Interleukin-6 and Hepcidin Levels during Hormone-Deplete and Hormone-Replete Phases of an Oral Contraceptive Cycle: A Pilot Study

Ann Nutr Metab. 2017;70(2):100-105. doi: 10.1159/000465530. Epub 2017 Mar 23.


Background: In the past, elevated estradiol levels were reported to downregulate the iron regulatory hormone hepcidin, thereby potentially improving iron metabolism. As estrogen plays a role in regulating the menstrual cycle and can influence the cytokine interleukin-6 (IL-6; a hepcidin up-regulator), this investigation examined the effects of estradiol supplementation achieved by the use of a monophasic oral contraceptive pill (OCP) on IL-6, hepcidin levels and iron status during the hormone-deplete versus hormone-replete phases within an oral contraceptive cycle (OCC).

Methods: Fifteen healthy female OCP users were recruited and provided a venous blood sample on 2 separate mornings during a 28-day period. These included (a) days 2-4 of the OCC, representing a hormone-free withdrawal period (WD); (b) days 12-14 of the OCC, representing the end of the first week of active hormone therapy (AHT).

Results: IL-6 and hepcidin levels were not significantly different at WD and AHT. Serum ferritin was significantly higher (p = 0.039) during AHT as compared to WD.

Conclusions: Fluctuations in OCP hormones (estradiol and/or progestogen) had no effect on basal IL-6 and hepcidin levels in young women. Nevertheless, elevated ferritin levels recorded during AHT may indicate that OCP hormones can positively influence iron stores within an OCC despite unchanged hepcidin levels.

Keywords: Estrogen; Iron deficiency; Iron metabolism; Menstrual cycle; Progesterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Body Mass Index
  • Contraceptives, Oral, Hormonal / administration & dosage*
  • Contraceptives, Oral, Hormonal / blood
  • Estradiol / blood*
  • Female
  • Ferritins / blood
  • Hepcidins / blood*
  • Humans
  • Interleukin-6 / blood*
  • Iron / blood
  • Menstrual Cycle / drug effects
  • Pilot Projects
  • Progestins / blood*
  • Young Adult


  • Contraceptives, Oral, Hormonal
  • Hepcidins
  • IL6 protein, human
  • Interleukin-6
  • Progestins
  • Estradiol
  • Ferritins
  • Iron