Effect of a Contraceptive Patch vs. Placebo (PBO) on Serum Lipid Profile

Abstract

Objectives: A contraceptive patch (ORTHO EVRA™/EVRA™[EVRA™]), which delivers norelgestromin 150 μg and ethinyl estradiol 20 μg daily to the systemic circulation, has been developed. The primary objective of this study was to evaluate the metabolic impact on serum lipids of EVRA vs. a PBO patch. Design: This study was a double-blind, 9-cycle trial conducted at 5 centers. Healthy adult female subjects who had not received steroid hormonal therapy within 3 months prior to the study were randomized (2:1) to EVRA (n=99) or a PBO patch (n=47), which were identical in appearance. Patch treatment was 3 consecutive 7-day patches (21 days), followed by 1 patch-free week. Materials and Methods: After a 10- to 12-hour overnight fast, blood samples were obtained at baseline and between Days 19–21 (±2 days) of Cycles 3, 6, and 9 (or early withdrawal) for determination of the serum lipid profile: total high-density lipoprotein (HDL), HDL2, HDL3, measured low-density lipoprotein (LDL), and total cholesterol, LDL/HDL ratio, and total triglycerides. Validated assay methods were used. Between-regimen differences in mean changes from baseline were assessed with 2-sided, 95% confidence intervals. Subjects recorded on diary cards when a patch fell off. Safety was evaluated based on adverse events, laboratory tests, vital signs, and body weight. Results: Mean increases from baseline were noted with EVRA for all lipid parameters, except HDL2 cholesterol at Cycles 3 (−0.01 mmol/L) and 6 (0.0 mmol/L). At Cycles 3, 6, 9, and the final visit, these increases were significantly greater (p<0.05) with EVRA vs. PBO for total HDL cholesterol (0.10 to 0.14 vs. −0.05 to −0.08 mmol/L), HDL3 cholesterol (0.08 to 0.13 vs. −0.05 to −0.07 mmol/L), LDL cholesterol (0.23 to 0.44 vs. −0.09 to 0.11 mmol/L), total cholesterol (except Cycle 6) (0.28 to 0.48 vs. 0.00 to 0.11 mmol/L), and total triglycerides (0.42 to 0.51 vs. 0.05 to 0.07 mmol/L). No significant differences were observed between the 2 groups for the LDL/HDL ratio or HDL2 cholesterol. Baseline to end of study changes for EVRA and PBO were evaluated using National Cholesterol Education Program criteria. A small and comparable number of subjects migrated from “desirable” LDL cholesterol, total cholesterol, and total triglyceride values prestudy to “high” values at the end of the study. Only 1.3% of EVRA patches and 2.0% of PBO patches fell off during the study, with more patches falling off during the early cycles. The most common adverse events were headache and brief mild-to-moderate breast discomfort in early cycles. There were no clinically important changes in laboratory tests or vital signs. Mean body weight increased from baseline by <2 lbs with both EVRA and PBO. Conclusions: ORTHO EVRA/EVRA did not significantly alter the LDL/HDL ratio or HDL2 cholesterol vs. PBO. Increases in total HDL cholesterol, HDL3 cholesterol, LDL cholesterol, total cholesterol, and total triglycerides vs. PBO were observed. This study was supported by the R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ.