Disruption and recovery of testicular function during and after androgen abuse: the HAARLEM study

Abstract

STUDY QUESTION What is the speed and extent by which endogenous testosterone production and spermatogenesis recover after androgen abuse? SUMMARY ANSWER Testosterone concentrations normalized within 3 months after discontinuation of androgen abuse in most subjects but recovery of spermatogenesis took longer—approximately 1 year. WHAT IS KNOWN ALREADY An estimated 4–6% of amateur strength athletes use androgens. Abuse of supraphysiological doses of androgens completely suppresses endogenous testosterone production and spermatogenesis. STUDY DESIGN, SIZE, DURATION Prospective and observational cohort study in which 100 male amateur athletes participated for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects (≥18 years) were included if they had not used androgens for at least 3 months and intended to start an androgen cycle within 2 weeks. Clinic visits took place before (T0), at the end (T1), and 3 months after the end of the cycle (T2), and 1 year after start of the cycle (T3), and included a blood test for gonadotrophins and sex hormones, and semen analysis. MAIN RESULTS AND THE ROLE OF CHANCE During androgen abuse, 77% of subjects had a total sperm count (TSC) below 40 million. Three months after the end of the cycle (T2), total (−1.9 nmol/l, CI −12.2 to 8.33, P = 0.71) and free (−38.6 pmol/l, CI −476 to 399, P = 0.86) testosterone concentrations were not different compared to baseline, whereas mean TSC was 61.7 million (CI 33.7 to 90.0; P < 0.01) lower than baseline. At the end of follow-up (T3), there was no statistically significant difference for total (−0.82 nmol/l, CI −11.5 to 9.86, P = 0.88) and free (−25.8 pmol/l, CI −480 to 428, P = 0.91) testosterone compared to baseline, but there was for TSC (−29.7 million, CI −59.1 to −0.39, P = 0.05). In nine (11%) subjects, however, testosterone concentrations were below normal at the end of follow-up (T3), and 25 (34%) subjects still had a TSC below 40 million. LIMITATIONS, REASONS FOR CAUTION The follow-up period (after the cycle) was relatively short, especially considering the long recovery time of spermatogenesis after discontinuation of androgens. WIDER IMPLICATIONS OF THE FINDINGS Endogenous testosterone production and spermatogenesis recover following androgen abuse in the vast majority of users. Nevertheless, not all users achieve a normalized testicular function. This may especially be the case for athletes with a high past exposure to androgens. STUDY FUNDING/COMPETING INTEREST(S) There is no conflict of interest. The study was funded by the Spaarne Gasthuis academy. TRIAL REGISTRATION NUMBER N/A.

Investigating anabolic-androgenic steroid dependence and muscle dysmorphia with network analysis

“…The problems related to ongoing AAS use include both physical and mental health issues such as gynecomastia, cardiovascular and liver pathology, mood swings, irritability, and aggressiveness (Horwitz et al, 2019;Piacentino et al, 2015). Withdrawal symptoms related to hypogonadism are commonly experienced for months during off periods (Smit et al, 2021), contributing to continued AAS use to relieve these symptoms. The most central symptoms to the network indicate that this cycle of experiencing side effects and potentially continuing AAS use to alleviate these side effects typifies AAS dependence.…”

The Use of Anabolic Androgenic Steroids as a Public Health Issue

“…While the potential benefits of various substances have been identified in small scale studies (Anawalt, 2019;Tan & Scally, 2009) and supported by anecdotal evidence (Griffiths, Henshaw, McKay, & Dunn, 2016;Llewellyn, 2017), there has been little research conducted in relation to PCT. In fact, in direct contradiction regarding the benefits of PCT and suggestions from a recent study of 80 users of PCT concluded that, there was hardly any evidence to support its use, that tamoxifen had negligible effects on the actions of AAS and that hCG had no detectable effect on testicular size or spermatogenesis (Smit, Buijs, de Hon, den Heijer, & de Ronde, 2021). Caution is required in the interpretation of research with relatively small sample sizes and the use of illicitly obtained medications with a lack of data on drug provenance however this illustrates the lack of progress in relation to answering a key question regarding AAS and a tenet of any harm reduction activity.…”

Health effects of androgen abuse: a review of the HAARLEM study

“…Measurements took place before, during and twice after the cycle. Health effects were divided into several categories: positive and negative adverse effects reported by the subjects, the results of kidney and liver biochemistry in blood, and the outcome of psychological questionnaires [4 ▪ ]; the disruption and recovery of endogenous testosterone production and spermatogenesis [5 ▪ ]; the change of cardiovascular parameters during androgen abuse, such as blood pressure, lipid metabolism and erythrocytosis [6 ▪ ]; and change of cardiac structure and function as evaluated with 3D echocardiography [7].…”

“…In the last 2−3 years several publications reported data from the HAARLEM study [3,4 ▪ –6 ▪ ,7], which is an acronym for health risks of anabolic androgenic steroid use by male amateur athletes. This cohort study takes precedence over much of the existing literature in this field due to its prospective design and relatively large size.…”