Author(s):
Eko Susetyarini, Poncojari Wahyono, Sri Wahyuni, H. Husamah, Endrik Nurrohman
Email(s):
susetyorini@umm.ac.id , poncojari@umm.ac.id , sriwahyuni@umm.ac.id , usya_bio@umm.ac.id , endrik@umm.ac.id
DOI:
10.52711/0974-360X.2026.00276 
Address:
Eko Susetyarini*, Poncojari Wahyono, Sri Wahyuni, H. Husamah, Endrik Nurrohman
Department of Biology Education, Faculty of Teacher Training and Education, Universitas Muhammadiyah Malang, Malang 61544, East Java, Indonesia.
*Corresponding Author
Published In:
Volume - 19,
Issue - 4,
Year - 2026
ABSTRACT:
Stigmasterol, a plant-derived phytosterol, has gained attention for its potential antifertility properties, yet no systematic synthesis has been conducted. This review analyzed bibliometric trends, experimental and contextual evidence, biological mechanisms, and research gaps using PRISMA 2020 guidelines and a Scopus search for “stigmasterol AND antifertility.” Twenty-five articles were classified as Direct (n=3), Indirect (n=2), and Contextual (n=20) evidence. Findings indicate a shift from sterol profiling to targeted reproductive pharmacology. Direct studies confirmed antifertility effects in animal models, while indirect and contextual works linked stigmasterol to ethnomedicinal plants and diverse pharmacological activities such as anti-inflammatory, antiproliferative, and phytoestrogenic effects. Mechanisms involve endocrine modulation, apoptosis, and receptor interactions. Despite promising potential, stigmasterol remains underexplored; future research should focus on purified compound assays, standardized in vivo methods, clinical validation, and safety assessment to advance its development as a natural contraceptive.
Cite this article:
Eko Susetyarini, Poncojari Wahyono, Sri Wahyuni, H. Husamah, Endrik Nurrohman. Exploring the Antifertility Potential of Stigmasterol: Evidence from a Systematic Review. Research Journal of Pharmacy and Technology. 2026;19(4):1919-7. doi: 10.52711/0974-360X.2026.00276
Cite(Electronic):
Eko Susetyarini, Poncojari Wahyono, Sri Wahyuni, H. Husamah, Endrik Nurrohman. Exploring the Antifertility Potential of Stigmasterol: Evidence from a Systematic Review. Research Journal of Pharmacy and Technology. 2026;19(4):1919-7. doi: 10.52711/0974-360X.2026.00276 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-4-65
REFERENCES:
1. Tal A. The Environmental Impacts of Overpopulation. Encyclopedia. 2025; 5(2). https://doi.org/10.3390/encyclopedia5020045
2. Ahmed SK, Mohammed RA. Obesity: Prevalence, causes, consequences, management, preventive strategies and future research directions. Metab Open. 2025; 27: 100375. https://doi.org/10.1016/j.metop.2025.100375
3. Wang J, Azam W. Natural resource scarcity, fossil fuel energy consumption, and total greenhouse gas emissions in top emitting countries. Geosci Front [Internet]. 2024; 15(2): 101757. https://doi.org/10.1016/j.gsf.2023.101757
4. United Nations Population Fund. Nearly half of all pregnancies are unintended—a global crisis, says new UNFPA report. Unfpa. United Nations Population Fund; 2022. p. 1–7.
5. Bearak J, Popinchalk A, Ganatra B, Moller A-B, Tunçalp Ö, Beavin C, et al. Unintended pregnancy and abortion by income, region, and the legal status of abortion: estimates from a comprehensive model for 1990–2019. Lancet Glob Heal. 2020 Sep; 8(9): e1152–61.
6. Oguz SH, Yildiz BO. An Update on Contraception in Polycystic Ovary Syndrome. Endocrinol Metab. 2021 Apr; 36(2): 296–311. https://doi.org/10.3803/EnM.2021.958
7. Metz L, Isacco L, Redman LM. Effect of oral contraceptives on energy balance in women: A review of current knowledge and potential cellular mechanisms. Metabolism. 2022; 126: 154919. https://doi.org/https://doi.org/10.1016/j.metabol.2021.154919
8. Bhullar SK, Rabinovich-Nikitin I, Kirshenbaum LA. Oral hormonal contraceptives and cardiovascular risks in females. Can J Physiol Pharmacol. 2024;102(10):572–84.
9. Shufelt CL, Bairey Merz CN. Contraceptive hormone use and cardiovascular disease. J Am Coll Cardiol. 2009 Jan; 53(3): 221–31. https://doi.org/10.1016/j.jacc.2008.09.042 PMID: 19147038
10. Ramya R, Sivasakthi R, Senthilkumar C, Anudeepa J, Santhi N, Narayanan RV. Preliminary Phytochemical and Antifertility Studies on Dodonea viscosa Linn. Asian J Res Pharm Sci. 2011; 1(3): 77–9.
11. Rani R, Mishra S, Vidyapith B. Antifertility activity of Kaempferol-7-O-Glucoside isolate from Cassia nodosa Bunch. Asian J Res Chem. 2012; 5(8): 985–9.
12. Ojha M, Meshram N, Singh A, Alexander A, Sharma M. The Scope of Herbal Plants as the Source of Contraceptive Values in Males. Asian J Res Pharm Sci. 2015; 5(1): 59–65.
13. Shivarkar R, Patil S. Curcuma longa and Azadirachta indica : Herbals for Fertility Control. Res J Pharmacogn Phytochem. 2011;3(3):124–7.
14. Shubhangi P, Mandakini P, Nandkishore D, Subhash B. Antifertility Activity of Ficus bengalensis Linn : Special Emphasis on Histoarchitecture Changes of Female Reproductive System of Rat ABSTRACT : Res J Pharm Technol. 2010;3(3):1285–7.
15. Nickels L, Yan W. Nonhormonal Male Contraceptive Development—Strategies for Progress. Pharmacol Rev. 2024;76(1):37–48. https://doi.org/https://doi.org/10.1124/pharmrev.122.000787
16. Bhatt N, Deshpande M. A Critical Review and Scientific Prospective on Contraceptive Therapeutics from Ayurveda and Allied Ancient Knowledge. Front Pharmacol. 2021;12(June). https://doi.org/10.3389/fphar.2021.629591
17. Amalia A, Fitri M, Nugraha I, Elya B. The Single Compound Isolate of Eleocharis dulcis having the Antibacterial activity on Fish Diseases. Res J Pharm Technol. 2024;17(10):4817–25. https://doi.org/10.52711/0974-360X.2024.00741
18. Mazumder K, Khanra R, Biswas K. Exploration of anti-inflammatory activity of extract and isolated compounds obtained from the aerial root of Ficus benghalensis Linn . ABSTRACT : Res J Pharm Technol. 2022;15(10):4584–8. https://doi.org/10.52711/0974-360X.2022.00769
19. Rajput AP, Patel MK. Isolation and characterization of phytoconstituents from the chloroform extract of Abutilon indicum leaves (Family : Malvaceae). Asian J Res Chem. 2012;5(11):1375–80.
20. Li J, Zheng X, Qi J. Research Progress on the Therapeutic Mechanisms of Stigmasterol for Multiple Diseases. Molecules. 2025;30(9). https://doi.org/10.3390/molecules30091874
21. Bakrim S, Benkhaira N, Bourais I, Benali T, Lee L-H, El Omari N, et al. Health Benefits and Pharmacological Properties of Stigmasterol. Antioxidants. 2022;11(10). https://doi.org/10.3390/antiox11101912
22. Keber R, Rozman D, Horvat S. Sterols in spermatogenesis and sperm maturation. J Lipid Res. 2013 Jan;54(1):20–33. https://doi.org/10.1194/jlr.R032326 PMID: 23093550
23. Al-Shuhaib MBS, Al-Shuhaib JMB. Assessing Therapeutic Value and Side Effects of Key Botanical Compounds for Optimized Medical Treatments. Chem Biodivers. 2025 Jan;22(1):e202401754.
24. Yamanashi Y, Komine T, Hirota Y, Suzuki H, Osuga Y, Takada T. Dietary phytosterols induce infertility in female mice via epigenomic modulations. Commun Biol. 2024;7(1):1535.
25. Newill H, Loske R, Wagner J, Johannes C, Lorenz RL, Lehmann L. Oxidation products of stigmasterol interfere with the action of the female sex hormone 17beta-estradiol in cultured human breast and endometrium cell lines. Mol Nutr Food Res. 2007 Jul;51(7):888–98.
26. Buț M-G, Tero-Vescan A, Pușcaș A, Jîtcă G, Marc G. Exploring the Inhibitory Potential of Phytosterols β-Sitosterol, Stigmasterol, and Campesterol on 5-Alpha Reductase Activity in the Human Prostate: An In Vitro and In Silico Approach. Plants (Basel, Switzerland). 2024 Nov;13(22).
27. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Int J Surg. 2010;8(5):336–41.
28. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar;372:n71.
29. Selçuk AA. A Guide for Systematic Reviews: PRISMA. Turkish Arch Otorhinolaryngol. 2019 Mar;57(1):57–8. https://doi.org/10.5152/tao.2019.4058 PMID: 31049257
30. Bairagi J, Saikia PJ, Boro F, Hazarika A. Fertility regulatory potential of Persicaria hydropiper (L.) Delarbre methanolic root extract in female albino mice: An insight into the phytochemicals present and role of the extract in contraception. Saudi Pharm J. 2022;30(11):1623–38.
31. Rabadia JP, Desai TR, Thite VS. The pharmacological evaluation of antifertility role of Plumeria acuminata on the reproduction of female Wistar rats. J Appl Pharm Sci. 2022;12(8):202–13.
32. Fan M, Kim E-K, Choi Y-J, Tang Y, Moon S-H. The role of momordica charantia in resisting obesity. Int J Environ Res Public Health. 2019;16(18). https://doi.org/10.3390/ijerph16183251
33. Ilyas S, Hutahaean S. Transforming growth factor beta of testis germinal cell in Guinea pig (Cavia porcellus) after exposure to methanol extract of the seeds of bitter melon (momordica charantia) and depot medroxyprogesterone acetate. Asian J Pharm Clin Res. 2018;11(12):149–54.
34. Idowu TO, Ogundaini AO, Adesanya SA, Onawunmi GO, Osungunna MO, Obuotor EM, et al. Isolation and characterization of chemical constituents from Chrysophyllum albidum G. Don-Holl. stem-bark extracts and their antioxidant and antibacterial properties. African J Tradit Complement Altern Med. 2016;13(5):182–9. https://doi.org/10.21010/ajtcam.v13i5.24
35. Sheba LAA, Anuradha V. An updated review on Couroupita guianensis Aubl: A sacred plant of India with myriad medicinal properties. J HerbMed Pharmacol. 2020;9(1):1–11. https://doi.org/10.15171/JHP.2020.01
36. Abdu A, Prakash A, Kondal R, Sharma S, Bhagat M, Pal R, et al. Comprehensive review on Plumbago indica: Traditional, pharmacological insights and conservation strategies. J Appl Pharm Sci. 2024;14(11):1–16. https://doi.org/10.7324/JAPS.2024.200049
37. Ashagrie YN, Tadesse MG, Bachheti RK, Bachheti A, Tyagi M, Rai N. Exploring the bioactive potential and safety profile of Caesalpinia decapetala seeds and seed oil. Environ Conserv J. 2024;25(3):747–60.
38. Harakeh S, Niyazi HA, Niyazi HA, Abdalal SA, Mokhtar JA, Almuhayawi MS, et al. Integrated Network Pharmacology Approach to Evaluate Bioactive Phytochemicals of Acalypha indica and Their Mechanistic Actions to Suppress Target Genes of Tuberculosis. ACS Omega. 2024;9(2):2204–19.
39. Rizwan K, Majeed I, Bilal M, Rasheed T, Shakeel A, Iqbal S. Phytochemistry and Diverse Pharmacology of Genus Mimosa: A Review. Biomolecules. 2022;12(1). https://doi.org/10.3390/biom12010083
40. Pandey DK, Kaur P, Kumar V, Banik RM, Malik T, Dey A. Screening the elite chemotypes of Gloriosa superba L. in India for the production of anticancer colchicine: simultaneous microwave-assisted extraction and HPTLC studies. BMC Plant Biol. 2021;21(1). https://doi.org/10.1186/s12870-021-02843-8
41. Kundu BB, Vanni K, Farheen A, Jha P, Pandey DK, Kumar V. Dioscorea bulbifera L. (Dioscoreaceae): A review of its ethnobotany, pharmacology and conservation needs. South African J Bot. 2021;140:365–74.
42. Kandil ZA, Esmat A, Salah El Dine RS, Mohamed Ezzat SM. Anti-inflammatory activity of the lipophilic metabolites from Scolymus hispanicus L. South African J Bot. 2020;131:43–50.
43. Huang L, Liu T, Jiang M, Bai C, Xu J, Liu S, et al. Network pharmacology-based prediction and verification of the mechanism for Bushen Chengyun granule on low endometrial receptivity. J Tradit Chinese Med Sci. 2020;7(1):2–11. https://doi.org/10.1016/j.jtcms.2020.01.002
44. El-Ishaq A, Alshawsh MA, Mun K-S, Chik Z. Phytochemical screening and anti-implantation activity of Asparagus africanus root extract in female Sprague–Dawley rats. Rev Bras Farmacogn. 2019;29(5):621–30. https://doi.org/10.1016/j.bjp.2019.06.003
45. El-Ishaq A, Alshawsh MA, Chik ZB. Evaluating the oestrogenic activities of aqueous root extract of Asparagus africanus Lam in female Sprague-Dawley rats and its phytochemical screening using Gas Chromatography-Mass Spectrometry (GC/MS). PeerJ. 2019;2019(7). https://doi.org/10.7717/peerj.7254
46. Seethalakshmi B, Kavitha K. Qualitative analysis of inorganic acid, basic radicals, and estimation of biomolecules in the flower extract of butea superba roxb. Asian J Pharm Clin Res. 2018;11(10):161–6.
47. Qasimi MI, Mohibbi H, Nagaoka K, Watanabe G. Effects of phytosterols as food additives on adrenal and reproductive endocrine function during sexual maturation in male Japanese Quail (Coturnix coturnix Japonica). J Poult Sci. 2018;55(2):155–61. https://doi.org/10.2141/jpsa.0170022
48. Elufioye TO, Obuotor EM, Agbedahunsi JM, Adesanya SA. Anticholinesterase constituents from the leaves of Spondias mombin L. (Anacardiaceae). Biol Targets Ther. 2017;11:107–14.
49. Konsue A, Picheansoonthon C, Talubmook C. Fasting blood glucose levels and hematological values in normal and streptozotocin-induced diabetic rats of mimosa pudica L. extracts. Pharmacogn J. 2017;9(3):315–22. https://doi.org/10.5530/pj.2017.3.54
50. Ghori MK, Ghaffari M, Hussain S, Manzoor M, Aziz M, Sarwer W. Ethnopharmacological, phytochemical and pharmacognostic potential of genus heliotropium L. Turkish J Pharm Sci. 2016;13(2):259–80.
51. Pal D, Mazu̧mder UK, Gupta M. Fractionation of stigmasterol derivative and study of the effects of Celsia coromandelina aerial parts petroleum ether extract on appearance of puberty and ovarian steroidogenesis in immature mice. Pharm Biol. 2012;50(6):747–53. https://doi.org/10.3109/13880209.2011.628321
52. Murkunde Y V, Murthy PB. Developmental toxicity of homobrassinolide in wistar rats. Int J Toxicol. 2010;29(5):517–22. https://doi.org/10.1177/1091581810375620
53. Banerji R, Bajpai A, Verma SC. Oil and fatty acid diversity in genetically variable clones of Moringa oleifera from India. J Oleo Sci. 2009;58(1):9–16. https://doi.org/10.5650/jos.58.9
54. Wang YD, Lorenzo B, Reidenberg MM. Inhibition of 11β-hydroxysteroid dehydrogenase obtained from guinea pig kidney by furoemide, naringenin and some other compounds. J Steroid Biochem Mol Biol. 1994;49(1):81–5. https://doi.org/10.1016/0960-0760(94)90304-2
55. Fadeyi OJ, Akwu NA, Lekhooa M, Hayeshi R, Aremu AO. Utilisation of medicinal plants for their antifertility activities: A bibliometric analysis of research endeavours from 1968 to 2023. Phytomedicine Plus. 2024;4(3):100580. https://doi.org/10.1016/j.phyplu.2024.100580
56. Valitova J, Renkova A, Beckett R, Minibayeva F. Stigmasterol: An Enigmatic Plant Stress Sterol with Versatile Functions. Int J Mol Sci. 2024 Jul;25(15). https://doi.org/10.3390/ijms25158122
57. Singh D, Sharma SK, Bansal A, Sharma P, Hashmi A. A Comparative Study of Isolated Phytosteroles from Different Plant Parts of Selected Cassia species. Asian J Res Chem. 2013;3(3):117–21.
58. Preethi PJ, Lohita M, Latha PS, Zameerullah S, Veeranjineyulu K, Manohara A. Rising Trends towards Natural Contraception : A Review. Asian J Res Chem. 2014;4(3):130–4.
59. Renuka R, Jeyarathnam M. Women ’ s Autonomy and Family Planning Practices among Married Women in Coimbatore. Asian J Nurs Educ Res. 2016;6(2):214–6. https://doi.org/10.5958/2349-2996.2016.00039.2
60. Renuka R. Women ’ s Educa tion and Contraceptive Practice. Asian J Nurs Educ Res. 2019;9(4):539–41.
61. Kaur M. Preparation of Childbirth and Parenthood. Int J Adv Nurs Manag. 2020;8(3):263–7.