Off-label use of Clomiphene citrate to Treat Anabolic-androgenic Steroid induced Hypogonadism upon cessation among men (CloTASH) - a pilot study protocol

Abstract

Introduction: Non-prescribed anabolic-androgenic steroid (AAS) use is widespread and may induce hypogonadism, and metabolic, cardiovascular and mental health risks. The study aims to explore feasibility and safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. Methods and analysis: This is a non-randomized proof of concept pilot study to test the feasibility of an off-label hormone intervention. In this open-labeled intervention study, we shall include males with AAS dependence intending to quit AAS use. Clomiphene citrate will be given for a period of 16 weeks to stimulate the endogenous testosterone production. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention period, and at follow-up 6- and 12-months post-cessation. Change in self-reported symptoms of hypogonadism (fatigue, depression, anxiety, sexual dysfunction) and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without any medical intervention. Discussion: This pilot study is the first study to test feasibility of off-label use of CC with the intention to restart endogenous testosterone production upon cessation of AAS among men with AAS-induced hypogonadism. The study may provide valuable clinical insights, enabling the exploration of whether adjustments are needed for the intervention. The results may be used to determine the sample size and informing the design of future RCTs or case comparison studies. Ethics and dissemination: The study is initiated by investigators, funded by public grants and is approved by the Regional Committee for Medical and Health Research Ethics (REC) in Norway, Norwegian Medicines Agency and the Data Protection Officer for Research at Oslo University Hospital. Trial registration: EudraCT, EudraCT 2020-005938-15, Registered by Norwegian Medicines Agency 3^rd November 2021. https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-005938-15/NO