Effect of Norelgestromin and Ethinylestradiol in Transdermal Patches on the Clinical Outcomes and Biochemical Parameters of COVID-19 Patients: A Clinical Trial Pilot Study

Abstract

The disease caused by SARS-CoV-2 is still considered a global pandemic. Transdermal patches (TP) with immunoregulators such as estrogen and progesterone compounds could be a feasible option to treat COVID-19 because of their accessibility and relative safety. The objective of the current study was to evaluate the additional treatment with norelgestromin and ethinylestradiol in TP on the clinical and biochemical evolution of COVID-19 patients. The present is a clinical-trial pilot study that included subjects diagnosed with COVID-19, randomized into two groups; the experimental Evra® TP (norelgestromin 6 mg and ethinylestradiol 0.60 mg) was administered such that it was applied on arrival and replaced at day 8 and day 15. The control continued with the conventional COVID-19 treatment protocol. A blood sample was taken each week in order to evaluate relevant biochemical parameters, clinical signs, and evolution. In total, 44 subjects participated in this study, 30 in the experimental group and 14 in the control group. Both groups were homogeneous in terms of age and comorbidities. The experimental group had a significantly lower hospital stay (p = 0.01), high flow supplemental oxygen (p = 0.001), mechanical ventilation (p = 0.003), and intubation (p = 0.01), and the oxygen saturation significantly increased (p = 0.01) in comparison with control group when patients were exposed to room air. A decrease in ferritin (p < 0.05) was observed, with no significant increase in ESR (p > 0.05), D dimer (p > 0.05) and platelets (p > 0.05) in an auto-controlled analysis in the experimental group. Norelgestromin and ethinylestradiol TP could be a safe and effective treatment for moderate and severe COVID-19 patients.

Keywords: COVID-19; estrogens; ethinylestradiol; norelgestromin.

Figure 1

Comparisons between experimental and control groups of principal outcomes evaluated in COVID-19 patients. In (A) we observed the hospital stay; in (B) we observed the high flow oxygen supplementation; in (C) we observed the mechanical ventilation; in (D) we observed the intubation and in (E) we observed the oxygen saturation during hospital stay days comparing both experimental vs control group. The experimental group presented significantly fewer hospital stay days (p = 0.01), high-flow-oxygen-supplementation days (p = 0.001), mechanical-ventilation days (p = 0.003), and intubated days (p = 0.01); in contrast, oxygen saturation significantly increased (p = 0.01 * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 2

Inflammatory parameters between experimental and control groups evaluated in COVID-19 patients. Ferritin diminishes in the experimental group approximately by 50% (p = 0.001). In (A) we observe ferritin values; (B) CRP levels; in (C) albumin; (D) ESR and (E) procalcitonin during hospital stay days comparing both experimental vs control group. Auto-controlled analysis did not show significant changes in the experimental in ESR (p > 0.05), but in the control group, it significantly increased (p = 0.0001). Considering a covariate adjustment, experimental group ESR was significantly decreased in comparison with the control group (p = 0.01). CRP and procalcitonin did not significantly decrease in the experimental group (74% and 33%, respectively; p > 0.05 in both). * p < 0.05.

Figure 3

Blood count parameters between experimental and control group evaluated in COVID-19 patients (A) leukocytes; (B) lymphocytes; (C) hemoglobin; (D) hematocrit; (E) erythrocytes and (F) neutrophils during hospital stay days comparing both experimental vs control group. Hemoglobin and hematocrit decreased in the experimental group by 5.6 and 9.7%, respectively (p > 0.05). Cellular counting shows that erythrocyte and neutrophils decreased (44% and 10%, respectively), but not significantly, in the experimental group while leukocytes and lymphocytes increased, but not significantly (10.2% and 34.3%, respectively). * p < 0.05.