Reviewed: Agha-Hosseini M, Kashani L, Aleyaseen A, et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomized and placebo-controlled trial. BJOG. 2008;115(4):515-519.

Premenstrual syndrome (PMS), characterized by mood and behavioral changes, is among the most common health problems reported by women of reproductive age. Although the etiology is not fully understood, the symptoms of PMS are suggested to be partly associated with changes in the production of the neurochemical serotonin. Manufactured in the brain from the amino acid tryptophan, serotonin is involved in mood stability.

Clinical trials have indicated that saffron (dried stigma of Crocus sativus, Iridaceae) is effective in the treatment of mild to moderate depression via serotonergic mechanisms. The aim of this randomized, double-blind, placebo-controlled trial was to investigate whether saffron could relieve symptoms of PMS.

The saffron used in this study was identified by the Department of Cultivation and Development, Institute of Medicinal Plants, Tehran, Iran. Dried, ethanolic extracts of the stigma of C. sativus were encapsulated, with each capsule containing 15 mg of saffron extract. Women aged 20 to 45 years with regular menstrual cycles and PMS symptoms for at least 6 months were randomly assigned to receive placebo or 30 mg of saffron extract per day (15 mg twice a day) for 2 menstrual cycles (cycles 3 and 4). This daily dose of saffron was based on previous studies demonstrating an antidepressant effect of saffron extract in the treatment of depression conducted by one of the authors, Professor S. Akhondzadeh.

Women underwent screening in cycle 1. To complete baseline measurements, they returned for a second visit at the end of cycle 2 (premenstrual stage-as close as possible to 2 days prior to the onset of menstruation). Daily symptom ratings were completed through-out the duration of the trial (cycles 1-4). Participants returned for 2 more visits for depression ratings by a psychiatrist (at the premen-strual stage of cycles 3 and 4). The effect of treatment was assessed by comparing baseline (cycle 2) scores from the Premenstrual Daily Symptom Report (DSR) and the Hamilton Depression Rating Scale (HDRS) with the premenstrual scores after 2 cycles of treatment with intervention (cycles 3 and 4).

A total of 50 women were randomized in the trial (25 women in each group). Three women discontinued the trial due to personal reasons (1 from the saffron group and 2 from the placebo group). No significant differences were identified between women in the saffron or placebo groups with regard to basic demographics. Furthermore, there were no significant baseline differences between the 2 groups in DSR ratings or HDRS scores.

During cycles 3 and 4, the women in the saffron group demonstrated a significant improvement as compared with the placebo group in the DSR ratings (P<0.001) and in the HDRS scores (P<0.001). The authors defined a responder as a woman showing 50% reduction in severity of symptoms. With respect to the DSR ratings, the number of responders were 19 (76%) in the saffron group and 2 (8%) in the placebo group (P<0.0001). Likewise, for the HDRS scores, there were 15 (60%) responders in the saffron group and 1 (4%) in the placebo group (P<0.0001).

In general, the adverse events were dispersed evenly between the saffron and placebo groups. However, appetite changes and headache occurred more in the saffron group, albeit these differences were not significant. None of adverse effects were severe.

The results of this study suggest that saffron extract may be effective in the treatment of PMS. However, because this is likely the first published study of saffron in the treatment of PMS, it is not possible to draw any comparisons with other studies. The authors suggest that the tolerable adverse effect profile of saffron may suggest the application of saffron as an alternative treatment for PMS. Further studies are warranted and should include different doses of saffron, a larger number of participants, and inclusion of a follow-up period. In addition, a comparison study using a known agent (i.e., fluoxetine [Prozac_®]) that works via the serotonergic system would help delin-eate any serotonergic-related mechanisms of action by saffron.

-Jennifer Minigh, PhD