Combined oral contraceptives modify the effect of smoking on inflammatory cellular indexes and endothelial function in healthy subjects

Eur J Pharmacol. 2021 Jan 15:891:173762. doi: 10.1016/j.ejphar.2020.173762. Epub 2020 Nov 27.

Abstract

Little information is available on the influence of sex in combination with smoking habits and combined oral contraceptives (COC) use on cellular inflammatory indexes such as neutrophil/lymphocyte ratio (NLR), derived NRL (dNLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), mean platelet volume/platelet count (MPV/PLT), aggregate inflammation systemic index (AISI), and systemic inflammation response index (SIRI), which are cost-effective biomarkers to assessing inflammation. Therefore, the effect of COC was studied alone or in association with smoking and compared with results from healthy COC-free women and men. Furthermore, the association of cellular inflammatory indexes with endothelial function (arginine (Arg), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and lipid peroxidation (malondialdehyde MDA) biomarkers was evaluated. Blood was collected for hematological and biochemical analysis, which were used to calculate PLR, NLR, dNLR, MLR, MPV/PLT, AISI, and SIRI. Serum samples were assayed for Arg, ADMA, SDMA, and MDA. Monocytes, MLR, SIRI, and MPV/PLT were higher in men, while PLT count was higher in women. COC use increased lymphocytes and lowered PLR and MLR. Smoking reduced sexually divergent parameters, especially in COC users: smoking and non-smoking COC-free women displayed six divergent parameters, while COC users displayed only two (monocytes and MPV). In addition, COC affected endothelial function, reducing ADMA and Arg. Moreover, COC-free women had lower Arg levels than men. In conclusion, COC use strongly influence the effects of tobacco smoking, which are sex and parameter specific. Further, these data stress that COC use and smoking attitude select different cohorts indicating that sex and gender studies need intersectionality.

Keywords: Combined oral contraceptives; Inflammation indexes; Intersectionality; Sex and gender differences; Smoking habit.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / immunology
  • Blood Platelets / metabolism
  • Contraceptives, Oral, Combined / adverse effects*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism
  • Female
  • Healthy Volunteers
  • Humans
  • Inflammation / blood
  • Inflammation / etiology*
  • Inflammation / immunology
  • Leukocytes / drug effects*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Lipid Peroxidation / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Male
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Smoking / adverse effects*
  • Smoking / blood
  • Smoking / immunology

Substances

  • Biomarkers
  • Contraceptives, Oral, Combined