Low-dose COC effective in studies

OB/GYN News, Nov 15, 2005 by Bob Babinski

Two studies demonstrated a positive response to an investigational low-dose continuous oral contraceptive in terms of suppression of ovulation and premenstrual symptoms and return to normal ovulation, researchers reported at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Both studies were sponsored by Wyeth, which has submitted the contraceptive for approval by the Food and Drug Administration. If approved, the contraceptive would be marketed under the trade name Lybrel.

The oral formulation of 20-mcg ethinyl estradiol and 90-mcg levonorgestrel is designed to be taken daily with no hormone-free intervals.

One study, involving 37 women aged 18-35 years, showed complete inhibition of ovulation in all women while on the oral formulation.

"We showed that none of the subjects developed follicles equal to or greater than 10 mm during treatment," said investigator Susan A. Ballagh, M.D., of the Contraceptive Research and Development program, Arlington, Va., of the Eastern Virginia Medical School, Norfolk.

Participants followed the continuous oral contraception (COC) regimen for 84 days, using three pill-pack segments.

After discontinuation of contraception, the time to return to normal ovulation--defined as serum progesterone levels greater than 5 ng/mL--was a mean of 20 days. A total of 95% of subjects ovulated within 25 days after discontinuation.

The study did not include women unable to meet the compliance demands, and Dr. Ballagh said that's an element that will have to be explored in a future study.

"Our next question is, when women are taking the pills in less controlled circumstances, does this COC formulation in fact lead to less chance of them becoming pregnant," she said. "Patient failure rates of pills in common use is estimated to be at least 3%, and some have recently suggested that it may be as high as 7%."

The second study found that the same COC regimen significantly alleviated premenstrual symptoms.

A total of 278 women with a history of cycle-related symptoms or dysmenorrhea were monitored during three cycles of the COC regimen, with no pill-free interval. The subjects maintained a daily diary, rating mood, behavior, pain, and physical symptoms using the Penn Daily Symptom Rating scale. Two-thirds of the women improved their scores by 50% in the first 28-day cycle (one pill pack). In addition, work productivity improved.

"What impressed me the most was the very immediate response of the first cycle and the strong response at end point," said lead investigator Ellen Freeman, Ph.D., of the University of Pennsylvania in Philadelphia. "Almost all the response occurred right away. That's fast. Secondly, I was surprised that all four of the symptom subscales seemed to respond similarly."

The study--not placebo controlled--shows the impact of the COC on PMS symptoms as more effective than what has been reported with selective serotonin reuptake inhibitors.

"The biggest limitation of this study is that it's not placebo controlled," said Dr. Freeman. "Still, SSRIs don't appear to reduce the symptoms to their post-menstrual level for women overall, which is what is considered the normal asymptomatic level. This data suggest this therapy does, but that has to be confirmed with a placebo-controlled study."

BY BOB BABINSKI

Contributing Writer