Selective progesterone receptor modulator may help treat premenstrual dysphoric disorder

Ulipristal acetate may be beneficial for treating premenstrual dysphoric disorder, according to results of a proof-of-concept randomized controlled trial published in American Journal of Psychiatry.

“Fluctuations in ovarian steroids, in particular progesterone, are thought to underlie the pathophysiology of [premenstrual dysphoric disorder],” Erika Comasco, PhD, of the department of neuroscience at Uppsala University in Sweden, and colleagues wrote. “Research in support of this include the temporal relationship with progesterone during the menstrual cycle, symptom relief during gonadotropin-releasing hormone (GnRH) agonist–induced anovulatory cycles, the reinstatement of symptoms when add-back progesterone (and estradiol) is administered together with GnRH agonists and findings of progestin-induced mood symptoms in postmenopausal women. The critical impact of acute variations in progesterone and estradiol on [premenstrual dysphoric disorder] symptoms further supports the pathophysiologic role of fluctuations in ovarian steroids in [premenstrual dysphoric disorder].”

The researchers sought to determine whether ulipristal acetate, a selective progesterone receptor modulator, can serve as a potential treatment for premenstrual dysphoric disorder. They included 95 women with premenstrual dysphoric disorder in the current investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial. They assigned participants to either 5 mg per day of ulipristal acetate or placebo during three 28-day treatment cycles. Change in premenstrual total score from baseline to end of treatment on the Daily Record of Severity of Problems (DRSP) served as the primary outcome. The researchers captured DRSP scores by daily ratings via a smartphone application and used linear mixed models to conduct analysis for repeated measures.

Results showed mean improvement in DRSP score after 3 months of 41% among the ulipristal acetate group vs. 22% among the placebo group, for a mean difference of 218%. Comasco and colleagues noted treatment effects for the DRSP depressive symptom subscale and the DRSP anger/irritability subscale, but not the DRSP physical symptom subscale. A total of 20 women (50%) in the ulipristal acetate group achieved remission based on DRSP score compared with eight women (21.1%) in the placebo group, which was a statistically significant difference.

“UPA is a promising drug for treatment of [premenstrual dysphoric disorder], particularly for the psychological symptoms associated with the syndrome and as an alternative pharmacologic treatment to antidepressants for patients who do not respond or cannot tolerate [SSRIs], the current standard of care,” the researchers wrote. “Moreover, the unique

mechanism of action of this study, namely, modulation of progesterone receptors, provides insights into the potential molecular mechanisms underlying [premenstrual dysphoric disorder] and its treatment.

“Further validating studies, as well as more reassuring information regarding the effect on liver function, are needed before this potentially highly effective treatment is made available to affected women,” they added.