Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.
BACKGROUND
Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status.


METHODS
A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed.


RESULTS
Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of beta-carotene (-41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log(2) fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log(2) fold change=-0.24, p<.05) in the OCU compared to the NCU.


CONCLUSIONS
The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk.
De Groote
Donat
D
PROBIOX SA, Campus Universitaire du Sart-Tilman, Avenue de l'hôpital, Tour GIGA, Bât. B34, B-4000 Liège, Belgium. d.degroote@probiox.com
Perrier d'Hauterive
Sophie
S
Pintiaux
Axelle
A
Balteau
Bénédicte
B
Gerday
Colette
C
Claesen
Jürgen
J
Foidart
Jean-Michel
JM
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000009:adverse effects* / Q000097:blood; D016022:Case-Control Studies; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000097:blood; D003300:Copper / Q000097:blood; D015536:Down-Regulation; D004997:Ethinyl Estradiol / Q000009:adverse effects* / Q000097:blood; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D018840:HSP70 Heat-Shock Proteins; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D004997:Ethinyl Estradiol; D003300:Copper; D019001:Nitric Oxide Synthase; C035144:drospirenone