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. 2025 Mar;87(3):1314-1322.
doi: 10.1007/s12020-024-04150-2. Epub 2024 Dec 30.

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

Naile Gokkaya  1 , Gizem Gecmez  2 , Serhat Ozcelik  3 , Mithat Biyikli  3 , Kadriye Aydin  3
Affiliations

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

Naile Gokkaya et al. Endocrine. 2025 Mar.

Abstract

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.

Keywords: Ethinyl estradiol drospirenone; Ferritin; Iron metabolism; Polycystic ovary syndrome.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethics approval: The study was conducted in agreement with the Declaration of Helsinki II and was approved by Kartal Dr. Lutfi Kirdar City Hospital Ethical Committee (reference number: 2024/0l0.99/2/49, date: 27.03.2024).

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