Abstract:
The association between hypercoagulability and use of drospirenone (DRSP) and ethinylestradiol (EE) containing
combined oral contraceptives (COCs) is an important clinical concern. We have previously reported that
the two formulations of DRSP combined with EE (namely, DRSP/20EE and DRSP/30EE) bring about a
prothrombotic state in hemostatic traits of female users. We report here the serum metabolomic changes in the
same study cohort in relation to the attendant prothrombotic state induced by COC use, thus offering new
insights on the underlying biochemical mechanisms contributing to the altered coagulatory profile with COC
use. A total of 78 healthy women participated in this study and were grouped as follows: control group not using
oral contraceptives (n = 25), DRSP/20EE group (n = 27), and DRSP/30EE group (n = 26). Untargeted metabolomics
revealed changes in amino acid concentrations, particularly a decrease in glycine and an increase in both
cysteine and lanthionine in the serum, accompanied by variations in oxidative stress markers in the COC users
compared with the controls. Of importance, this study is the first to link specific amino acid variations, serum
metabolites, and the oxidative metabolic profile with DRSP/EE use. These molecular changes could be linked to
specific biophysical coagulatory alterations observed in the same individuals. These new findings lend evidence
on the metabolomic substrates of the prothrombotic state associated with COC use in women and informs future
personalized/precision medicine research. Moreover, we underscore the importance of an interdisciplinary
approach to evaluate venous thrombotic risk associated with COC use.
