New company plans progestin-only ECP

A new American company plans to build on the results of a recent international study showing the superiority of a levonorgestrel-only emergency contraceptive in gaining federal approval of the method.

The study, which compares the progestin-only method with the Yuzpe regimen of both estrogen and progestin pills, found that the levonorgestrel-only method was more effective and resulted in fewer side effects than the combination regimen.1 The trial included 1,998 women in 21 centers around the world and was coordinated by the Special Programme of Research, Development, and Research Training in Human Reproduction (HRP/WHO), a division of the World Health Organization in Geneva, Switzerland.

With these data in hand and a pharmacokinetic study planned, Women’s Capital Corp. of Seattle and Washington, DC, is forging ahead in preparing its New Drug Application to the federal Food and Drug Administration (FDA). The company joins Gynétics of Somerville, NJ, in moving toward introduction of such a progestin-only product.

Researchers who first attempted to develop progestins for regular postcoital contraception about 30 years ago met with failure, mainly due to the fact that repeated postcoital use causes cycle disturbances, recounts Helena von Hertzen, medical officer with HRP/WHO. However, studies in which progestins had only been taken in the mid-cycle suggested that this kind of administration would not disturb the length of the cycle, she says.

"We therefore wished to test the 0.75 mg tablets of levonorgestrel for emergency contraception and collaborated on this issue with our colleagues in Hong Kong,"2 von Hertzen states. "The results of this randomized study were encouraging: Levonorgestrel appeared to be at least as effective as the Yuzpe regimen, but it caused significantly less side effects such as nausea and vomiting."

Committed to confirming these results in a larger multinational study, HRP/WHO enrolled women in the recent double-blind, randomized trial. Women who had regular menses, were not using hormonal contraception, and were requesting emergency contraception after one unprotected coitus received levonorgestrel (0.75 mg, repeated 12 hours later) or the Yuzpe regimen (100 mcg ethinyl estradiol plus levonor gestrel 0.5 mg, repeated 12 hours later). Both regimens were started within 72 hours of unprotected intercourse.

The overall method failure rate (the percentage of women who became pregnant in spite of taking the treatment) was higher in the group using the Yuzpe regimen (3.2%) than in the progestin-only group (1.1%). Calculations of the number of pregnancies that could have occurred if no treatment had been given showed that the levonor gestrel method had prevented 85% of unintended pregnancies, compared with 57% for the Yuzpe regimen.

The researchers found that both regimens were more effective the earlier the treatment was given, notes von Hertzen. However, levonorges trel appeared to be more effective than the Yuzpe regimen within 24-, 48-, and 72-hour intervals after intercourse.

This finding has practical implications for both methods, stresses von Hertzen. Women should use these contraceptives as soon as possible for the highest level of efficacy, she observes.

In other findings, the levonorgestrel method was found to be better tolerated by the women in the study group. While both sets reported the same side effects of nausea, vomiting, dizziness, fatigue, headache, breast tenderness, and low abdominal pain, those in the progestin-only group reported them less frequently.

While half of the women in the combined hormonal contraceptive group reported nausea, only 25% of the progestin-only group users noted the symptom. Vomiting occurred in 20% of women enrolled in the Yuzpe regimen, compared with 6% of those in the levonorgestrel group.

"This is not surprising as it is known that high doses of ethinyl estradiol, one of the two components in the Yuzpe regimen, cause nausea and vomiting in many women," says von Hertzen.

Giving women choices

The Women’s Capital Corporation is a novel public/private sector partnership involving not-for-profit organizations such as the Seattle-based Program for Appropriate Technology in Health. It has received major financing from U.S. foundations such as the David and Lucile Packard Foun dation in Los Altos, CA, the Wallace Alexander Gerbode Foundation in San Francisco, CA, and the Compton Foundation in Menlo Park, CA. The company is dedicated to offering women choices in all aspects of reproductive health, says its president, Sharon Camp, PhD.

"I am trying to marry the resources of the non-profit and for-profit sectors to leverage public interest in socially important products to see if we can’t get things to market more quickly, so Ameri can women do have more choices," Camp says. "I think if this succeeds, this sort of unique hybrid that we’ve built of for-profit and nonprofit efforts, perhaps it will be a model for helping to get vaginal microbicides and other things that women really need to market."

The company is committed to affordable pricing for its progestin-only product, she says.

"I’m sure there are Title X clinics out there now who can’t afford to take on new adolescent or low-income clients because they don’t have the budget to provide free services," she observes. "We want to be sure that those clinics can afford to offer emergency contraception."

References

1. Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998; 352:428-33.

2. Ho PC, Kwan MSW. A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception. Hum Reprod 1993; 8:389-392.