Endocrine Abstracts

Background and aims: Non-prescribed use of anabolic-androgenic steroids (AAS) is associated with a wide range of health risks including AAS-induced hypogonadism (ASIH) caused by negative feedback suppression on the hypothalamic-pituitary-gonadal (HPG) axis. Testicular function might be reduced for months up to years after AAS-cessation, increasing the risk of developing fatigue, decreased libido, erectile dysfunction, infertility, sleep disorder, depression and anxiety. There is no consensus on whether endocrine therapy should be used in the treatment of ASIH. In our study, a group of AAS-dependent men will receive endocrine therapy consisting of clomiphene citrate, a selective oestrogen receptor modulator. According to the theory, clomiphene citrate might stimulate endogenous testosterone production by blocking the negative feedback mechanism on the HPG-axis. The primary aim is to explore whether use of clomiphene citrate is safe and effective for AAS-withdrawal. The secondary aims are to detect health risks during ongoing AAS use and assess whether physical and mental health risks are reversed 12 months after cessation.

Methods: This one-site open off-label longitudinal pilot study at Oslo University Hospital in Norway will include 25-30 AAS-dependent men referred to outpatient addiction treatment with a desire to end AAS use permanently. The intervention group will be given endocrine therapy consisting of clomiphene citrate for 16 weeks including exogenous testosterone replacement for the first four weeks following AAS-cessation to ensure that the testosterone level is within normal range before reaching a HPG response. They will be compared to male participants in an already ongoing study of men who end AAS use temporarily without endocrine treatment. Participants from both studies will self-report withdrawal symptoms and other health measures every 2 weeks for 6 months and have visits at inclusion and after 6 months. The intervention group will be monitored using within-subjects repeated measures design on physical and mental health before, during 16 weeks of intervention, and at follow-up 6 and 12 months after AAS-cessation. Physical health parameters are obtained via clinical examinations, investigation of cardiovascular status, blood and fat tissue sampling, dual-energy x-ray absorptiometry (DXA), testicular ultrasound and semen analysis.

Results: Study inclusion started in December 2021. The study protocol and preliminary results will be presented at the conference.

Conclusion: This pilot is the first intervention study to test safety and efficacy of off-label use of clomiphene citrate among withdrawing AAS-dependent men. If this therapeutic approach works, full-fledged clinical trials need to be conducted.