Colonnello Elena, Graziani Andrea, Rossetti Rebecca, Voltan Giacomo, Masi Davide, Lubrano Carla, Mariani Stefania, Watanabe Mikiko, Isidori Andrea Marcello, Ferlin Alberto, Gnessi Lucio
Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy.
Chair of Endocrinology and Medical Sexology (ENDOSEX), University of Tor Vergata, 00133 Rome, Italy.
Endocr Rev. 2025 Sep 16;46(5):670-689. doi: 10.1210/endrev/bnaf013.
Pharmacotherapy involving hormones and hormone-derived molecules has various potential treatment targets. This includes addressing (partial) hormonal deficiencies, pursuing osteoanabolic effects, providing contraceptive options, or supporting gender-affirming transitions. In chronotherapy, the timing of the administration of active ingredients and different pharmaceutical forms is leveraged to maximize therapeutic efficacy while minimizing adverse effects, based on the principle that it is optimal for drugs to be administered according to the body's circadian rhythms. Just as a drummer sets the pace and keeps the rhythm steady for the entire band, the physician, through the application of chronotherapy, ensures the treatment regimen is harmonized with the body's internal clock. However, while this is a consolidated aspect for several endocrine treatments, for others, it represents a novelty. The new advancements in the treatment of osteoporosis, with the latest parathyroid hormone-related protein analogue, abaloparatide, or in congenital adrenal hyperplasia with the new long-lasting hydrocortisone formulation, are notable examples. We herein summarized the state of the art regarding the hormonal circadian rhythm to discuss in depth the evidence available regarding the correct timing of commonly administered hormonal therapies in adult patients. By offering clear indications, this manuscript delves into the importance of harmonizing hormonal therapy with circadian rhythms through chronotherapy, exploring its potential to enhance therapeutic outcomes while minimizing adverse effects.
涉及激素和激素衍生分子的药物治疗有多种潜在治疗靶点。这包括解决(部分)激素缺乏问题、追求骨合成代谢效应、提供避孕选择或支持性别肯定转变。在时间治疗中,根据药物应根据人体昼夜节律给药这一原则,利用活性成分和不同剂型的给药时间来最大化治疗效果,同时最小化不良反应。就像鼓手为整个乐队设定节奏并保持节奏稳定一样,医生通过应用时间治疗,确保治疗方案与人体内部时钟相协调。然而,虽然这对几种内分泌治疗来说是一个统一的方面,但对其他治疗来说,它却是一个新事物。骨质疏松症治疗的新进展,如最新的甲状旁腺激素相关蛋白类似物阿巴洛肽,或先天性肾上腺皮质增生症治疗中使用的新型长效氢化可的松制剂,都是显著的例子。我们在此总结了激素昼夜节律的最新情况,以深入讨论成年患者常用激素治疗正确给药时间的现有证据。通过提供明确的指导,本手稿深入探讨了通过时间治疗使激素治疗与昼夜节律相协调的重要性,探索其在提高治疗效果同时最小化不良反应的潜力。