Effects of oral and transdermal hormonal contraception on vascular risk markers: a randomized controlled trial.
OBJECTIVE
To compare the effects of oral and transdermal contraceptives containing similar hormone formulations on vascular risk markers.


METHODS
We conducted a randomized, investigator-blinded, crossover, clinical trial with 24 healthy women, aged 18-35 years, who received 2 months of transdermal or oral contraceptive, 2 months washout, then 2 months of the alternative medication. The transdermal contraceptive contained 0.75 mg ethinyl estradiol and 6 mg norelgestromin. The oral contraceptive contained 35 mcg ethinyl estradiol and 250 mcg norgestimate. Blood samples taken before and after each treatment were analyzed in batch for D-dimer, von Willebrand factor, factor VIII, total and free protein S, antithrombin, fibrinogen, C-reactive protein, and normalized activated protein C sensitivity ratio (nAPCsr) determined with two thrombin generation-based assays, the alpha2macroglobulin-thrombin end point method (alpha2M-IIa) and calibrated automated thrombinography. Repeated measures analysis of variance was used for analysis.


RESULTS
For both contraceptives (transdermal, oral) there were significant declines in free (19%, 11%) and total protein S (19%, 13%) and antithrombin (13%, 10%); increases in fibrinogen (8%, 10%), C-reactive protein (220%, 292%), nAPCsr alpha2M-IIa (81%, 61%), and nAPCsr calibrated automated thrombinography (102%, 68%), all P<.05. Transdermal contraceptives had a greater effect than oral contraceptives on free protein S (P=.07), nAPCsr alpha2M-IIa (P=.06), and nAPCsr calibrated automated thrombinography (P=.03).


CONCLUSIONS
Oral and transdermal contraception with similar hormones had similar adverse effects on vascular risk markers. This suggests that this transdermal contraceptive has at least a similar thrombosis risk as its oral counterpart.


BACKGROUND
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00554632


METHODS
I.
Johnson
Julia V
JV
Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont 0450, USA. Julia.Johnson@vtmednet.org
Lowell
Jane
J
Badger
Gary J
GJ
Rosing
Jan
J
Tchaikovski
Svetlana
S
Cushman
Mary
M
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000991:Antithrombins / Q000032:analysis / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D002097:C-Reactive Protein; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D005169:Factor VIII / Q000032:analysis / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000378:metabolism; D006801:Humans; D009644:Norgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects; D017293:Protein S / Q000032:analysis / Q000378:metabolism; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism
D000991:Antithrombins; D001798:Blood Proteins; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D010091:Oximes; D017293:Protein S; D014841:von Willebrand Factor; D009644:Norgestrel; D004997:Ethinyl Estradiol; D005169:Factor VIII; D005340:Fibrinogen; D002097:C-Reactive Protein; C017576:norgestimate; C449219:norelgestromin