Sindrom ovarium polikistik atau polycystic ovarian syndrome (PCOS) dilaporkan dapat diterapi dengan artemisinin. Artemisinin sendiri merupakan obat antimalaria dengan mekanisme mengurangi parasitemia. PCOS adalah gangguan endokrin reproduksi yang umum terjadi pada wanita usia subur, dengan prevalensi 10–13%. PCOS ditandai oleh kelebihan androgen, disfungsi ovulasi, morfologi ovarium polikistik, dan sering kali disertai gangguan metabolik.[1,2]
Androgen pada Wanita
Androgen pada wanita sebagian besar disintesis oleh kelenjar adrenal dan ovarium, yang berasal dari kolesterol melalui serangkaian reaksi enzimatik yang dikatalisis oleh CYP11A1, CYP17A1, HSD3B2, dan HSD17B. Steroidogenesis ovarium sangat responsif terhadap rangsangan androgenik seperti luteinizing hormone (LH) atau human chorionic gonadotropin (hCG). Peningkatan ekspresi CYP11A1 dan CYP17A1 serta aktivitas enzim yang tinggi dari CYP17A1, HSD3B, dan HSD17B di sel teka ovarium mengakibatkan peningkatan produksi progesteron, 17a–hidroksiprogesteron (17a-OHP), dan testosteron di kondisi PCOS.[3,4]
(Konten ini khusus untuk dokter. Registrasi untuk baca selengkapnya)
Referensi
1. Teede HJ et al. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 108, 2447–2469 (2023). doi: 10.1210/clinem/dgad463
2. Rosenfield RL. D. A. Ehrmann, The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr. Rev. 37, 467–520 (2016). doi: 10.1210/er.2015-1104
3. Kempegowda P et al. Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome. Ther. Adv. Endocrinol. Metab. 11, 2042018820934319 (2020). doi: 10.1177/2042018820934319
4. Risal S et al. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat. Med. 25, 1894–1904 (2019). doi: 10.1038/s41591-019-0666-1
5. Hoeger KM, Dokras A, Piltonen T. Update on PCOS Consequences, Challenges, and Guiding Treatment. J. Clin. Endocrinol. Metab. 106, e1071–e1083 (2021). doi: 10.1210/clinem/dgaa839
6. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat. Med. 17, 1217–1220 (2011). doi: 10.1038/nm.2471
7. Lu P et al. Artemisinin derivatives prevent obesity by inducing browning of WAT and enhancing BAT function. Cell Res. 26, 1169–1172 (2016). doi: 10.1038/cr.2016.108
8. Liu Y et al. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction. Science 384, 1187 (2024). doi: 10.1126/science.adh5382
9. Baskind NE, Balen AH. Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome. Best Pract. Res. Clin. Obstet. Gynaecol. 37, 80–97 (2016). doi: 10.1016/j.bpobgyn.2016.03.005
10. Chien Y, Rosal K, Chung BC. Function of CYP11A1 in the mitochondria. Mol. Cell. Endocrinol. 441, 55–61 (2017). doi: 10.1016/j.mce.2016.10.030
11. Schreiber SL. The Rise of Molecular Glues. Cell 184, 3–9 (2021). doi: 10.1016/j.cell.2020.12.020
12. Harding CR et al. Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility. Nat. Commun. 11, 4813 (2020). doi: 10.1038/s41467-020-18624-0
13. Wang J et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nat. Commun. 6, 10111 (2015). doi: 10.1038/ncomms10111