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Clinical Trial
. 2021 Oct 10;18(20):10607.
doi: 10.3390/ijerph182010607.

Health Status Is Affected, and Phase I/II Biotransformation Activity Altered in Young Women Using Oral Contraceptives Containing Drospirenone/Ethinyl Estradiol

Gerda Venter  1 , Carien L van der Berg  1 , Francois H van der Westhuizen  1 , Elardus Erasmus  1
Affiliations
Clinical Trial

Health Status Is Affected, and Phase I/II Biotransformation Activity Altered in Young Women Using Oral Contraceptives Containing Drospirenone/Ethinyl Estradiol

Gerda Venter et al. Int J Environ Res Public Health. .

Abstract

Combined oral contraceptive (COC) use has been associated with various adverse effects. Formulations containing drospirenone (DRSP) and ethinyl estradiol (EE) are generally regarded as milder COCs. Whether long term use of these pills indeed has a low health risk remains questionable. COC use may affect the biotransformation balance by increasing the toxic load or by interfering with the pharmacokinetics of other drugs. This may negatively impact overall health via the production of toxic biotransformation metabolites and induction of oxidative stress. Although individual enzymes involved in biotransformation are known to be regulated by COCs, the effect of COC use on the overall liver biotransformation efficiency has not been reported. Here, we evaluated the general subjective health status and overall liver biotransformation efficiency of healthy young women who were either long term chronic users of COCs containing DRSP/EE, or who were not using any hormonal products. COC users suffered from moderate to severe fatigue and reported more health-related symptoms. Furthermore, phase I (CYP1A2) activity was reduced whereas phase II conjugation reactions (glucuronide conjugation and glycine conjugation) were increased in COC users. Finally, serum peroxide levels were markedly elevated and antioxidant capacity of plasma was reduced in COC users. COCs containing DRSP/EE may, therefore, adversely affect health status and disturb the balance between phase I and II biotransformation reactions. These effects may be mediated by oxidative stress.

Keywords: biotransformation; fatigue; health status; oral contraceptives; oxidative stress.

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Conflict of interest statement

G.V., C.L.v.d.B., F.H.v.d.W., and E.E. declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Dietary evaluation and nutritional supplement use. (a) The consumption frequency of specific food items per week was converted to an average frequency per day for statistical analysis. No correlations were found between any of the food items listed and either of the groups. (b) Proportion of participants that used nutritional supplements per group.
Figure 2
Figure 2
Overall scores for the (a) medical symptoms questionnaire and the (b) Piper fatigue scale. Dashed lines indicate the cut-off points of the severity levels listed on the right of each graph (as generally applied for the MSQ by physicians affiliated with the Institute for Functional Medicine [38,39] and described in Piper et al. [40] for the PFS). Squares and triangles represent individual controls and COC users, respectively. Horizontal solid lines and error bars indicate means ± SD.
Figure 3
Figure 3
Untransformed data of phase I and II biotransformation efficiency, serum peroxides, and antioxidant capacity. (a) Phase I (CYP1A2) activity was measured as the caffeine clearance rate in saliva. Phase II (conjugation) efficiency was assessed by measuring the recovery of (b) APAP glucuronide, (c) salicyluric acid, (d) APAP mercapturic acid, and (e) APAP sulfate in urine. (f) Serum peroxides were measured as an indicator of oxidative stress and (g) total red blood cell glutathione and (h) ferric reducing ability of plasma as indicators of antioxidant capacity. Squares and triangles represent individual controls and COC users, respectively. Horizontal lines and error bars indicate means ± SD. Shaded background indicates reference ranges obtained by our own laboratory from a South African Caucasian group of 46 healthy individuals between the age of 18 and 35 years (22 men and 24 women).
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