Effects of anabolic androgenic steroids on the reproductive system of athletes and recreational users: a systematic review and meta-analysis

Maria A. Christou1,2, Panagiota A. Christou1, Georgios Markozannes2, Agathocles Tsatsoulis1, George Mastorakos3, Stelios Tigas1

1 Department of Endocrinology, University of Ioannina, Ioannina, Greece, 2 Department of Hygiene and Epidemiology, Medical School, University of Ioannina, Ioannina, Greece, 3 Endocrine Unit, “Aretaieion” Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

Abstract
Background Use of anabolic androgenic steroids (AAS) to improve athletic performance may affect the reproductive system, leading to changes in sex hormone blood levels and hypogonadism. Objective This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes. Methods An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes of any age, gender, level or type of sport; subjects used any type, dose, form or duration of AAS; AAS effects on the reproductive system of athletes, were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects metaanalysis was performed to assess the weighted mean difference of serum gonadotropin (LH, FSH) and testosterone levels compared to baseline, during the period of AAS use, as well as following AAS discontinuation. Results Thirty-three studies (3 randomized clinical trials, 11 cohort, 18 cross-sectional and 1 non-randomized parallel clinical trial) were included in the systematic review (3,879 participants; 1,766 AAS users and 2,113 non-AAS users). The majority of the participants were men; only 6 studies provided data for female athletes. A meta-analysis was conducted, of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (6 studies, n=65 AAS users; 7 studies, n=59, evaluating gonadotropin and testosterone levels respectively), (2) during AAS use and following AAS discontinuation (4 studies, n=35; 6 studies, n=39, respectively), as well as (3) prior to AAS use and following AAS discontinuation (3 studies, n=17; 5 studies, n=27, respectively). During AAS intake, significant reductions in LH (WMD: -3.37 IU/l, 95% CI: -5.05 to -1.70, p <0.001), FSH (WMD: -1.73 IU/l, 95%CI: -2.67 to -0.79, p <0.001) and endogenous testosterone levels (WMD: -10.75 nmol/l, 95% CI: -15.01 to -6.49, p<0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values, whereas serum testosterone levels remained lower as compared to baseline (WMD: -9.40 nmol/l, 95% CI: -14.38 to -4.42, p<0.001). In addition, AAS abuse resulted in structural and functional sperm changes, reduction of testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities and subfertility. Conclusion The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. AAS use results in profound and prolonged effects on the reproductive system of athletes and potentially on fertility.

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