Kashani L, Raisi F, Saroukhani S, et al. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: Randomized double-blind placebo-controlled study. Hum Psychopharmacol Clin Exp. 2012;28(1):54-60.
This study examined the safety and efficacy of saffron on selective serotonin reuptake inhibitor–induced sexual dysfunction. It was tested in a randomized double-blind placebo-controlled trial.
The participants were 34 women with major depression who were stabilized on fluoxetine (40 mg/day) for a minimum of 6 weeks and had experienced subjective feelings of sexual dysfunction. The women (M age=35.35 years) were randomly assigned to a saffron (30 mg/day, n=17) or a placebo control group (n=17) for 4 weeks.
Study Parameters Assessed
The measurements were performed at baseline, week 2, and week 4.
Primary Outcome Measures
The Female Sexual Function Index was used to assess sexual function. This index is a 19-question self-report questionnaire comprising the following 6 domains related to sexual function: desire, arousal, lubrication, orgasm, satisfaction, and pain. Side effects were systematically recorded during the course of the trial using a side-effect checklist.
At the end of the 4th week, the women in the saffron group had experienced significantly more improvements in their total Female Sexual Function Index score, as well as the arousal, lubrication, and pain domains compared to the placebo control group. No significant improvements, however, were evidenced for the desire, satisfaction, and orgasm domains. The frequency of side effects was similar between the saffron and placebo groups. The authors concluded that because the baseline data of the women were similar between the 2 groups, the beneficial effect observed in the saffron group may be attributed to the aphrodisiac effect of saffron.
Saffron, the dried stigmata (thread-like parts) of the flower Crocus sativus L., has a long history of use as a spice, coloring agent, and medicine. It takes about 75,000 saffron blossoms to produce a single pound of saffron spice, and it is largely cultivated and harvested by hand. Due to the amount of labor involved in harvesting, saffron is one of the world's most expensive spices. Apart from its traditional value as a spice and coloring agent, saffron has a long medical history spanning over 2,500 years.1 Modern in vitro and in vivo research provides validation of saffron as a potential medicinal plant, with studies indicating saffron has possible anticarcinogenic, antimutagenic, antioxidant, antidepressant, and memory-enhancing properties.2
Over the last 3 decades, more than 20 controlled and uncontrolled studies have been published examining saffron’s potential to lower the risk of several diseases and improve health conditions (eg, depression, premenstrual syndrome, Alzheimer’s disease) in human participants. Six studies have examined saffron's effects on sexual dysfunction (ie, 3 randomized controlled trials, 2 case series studies, 1 crossover study). Heidary et al conducted a case series study in which 52 nonsmoking infertile men were treated with 50 mg of saffron that was administered 3 times a week for 3 months. Semen analysis was conducted before and after treatment.3 The researchers found that saffron had positive effects on sperm morphology and motility in infertile men, but it did not increase sperm count.
In another case series design with a higher saffron dose (300 mg/day for 10 days), Shamsa et al found significant improvements in self-reported erectile dysfunction and nocturnal penile tumescence scores in 20 male patients with erectile dysfunction.4
Saffron may improve sexual function in men and women with major depression who are experiencing fluoxetine-induced sexual dysfunction.
In more rigorous study designs, however, positive aphrodisiac effects of saffron in male populations were not evidenced.5,6 For example, using an open-label, randomized, fixed-dose, crossover study, Safarinejad et al compared saffron (60 mg/day) to sildenafil (50 mg/day) in 307 men with erectile dysfunction.5 They found no beneficial effect of saffron administration for 12 weeks (30 mg/day) in men with erectile dysfunction. Similarly, in a larger-scale randomized clinical trial, no group differences were evidenced in semen parameters in 260 infertile men with idiopathic oligoasthenoteratozzspermia (OAT) who had taken 60 mg/day of saffron compared to placebo for 26 weeks.6
Finally, 2 studies have examined the effects of saffron supplementation for treating sexual issues in patients with major depression who have fluoxetine-induced sexual dysfunction. Modabbernia et al found that saffron supplementation (30 mg/day for 4 weeks) was efficacious in treating fluoxetine-related erectile dysfunction in married men with major depression whose depression had been stabilized on fluoxetine.7 The Kashani et al study reviewed for this article supports the results of Modabbernia et al regarding the efficacy and safety of saffron for treating sexual dysfunction and extends the study findings to women who have fluoxetine-induced sexual dysfunction.8 These 2 studies provide preliminary support that 30 mg/day of saffron supplementation may result in improvements in sexual function in men and women with major depression who are experiencing fluoxetine-induced sexual dysfunction. Of importance, the side effect profile of the saffron group was comparable to the placebo group in both of these studies. This safety finding is important because most pharmacotherapies for selective serotonin reuptake inhibitors (SSRI)-induced sexual impairment are associated with significant side effects, and some may even reverse the beneficial effects of SSRIs on mood. On the other hand, the antidepressant effects of saffron may be an additional advantage to its aphrodisiac effect, which makes it a potentially useful adjunct to SSRIs in the treatment of depression.
Although the studies reviewed have revealed sound scientific evidence for saffron as a possible sexual dysfunction treatment for men and women with major depression, the short duration, use of a single self-report measure, lack of specific data on saffron’s mechanism of action, and small sample sizes prevent us from drawing firm conclusions about the effects on saffron treating sexual dysfunction in this special population. In short, while findings of improved sexual function combined with excellent short-term safety point to a promising future, there is no way to know if these findings regarding saffron supplementation will translate into long-term health benefits until well-controlled studies are performed. Larger-scale studies with multi-site trials are needed to elucidate saffron’s potential role and mechanisms of action for the treatment of sexual dysfunction, in particular with men and women with fluoxetine-induced sexual dysfunction.
- Moghaddasi MS. Saffron chemicals and medical usage. J of Med Plants Res. 2010;4(6):427-430.
- Srivastava R, Ahmed H, Dixit RK, Dharamveer, Saraf SA. Crocus sativus L.: A comprehensive review. Parmacogn Rev. 2010;4(8): 200-08.
- Heidary M, Nejadi JR, Delfan B, et al. Effect of saffron on semen parameters of infertile men. Urol J. 2008;5(4):255-259.
- Shamsa A, Hosseinzadeh H, Molaei M,Shakeri MT, Rajabi O. Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: A pilot study. Phytomedicine. 2009;16(8):690-693.
- Safarinejad MR, Shafiei N, Safarinejad S. An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for treating erectile dysfunction in men naïve to treatment. Int J Impot Res. 2010;22(4):249-250.
- Safarinejad MR, Shafiei N, Safarinejad S. A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. Phytother Res. 2011;25(4):508-516.
- Modabbernia A, Sohrabi H, Nasehi AA, et al. Effect of saffron on fluoxetine-induced sexual impairment in me: Randomized double-blind placebo-controlled trial. Psychopharmacology. 2012; 223(4):381-388.
- Kashani L, Raisi F, Saroukhani S, et al. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: Randomized double-blind placebo-controlled study. Hum Psychopharmacol Clin Exp. 2012;28(1):54-60.