Does weight play a role in effectiveness?

As the contraceptive transdermal system (Ortho Evra, manufactured by Ortho-McNeil Pharmaceutical of Raritan, NJ) moves into wide availability in the United States this summer, providers can expect plenty of questions from women interested in the new method. What will you tell your heavier patients about the contraceptive efficacy of the patch?

An analysis of pooled data from three pivotal studies show that in contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%.1 While contraceptive failure was low and uniformly distributed across the range of body weights in women lighter than 198 pounds, in women at or more than that weight, contraceptive failures may be increased, researchers conclude.

Body weight equal to or more than 198 pounds is the first item listed under "Precautions" in the Ortho Evra labeling, notes Kellie McLaughlin, director of global pharmaceutical communications for New Brunswick, NJ-based Johnson & Johnson, Ortho-McNeil’s parent company. The labeling states: "Results of clinical trials suggest that Ortho Evra may be less effective in women with body weight >198 lbs. (90 kg) than in women with lower body weights."

When it comes to efficacy and the contraceptive patch, there are a number of theories as to why weight may play a factor:2

  • Women with more subcutaneous fat may have poorer absorption since the distribution of hormones into the serum is dependent on transdermal absorption.
  • Absorption of hormones in larger women may vary between sites.
  • Steady-state levels may take longer to reach in heavier women, reducing efficacy during the initial week of the cycle.
  • Clearance of norelgestromin and ethinyl estradiol may be increased in larger women, by renal clearance or total body clearance.
  • Larger women may have lower circulating levels of the hormones contained in contraceptive methods because of dilution in a larger total blood volume.
  • Ovulation rates and cervical mucus effects may be differentially affected by confounding factors in obese women.

While more research may be indicated on patch efficacy and weight, the company does not plan to pursue further studies at this time, says McLaughlin.

What about the Pill?

Consideration of a woman’s weight may be an important element when it comes to prescribing oral contraceptives (OCs), suggest results from a just-published study.3 Investigators conducted a retrospective cohort analysis of data from 755 randomly selected female enrollees of Group Health Cooperative of Puget Sound who completed an in-person interview and dietary questionnaire between 1990 and 1994 as control subjects for a case-control study of ovarian cysts. Among the 618 women who were OC ever-users, scientists used mathematical models to estimate the relative risk of pregnancy while using OCs associated with body weight quartile.

During 2,822 person-years of OC use, 106 confirmed pregnancies occurred (3.8 per 100 person-years of exposure). After controlling for parity, women in the highest body-weight quartile (70.5 kg or more) had a significantly increased risk of OC failure (RR 1.6, 95% confidence interval [CI] 1.1, 2.4) compared with women of lower weight. Higher elevations of risk associated with the highest-weight quartile were seen among very low-dose OC users (RR 4.5, 95% CI 1.4, 14.4) and low-dose OC users (RR 2.6, 95% CI 1.2, 5.9), controlling for parity, race, religion, and menstrual cycle regularity.

Scientists plan to further examine this issue, reports the paper’s lead author, Victoria Holt, PhD, MPH, professor in the department of epidemiology at the Seattle-based University of Washington. With funding from the Bethesda, MD-based National Institute of Child Health and Human Development, Holt and collaborating researchers are conducting a case-control study of pregnancies among current OC users. Scientists are obtaining information about women’s weight before and during OC use, and they also are obtaining details of their pill-taking habits and concurrent illnesses and medications that might influence OC effectiveness.

Holt says her published paper does not indicate that it is advisable to just prescribe a higher-dose pill for heavy women, as side effects of higher-dose pills may be greater, especially for overweight women.

If the findings of the initial paper are confirmed through further studies, providers may want to discuss other contraceptive options with heavy women who have a strong desire to avoid unintended pregnancy, says Holt. These women may wish to consider use of a second type of contraception along with OCs, or choose another form of birth control, she suggests.

References

1. Zieman M, Guillebaud J, Weisberg E, et al. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: The analysis of pooled data. Fertil Steril 2002; 77(2 Suppl 2):S13-18.

2. Transdermal contraceptive patch: Efficacy in heavier women. Contraceptive Report 2002; March. Accessed at www.contraceptiononline.org/contrareport/article01.cfm?art=204

3. Holt VL, Cushing-Haugen KL, Daling JR. Body weight and risk of oral contraceptive failure. Obstet Gynecol 2002; 99:820-827.