Promising Effects of Vitex Agnus-Castus on Quality of Life and Sexual Function in Premenopausal Relapsing Remitting Multiple Sclerosis Patients

Document Type : Original Article


1 Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2 Department of Toxicology and Pharmacology ,Faculty of Pharmacy and Pharmaceutical Sciences ,Islamic Azad University, Tehran Medical Sciences (IAUTMU),Tehran-Iran.

3 Loghman Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

5 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


Background and aims:Current therapeutic regimens are not able to solve hormonal imbalance in young multiple sclerosis (MS) women and the clinical benefits of hormone therapy in MS patients remain controversial. This open labeled pilot study was aimed to find the role of Vitex agnus-castus plant supplement daily regimen in serum testosterone level , Expanded Disability Status Scale (EDSS), sexual function and overall quality of life in premenopausal MS patients.
Methods: To achieve these goals, Molecular Docking on Vitex agnus-castus standard fruit extract constitutes performed and 30 eligible patients were selected for the clinical part of this study. Patients received two Vitagnus® film tablets in addition to their drugs for 90 days.
Results: Some plant extract components showed strong affinity to Androgen Receptor Ligand binding domain. Significant reduction in EDSS (1.839 vs.1.643, p=0.003) and significant elevation in serum testosterone levels [388.6(±0.16900) vs. 468. (±0.18144) 2ng/dL (p=0.026)] were also observed at the completion of the intervention. Menstrual irregularities disappeared in all 28 patients who completed this study. MSQL-54 criteria at the completion of study (day 91) showed lower stress levels, improved vitality/emotional health and normalized sexual activities without significant effect on sleep disorders and cognitive functions of patients. Vitex agnus-castus treatment by predictable AR LBD affinity improved the emotional state, sexual life, EDSS score and overall quality of life in premenopausal RRMS patients.
Conclusion: Our results suggest Vitagnus® film tablet as safe and promising supplement with some benefits in MS women who are suffering from disease induced emotional and sexual impairments.


1.Sex differences in outcomes of disease-modifying treatments for multiple sclerosis: A systematic review. Li R, Sun X, Shu Y, Mao Z, Xiao L, Qiu W, Lu Z, Hu X. 12, 2017, Mult Scler Relat Disord., pp. 23-28.
2.A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview. Marrie RA, Cohen J, Stuve O, Trojano M, Sørensen PS, Reingold S, Cutter G, Reider N. 3, 2016, Mult Scler. , Vol. 21, pp. 263-81.
3.Multiple sclerosis update. CE., Markowitz. 16 Suppl, 2013, Am J Manag Care. 2013, Vol. 19, pp. s294-300.
4.Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Olsson T, Barcellos LF, Alfredsson L. 1, 2017, Nat Rev Neurol. , Vol. 13, pp. 25-36.
5.Epidemiology of multiple sclerosis. Leray E, Moreau T, Fromont A, Edan G. 1, 2016, Rev Neurol (Paris). , Vol. 172, pp. 3-13.
6.Association between suicide and multiple sclerosis: An updated meta-analysis. Shen Q, Lu H, Xie D, Wang H, Zhao Q, Xu Y. 2019, Mult Scler Relat Disord., Vol. 34, pp. 83-90.
7.Life behind the mask”: Sexual life of Iranian women with multiple sclerosis. Dehghan-Nayeri N, Khakbazan Z, Ghafoori F. 2, 2018, Disabil Health J., Vol. 11, pp. 274-280. .
8.Sex-Based Differences in Multiple Sclerosis (Part I): Biology of Disease Incidence. Dunn SE, Lee H, Pavri FR, Zhang MA. 2015, Curr Top Behav Neurosci. , Vol. 26, pp. 29-56.
9.Androgen-Induced Immunosuppression. Gubbels Bupp MR, Jorgensen TN. 2018, Front Immunol. , Vol. 9, p. 794.
10.Suppressive effects of androgens on the immune system. Trigunaite A, Dimo J, Jørgensen TN. 2, 2015, Cell Immunol., Vol. 294, pp. 87-94.
11.The Level of Testosterone, Vitamin D, and Irregular Menstruation More Important than Omega-3 in Non-Symptomatic Women Will Define the Fate of Multiple Scleroses in Future. Tavakol S, Shakibapour S, Bidgoli SA. 1, 2018, Mol Neurobiol. , Vol. 55, pp. 462-469.
12.Sexual communication, sexual satisfaction, and relationship quality in people with multiple sclerosis. Valvano AK, Rollock MJD, Hudson WH, Goodworth MR, Lopez E, Stepleman L. 2, 2018, Rehabil Psychol., Vol. 63, pp. 267-275.
13.Vitex agnus castus for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Cerqueira RO, Frey BN, Leclerc E, Brietzke E. 6, 2017, Arch Womens Ment Health. , Vol. 20, pp. 713-719.
14.The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice. Nasri S, Oryan S, Rohani AH, Amin GR. 14, 2007, Pak J Biol Sci. , Vol. 10, pp. 2300-7.
15.Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation. Sehmisch S, Boeckhoff J, Wille J, Seidlova-Wuttke D, Rack T, Tezval M, Wuttke W, Stuermer KM, Stuermer EK. 6, 2009, Phytother Res., Vol. 23, pp. 851-8.
16.Pharmacological activities of Vitex agnus-castus extracts in vitro. Meier B, Berger D, Hoberg E, Sticher O, Schaffner W. 5, 2000, Phytomedicine., Vol. 7, pp. 373-81.
17.Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS. Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ. 2, 2006, J Ethnopharmacol. , Vol. 106, pp. 216-21.
18.Molecular docking simulation analysis of the interaction of dietary flavonols with heat shock protein 90. Singh SP, Deb CR, Ahmed SU, Saratchandra Y, Konwar BK. 2015, J Biomed Res. , p. 30.
19.Discovery of Novel Androgen Receptor Ligands by Structure-based Virtual Screening and Bioassays. Zhou W, Duan M, Fu W, Pang J, Tang Q, Sun H, Xu L, Chang S, Li D, Hou T. 6, 2018 , Genomics Proteomics Bioinformatics., Vol. 16, pp. 416-427.
20.A Validated HPTLC-Densitometric Method for Assay of Aucubin in Vitexagnus-castusL. Hajimehdipoor H, Shekarchi M, Piralihamedani M, Abedi Z, Zahedi H, Shekarchi M, Gohari AR. 4, 2011, Iran J Pharm Res., Vol. 10, pp. 705-10.
21.2017 McDonald diagnostic criteria: A review of the evidence. McNicholas N, Hutchinson M, McGuigan C, Chataway J. 2018, Mult Scler Relat Disord. , Vol. 24, pp. 48-54.
22.Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). JF., Kurtzke. 11, 1983, Neurology., Vol. 33, pp. 1444-52.
23.Assessment of plasma biomarkers for their association with Multiple Sclerosis progression. Jacob S, Al-Kandari A, Alroughani R, Al-Temaimi R. 2017, J Neuroimmunol. , Vol. 305, pp. 5-8.
24.The safety of testosterone therapy in women. Al-Imari L, Wolfman WL. 9, 2012, J Obstet Gynaecol Can., Vol. 34, pp. 859-865.
25.Androgen therapy in women: for whom and when. Pluchino N, Carmignani A, Cubeddu A, Santoro A, Cela V, Errasti T. 4, 2013, Arch Gynecol Obstet. , Vol. 288, pp. 731-7.
26.Testosterone therapy in premenopausal women. Kalantaridou SN, Calis KA. 2, 2006, Semin Reprod Med. , Vol. 24, pp. 106-14.
27.Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics. Collongues N, Patte-Mensah C, De Seze J, Mensah-Nyagan AG, Derfuss T. 6, 2018, Expert Rev Neurother. , Vol. 18, pp. 515-522.
28.The importance of studying sex differences in disease: The example of multiple sclerosis. Golden LC, Voskuhl R. 1-2, 23017, J Neurosci Res. 2017 Jan 2;95(1-2):, Vol. 95, pp. 633-643.
29.Multiple sclerosis and suicide. Feinstein A, Pavisian B. 7, 2017, Mult Scler. , Vol. 23, pp. 923-927.
30.G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids. Wang C, Liu Y, Cao JM. 9, 2014, Int J Mol Sci. , Vol. 15, pp. 15412-25.
31.Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics. Collongues N, Patte-Mensah C, De Seze J, Mensah-Nyagan AG, Derfuss T. 6, 2018, Expert Rev Neurother. , Vol. 18, pp. 515-522.