Shigehara Kazuyoshi, Izumi Kouji, Nakashima Kazufumi, Kawaguchi Shohei, Nohara Takahiro, Kadono Yoshifumi, Mizokami Atsushi
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Transl Androl Urol. 2023 Aug 31;12(8):1273-1282. doi: 10.21037/tau-23-121. Epub 2023 Aug 28.
The current study attempted to elucidate the mechanisms of keishibukuryogan (TJ-25) efficacy by focusing on hormonal and cytokine levels. This is a sub-analysis of serum hormonal and cytokine levels extracted from the single-arm prospective study.
Twenty-five participants were administrated TJ-25 at a dose of 2.5 g three times daily for 12 weeks, and competed for a diary of their hot flashes conditions. Various hormonal and cytokine values, including interleukin (IL)-8 and tumor necrosis factor-α (TNF-α), were measured at the baseline and 12-week visits. The correlation of hot flashes with hormonal and cytokine levels at baseline was investigated. As part of the responder analyses, all participants were divided into two groups based on the median baseline values of all hormones and cytokines at baseline, and the change amounts in strength and frequency of hot flashes from baseline to 12-week visits in both groups were compared. Furthermore, a correlation in change amounts (Δ values) by TJ-25 administration between hot flashes and each parameter was also conducted.
Hot flashes intensity was inversely related to estradiol levels (r=-0.433, P=0.019), and frequency was inversely related to progesterone levels (r=-0.415, P=0.025). In the responder analyses, the effectiveness of TJ-25 for hot flash strength increased in the patients with higher levels of TNF-α at baseline (P=0.0372). TJ-25 was more efficient in frequency in the patients with higher levels of IL-8 (P=0.0312). TJ-25 efficacy, on the other hand, was not significantly associated with changes in any hormonal or cytokine levels between the baseline and 12-week visits. However, ΔIL-8 and ΔTNF-α were not significantly correlated with Δstrength and Δfrequency of hot flashes by TJ-25 administration.
Hot flashes were inversely correlated with estradiol and progesterone levels. TJ-25 was more effective in patients with higher TNF-α and IL-8 levels, with no significant change in serum levels caused by the treatment. The suggestive mechanism for the effects of keishibukuryogan is that this drug doesn't suppress the production of IL-8 and TNF-α, but may inhibit some actions of these cytokines.
本研究试图通过关注激素和细胞因子水平来阐明加味逍遥散（TJ - 25）疗效的机制。这是一项对单臂前瞻性研究中提取的血清激素和细胞因子水平进行的亚分析。
25名参与者每日3次服用剂量为2.5 g的TJ - 25，持续12周，并记录潮热情况的日记。在基线和第12周就诊时测量各种激素和细胞因子值，包括白细胞介素（IL）- 8和肿瘤坏死因子 - α（TNF - α）。研究基线时潮热与激素和细胞因子水平的相关性。作为应答者分析的一部分，根据所有激素和细胞因子在基线时的中位数基线值将所有参与者分为两组，并比较两组从基线到第12周就诊时潮热强度和频率的变化量。此外，还对TJ - 25给药引起的潮热变化量（Δ值）与每个参数之间的相关性进行了研究。
潮热强度与雌二醇水平呈负相关（r = - 0.433，P = 0.019），频率与孕酮水平呈负相关（r = - 0.415，P = 0.025）。在应答者分析中，基线时TNF - α水平较高的患者中，TJ - 25对潮热强度的有效性增加（P = 0.0372）。IL - 8水平较高的患者中，TJ - 25在频率方面更有效（P = 0.0312）。另一方面，TJ - 25的疗效与基线和第12周就诊之间任何激素或细胞因子水平的变化均无显著相关性。然而，ΔIL - 8和ΔTNF - α与TJ - 25给药引起的潮热强度变化量（Δ强度）和频率变化量（Δ频率）无显著相关性。
潮热与雌二醇和孕酮水平呈负相关。TJ - 25在TNF - α和IL - 8水平较高的患者中更有效，治疗后血清水平无显著变化。加味逍遥散作用的潜在机制是该药物不抑制IL - 8和TNF - α的产生，但可能抑制这些细胞因子的某些作用。
