FRI441 Antiestrogens To Treat Hypogonadotropic Hypogonadism In Male Users Of Anabolic-androgenic Steroids - A Clinical Pilot Study

Abstract

Abstract Disclosure: H.C. Henriksen: None. A.P. Jørgensen: None. A. Bjørnebekk: None. S.P. Neupane: None. I.A. Havnes: None. Background: Anabolic-androgenic steroids (AAS) used recreationally in supra-physiological doses is a growing public health concern. The use is associated with cardiovascular, metabolic and endocrine disturbances including AAS induced hypogonadism (ASIH). ASIH is a form of hypogonadotropic hypogonadism caused by AAS’ long-term negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, promoting fatigue, depression and sexual dysfunction. Aims: The primary objective of the study is to explore the safety and efficacy of clomiphene citrate (CC) in treating ASIH. Secondary aims are to detect AAS associated health risks and assess whether these risks are reversed 12 months after cessation. Methods: In this open longitudinal pilot study at Oslo University Hospital in Norway, men with AAS dependence, continuous use and a desire to quit are treated for 16 weeks with an antiestrogen (CC). The CC is given to stimulate endogenous secretion of gonadotropin-releasing hormone (GnRH), gonadotropins (luteinizing hormone (LH)) and testosterone by blocking the estrogenic negative feedback on the HPG-axis. Transdermal testosterone is administered daily during the first four weeks to prevent a sudden drop in androgen levels. If HPG response is subpar, human chorionic gonadotropin (hCG), a synthetic LH analog, is added. The participants are monitored every 4th week during intervention, and at follow-up at 6 and 12 months. Physical health is assessed through clinical examinations, blood and fat tissue sampling, cardiovascular examination, dual-energy x-ray absorptiometry, testicular ultrasound and semen analysis. Results: Preliminary results are available from 11 men that were eligible for endocrine intervention with median age of 33 (range 26-57) and median cumulative lifetime AAS use of 11 years (1-20). Cardiovascular findings were recurrent and included hypertension, myocardial hypertrophy, increased arterial stiffness, reduced flow-mediated dilation and lower carotid artery reactivity. Polycythemia, testicular atrophy and oligozoospermia were other common findings at inclusion. Intervention with CC showed varying HPG response: While some participants responded poorly to treatment, others developed normalized endogenous levels of gonadotropins and testosterone after only 4-8 weeks of therapy. No serious adverse events from CC use were reported. Among the few reported less severe adverse effects were headache, nausea and mood swings. Conclusion: Preliminary results of this ongoing study indicate that treatment with CC and hCG is safe and effective in treating ASIH from long-term continuous AAS use. Insufficient HPG response after 16 weeks of intervention might indicate persisting hypogonadotropic hypogonadism, but further monitoring is needed. Presentation: Friday, June 16, 2023