glucose tolerance testing in accordance with national guidelines. Plasma GDF-15 levels were measured using an enzyme-linked immunosorbent assay, and mtDNA deletions were detected via long-range polymerase chain reaction. Reproductive and thyroid hormones, metabolic indices, and multisystem clinical symptoms were also assessed.
Results: Plasma GDF-15 levels were significantly higher in insulin-resistant patients than in controls, and were associated with body mass index and metabolic severity. MtDNA deletions were most prevalent in the insulin resistance (IR)-only subgroup, suggesting that mitochondrial impairment may precede overt reproductive dysfunction. Elevated GDF-15 levels and mtDNA deletions were associated with multisystem clinical features and endocrine alterations. Free thyroxine emerged as an independent predictor of GDF-15. Reduced AMH/FSH ratios and age-related alterations in AMH, particularly in women with mtDNA deletions, indicated impaired ovarian reserve and accelerated reproductive aging.
Conclusion: These findings suggest that mitochondrial dysfunction is a key biological mechanism that links insulin resistance to systemic manifestations and reproductive endocrine decline. GDF-15 and mtDNA deletions act as complementary biomarkers of mitonuclear stress, reflecting metabolic load and the onset of aging processes. Together, they may help to identify women at increased risk of reproductive impairment and accelerated aging, which could have implications for personalised metabolic and reproductive management.
