Thesis title: The Impact of Polycystic Ovary Syndrome Treatment on Inflammatory Markers and Homocysteine Levels: A Prospective Cohort Study
Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and metabolic issues. Chronic low-grade inflammation is a key feature of the syndrome and may contribute to its pathogenesis and the wide range of clinical manifestations. Although numerous studies have evaluated the effect of PCOS treatment on inflammatory markers and homocysteine levels, the findings have often been inconsistent and inconclusive.
Objective: This study aimed to evaluate the impact of treatment on inflammatory markers (IL-6, IL-1β, TNF-α) and homocysteine levels in women with PCOS over a six-month period. Additionally, it sought to assess the effects of different PCOS treatment regimens on these markers, as well as their influence on androgen levels, homeostatic model assessment of insulin resistance (HOMA-IR), and body mass index (BMI).
Methods: This is a multicentric observational prospective cohort study conducted across three outpatient centers in Tirana, Albania, enrolling women aged 18-40 diagnosed with PCOS based on Rotterdam criteria, from February 2022 to March 2024. Patients were categorized into three subgroups based on their clinical and biochemical features (metabolic, hyperandrogenic, and combined phenotype) and received tailored treatment protocols. Inflammatory markers and homocysteine levels were measured at baseline and after six months.
Results: Of the 156 participants, 135 completed follow-up (mean age 26.21 ± 5.33 years). Significant reductions in inflammatory markers and homocysteine levels were observed across the entire cohort: IL-6 decreased from 8.44 ± 11.08 to 4.36 ± 3.55 pg/mL (p < 0.001), IL-1β from 15.34 ± 15.37 to 10.19 ± 28.21 pg/mL (p = 0.012), TNF-α from 5.88 ± 2.55 to 3.48 ± 1.59 pg/mL (p < 0.001), and homocysteine from 10.89 ± 6.01 to 6.77 ± 3.03 µmol/L (p < 0.001). Consistent reductions following treatment were noted across all subgroups, with the greatest declines observed in subgroup 3 for IL-6 and TNF-α (mean difference of 4.8 pg/mL for IL-6 and 2.66 pg/mL for TNF-α) and in subgroup 2 for IL-1β (mean difference of 8.38 pg/mL). Statistically significant differences in median levels of inflammatory cytokines and homocysteine were observed across the three subgroups. Additionally, significant reductions in BMI, HOMA-IR, and androgen levels were observed throughout the cohort.
Conclusions: Tailored treatment significantly reduces inflammatory markers and homocysteine levels in women with PCOS. These findings support the effectiveness of phenotype-based treatment approaches for managing inflammation and clinical disturbances in PCOS. However, further research should focus on determining the persistence of these improvements over time and their long-term clinical implications.