Changes in peripheral mitochondrial DNA copy number in metformin-treated women with polycystic ovary syndrome: a longitudinal study

Abstract

Background: Patients with polycystic ovarian syndrome (PCOS) are associated with known alterations in mitochondria DNA copy number (mtDNA-CN). The aim of this study is to study the change in mtDNA-CN in patients with PCOS who were treated with metformin. Methods: This is a prospective cohort of patients with PCOS, who received metformin for one year. From 2009 to 2015, 88 women diagnosed with PCOS, based on the Rotterdam criteria, were enrolled. Serial measurements of mtDNA-CN, 8-hydroxydeoxyguanosine (8-OHdG), anthropometric, metabolic, endocrine, and inflammatory markers were obtained before and after 3, 6, and 12 months of treatment. Results: A significant decrease in mtDNA-CN was seen over the course of one year. Other markers, including 8-OHdG, testosterone, free androgen index, blood pressure and liver enzymes, also decreased in the same interval. On regression analysis, there was a significant association between the change in mtDNA-CN and serum total testosterone, and no association between mtDNA-CN and metabolic factors. Conclusions: Treatment with metformin is associated with a time-dependent decrease in mtDNA-CN in patients with PCOS who are treated over the course of one year. This may signify a reduction in mitochondria dysfunction. The change in mtDNA-CN corresponds to a similar change in serum total testosterone, and suggests a possible relationship between mtDNA-CN and testosterone.

Preoperative Lymphocyte-to-monocyte Ratio and CA125 Level as Risk Factors for Advanced Ovarian Cancer

“…Descriptive statistics were used to show the baseline characteristics of participants in this study. [9]. Age was classi ed as ≥ 50 or < 50 (years) [7]; white blood cell as > 6.4 or ≤ 6.4 [4].…”

Preoperative LMR and Serum CA125 Level as Risk Factors for Advanced Stage of Ovarian Cancer

“…The optimal cut-off values were determined according to ROC. BMI was categorized as >24 or ≤24 16 . Age was classified as ≥50 or <50 (years) 11 ; white blood cell as >6.4 or ≤6.4 8 .…”

The potential diagnostic use of clinical characteristics and mitochondrial DNA copy numbers of peripheral blood and ovarian tissue in polycystic ovary syndrome (PCOS) patient

“…Lee et al observed that decreased mtDNA copy number was found in peripheral blood of Korean PCOS patients when compared to controls and it was independent of insulin resistance or other metabolic factors [19]. Another study showed treatment with metformin for one year caused a timedependent decrease in mtDNA copy number in patients with PCOS [20]. Also, this study showed that the change in mtDNA copy number was positively correlated to the serum level of total testosterone, however other studies did not show any correlations with most of the clinical indexes.…”

“…Also, this study showed that the change in mtDNA copy number was positively correlated to the serum level of total testosterone, however other studies did not show any correlations with most of the clinical indexes. From the generalized estimating equations (GEE) models, only testosterone was signi cantly associated with mtDNA after metformin treatment [20].…”