PERAN HORMONAL TERHADAP TERJADINYA OSTEOARTHRITIS LUTUT PADA PEREMPUAN POST MENOPAUSE : SYSTEMATIC LITERATURE REVIEW
THE ROLE OF HORMONES IN THE DEVELOPMENT OF KNEE OSTEOARTHRITIS IN POSTMENOPAUSAL WOMEN: A SYSTEMATIC LITERATURE REVIEW
Abstract
Osteoartritis (OA) lutut merupakan penyebab utama kecacatan pada usia lanjut, dengan prevalensi lebih tinggi pada perempuan pascamenopause akibat penurunan estrogen. Defisiensi estrogen berperan dalam inflamasi, degradasi matriks tulang rawan, dan kerusakan tulang subkondral. Penelitian ini menggunakan systematic literature review (SLR) untuk menganalisis hubungan menopause dan perubahan hormonal dengan kejadian OA lutut. Literatur ditelusuri menggunakan pedoman PRISMA melalui PubMed, Google Scholar, dan ScienceDirect, dengan inklusi studi kohort, kasus-kontrol, atau potong lintang pada wanita pascamenopause ≥45 tahun, penelitian rentang tahun 2015-2025. Dari 226 artikel yang ditemukan, diperoleh 9 artikel yang memenuhi kriteria. 6 artikel menilai hubungan estrogen dengan OA, dimana 5 menunjukkan hubungan positif bahwa semakin rendah kadar estrogen, seperti pada menopause dini, maka progresivitas OA semakin meningkat. Sebaliknya, 1 artikel menunjukkan hubungan negatif, yaitu penggunaan terapi hormon (HT) dengan suplementasi estrogen dikaitkan dengan peningkatan risiko OA lutut. Selain itu, 2 artikel menyoroti peran Anti-Müllerian Hormone (AMH) sebagai biomarker deteksi dini OA, dan 1 artikel membahas peran Follicle-Stimulating Hormone (FSH) dalam patofisiologi OA. Kesimpulannya, perubahan hormonal pada menopause, terutama defisiensi estrogen, rendahnya AMH, dan tingginya FSH, memiliki kontribusi penting terhadap patogenesis OA lutut.
References
IHME. Global burden of disease 2021: findings from the GBD 2021 study. Institute for health metrics and evaluation. Published online 2024.
Ren JL, Yang J, Hu W. The global burden of osteoarthritis knee: a secondary data analysis of a population-based study. Clin Rheumatol. 2025;44(4):1769-1810. doi:10.1007/s10067-025-07347-6
Perhimpunan Reumatologi Indonesia. Diagnosis dan Pengelolaan Osteoartritis (Lutut, Tangan, dan Panggul). Jakarta: Perhimpunan Reumatologi Indonesia. Published online 2021.
Lie YS, Kusumaningrum S, Budiningsih F, Wijaya BB. Radiographic findings and body mass index in elderly patients with knee osteoarthritis: A cross-sectional study. Jurnal Kedokteran dan Kesehatan Indonesia. Published online December 27, 2024:291-299. doi:10.20885/JKKI.Vol15.Iss3.art3
Nguyen USDT, Saunders FR, Martin KR. Sex Difference in OA: Should We Blame Estrogen? Eur J Rheumatol. 2023;11(1):S7-S14. doi:10.5152/eurjrheum.2023.20193
Herrera Ortiz AF, Cadavid Camacho E, Cubillos Rojas J, et al. A Practical Guide to Perform a Systematic Literature Review and Meta-analysis. Principles and Practice of Clinical Research Journal. 2021;7(4):47-57. doi:10.21801/ppcrj.2021.74.6
Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. Williams Gynecology. McGraw Hill Professional; 2020.
Hughbanks ML, Rodriguez-Fontan F, Kleck CJ, Burger–Van der Walt E. Estrogen receptor Alpha in human knee articular cartilage of healthy and osteoarthritic females. J Orthop. 2021;27:1-8. doi:10.1016/j.jor.2021.08.005
Lou C, Xiang G, Weng Q, et al. Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women. Menopause. 2016;23(11):1239-1246. doi:10.1097/GME.0000000000000697
Yang X, Fu Z, Ren Q, Wang S, Yin S, Liu J. Correlation of synovial tissue protein abundance with menopause in osteoarthritis. Am J Transl Res. 2022;14(10):7403-7412.
Liu YP, Li J, Xin SB, Xu J. Study the relevance between inflammatory factors and estradiol and their association with knee osteoarthritis in postmenopausal women. Eur Rev Med Pharmacol Sci. 2018;22(2).
Jung JH, Bang CH, Song GG, Kim C, Kim JH, Choi SJ. Knee osteoarthritis and menopausal hormone therapy in postmenopausal women: a nationwide cross-sectional study. Menopause. 2019;26(6):598-602. doi:10.1097/GME.0000000000001280
Wang J, Zhang X, Ge L, et al. Hormone therapy and oral contraceptives in the risk of knee osteoarthritis: a prospective cohort study. Menopause. 2025;32(8):710-718. doi:10.1097/GME.0000000000002560
Hou WY, Zhu CY, Gu YF, Zhu L, Zhou ZX. Association of hormone replacement therapy and the risk of knee osteoarthritis: A meta-analysis. Medicine. 2022;101(51):e32466. doi:10.1097/MD.0000000000032466
Ye T, Sun D, Mu T, et al. Differential effects of high-physiological oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone. Bone. 2018;111:9-22. doi:10.1016/j.bone.2018.03.008
Wang W, Wang L, Xu Z, et al. Effects of estradiol on reduction of osteoarthritis in rabbits through effect on matrix metalloproteinase proteins. Iran J Basic Med Sci. 2016;19(3):310-315.
Sasono B, Amanda NA, Dewi DNSS. Faktor Dominan Pada Penderita Osteoarthritisdi Rsud Dr. Mohamad Soewandhie, Surabaya, Indonesia. Published online 2020.
Mei R, Lou P, You G, Jiang T, Yu X, Guo L. 17β-Estradiol Induces Mitophagy Upregulation to Protect Chondrocytes via the SIRT1-Mediated AMPK/mTOR Signaling Pathway. Front Endocrinol (Lausanne). 2021;11. doi:10.3389/fendo.2020.615250
Cardoso JM, Ribeiro AC, Botelho J, Proença L, Noronha S, Alves RC. The Influence of Genetic Polymorphisms on the Expression of Interleukin-1beta, Prostaglandin E2 and Tumor Necrosis Factor Alpha in Peri-Implant Crevicular Fluid: A Cross-Sectional Study. Int J Mol Sci. 2024;25(1):651. doi:10.3390/ijms25010651
Zhao H, Yu F, Wu W. The Mechanism by Which Estrogen Level Affects Knee Osteoarthritis Pain in Perimenopause and Non-Pharmacological Measures. Int J Mol Sci. 2025;26(6):2391. doi:10.3390/ijms26062391
Gilmer G, Iijima H, Hettinger ZR, et al. Menopause-induced 17β-estradiol and progesterone loss increases senescence markers, matrix disassembly and degeneration in mouse cartilage. Nat Aging. 2025;5(1):65-86. doi:10.1038/s43587-024-00773-2
Atasoy-Zeybek A, Showel KK, Nagelli C V., Westendorf JJ, Evans CH. The intersection of aging and estrogen in osteoarthritis. npj Women’s Health. 2025;3(1):15. doi:10.1038/s44294-025-00063-1
Chen Q, Zhang W, Sadana N, Chen X. Estrogen receptors in pain modulation: cellular signaling. Biol Sex Differ. 2021;12(1):22. doi:10.1186/s13293-021-00364-5
Romero-Martínez BS, Sommer B, Solís-Chagoyán H, et al. Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle. Int J Mol Sci. 2023;24(9):7879. doi:10.3390/ijms24097879
Atasoy-Zeybek A, Showel KK, Nagelli C V., Westendorf JJ, Evans CH. The intersection of aging and estrogen in osteoarthritis. npj Women’s Health. 2025;3(1):15. doi:10.1038/s44294-025-00063-1
Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Müllerian hormone in women. Hum Reprod Update. 2014;20(3):370-385. doi:10.1093/humupd/dmt062
Sasaki E, Chiba D, Ota S, et al. Epidemiological study on the relationship among menopausal condition, bone fragility, and knee osteoarthritis. Preprint posted online October 6, 2020. doi:10.21203/rs.3.rs-84980/v1
Sasaki E, Chiba D, Ota S, et al. Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition. Sci Rep. 2021;11(1):4931. doi:10.1038/s41598-021-84584-0
Liu Y, Zhang M, Kong D, et al. High follicle‐stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/NF‐κB pathway. FEBS Open Bio. 2020;10(10):2235-2245. doi:10.1002/2211-5463.12975
Huan Z, Wang Y, Zhang M, et al. Follicle-stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation. FEBS Open Bio. 2021;11(8):2292-2303. doi:10.1002/2211-5463.13238
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