Cover Image

Effect of Aslagh Capsule, a Traditional Compound Herbal Product on Oligomenorrhea in Patients with Polycystic Ovary Syndrome: A Three-Arm, Open-label, Randomized, Controlled Trial

Maryam Bahman, Homa Hajimehdipoor, Soodabeh Bioos, Fataneh Hashem-Dabaghian, Maryam Afrakhteh, Mojgan Tansaz

Background: Oligomenorrhea is a common complaint in patients with polycystic ovary syndrome (PCOS). There are some useful medicinal recommendations such as Aslagh product (include fennel fruits, carrot seeds, chaste tree fruits) in Iranian traditional medicine for the treatment of oligomenorrhea in PCOS. Hence, the present investigation was designed to compare Aslagh capsule with metformin on the oligomenorrhea. Materials and Methods: One hundred fifty women aged between 18-43 years with oligomenorrhea due to PCOS were randomly divided into Aslagh, metformin, and Aslagh + metformin groups. The occurrence of menstrual bleeding was considered as the primary outcome. Menstrual cyclicity, duration, and volume of the bleeding were also evaluated. Results: Occurrence of menstrual bleeding was 87.2% in all patients, with no significant difference between the three groups (P> 0.05). Menstrual cyclicity significantly improved from baseline in Aslagh and Aslagh+ metformin groups (P=0.02). Duration of menstrual bleeding was significantly higher in Aslagh group in the first and the second menstrual bleeding cycle compared to the other two groups (P<0.05). No significant change was observed in the volume of the bleeding after the intervention in any of the three groups. The occurrence of menstrual bleeding in Aslagh group was significantly (P=0.03) higher than the other two groups in the fourth month (drug-free period). Conclusion: Aslagh capsule showed beneficial effects similar to metformin in the treatment of oligomenorrhea in PCOS women and could be suggested for use as an alternative treatment in these patients. [GMJ.2019;8:e1261]

Aslagh; Polycystic Ovary Syndrome; Iranian Traditional Medicine; Vitex; Oligomenorrhe

Harborne L, Fleming R, Lyall H, Norman J, Sattar N. Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. Lancet. 2003;361(9372):1894-901.

https://doi.org/10.1016/S0140-6736(03)13493-9

Boyle J, Teede HJ. Polycystic ovary syndrome - an update. Aust Fam Physician. 2012;41(10):752-6.

PMid:23210095

Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC Complement Altern Med. 2014;14:511.

https://doi.org/10.1186/1472-6882-14-511

PMid:25524718 PMCid:PMC4528347

Hahn S, Janssen OE, Tan S, Pleger K, Mann K, Schedlowski M et al. Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome. Eur J Endocrinol. 2005;153(6):853-60.

https://doi.org/10.1530/eje.1.02024

PMid:16322391

Hart R, Hickey M, Franks S. Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):671-83.

https://doi.org/10.1016/j.bpobgyn.2004.05.001

PMid:15380140

Balen AH, Conway GS, Kaltsas G, Techatrasak K, Manning PJ, West C et al. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod. 1995;10(8):2107-11.

https://doi.org/10.1093/oxfordjournals.humrep.a136243

PMid:8567849

Chang RJ, Nakamura RM, Judd HL, Kaplan SA. Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab. 1983;57(2):356-9.

https://doi.org/10.1210/jcem-57-2-356

PMid:6223044

Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab. 1997;82(12):4075-9.

PMid:9398716

De Leo V, Musacchio MC, Palermo V, Di Sabatino A, Morgante G, Petraglia F. Polycystic ovary syndrome and metabolic comorbidities: therapeutic options. Drugs Today (Barc). 2009;45(10):763-75.

https://doi.org/10.1358/dot.2009.45.10.1429463

Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1-13.

https://doi.org/10.2147/CLEP.S37559

PMid:24379699 PMCid:PMC3872139

Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet. 2003;361(9371):1810-2.

https://doi.org/10.1016/S0140-6736(03)13409-5

Eisenhardt S, Schwarzmann N, Henschel V, Germeyer A, Von Wolff M, Hamann A et al. Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial. Int J Clin Endocrinol Metab. 2006;91(3):946-52.

https://doi.org/10.1210/jc.2005-1994

PMid:16352680

Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol. 1998;138(3):269-74.

https://doi.org/10.1530/eje.0.1380269

PMid:9539300

Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002;87(2):569-74.

https://doi.org/10.1210/jcem.87.2.8261

PMid:11836287

Sills ES, Perloe M, Tucker MJ, Kaplan CR, Genton MG, Schattman GL. Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports. BMC Womens Health. 2001;1(1):3.

https://doi.org/10.1186/1472-6874-1-3

PMid:11545683 PMCid:PMC55341

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356(6):551-66.

https://doi.org/10.1056/NEJMoa063971

PMid:17287476

Ibn-e-sina A. Al-Qanun fit-tib (The canon Of medicine). Beirut: Alaalami Beirut library: Press; 2005.

Salehi M, Setayesh M, Mokaberinejad R. Treatment of Recurrent Ovarian Cysts and Primary Infertility by Iranian Traditional Medicine: A Case Report. J Evid Based Complementary Altern Med. 2016;22(3):374-7.

https://doi.org/10.1177/2156587216681937

PMid:27932523 PMCid:PMC5871164

Farzana A, Umraz M, Humyra T, Hina R. Physiological perspective of Hirsutism in Unani Medicine: An Overview and Update. Int J Herb Med. 2013;1(3):79-85.

Firdose KF, Shameem I. An approach to the management of poly cystic ovarian disease in Unani system of medicine: A review. Int j appl res. 2016;2(6):585-90.

Nagarathna P, Rajan PR, Koneri R. A detailed study on poly cystic ovarian syndrome and it's treatment with natural products. Int J Toxicol Pharmacol Res. 2014;5(4):109-20.

Nazem E. Darooname tooba. Tehran: Almaii; 2011.

van Die MD, Burger HG, Teede HJ, Bone KM. Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials. Planta Med. 2013;79(7):562-75.

PMid:23136064

Momoeda M, Sasaki H, Tagashira E, Ogishima M, Takano Y, Ochiai K. Efficacy and Safety of Vitex agnus-castus Extract for Treatment of Premenstrual Syndrome in Japanese Patients: A Prospective, Open-label Study. Adv Ther. 2014;31(3):362-73.

https://doi.org/10.1007/s12325-014-0106-z

PMid:24604699

Bergmann J, Luft B, Boehmann S, Runnebaum B, Gerhard I. The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study. Forsch Komplementarmed Klass Naturheilkd. 2000;7(4):190-9.

PMid:11025394

Peet PR, Watts M. Liberation ecologies: environment, development and social movements. Routledge; 2nd edition, 2000.

Albert-Puleo M. Fennel and anise as estrogenic agents. J Ethnopharmacol. 1980;2(4):337-44.

https://doi.org/10.1016/S0378-8741(80)81015-4

Modaress Nejad V, Asadipour M. Comparison of the effectiveness of fennel and mefenamic acid on pain intensity in dysmenorrhoea. East Mediterr Health J. 2006;12(3-4):423-7.

PMid:17037712

Namavar Jahromi B, Tartifizadeh A, Khabnadideh S. Comparison of fennel and mefenamic acid for the treatment of primary dysmenorrhea. Int JGynaecol Obstet. 2003;80(2):153-7.

https://doi.org/10.1016/S0020-7292(02)00372-7

Omidvar S, Esmailzadeh S, Baradaran M, Basirat Z. Effect of fennel on pain intensity in dysmenorrhoea: A placebo-controlled trial. Ayu. 2012;33(2):311-3.

https://doi.org/10.4103/0974-8520.105259

PMid:23559811 PMCid:PMC3611645

Ostad SN, Soodi M, Shariffzadeh M, Khorshidi N, Marzban H. The effect of fennel essential oil on uterine contraction as a model for dysmenorrhea, pharmacology and toxicology study. J Ethnopharmacol. 2001;76(3):299-304.

https://doi.org/10.1016/S0378-8741(01)00249-5

Park S, Kang S, Jeong DY, Jeong SY, Park JJ, Yun HS. Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation. Genes Nutr. 2015;10(2):455.

https://doi.org/10.1007/s12263-015-0455-5

PMid:25701199 PMCid:PMC4336299

Bishayee A, Sarkar A, Chatterjee M. Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. J Ethnopharmacol. 1995;47(2):69-74.

https://doi.org/10.1016/0378-8741(95)01254-B

Rezaei-Moghadam A, Mohajeri D, Rafiei B, Dizaji R, Azhdari A, Yeganehzad M et al. Effect of turmeric and carrot seed extracts on serum liver biomarkers and hepatic lipid peroxidation, antioxidant enzymes and total antioxidant status in rats. Bioimpacts. 2012;2(3):151-7.

PMid:23678453 PMCid:PMC3648928

Jeyabalan J, Aqil F, Soper L, Schultz DJ, Gupta RC. Potent Chemopreventive/Antioxidant Activity Detected in Common Spices of the Apiaceae Family. Nutr Cancer. 2015;67(7):1201-7.

https://doi.org/10.1080/01635581.2015.1075051

PMid:26381237 PMCid:PMC4684170

Li X, Zhang Y, Yuan Y, Sun Y, Qin Y, Deng Z et al. Protective Effects of Selenium, Vitamin E, and Purple Carrot Anthocyanins on D-Galactose-Induced Oxidative Damage in Blood, Liver, Heart and Kidney Rats. Biol Trace Elem Res. 2016;173(2):433-42.

https://doi.org/10.1007/s12011-016-0681-8

PMid:27025718

Jasicka-Misiak I, Wieczorek PP, Kafarski P. Crotonic acid as a bioactive factor in carrot seeds (Daucus carota L.). Phytochemistry. 2005;66(12):1485-91.

https://doi.org/10.1016/j.phytochem.2005.04.005

PMid:15960983

Group REA-SPCW. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.

https://doi.org/10.1016/j.fertnstert.2003.10.004

Essah PA, Apridonidze T, Iuorno MJ, Nestler JE. Effects of short-term and long-term metformin treatment on menstrual cyclicity in women with polycystic ovary syndrome. Fertil Steril. 2006;86(1):230-2.

https://doi.org/10.1016/j.fertnstert.2005.12.036

PMid:16716324

Kort DH, Lobo RA. Preliminary evidence that cinnamon improves menstrual cyclicity in women with polycystic ovary syndrome: a randomized controlled trial. Am J Obstet Gynecol. 2014;211(5):487 e1-6.

Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990;97(8):734-9.

https://doi.org/10.1111/j.1471-0528.1990.tb16249.x

PMid:2400752

Pharmacopoeia B. British Pharmacopoeia Commission London; the Department of Health. Social Services and Public Safety. 2013.

Mohebbi-Kian E, Mohammad-Alizadeh-Charandabi S, Bekhradi R. Efficacy of fennel and combined oral contraceptive on depot medroxyprogesterone acetate-induced amenorrhea: a randomized placebo-controlled trial. Contraception. 2014;90(4):440-6.

https://doi.org/10.1016/j.contraception.2014.05.001

PMid:24981150

Yavari M, Rouholamin S, Tansaz M, Esmaeili S. Herbal Treatment of Oligomenorrhea with Sesamum indicum L.: A Randomized Controlled Trial. Galen. 2016;5(3):114-21.

Essah P, Nestler J. The metabolic syndrome in polycystic ovary syndrome. J Endocrinol Invest. 2006;29(3):270-80.

https://doi.org/10.1007/BF03345554

PMid:16682845

Cerda C, Perez-Ayuso RM, Riquelme A, Soza A, Villaseca P, Sir-Petermann T et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. J Hepatol. 2007;47(3):412-7.

https://doi.org/10.1016/j.jhep.2007.04.012

PMid:17560682

Aghili Khorasani M. Makhzan-al-Advia. Tehran: Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences; 2001.

Ibn-e-nafis A. Al-shamel fi-al sanaate al tebbieh (al advieh va al aghzieh). Tehran: Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences; 2008.

Webber LJ, Stubbs S, Stark J, Trew GH, Margara R, Hardy K et al. Formation and early development of follicles in the polycystic ovary. Lancet. 2003;362(9389):1017-21.

https://doi.org/10.1016/S0140-6736(03)14410-8

Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol. 1994;102(6):448-54.

https://doi.org/10.1055/s-0029-1211317

PMid:7890021

Wuttke W, Gorkow C, Jarry H. Dopaminergic compounds in Vitex agnus castus. Phytopharmaka in Forschung und klinischer Anwendung. Springer; 1995. p. 81-91.

https://doi.org/10.1007/978-3-642-85434-7_6

PMid:7553079

Dericks-Tan JS, Schwinn P, Hildt C. Dose-dependent stimulation of melatonin secretion after administration of Agnus castus. Exp Clin Endocrinol Diabetes. 2003;111(1):44-6.

https://doi.org/10.1055/s-2003-37500

PMid:12605350

Maganhin CC, Fuchs LF, Simoes RS, Oliveira-Filho RM, de Jesus Simoes M, Baracat EC et al. Effects of melatonin on ovarian follicles. Eur J Obstet Gynecol Reprod Biol. 2013;166(2):178-84.

https://doi.org/10.1016/j.ejogrb.2012.10.006

PMid:23102587

Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L et al. The role of melatonin as an antioxidant in the follicle. J Ovarian Res. 2012;5:5.

https://doi.org/10.1186/1757-2215-5-5

PMid:22277103 PMCid:PMC3296634

Yin F, Giuliano AE, Law RE, Van Herle AJ. Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells. Anticancer Res. 2001;21(1A):413-20.

PMid:11299771

Knowles LM, Zigrossi DA, Tauber RA, Hightower C, Milner JA. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer. 2000;38(1):116-22.

https://doi.org/10.1207/S15327914NC381_16

PMid:11341036

Lindenmeyer F, Li H, Menashi S, Soria C, Lu H. Apigenin acts on the tumor cell invasion process and regulates protease production. Nutr Cancer. 2001;39(1):139-47.

https://doi.org/10.1207/S15327914nc391_19

PMid:11588896

Mohammadbygi R, Yousefi SR, Shahghaybi S, Zandi S, Sharifi K, Gharibi F. Effects of Cabergoline administration on uterine perfusion in women with polycystic ovary syndrome. Pak J Med Sci. 2013;29(4):919-22.

https://doi.org/10.12669/pjms.294.3558

PMid:24353659 PMCid:PMC3817777

Dugoua JJ, Seely D, Perri D, Koren G, Mills E. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Can J Clin Pharmacol. 2008;15(1):e74-9.

PMid:18204102

Ozbek H, Ugras S, Dulger H, Bayram I, Tuncer I, Ozturk G et al. Hepatoprotective effect of Foeniculum vulgare essential oil. Fitoterapia. 2003;74(3):317-9.

https://doi.org/10.1016/S0367-326X(03)00028-5

Elghblawi E. Idiopathic hirsutism: excessive bodily and facial hair in women. Br J Nurs. 2008;17(3):192-7.

https://doi.org/10.12968/bjon.2008.17.3.28410

PMid:18414261

Franks S, Kiddy DS, Hamilton-Fairley D, Bush A, Sharp PS, Reed MJ. The role of nutrition and insulin in the regulation of sex hormone binding globulin. J Steroid Biochem Mol Biol. 1991;39(5B):835-8.

https://doi.org/10.1016/0960-0760(91)90033-2

Rahimi R, Ardekani MR. Medicinal properties of Foeniculum vulgare Mill. in traditional Iranian medicine and modern phytotherapy. Chin J Integr Med. 2013;19(1):73-9.

https://doi.org/10.1007/s11655-013-1327-0

PMid:23275017

Shahat AA, Ibrahim AY, Hendawy SF, Omer EA, Hammouda FM, Abdel-Rahman FH et al. Chemical composition, antimicrobial and antioxidant activities of essential oils from organically cultivated fennel cultivars. Molecules. 2011;16(2):1366-77.

https://doi.org/10.3390/molecules16021366

PMid:21285921

Rosenblum ER, Stauber RE, Van Thiel DH, Campbell IM, Gavaler JS. Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer. Alcohol Clin Exp Res. 1993;17(6):1207-9.

https://doi.org/10.1111/j.1530-0277.1993.tb05230.x

PMid:8116832

Sadrefozalayi S, Farokhi F. Effect of the aqueous extract of Foeniculum vulgare (fennel) on the kidney in experimental PCOS female rats. Avicenna J Phytomed. 2014;4(2):110-7.

PMid:25050308 PMCid:PMC4103710

Genazzani AD, Ricchieri F, Lanzoni C. Use of metformin in the treatment of polycystic ovary syndrome. Womens Health (Lond Engl). 2010;6(4):577-93.

https://doi.org/10.2217/WHE.10.43

PMid:20597621

Shastri B. Wealth of India-Raw Materials. New Delhi: CSIR Publication:, 1952.

Hammam FH. Protective effect of carrot juice against the toxicity of carbon tetrachloride on liver and kidneys in rabbits. World J Pharm Pharm Sci. 2014;3(5):1229-39.

Li C, Ford ES, Zhao G, Balluz LS, Giles WH, Liu S. Serum alpha-carotene concentrations and risk of death among US Adults: the Third National Health and Nutrition Examination Survey Follow-up Study. Arch Intern Med. 2011;171(6):507-15.

https://doi.org/10.1001/archinternmed.2010.440

PMid:21098341

Pelucchi C, Dal Maso L, Montella M, Parpinel M, Negri E, Talamini R et al. Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study. Cancer Causes Control. 2008;19(10):1209-15.

https://doi.org/10.1007/s10552-008-9190-1

PMid:18592384

Steinmetz KA, Potter JD. Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control. 1991;2(6):427-42.

https://doi.org/10.1007/BF00054304

PMid:1764568

Tan S, Vollmar N, Benson S, Sowa J-P, Bechmann LP, Gerken G et al. Liver injury indicating fatty liver but not serologic NASH marker improves under metformin treatment in polycystic ovary syndrome. Int J Endocrinol. 2015;2015.

Tang T, Balen AH. Use of metformin for women with polycystic ovary syndrome. Hum Reprod Update. 2013;19(1):1.

https://doi.org/10.1093/humupd/dms040

PMid:23114640

Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril. 2000;73(6):1149-54.

https://doi.org/10.1016/S0015-0282(00)00501-X

Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003;327(7421):951.

https://doi.org/10.1136/bmj.327.7421.951

PMid:14576245 PMCid:PMC259161

Moll E. Metformin in polycystic ovary syndrome. Ridderprint: University of Amsterdam; 2013.

Ibanez L, Valls C, Potau N, Marcos MV, de Zegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab. 2000;85(10):3526-30.

https://doi.org/10.1210/jc.85.10.3526

Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000;85(1):139-46.

PMid:10634377

Velazquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol. 1997;90(3):392-5.

https://doi.org/10.1016/S0029-7844(97)00296-2

Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H, Tapanainen JS. Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2003;88(1):148-56.

https://doi.org/10.1210/jc.2002-020997

PMid:12519844

Refbacks

  • There are currently no refbacks.