Crocus sativus (saffron) in the treatment of female sexual dysfunction: a three-center, double-blind, randomized, and placebo-controlled clinical trial

Document Type : Original Research Article

Authors

1 Infertility Ward, Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Canada

Abstract

Objective: One of the traditional aphrodisiacs used in various cultures is Crocus sativus, commonly called saffron. Previous studies have pointed to the possible applicability of saffron for sexual dysfunction in both men and women. This study investigates the effects of saffron capsules on female sexual dysfunction.
Materials and Methods: This study was a parallel-group, double-blind, randomized, placebo-controlled clinical trial. Participants, who were married women between 18 and 55 years of age suffering from severe sexual dysfunction, were randomized to receive either 15 mg Crocus sativus capsules twice daily or placebo. The treatment continued for 6 weeks, and patients were evaluated every 2 weeks. The primary outcome was the change in the female sexual function index score. Other outcomes included the female sexual function index sub-domains.
Results: Seventy-four patients were equally randomized to each group, and 34 in each group completed the trial. Participants in both groups experienced improved total scores at each visit. However, a repeated-measures ANOVA revealed that time ´ treatment differed between groups in favor of the saffron group (p=0.050). During the 6th week follow-up, the saffron group had a 62% score improvement from baseline. Desire, lubrication, and satisfaction were female sexual function index domains in which saffron demonstrated superiority over placebo. The adverse event profile was similar for the groups, and no participant discontinued treatment.
Conclusion: Findings of this study suggest that saffron might be a safe and effective option to ameliorate female sexual dysfunction. Further robust research is warranted.

Keywords


Abedimanesh N, Ostadrahimi A, Bathaie SZ,
Abedimanesh S, Motlagh B, Asghari
Jafarabadi M, Taban Sadeghi M. 2017.
Effects of saffron aqueous extract and its
main constituent, crocin, on health-related
quality of life, depression, and sexual
desire in coronary artery disease patients: a
double-blind, placebo-controlled,
randomized clinical trial. Iran Red
Crescent Med J, 19: 1-8.
Agha-Hosseini M, Kashani L, Aleyaseen A,
Ghoreishi A, Rahmanpour H, Zarrinara
AR, Akhondzadeh S. 2008. Crocus sativus
L. (saffron) in the treatment of
premenstrual syndrome: a double-blind,
randomised and placebo-controlled trial.
BJOG, 115: 515-519.
Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi A-H, Abbasi SH,
Akhondzadeh S. 2007. Comparison of
petal of Crocus sativus L. and fluoxetine
in the treatment of depressed outpatients: a
pilot double-blind randomized trial. Prog
Neuropsychopharmacol Biol Psychiatry,
31: 439-442.
Akhondzadeh S, Fallah-Pour H, Afkham K,
Jamshidi A-H, Khalighi-Cigaroudi F.
2004. Comparison of Crocus sativus L.
and imipramine in the treatment of mild to
moderate depression: a pilot double-blind
randomized trial [ISRCTN45683816].
BMC Complement Altern Med, 4: 12.
Akhondzadeh S, Mostafavi S-A, Keshavarz
SA, Mohammadi MR, Hosseini S,
Eshraghian MR. 2020. A placebo
controlled randomized clinical trial of
Crocus sativus L. (saffron) on depression
and food craving among overweight
women with mild to moderate depression.
J Clin Pharm Ther, 45: 134-143.
Akhondzadeh S, Sabet MS, Harirchian MH,
Togha M, Cheraghmakani H, Razeghi S,
Hejazi SS, Yousefi MH, Alimardani R,
Jamshidi A, Zare F, Moradi A. 2010.
Saffron in the treatment of patients with
mild to moderate Alzheimer’s disease: a
16-week, randomized and placebocontrolled trial. J Clin Pharm Ther, 35:
581-588.
Akhondzadeh S, Tahmacebi-Pour N, Noorbala
A-A, Amini H, Fallah-Pour H, Jamshidi
A-H, Khani M. 2005. Crocus sativus L. in
the treatment of mild to moderate
depression: a double-blind, randomized
and placebo-controlled trial. Phytother
Res, 19: 148-151.
American Psychiatric Association. 2013.
Diagnostic and statistical manual of
mental disorders: DSM-5. 5th edn.
Washington, D.C.: American Psychiatric
Publishing.
Basson R, Berman J, Burnett A, Derogatis L,
Ferguson D, Fourcroy J, Goldstein I,
Graziottin A, Heiman J, Laan E, Leiblum
S, Padma-Nathan H, Rosen R, Segraves K,
Segraves RT, Shabsigh R, Sipski M,
Wagner G, Whipple B. 2001. Report of
the International Consensus Development
Conference on female sexual dysfunction:
definitions and classifications. J Sex
Marital Ther, 27: 83-94.
Basson R, Gilks T. 2018. Women’s sexual
dysfunction associated with psychiatric
disorders and their treatment. Womens
Health (Lond), 14: 1-16.
Brown AD, Blagg J, Reynolds DS. 2007.
Designing drugs for the treatment of
female sexual dysfunction. Drug Discov
Today, 12: 757-766.
Fakhri A, Pakpour AH, Burri A, Morshedi H,
Zeidi IM. 2012. The female sexual
function index: translation and validation
of an Iranian version. J Sex Med, 9: 514-
523.
Frohlich P, Meston C. 2002. Sexual
functioning and self-reported depressive
symptoms among college women. J Sex
Res, 39: 321-325.
Goldstein I. 2008. Sexual dysfunction in
women: what can urologists contribute?
Curr Urol Rep, 9: 475-482.
Graziottin A, Serafini A, Palacios S. 2009.
Aetiology, diagnostic algorithms and
prognosis of female sexual dysfunction.
Maturitas, 63: 128-134.
Hayes RD, Bennett CM, Fairley CK,
Dennerstein L. 2006. What can prevalence
studies tell us about female sexual
difficulty and dysfunction? J Sex Med, 3:
589-595.
Hensley PL, Nurnberg HG. 2002. SSRI sexual
dysfunction: a female perspective. J Sex
Marital Ther, 28 Suppl 1: 143-153.
Hosseinzadeh H, Jahanian Z. 2010. Effect of
Crocus sativus L. (saffron) stigma and its
constituents, crocin and safranal, on
morphine withdrawal syndrome in mice.
Phytother Res, 24: 726-730.
Saffron for female sexual dysfunction
AJP, Vol. 12, No. 3, May-Jun 2022 267
Hosseinzadeh H, Younesi HM. 2002.
Antinociceptive and anti-inflammatory
effects of Crocus sativus L. stigma and
petal extracts in mice. BMC Pharmacol, 2:
1-8.
Hosseinzadeh H, Ziaee T, Sadeghi A. 2008.
The effect of saffron, Crocus sativus
stigma, extract and its constituents,
safranal and crocin on sexual behaviors in
normal male rats. Phytomedicine, 15: 491-
495.
Imprialos KP, Stavropoulos K, Doumas M,
Tziomalos K, Karagiannis A, Athyros VG.
2018. Sexual dysfunction, cardiovascular
risk and effects of pharmacotherapy. Curr
Vasc Pharmacol, 16: 130-142.
Jackson G. 1999. Sexual dysfunction and the
cardiac patient--no room for gender bias.
Int J Clin Pract, 53: 411-411.
Kashani L, Raisi F, Saroukhani S, Sohrabi H,
Modabbernia A, Nasehi A-A., Jamshidi A,
Ashrafi M, Mansouri P, Ghaeli P,
Akhondzadeh S. 2013. Saffron for
treatment of fluoxetine-induced sexual
dysfunction in women: randomized
double-blind placebo-controlled study.
Hum Psychopharmacol, 28: 54-60.
Kostis JB, Jackson G, Rosen R, BarrettConnor E, Billups K, Burnett AL, Carson
C, Cheitlin M, Debusk R, Fonseca V,
Ganz P, Goldstein I, Guay A,
Hatzichristou D, Hollander JE, Hutter A,
Katz S, Kloner RA, Mittleman M,
Montorsi F, Montorsi P, Nehra A,
Sadovsky R, Shabsigh R. 2005. Sexual
dysfunction and cardiac risk (the Second
Princeton Consensus Conference). Am J
Cardiol, 96: 313-321.
Lo SS-T, Kok W-M. 2018. Prevalence and risk
factors for sexual problems and distress in
chinese unmarried young women: an
observational study. J Sex Med, 15: 1620-
1628.
Lodise NM. 2017. Female sexual dysfunction:
a focus on flibanserin. Int J Womens
Health, 9: 757-767.
Mahmoud OE, Ahmed AR, Arafa AE. 2018.
Patterns of female sexual dysfunction in
premenopausal women with moderate to
severe depression in Beni-Suef, Egypt.
Middle East Fertil Soc J, 23: 501-504.
Milajerdi A, Jazayeri S, Shirzadi E,
Hashemzadeh N, Azizgol A, Djazayery A,
Esmaillzadeh A, Akhondzadeh S. 2018.
The effects of alcoholic extract of saffron
(Crocus satious L.) on mild to moderate
comorbid depression-anxiety, sleep
quality, and life satisfaction in type 2
diabetes mellitus: a double-blind,
randomized and placebo-controlled
clinical trial. Complement Ther Med, 41:
196-202.
Miller MK, Smith JR, Norman JJ, Clayton
AH. 2018. Expert opinion on existing and
developing drugs to treat female sexual
dysfunction. Expert Opin Emerg Drugs,
23: 223-230.
Mitchell KR, Mercer CH, Ploubidis GB, Jones
KG, Datta J, Field N, Copas AJ, Tanton C,
Erens B, Sonnenberg P, Clifton S,
Macdowall W, Phelps A, Johnson AM,
Wellings K. 2013. Sexual function in
Britain: findings from the third National
Survey of Sexual Attitudes and Lifestyles
(Natsal-3). Lancet, 382: 1817-1829.
Ranjbar H, Ashrafizaveh A. 2019. Effects of
saffron (Crocus sativus) on sexual
dysfunction among men and women: a
systematic review and meta-analysis.
Avicenna J Phytomed, 9: 419-427.
Rosen R, Brown C, Heiman J, Leiblum S,
Meston C, Shabsigh R, Ferguson D,
D’Agostino R Jr. 2000. The female sexual
function index (FSFI): a multidimensional
self-report instrument for the assessment
of female sexual function. J Sex Marital
Ther, 26: 191-208.
Rosen RC. 2002. Assessment of female sexual
dysfunction: review of validated methods.
Fertil Steril, 77: 89-93.
Rosman L, Cahill JM, McCammon SL, Sears
SF. 2014. Sexual health concerns in
patients with cardiovascular disease.
Circulation, 129: e313-e316.
Shamsa A, Hosseinzadeh H, Molaei M,
Shakeri MT, Rajabi O. 2009. Evaluation
of Crocus sativus L. (saffron) on male
erectile dysfunction: a pilot study.
Phytomedicine, 16: 690-693.
Shifren JL, Monz BU, Russo PA, Segreti A,
Johannes CB. 2008. Sexual problems and
distress in United States women:
prevalence and correlates. Obstet Gynecol,
112: 970-978.
Tabaghdehi MH, Keramat A, Khosravi A.
2017. Prevalence of female sexual
dysfunction in Iran: a meta-analysis study.
International Journal of Health Studies, 2:
10-13.
Waldinger MD. 2015. Psychiatric disorders
Kashani et al.
AJP, Vol. 12, No. 3, May-Jun 2022 268
and sexual dysfunction. Handb Clin
Neurol, 130: 469-489.
Wilson LA, Wayman CP, Jackson VM. 2009.
Neuropeptide modulation of a lumbar
spinal reflex: potential implications for
female sexual function. J Sex Med, 6: 947-
957.