The Chronobiology of Hormone Administration

Elena Colonnello, Andrea Graziani, Rebecca Rossetti, Giacomo Voltan, Davide Masi, Carla Lubrano, Stefania Mariani, Mikiko Watanabe, Andrea Marcello Isidori, Alberto Ferlin, Lucio Gnessi
Endocrine Reviews, First published online April 19, 2025, bnaf013
https://doi.org/10.1210/endrev/bnaf013

Abstract

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.

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