Increased ferritin with contraceptives containing ethinyl estradiol drospirenone in polycystic ovary syndrome: a paradox of iron storage and iron deficiency

Objectives: The relationship between elevated ferritin levels and metabolic abnormalities in PCOS patients, and whether ferritin is a cause or a consequence, is still debated. This study aimed to evaluate the impacts of the fourth generation combined oral contraceptive containing ethinyl estradiol/drospirenone (EE 30 mcg/DRSP 3 mg), known for its favorable metabolic profile and lower side effect risk, on iron metabolism in PCOS patients, while also exploring the potential relationship between metabolic parameters and iron status.

Methods: The retrospective analysis was conducted on 81 women aged 18-45, diagnosed with PCOS according to the Rotterdam criteria and treated with EE/DRSP for six months. Exclusion criteria were lack of data, secondary hyperandrogenemia, major medical conditions, or recent use of medications affecting hormone levels or iron metabolism. Pre- and post-treatment anthropometric measurements, hormonal and metabolic markers, and iron parameters were obtained from records.

Results: Post-treatment ferritin levels significantly increased (p = 0.001), while hemoglobin, hematocrit, and transferrin saturation decreased especially in overweight/obese patients (p = 0.012, p = 0.002, p = 0.017 respectively), suggesting a response to inflammation rather than iron storage disorders. Although overall CRP levels did not change significantly, post-treatment CRP levels were higher in overweight/obese patients compared to lean PCOS patients (p = 0.003). Ferritin levels were positively correlated with body mass index (p = 0.008, r = 0.310), insulin resistance indices (p = 0.027, r = 0.248), and the free androgen index (p = 0.001, r = 0.367) after treatment. Pre-treatment menstrual cycle length had no effect on ferritin.

Conclusions: The study revealed a paradoxical increase in ferritin levels with EE/DRSP treatment, highlighting the complex role of ferritin as a metabolic marker in PCOS patients, particularly in relation to obesity, which is typically associated with low-grade chronic inflammation.