Table 4_Hekun decoction versus Femoston for women with amnestic mild cognitive impairment in early menopause: a randomized, three-arm, double-blind clinical trial.docx

BackgroundAmnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer’s disease (AD), carries a high risk of progression to dementia. However, few clinical trials have focused on interventions to delay this progression. Hekun Decoction, an herbal-based oral medicine, has shown potential in improving memory loss during early menopause. Here we performed a randomized controlled trial to evaluate the efficacy and safety of Hekun Decoction in women with aMCI.
MethodsThis prospective, randomized, three-arm, double-blind clinical trial enrolled women aged 40–60 years with aMCI during early menopause. Participants were randomized to Hekun Decoction, Femoston, or placebo for 24 weeks. The primary outcome was the change in the Montreal Cognitive Assessment (MoCA) score at 0 and 24 weeks. The secondary outcomes included the Menopause Rating Scale (MRS), Modified Kupperman Index (KI), and Insomnia Severity Index (ISI), along with adverse events.
ResultsBetween October 2021 and February 2024, a total of 292 patients were randomized to Hekun Decoction (n = 98), Femoston (n = 98), and placebo (n = 96). After 24 weeks, both Hekun Decoction (MD = 3.18, 95% CI [2.44–3.92]) and Femoston (MD = 3.67, 95% CI [2.93–4.42]) were more effective than placebo in improving MoCA scores. Meanwhile, better outcomes were observed in the Hekun Decoction group and Femoston group compared with the placebo group for MRS (MD = −5.87, 95% CI [−7.02, −4.71], and MD = −6.01, 95% CI [−7.02, −5.01]), KI (MD = −6.74, 95% CI [−8.16, −5.33], and MD = −6.93, 95% CI [−8.27, −5.59]), and ISI (MD = −6.53, 95% CI [−7.66, −5.39], and MD = −6.51, 95% CI [−7.58, −5.43]). As for the adverse events, no cases of abdominal distension, pain, breast pain, or abnormal uterine bleeding were observed in the Hekun Decoction group.
ConclusionIn women with aMCI during early menopause, Hekun Decoction demonstrated non-inferior efficacy to Femoston in improving cognitive function over 24 weeks, with a favorable safety profile. Notably, women in the Hekun Decoction group showed fewer adverse events compared with Femoston. However, further trials with longer follow-up periods are needed to confirm the efficacy of Hekun Decoction in women with aMCI.
Clinical trial registrationhttp://chictr.org.cn, ChiCTR2000036772.

背景：遗忘型轻度认知障碍（amnestic mild cognitive impairment, aMCI）是阿尔茨海默病（Alzheimer’s disease, AD）的前驱阶段，进展为痴呆的风险极高，但目前针对延缓其进展的干预措施相关临床试验仍较为匮乏。和坤汤（Hekun Decoction）作为一种草本口服制剂，在改善绝经早期女性的记忆减退方面已展现出潜在疗效。本研究开展一项随机对照试验，旨在评估和坤汤对绝经早期遗忘型轻度认知障碍女性患者的疗效与安全性。
方法：本项前瞻性、随机、三臂、双盲临床试验，纳入年龄40~60岁的绝经早期遗忘型轻度认知障碍女性受试者。将受试者随机分为和坤汤组、芬吗通（Femoston）组与安慰剂组，干预时长为24周。主要结局指标为0周与24周时蒙特利尔认知评估量表（Montreal Cognitive Assessment, MoCA）评分的变化值。次要结局指标包括绝经评定量表（Menopause Rating Scale, MRS）、改良库珀曼指数（Modified Kupperman Index, KI）、失眠严重指数量表（Insomnia Severity Index, ISI），以及不良事件发生情况。
结果：2021年10月至2024年2月期间，共计292例患者被随机分组，其中和坤汤组98例、芬吗通组98例、安慰剂组96例。干预24周后，与安慰剂组相比，和坤汤组（均数差=3.18，95%置信区间[2.44, 3.92]）与芬吗通组（均数差=3.67，95%置信区间[2.93, 4.42]）在改善MoCA评分方面均更具优势。同时，相较于安慰剂组，和坤汤组与芬吗通组在绝经评定量表（均数差分别为-5.87，95%置信区间[-7.02, -4.71]与-6.01，95%置信区间[-7.02, -5.01]）、改良库珀曼指数（均数差分别为-6.74，95%置信区间[-8.16, -5.33]与-6.93，95%置信区间[-8.27, -5.59]）及失眠严重指数量表（均数差分别为-6.53，95%置信区间[-7.66, -5.39]与-6.51，95%置信区间[-7.58, -5.43]）的改善效果更优。不良事件方面，和坤汤组未观察到腹胀、腹痛、乳房胀痛或异常子宫出血病例。
结论：在绝经早期遗忘型轻度认知障碍女性患者中，24周干预期间，和坤汤在改善认知功能方面的疗效非劣于芬吗通，且安全性良好。值得注意的是，和坤汤组受试者的不良事件发生率低于芬吗通组。但仍需开展更长随访周期的临床试验，以进一步验证和坤汤对遗忘型轻度认知障碍女性患者的疗效。
临床试验注册：中国临床试验注册中心（http://chictr.org.cn），注册号ChiCTR2000036772。