Treatment for PMDD? New OC regimen eyed

(Editor's note: This story discusses off label use of a medication)

Review the chart for the next patient. According to her history, for about 10 days of every month, she experiences depression, marked anxiety, sudden mood shifts, persistent irritability, and bloating. While the symptoms disappear with the onset of her menstrual cycle, when they are present, they are severe enough to interfere with her relationships and work activities. What's your call?

Look at premenstrual dysphoric disorder (PMDD). While premenstrual syndrome (PMS) and premenstrual dysphoric disorder are marked by the cyclic nature of symptoms that begin in the late luteal phase of the menstrual cycle and remit shortly after the onset of menstruation. PMDD is distinguished from PMS by the severity of symptoms, predominance of mood symptoms, and role dysfunction, particularly in personal relationships and marital/family relationships.1

About 3–9% of women of reproductive age meet the criteria for PMDD.2 In 2006, the Food and Drug Administration (FDA) gave approval to Yaz (Bayer HealthCare Pharmaceuticals, Wayne, NJ), an oral contraceptive with 24 days of active hormones and four days of placebo pills, for the treatment of emotional and physical symptoms of PMDD. The drug was approved for contraceptive use in March 2006.

Continuous use eyed

Researchers at the University of North Carolina at Chapel Hill (UNC) are studying the possible use of Yaz in a continuous dosing regimen to treat PMDD. The National Institute of Mental Health awarded researchers a $3 million grant to conduct the clinical trial.

The current trial is based on research conducted by David Rubinow, MD, the Asad Meymandi distinguished professor and chair of psychiatry in the UNC School of Medicine. Rubinow's earlier work indicates it is the change in, not the level of, reproductive hormones that triggers depression in women who are susceptible to PMDD.3 Women with the disorder do not have abnormal levels of reproductive hormones, but are more sensitive to the shifts in them that occur prior to menstruation, explains Rubinow. That sensitivity triggers mood symptoms, Rubinow notes.

During the trial, researchers will test three groups of 27 women for three months. One group will take a full 28-day dose of oral contraceptives continuously, while another takes the standard 21-7 regimen each month. A third group will be given a placebo. After the three months, researchers will measure hormone cycling, as well as metabolites of progesterone, which are involved in activating brain centers.

Continuous oral contraceptives potentially would benefit PMDD by stabilizing the levels of these hormones, explains Rubinow. Thus, after the initial administration, which would increase hormone levels and potentially precipitate symptoms, further symptoms should be prevented, he says. The way that oral contraceptives usually are given, with their pill-free intervals, would be expected to be ineffective in treating PMDD for that very reason, Rubinow believes.

Yaz contains drospirenone, a spironolactone antagonist that binds to the androgen receptor. Drospirenone does help with PMS/PMDD symptoms, says Mary Jane Minkin, MD, clinical professor in the Department of Obstetrics and Gynecology at the Yale University School of Medicine. Minkin presented on PMS, PMDD, and depression at the 2008 Contraceptive Technology seminar.4

Since premenstrual symptoms occur almost exclusively in ovulatory cycles, inhibiting ovulation could be expected to reduce or eliminate these symptoms, research indicates.5 Yaz's current shortened pill-free interval addresses this, Minkin observes.

She believes an extended cycle pill with drospirenone would work. Some providers already are using drospirenone-containing OCs in this off-label manner, Minkin reports.

[Review "Managing Premenstrual Symptoms," a quick reference guide for clinicians prepared by the Association of Reproductive Health Professionals (ARHP). To download a free guide, go to www.arhp.org. Click on "Publications & Resources," "Quick Reference Guides for Clinicians," and the publication title.]

References

  1. Steiner M, Pearlstein T, Cohen LS, et al. Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs. J Womens Health (Larchmt) 2006; 15:57-69.
  2. Freeman EW, Sondheimer SJ. Premenstrual dysphoric disorder: recognition and treatment. Primary Care Companion J Clin Psychiatry 2003; 5:30-39.
  3. Huo L, Straub RE, Roca C, et al. Risk for premenstrual dysphoric disorder is associated with genetic variation in ESR1, the estrogen receptor alpha gene. Biol Psychiatry 2007; 62:925-933.
  4. Minkin MJ. Mood Disorders in Women: PMS, PMDD and Depression. Presented at the 2008 Contraceptive Technology conference. Boston; March 2008.
  5. Sulak PJ. Ovulation suppression of premenstrual symptoms using oral contraceptives. Am J Manag Care 2005; 11(16 Suppl):S492–S497.