Efficacy evaluation of hormone replacement therapy combined with Kuntai capsule in the treatment of diminished ovarian reserve: a target trial emulation study_Chinese Journal of Evidence-Based Medicine

Authors：

XU Ye ^1,2,3,4 , JIA Yulong ^1,2,3,4 , LIANG Wengxue ^1,2,3,4 , XIONG Yiquan ^1,2,3,4 ,  TAN Jing ^1,2,3,4 ,  SUN Xin ^1,2,3,4 ,  REN Yan ^1,2,3,4

1. Clinical Epidemiology and Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. NHC Key Laboratory of Clinical Epidemiology and Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
3. Sichuan Center of Technology Innovation for Real World Data, Chengdu 610041, P. R. China;
4. Sichuan Provincial Center for Evidence-based Chinese Herbal Medicine Research, Chengdu 610041, P. R. China;

Corresponding?author：

TAN Jing, Email: tanjing84@outlook.com; SUN Xin, Email: sunxin@wchscu.cn; REN Yan, Email: ren_yan87@163.com

Keywords：

Diminished ovarian reserve; Target trial emulation; Kuntai capsule; Hormone replacement therapy

DOI：

10.7507/1672-2531.202511077

Video：

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Objective To evaluate the effectiveness of hormone replacement therapy (HRT) combined with Kuntai capsule in the treatment of diminished ovarian reserve (DOR) in the clinical practice based on real world data (RWD). Methods Employing a target trial emulation framework, this study utilized electronic medical record data from the Tianjin Regional Healthcare Database. The outcome measures were the changes from baseline in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels within 3 months of treatment. Inverse probability weighting was used to balance baseline confounders, and the average treatment effect (ATE) was estimated based on weighted linear models. The primary analysis included patients with complete FSH data, and multiple sensitivity analyses were conducted to verify the robustness of the results. Results A total of 239 patients with DOR who had at least one sex hormone outcome were included. Among them, 198, 142, and 223 patients had complete data for FSH, LH, and E2, respectively. In the primary analysis population (n=198), 131 patients were in the Western medicine group (HRT alone) and 67 were in the combination group (HRT plus Kuntai capsule). Compared to the Western medicine group, the combination group showed a significantly greater reduction in FSH levels (ATE=?5.92IU/L, 95%CI ?10.73 to ?1.12). In the population with complete E2 data, the combination group demonstrated a significantly greater increase in E2 levels (ATE=61.03pg/mL, 95%CI 33.16 to 88.91). For LH, the difference was not statistically significant between two groups. Conclusion In real world clinical practice, HRT combined with Kuntai capsule is superior to HRT alone in improving FSH and E2 levels in patients with DOR. These findings are consistent with previous clinical evidence and suggest that the target trial emulation framework holds significant methodological value for evaluating the efficacy of integrated Chinese and Western medicine therapies.

Citation： XU Ye, JIA Yulong, LIANG Wengxue, XIONG Yiquan, TAN Jing, SUN Xin, REN Yan. Efficacy evaluation of hormone replacement therapy combined with Kuntai capsule in the treatment of diminished ovarian reserve: a target trial emulation study. Chinese Journal of Evidence-Based Medicine, 2026, 26(6): 655-660. doi: 10.7507/1672-2531.202511077 Copy

1.	陳光樂, 冀開元, 劉利敏. 坤泰膠囊預處理聯合兩種冷凍載桿對卵巢功能減退患者胚胎移植結局的影響. 中華中醫藥學刊, 2025, 43(11): 69-74, 267.
2.	卵巢儲備功能減退臨床診治專家共識專家組, 中華預防醫學會生育力保護分會生殖內分泌生育保護學組. 卵巢儲備功能減退臨床診治專家共識. 生殖醫學雜志, 2022, 31(4): 425-434.
3.	陳瑤, 唐麗, 田賽男, 等. 文獻計量視域下中醫藥防治卵巢衰老研究現狀與熱點分析. 中草藥, 2025, 56(12): 4369-4386.
4.	陳瑤, 田賽男, 王彬安, 等. 歸腎丸治療卵巢功能減退性疾病的作用機制研究進展. 中國實驗方劑學雜志, 2026, 32(2): 317-324.
5.	車祺, 董曦. 卵巢儲備功能低下的診治進展. 實用婦產科雜志, 2024, 40(7): 517-519.
6.	Pastore LM, Christianson MS, Stelling J, et al. Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR. J Assist Reprod Genet, 2018, 35(1): 17-23.
7.	中華中醫藥學會. 卵巢早衰中西醫結合診療指南. 中國中西醫結合雜志, 2024, 44(10): 1167-1179.
8.	鄭晨思, 郝鳴昭, 許煥芳, 等. 卵巢低反應的診斷標準及中醫治療方法研究進展. 中華中醫藥雜志, 2020, 35(3): 1368-1372.
9.	Jiao Z, Bukulmez O. Potential roles of experimental reproductive technologies in infertile women with diminished ovarian reserve. J Assist Reprod Genet, 2021, 38(10): 2507-2517.
10.	Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder-a plea for universal definitions. J Assist Reprod Genet, 2015, 32(12): 1709-1712.
11.	譚妙霞, 陳苑紅, 農煒煜, 等. 激素替代療法聯合坤泰膠囊治療對卵巢早衰患者血脂及性激素水平的影響. 內科, 2019, 14(4): 411-413.
12.	劉萍, 陳億斌. 人工智能與無創中醫婦科經絡診治技術. 中國實用婦科與產科雜志, 2024, 40(9): 891-894.
13.	張麗葉, 張穎, 王妍, 等. 中醫婦科藥物外治法發展述評. 中華中醫藥學刊, 2024, 42(11): 192-196.
14.	孫愛軍, 唐旭東, 張巧利, 等. 卵巢儲備功能降低不孕癥中西醫結合治療的理論與臨床試驗研究探討. 中國實驗方劑學雜志, 2019, 25(8): 148-157.
15.	中華中醫藥學會婦科分會. 和顏坤泰膠囊臨床應用專家指導意見. 中草藥, 2020, 51(8): 2075-2081.
16.	郁琦. 坤泰膠囊臨床應用指導建議. 中國實用婦科與產科雜志, 2019, 35(10): 1120-1122.
17.	陳蓉. 《中國絕經管理與絕經激素治療指南2023版》解讀. 協和醫學雜志, 2023, 14(3): 514-519.
18.	中華醫學會婦產科學分會絕經學組. 早發性卵巢功能不全的臨床診療專家共識(2023版). 實用婦產科雜志, 2024, (7): 17-19.
19.	李自強, 呂春曉, 潘桂湘, 等. 以臨床獲益-風險為導向的中西藥相互作用研究策略與方法. 中草藥, 2024, 55(6): 1780-1787.
20.	張湘, 鄒圣蕙, 李倩, 等. 坤泰膠囊聯合雌二醇片/雌二醇地屈孕酮片治療卵巢儲備功能減退的臨床效果. 臨床合理用藥, 2025, 18(28): 109-111.
21.	王秀萍, 喬獻偉, 徐冰. 坤泰膠囊聯合雌二醇片/雌二醇地屈孕酮片治療卵巢儲備功能減退的臨床觀察. 中國藥房, 2025, 36(5): 589-593.
22.	趙殿紅. 坤泰膠囊配合激素替代治療對卵巢早衰患者卵巢功能及血清內分泌激素的影響分析. 中國實用醫藥, 2025, 20(2): 167-170.
23.	袁馳, 周祎靈, 曹雨滋, 等. 基于真實世界數據的觀察性研究因果推斷—目標試驗模擬實施要點及案例分析. 中國胸心血管外科臨床雜志, 2024, 31(12): 1743-1752.
24.	賈玉龍, 孫鑫, 譚婧, 等. 基于真實世界數據的中西藥聯用療效評價目標仿真試驗方法學探討. 中華流行病學雜志, 2025, (11): 2040-2046.
25.	Hernán MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol, 2016, 183(8): 758-764.
26.	Yan R, Yulong J, Wengxue L, et al. Best practice for developing integrative Chinese-Western medicine databases using electronic health records. World J Integ Trad West Med, 2025, 11(3): 174-186.
27.	Zhang X, Zhang L, Xiong L, et al. Kuntai capsule for the treatment of diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials. J Ethnopharmacol, 2025, 344: 119526.
28.	李珊珊, 沈瓏慧. 坤泰膠囊治療子宮內膜異位癥的機制研究: 網絡藥理學、分子對接及分子動力學模擬方法. 中國全科醫學, 2025, 28(28): 3573-3582.
29.	于秋敏, 伍娟娟. 探討坤泰膠囊治療卵巢早衰的作用機制. 中醫藥臨床雜志, 2024, 36(3): 495-501.
30.	武桐, 吳越, 李偉莉. 坤泰膠囊治療卵巢儲備功能下降的作用機制. 中醫藥臨床雜志, 2023, 35(6): 1137-1142.
31.	Deakin CT, De Stavola BL, Littlejohn G, et al. Comparative effectiveness of adalimumab vs tofacitinib in patients with rheumatoid arthritis in Australia. JAMA Netw Open, 2023, 6(6): e2320851.
32.	Matthews AA, Danaei G, Islam N, et al. Target trial emulation: applying principles of randomised trials to observational studies. BMJ, 2022, 378: e071108.
33.	Fu EL. Target trial emulation to improve causal inference from observational data: what, why, and how. J Am Soc Nephrol, 2023, 34(8): 1305-1314.
34.	Cashin AG, Hansford HJ, Hernán MA, et al. Transparent reporting of observational studies emulating a target trial: the TARGET statement. BMJ, 2025, 390: e087179.
35.	Cashin AG, Hansford HJ, Hernán MA, et al. Transparent reporting of observational studies emulating a target trial-the TARGET statement. JAMA, 2025, 334(12): 1084-1093.

1. 陳光樂, 冀開元, 劉利敏. 坤泰膠囊預處理聯合兩種冷凍載桿對卵巢功能減退患者胚胎移植結局的影響. 中華中醫藥學刊, 2025, 43(11): 69-74, 267.
2. 卵巢儲備功能減退臨床診治專家共識專家組, 中華預防醫學會生育力保護分會生殖內分泌生育保護學組. 卵巢儲備功能減退臨床診治專家共識. 生殖醫學雜志, 2022, 31(4): 425-434.
3. 陳瑤, 唐麗, 田賽男, 等. 文獻計量視域下中醫藥防治卵巢衰老研究現狀與熱點分析. 中草藥, 2025, 56(12): 4369-4386.
4. 陳瑤, 田賽男, 王彬安, 等. 歸腎丸治療卵巢功能減退性疾病的作用機制研究進展. 中國實驗方劑學雜志, 2026, 32(2): 317-324.
5. 車祺, 董曦. 卵巢儲備功能低下的診治進展. 實用婦產科雜志, 2024, 40(7): 517-519.
6. Pastore LM, Christianson MS, Stelling J, et al. Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR. J Assist Reprod Genet, 2018, 35(1): 17-23.
7. 中華中醫藥學會. 卵巢早衰中西醫結合診療指南. 中國中西醫結合雜志, 2024, 44(10): 1167-1179.
8. 鄭晨思, 郝鳴昭, 許煥芳, 等. 卵巢低反應的診斷標準及中醫治療方法研究進展. 中華中醫藥雜志, 2020, 35(3): 1368-1372.
9. Jiao Z, Bukulmez O. Potential roles of experimental reproductive technologies in infertile women with diminished ovarian reserve. J Assist Reprod Genet, 2021, 38(10): 2507-2517.
10. Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder-a plea for universal definitions. J Assist Reprod Genet, 2015, 32(12): 1709-1712.
11. 譚妙霞, 陳苑紅, 農煒煜, 等. 激素替代療法聯合坤泰膠囊治療對卵巢早衰患者血脂及性激素水平的影響. 內科, 2019, 14(4): 411-413.
12. 劉萍, 陳億斌. 人工智能與無創中醫婦科經絡診治技術. 中國實用婦科與產科雜志, 2024, 40(9): 891-894.
13. 張麗葉, 張穎, 王妍, 等. 中醫婦科藥物外治法發展述評. 中華中醫藥學刊, 2024, 42(11): 192-196.
14. 孫愛軍, 唐旭東, 張巧利, 等. 卵巢儲備功能降低不孕癥中西醫結合治療的理論與臨床試驗研究探討. 中國實驗方劑學雜志, 2019, 25(8): 148-157.
15. 中華中醫藥學會婦科分會. 和顏坤泰膠囊臨床應用專家指導意見. 中草藥, 2020, 51(8): 2075-2081.
16. 郁琦. 坤泰膠囊臨床應用指導建議. 中國實用婦科與產科雜志, 2019, 35(10): 1120-1122.
17. 陳蓉. 《中國絕經管理與絕經激素治療指南2023版》解讀. 協和醫學雜志, 2023, 14(3): 514-519.
18. 中華醫學會婦產科學分會絕經學組. 早發性卵巢功能不全的臨床診療專家共識(2023版). 實用婦產科雜志, 2024, (7): 17-19.
19. 李自強, 呂春曉, 潘桂湘, 等. 以臨床獲益-風險為導向的中西藥相互作用研究策略與方法. 中草藥, 2024, 55(6): 1780-1787.
20. 張湘, 鄒圣蕙, 李倩, 等. 坤泰膠囊聯合雌二醇片/雌二醇地屈孕酮片治療卵巢儲備功能減退的臨床效果. 臨床合理用藥, 2025, 18(28): 109-111.
21. 王秀萍, 喬獻偉, 徐冰. 坤泰膠囊聯合雌二醇片/雌二醇地屈孕酮片治療卵巢儲備功能減退的臨床觀察. 中國藥房, 2025, 36(5): 589-593.
22. 趙殿紅. 坤泰膠囊配合激素替代治療對卵巢早衰患者卵巢功能及血清內分泌激素的影響分析. 中國實用醫藥, 2025, 20(2): 167-170.
23. 袁馳, 周祎靈, 曹雨滋, 等. 基于真實世界數據的觀察性研究因果推斷—目標試驗模擬實施要點及案例分析. 中國胸心血管外科臨床雜志, 2024, 31(12): 1743-1752.
24. 賈玉龍, 孫鑫, 譚婧, 等. 基于真實世界數據的中西藥聯用療效評價目標仿真試驗方法學探討. 中華流行病學雜志, 2025, (11): 2040-2046.
25. Hernán MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol, 2016, 183(8): 758-764.
26. Yan R, Yulong J, Wengxue L, et al. Best practice for developing integrative Chinese-Western medicine databases using electronic health records. World J Integ Trad West Med, 2025, 11(3): 174-186.
27. Zhang X, Zhang L, Xiong L, et al. Kuntai capsule for the treatment of diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials. J Ethnopharmacol, 2025, 344: 119526.
28. 李珊珊, 沈瓏慧. 坤泰膠囊治療子宮內膜異位癥的機制研究: 網絡藥理學、分子對接及分子動力學模擬方法. 中國全科醫學, 2025, 28(28): 3573-3582.
29. 于秋敏, 伍娟娟. 探討坤泰膠囊治療卵巢早衰的作用機制. 中醫藥臨床雜志, 2024, 36(3): 495-501.
30. 武桐, 吳越, 李偉莉. 坤泰膠囊治療卵巢儲備功能下降的作用機制. 中醫藥臨床雜志, 2023, 35(6): 1137-1142.
31. Deakin CT, De Stavola BL, Littlejohn G, et al. Comparative effectiveness of adalimumab vs tofacitinib in patients with rheumatoid arthritis in Australia. JAMA Netw Open, 2023, 6(6): e2320851.
32. Matthews AA, Danaei G, Islam N, et al. Target trial emulation: applying principles of randomised trials to observational studies. BMJ, 2022, 378: e071108.
33. Fu EL. Target trial emulation to improve causal inference from observational data: what, why, and how. J Am Soc Nephrol, 2023, 34(8): 1305-1314.
34. Cashin AG, Hansford HJ, Hernán MA, et al. Transparent reporting of observational studies emulating a target trial: the TARGET statement. BMJ, 2025, 390: e087179.
35. Cashin AG, Hansford HJ, Hernán MA, et al. Transparent reporting of observational studies emulating a target trial-the TARGET statement. JAMA, 2025, 334(12): 1084-1093.

Chinese Journal of Evidence-Based Medicine

Efficacy evaluation of hormone replacement therapy combined with Kuntai capsule in the treatment of diminished ovarian reserve: a target trial emulation study

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