Comparing the Effect of Nigella sativa oil Soft Gel and Placebo on Oligomenorrhea, Amenorrhea and Laboratory Characteristics in Patients with Polycystic Ovarian Syndrome, a Randomized Clinical Trial

Document Type : Original paper

Authors

1 Department of Traditional Medicine, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Traditional Medicine and Materia Medica Research Center and Department of Traditional pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Medical clinic of Guilan University, Guilan University of Medical Sciences, Rasht, Iran.

Abstract

Background and objectives: Oligo-amenorrhea is one of the most common symptoms in poly cystic ovarian syndrome (PCOS) patients and Nigella sativa is a medicinal plant used in Iranian traditional medicine for the treatment of oligo-amenorrhea. The aim of this study was to evaluate the effect of N. sativa oil on oligo-amenorrhea in patients with PCOS. Methods: This study was a double-blinded placebo-controlled clinical trial conducted on 84 PCOS patients with oligo-amenorrhea. Patients were randomly assigned to intervention and placebo group. They used two soft gel capsules of N. sativa oil (500 mg, each capsule) or placebo at night for sixteen weeks. Four indices were used to assess menstruation; the interval between menstruations, duration of menstruation, the occurrence of menstruation and the severity of bleeding. The two groups were compared using analysis of covariance. Result: Fifty five patients completed the study (32 patients in N. sativa group and 23 patients in placebo group). The menstrual interval after the study in the intervention group (45 days, 95% CI) was significantly lower than the control group (86 days). The frequency of menstrual cycle in the intervention group (0.79) was significantly higher than the placebo group (0.48). No serious complication was reported in this clinical trial. Conclusion: findings suggest that N. sativa is an alternative treatment and could be useful for menstrual irregularities in women with PCOS. Further studies are recommended to find the exact mechanisms of N. sativa and its different derivatives.

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Main Subjects


[1] El Hayek S, Bitar L, Hamdar LH, Mirza FG2, Daoud G. Poly cystic ovarian syndrome: an updated overview. Front Physiol. 2016; 7(6): 124-132.
[2] Tracy L, Setji M, Ann J. Polycistic ovary syndrome; update on diagnosis and treatment.  Am J Med. 2014; 127(10): 912-919.
[3] Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004; 89(6): 2745-2749.
[4] Dewailly D, Hieronimus S, Mirakian P, Hugues JN. Polycystic ovary syndrome (PCOS). Annales D'endocrinologie. 2010; 71(1): 8-13.
[5] Brutocao CZaiem FAlsawas MMorrow ASMurad MHJaved A. Psychiatric disorders in women with polycystic ovary syndrome: a systematic review and meta-analysis. Endocrinology J. 2018; 62(2): 318-325
[6] Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2014; 6: 1-13.
[7] Yarnell E, Abascal K. Multiphasic herbal prescribing for menstruating women. Alternative Compl Ther. 2009; 15(3): 126-134.
[8] Emtiazy M, Keshavarz M, Khodadoost M, Kamalinejad M, Gooshahgir S, Bajestani HS, Hashem Dabbaghian F, Alizad M. Relation between body humors and hypercholesterolemia: an Iranian traditional medicine perspective based on the teaching of Avicenna. Iran Red Crescent Med J. 2012; 14(3): 133-138.
[9] Soleymani SA, Zargran AR. From food to drug: Avicenna,s perspective, a brief review. Res J Pharmacogn. 2018; 5(2): 65-69.
[10] Deena AS, Hussain M, Hossain M. Nigella sativa (black seed) is an effective herbal remedy for every disease except death -a prophetic statement which modern scientists confirm unanimously: a review. Adv Med Plant Res. 2016; 4: 27-57.
[11] Paarakh PM. Nigella sativa Linn- A comprehensive review. Int J Nurs Res Pract. 2010; 1(4): 409-429.
[12] Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Zoheir A. Damanhouri A, Anwar F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013; 3(5): 337-352.
[13] Ibn-e-Sina. Canon of Medicine (Al-Qanun fi-al-teb). Beirut: Syndicate of Publishers Union in Lebanon, 2005.
[14] Awad E, Austin D, Lyndon AR. Effect of black cumin seed oil (Nigella sativa) and nettle extract (quercetin) on enhancement of immunity in rainbow trout, Oncorhynchus mykiss (Walbaum). Aquaculture. 2013; 388-391: 193-197.
[15] Ismail M, AL-Nageeb G, Chan KW. Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats. Free Radic Biol Med. 2010; 48(5): 664-672.
[16] Boskabady MH, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomed. 2010; 17(10): 707-713.
[17] JrahHarzallah H, Kouidhi B, Flamini G, Bakhrouf A, Mahjoub T. Chemical composition, antimicrobial potential against cariogenic bacteria and cytotoxic activity of Tunisian Nigella sativa essential oil and thymoquinone. Food Chem. 2011; 129(4): 1469-1474.
[18] Kourosh HG, Latiff LA, Hanachi P, Lajis NH. Effect of unsaturated fatty acid ingredient of Nigella sativa (black seed) on human breast cancer cells. Clin Biochem. 2011; 44(13): 18-22.
[19] Hobbenaghi R, Javanbakht J, Sadeghzadeh S, Kheradmand D, Abdi FS, Jaberi MH, Mohammadiyan MR, Khadivar F, Mollaei Y. Neuroprotective effects of Nigella sativa extract on cell death in hippocampal neurons following experimental global cerebral ischemia-reperfusion injury in rats. J Neurol Sci. 2014; 337(1-2): 74-79.
[20] Ebru U,Burak U, Yusuf S, Reyhan B, Arif K, Faruk TH, Emin M, Aydin K, Atilla II, Semsettin S, Kemal E. Cardioprotective effects of Nigella sativa oil on cyclosporine A-induced cardiotoxicity in rats. Basic Clin Pharmacol Toxicol. 2008; 103(6): 574-580.
[21] Rizk FH, Ibrahim MAA, Abd-Elsalam MM, Soliman NA, Abd-Elsalam SM. Gastroprotective effects of montelukast and Nigella sativa oil against corticosteroid-induced gastric damage: they are much more than anti-asthmatic drugs. Can J Physiol Pharmacol. 2017; 95(6): 714-720.
[22] Tasawar Z, Zeshan S, Ahmad N, Lashari M. The effects of Nigella sativa (Kalonji) on lipid profile in patients with stable coronary artery disease in Multan, Pakistan. Pak J Nutr. 2011; 10(2): 162-167.
[23] Dehkordi F, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundame Clin Pharmacol. 2008; 22(4): 447-452.
[24] Mohtashami R, Amini M, Falah Hosseini H, Ghamarchehre M, Sadeqhi Z, Hajiagaee R, Fallah Huseini A. Blood glucose lowering effects of Nigella sativa L. seeds oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. J Med Plants. 2013; 12(47): 1-7.
[25] Najmi A, Nasriuddin M, Khan R, Haque SF. Therapeutic effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome. Int J Diabetes. 2008; 28(1): 11-14.
[26] Latiff LA, Dollah MA, Hanachi P, Rahman SA. A randomized control trial on the effect of black seeds (Nigella sativa) on climacteric symptoms and quality of life of perimenopausal women in Rawang, Selangor, Malaysia. Clin Biochem. 2011; 44(13): 20-21.
[27] Huseini HF, Kianbakht S, Mirshamsi MH, Zarch AB. Effectiveness of topical Nigella sativa seed oil in the treatment of cyclic mastalgia: a randomized, triple-blind, active, and placebo-controlled clinical trial. Planta Med. 2016; 82(4): 285-288.
[28] Zaoui A, Cherrah Y, Mahassini N, Alaoui K, Amarouch H, Hassar M. Acute and chronic toxicity of Nigella sativa fixed oil. Phytomed. 2002; 9(1): 69-74.
[29] Naeimi SA, Tansaz M, Sohrabvand F, Hajimehdipoor H, Nabimeybodi R, Saber S, Shakiba M, Rohani M.. Assessing the effect of processed Nigella sativa on oligomenorrhea and amenorrhea in patients with polycystic ovarian syndrome: A pilot study. Int J Pharm Sci Res. 2018; 9(11): 1000-1007.
[30] Higham JM, Obrien PMS, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990; 97(8): 734-739.
[31] Naftolin F, Stanburg MG. Phytostrogens: are they really estrogen mimics. Fertil Steril. 2002; 77(1): 15-17.
[32] Parhizkar S, Latif LA, Sabariah AR, Dollah MA. Evaluation of estrogen-like activity of Nigella sativa in ovariectomized rats. Afr J Pharm Pharmacol. 2011; 5(8): 1006-1011.
[33] Suzuki KM, Isohama Y, Maruyama H, Yamada Y, Narita Y, Ohta S, Araki Y, Miyata T, Mishima S. Estrogenic activities of fatty acids and a sterol isolated from royal jelly. Evid Base Complement Altern Med. 2008; 5(3): 295-302.
[34] Parhizkar S, Latif LA, Sabariah AR, Rashid I, Dollah M. In vivo estrogenic activity of Nigella sativa different extracts using vaginal cornification assay. J Med Plant Res. 2011; 5(32): 6939-6945.
[35] Intan NFS, Rashid I, Abdul Latif L, Dollah MA. Effect of Short-term supplementation of Nigella savita on estrogen level in ovariectomized rabbits. Proceeding of the 2nd seminar on veterinary sciences. 2007 Jan 15-19; Selangor, Malaysia.
[36] Mokaberinejad R, Zafarghandi N, Bioos S, Dabaghian FH, Naseri M, Kamalinejad M, Amin G, Ghobadi A, Tansaz M, Akhbari A, Hamiditabar M. Mentha longifolia syrup in secondary amenorrhea: a double-blind, placebo-controlled, randomized trials. Daru J Pharm Sci. 2012; 20(1): 1-8.
[37] Yavari M, Rouholamin S, Tansaz M, Bioos S, Esmaeili S. Sesame a treatment of menstrual bleeding cessation in Iranian traditional medicine: results from a pilot study. Shiraz E-Med J. 2014; 15(3): 1-4.
[38] Heidary M, Yazdanpanahi Z, Hossain Dabbaghmanesh M, Parsanezhad ME, Emamghoreish M, Akbarzadeh M. Effect of chamomile capsule on lipid- and hormonal-related parameters among women of reproductive age with polycystic ovary syndrome. J Res Med Sci. 2018; Article ID 29887901.
[39] Najaf M, Kasaian J, Kovatsi L, Leon G, KhaniSolout E, Hashemzaei M, Rezaee R, Modiramani P, Ghazanfarpour M. Phytoestrogens and the polycystic ovary syndrome: a systematic review of clinical evidence and laboratory findings. Farmacia. 2018; 66(2): 223-229.
[40] Shirsath A, Aundhakar N, Kamble P. Study of oxidative stress and antioxidant levels in polycystic ovarian. Int J Healthcare Biomed Res. 2015; 3(4): 16-24.
[41] Amini L, Tehranian N, Movahedin M, Tehrani FR, Ziaee S. Antioxidants and management of polycystic ovary syndrome in Iran: a systematic review of clinical trials. Iran J Reprod Med. 2015; 13(1): 1-8.
[42] Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytother Res.2000; 14(5): 323-328.
[43] Blagojevic IP, Ignjatovic S, Macut D, Kotur-Stevuljevic J, Bozic-Antic I, Vekic J, Bjekic-Macut J, Kastratovic-Kotlica B, Andric Z, Ilic D. Evaluation of a summary score for dyslipidemia, oxidative stress and inflammation (the doi score) in women with polycystic ovary syndrome and its relationship with obesity. J Med Biochem. 2018; 37(4): 1-11.
[44] Heshmati J, Nemati N. Effects of black seed (Nigella sativa) on metabolic parameters in diabetes melitus: a systematic review. Complement Ther Med. 2015; 23(2): 275-282.
[45] Kaatabi H, Bamosa AO, Lebda FM, Al Elq AH, Al-Sultan AI. Favorable impact of Nigella sativa seeds on lipid profile in type 2 diabetic patients. J Family Community Med. 2012; 19(3): 155-161.
[46] Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic b-cells of streptozotocin-induced diabetic rats. J Diabetes. 2010; 2(4): 256-266.
[47] DeLeo V, La Marca A, Ditto A, Morgante G, Cianci A. Effect of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome. Fertil Steril. 1999; 72(2): 282-285.