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Investigation is now under way in a large multicenter trial to determine if the newly approved oral contraceptive (OC) Yasmin is effective in treatment of premenstrual symptoms.
The clinical study of the drug, manufactured by Berlex Laboratories of Montville, NJ, seeks to confirm findings of a smaller-scale study that indicates the OC may be effective in easing the symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD).1
Yasmin, a monophasic oral contraceptive, contains 0.03 mg of ethinyl estradiol and 3 mg of drospirenone, a new progestin. The Food and Drug Administration (FDA) approved it in May 2001 for contraceptive use. (See the July 2001 issue of Contraceptive Technology Update, p. 73, for news of the regulatory approval, and Contraceptive Technology Reports, inserted in the September 2001 issue, for a clinical review of the drug.)
The FDA approved in July 2000 the selective serotonin reuptake inhibitor (SSRI) Sarafem (fluoxetine hydrochloride, marketed by Eli Lilly of Indianapolis) as the first prescription medication indicated for the treatment of PMDD. The drug also is marketed as Prozac, which has been in use for several years under approved indications for depression, obsessive-compulsive disorder, and bulimia.
While several studies have found that premenstrual symptoms are less severe among OC users than among other women, no OC currently carries an approved indication for relief of premenstrual symptoms.2
When premenstrual symptoms are severe enough to disrupt usual functioning and impact work and family, treatment is appropriate and will help the majority of those who suffer, reflects Ellen Freeman, PhD, research professor in the obstetrics and gynecology department in the University of Pennsylvania School of Medicine and co-director of the university’s Division of Human Behavior and Reproduction. Freeman served as lead author of the small-scale Yasmin study. At this point in time, the SSRIs have produced the most evidence of efficacy, Freeman observes.
"Yasmin is a promising treatment for PMS which offers a different class of medication and provides contraception as well," says Freeman.
The small-scale double-blind study enrolled 82 women, ages 18-40, to evaluate the efficacy of Yasmin in the treatment of PMDD. Qualified volunteers with PMDD were randomized and treated with Yasmin or a placebo.
Study participants recorded their PMDD symptoms each day for a three-month period, using the Calendar of Premenstrual Experiences (COPE), a prospective inventory statistical tool designed by researchers at the Department of Reproductive Medicine at the University of California, San Diego, now standardized for use in PMS/PMDD studies. Overall, the Yasmin users showed greater reduction in the severity of symptoms than the placebo group for all symptoms rated on the COPE scale. The researchers noted statistically significant improvement with the contraceptive in symptoms such as acne, increased appetite, and food cravings. In addition, Yasmin was well tolerated, and reports of adverse events were typical of those associated with oral contraceptive use.
"All PMS symptoms assessed — both mood and physical — decreased more on the OC than on the placebo," states Freeman. "These were consistent results, although most differences were not statistically significant in a relatively small sample."
The multicenter trial now in progress is designed to confirm or refute these results, she notes.
To qualify as PMS, symptoms must appear during the woman’s luteal phase and decrease greatly or disappear with the onset of menstruation or shortly thereafter. Common PMS symptoms include, among others, abdominal bloating, irritability, mood swings, headache, weight gain, fatigue, food cravings, tension, and breast swelling.
For a PMDD diagnosis, the patient must have:
• five or more of the following symptoms during most menstrual cycles in the past year: irritability, tension, depressed mood, mood swings, decreased interest in usual activities, difficulty concentrating, lethargy, marked change in appetite, insomnia or hypersomnia, sense of being overwhelmed, and physical symptoms such as breast tenderness and bloating. One or more of these symptoms must be depressed mood, tension, mood swings, or irritability.
• a disturbance that significantly interferes with social or occupational functioning;
• symptoms that are not an exacerbation of another disorder, such as major depressive disorder.3 (The April 2001 issue of CTU, p. 37, carries a complete overview of PMS, PMDD, and treatments.)
Studies showing that combination oral contraceptive pills have benefits beyond safe and effective contraception are powerful motivators for successful use, says Steven Sondheimer, MD, professor of obstetrics and gynecology at the University of Pennsylvania Medical Center and co-director of its Premenstrual Syndrome Treatment Program. "Yasmin is effective and safe contraception, and if it does not increase weight and helps premenstrual symptoms such as bloating, mood changes, and difficulty concentrating, many women will be grateful for these additional and important benefits," he notes.