Comparison of the effects of Ginger extract with clomiphene citrate on sex hormones in rats with polycystic ovarian syndrome

Shekoufeh Atashpour, Hossein Kargar Jahromi, Zahra Kargar Jahromi, Mozhgan Maleknasab


Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women which affect fertility. Clomiphene citrate is used as first-line treatment for this disorder, which is associated with some complications and therapeutic resistance. Objective: In this research, we compare the effectiveness of ginger with clomiphene on sexual hormones such as Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), estrogen and progesterone in order to treat PCOS effectively with fewer side effects. Materials and Methods: In this experimental study, 63 adult female rats (170-200 gr) were studied and divided randomly into 9 groups as control (not received any interventional substance for 60 and 89 days), sham (were given distilled water and ethyl alcohol intraperitoneally daily for 60 and 89 days), and 7 experimental groups receiving estradiol valerate (PCOS inducing agent, intramuscular) alone and with 100 mg/kg clomiphene or different doses of ginger extract (175 and 350 mg/kg) orally daily for 60 and 89 days. Sexual hormones were analyzed and compared in different groups. Results: Our results showed that in the PCOS-induced group, LH and estrogen concentration increased while progesterone and FSH concentration decreased remarkably (p<0.05) as compared to control group. Furthermore, in groups receiving clomiphene and ginger extract, we demonstrated significant (p<0.05) improvement in hormonal secretion as compared to the PCOS-induced group. Clomiphene, compared with the lower dose of ginger extract, had a better improving effect on balancing sexual hormones in PCOS. Moreover, ginger extract at higher doses has better effects in improving PCOS. Conclusion: As the long-term administration of clomiphene citrate has some side effects, the use of ginger as a herbal medicine without any side effects at high doses can be an effective and good alternative in improving PCOS.


Ginger, Clomiphene citrate, Polycystic ovarian syndrome


Gerli S, Gholami H, Manna C, Di Frega AS, Vitiello C, Unfer V. Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study. Fertil Steril 2000; 73: 85-89.

Madankumar R, Tsang J, Lesser ML, Kenigsberg D, Brenner S. Clomiphene citrate induced ovulation and intrauterine insemination: effect of timing of human chorionic gonadotropin injection in relation to the spontaneous LH surge on pregnancy rates. J Assist Reprod Genet 2005; 22: 155-159.

Van Santbrink EJ, Hop WC, Fauser BC. Classification of normogonadotropic infertility: polycystic ovaries diagnosed by ultrasound versus endocrine characteristics of polycystic ovary syndrome. Fertil Steril 1997; 67: 452-458.

Berek JS. Berek & Novak's Gynecology. 14th Ed. Philadelphia, Lippincott Williams & Wilkins; 2005.

Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 7th Ed. Philadelphia, Lippincott Williams & Wilkins; 2005a.

Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and infertility. 7th Ed. Philadelphia, Lippincott Williams & Wilkins; 2005b.

Biljan MM, Mahutte NG, Tulandi T, Tan SL. Prospective randomized double-blined Trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs. Fertil Steril 1999; 71: 633-638.

Mitwally MF, Casper RF. Aromatase inhibitors in ovaulation induction. Semin Reprod Med 2004; 22: 61-78.

Li Y, Tran VH, Duke CC, Roufogalis BD. Preventive and protective properties of zingiber officinale (ginger) in diabetes mellitus, diabetic complications, and associated lipid and other metabolic disorders: a brief review. Evid Based Complement Alternat Med 2012; 2012: 516870.

Desmet PGM. Advrse effect of herbel drugs. Germany, springer- verlag belin hedel berg, 1997: 215-228.

Khahi A, Nouri M, Fathi Azad F, Khaki AF. Evaluation of zingiber officinalis and allium cepa on spermatogenesis in rat. Med J Tabriz Univ Med Sci 2008; 30: 53-58.

Mohammadi F, Nikzad H, Taghizadeh M, Taherian A, Azami-Tameh A, Hosseini SM, et al. Protective effect of zingiber officinale extract on rat testis after cyclophosphamide treatment. Andrologia 2014; 46: 680-686.

Awang K, Ibrahim H, Rosmy Syamsir D, Mohtar M, Mat Ali R, Azah Mohamad Ali N. Chemical constituents and antimicrobial activity of the leaf and rhizome oils of alpinia pahangensis ridl., an endemic wild ginger from peninsular malaysia. Chem Biodivers 2011; 8: 668-673.

Dedov VN, Tran VH, Duke CC, Connor M, Christie MJ, Mandadi S, et al. Gingerols: a novel class of vanilloid receptor (VR1) agonists. Br J Pharmacol 2002; 137: 793-798.

Rahnama P, Montazeri A, Fallah-huseini H, Mohammadi K, Modares M, Khajavi S. The effects of

Atashpour et al

International Journal of Reproductive BioMedicine Vol. 15. No. 9. pp: 561-568, September 2017

zingiber officinal R. on primary dysmenorrhea. J Med Plants 2010; 9: 81-86.

Ness RB, Grisso JA, Cottreau C, Klapper J, Vergona R, Wheeler JE, et al. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer. Epidemiology 2000; 11: 111-117.

Shalaby MA, Hamowieh AR. Safety and efficacy of zingiber officinale roots on fertility of male diabetic rats. Food Chem Toxicol 2010; 48: 2920-2924.

Hafez DA. Effect of extracts of ginger goots and cinnamon bark on fertility of male diabetic rats. J Am Sci 2010; 6: 940-947.

Farzin D, Fathiazad F, Fazellian M. Antidepressant effect of methanolic ginger extract in diabetic mice using forced-swim test. J Mazand Univ Med Sci 2013; 23 :208-220.

DuRant EM, Leslie NS, Critch EA. Managing polycystic ovary syndrome: a cognitive behavioral strategy. Nurs Womens Health 2009; 13: 292-300.

Arif M, Thakur SC, Datta K. Implication of thymoquinone as a remedy for polycystic ovary in rat. Pharm Biol 2016; 54: 674-685.

Karampoor P, Azarnia M, Mirabolghasemi G, Alizadeh F. The effect of hydroalcoholic extract of fennel (foeniculum vulgare) seed on serum levels of sexual hormones in female wistar rats with polycystic ovarian syndrome (PCOS). Arak Med Univ J 2014; 17: 70-78.

Requena A, Herrero J, Landeras J, Navarro E, Neyro JL, Salvador C, et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update 2008; 14: 571-582.

Loffler S, Aust G, Kohler U, Spanel-Borowski K. Evidence of leptin expression in normal and polycystic human ovaries. Mol Hum Reprod 2001; 7: 1143-1149.

Kratzsch J, Lammert A, Bottner A, Seidel B, Mueller G, Thiery J, et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab 2002; 87: 4587-4594.

Kerin JF, Liu JH, Phillipou G, Yen SS. Evidence for a hypothalamic site of action of clomiphene citrate in women. J Clin Endocrinol Metab 1985; 61: 265-268.

Dickey RP, Olar TT, Taylor SN, Curole DN, Rye PH. Sequential clomiphene citrate and human menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotrophin alone. Hum Reprod 1993; 8: 56-59.

Yarali H, Yildiz BO, Demirol A, Zeyneloglu HB, Yigit N, Bukulmez O, et al. Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. Hum Reprod 2002; 17: 289-294.

Brown J, Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst Rev 2016; 12: CD002249.

Misso ML, Teede HJ, Hart R, Wong J, Rombauts L, Melder AM, et al. Status of clomiphene citrate and metformin for infertility in PCOS. Trends Endocrinol Metab 2012; 23: 533-543.

Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 2008; 46: 409-420.

Mokhtary M, Ebrahimpoor MR, Harfsheno S. The effects of alcoholic extract of marrubum vulgare on hormonal parameters in female rat model of polycystic ovarian syndrome. Med Sci J Islam Azad Univ Tehran Med 2014; 24: 74-80.

Jelodar G, Karami E. Effect of Hydroalcoholic Extract of Vitex Agnus-Castus Fruit on Ovarian Histology in Rat with Induced Polycystic Ovary Syndrome (PCOS). J Babol Univ Med Sci 2013; 15: 96-102.

Milewicz A, Gejdel E, Sworen H, Sienkiewicz K, Jedrzejak J, Teucher T, et al. vitex agnus castus extracted in the treatment of luteal phase defect due to latent hyperprolactinemia. Arzneimittelforschung 1993; 43: 752-756.

Liu J, Burdette JE, Sun Y, Deng S, Schlecht SM, Zheng W, et al. Isolation of linoleic acid as an estrogenic compound from the fruits of vitex agnus-castus L. (chaste-berry). Phytomedicine 2004; 11: 18-23.

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