Higher Myonuclei Density in Muscle Fibers Persists Among Former Users of Anabolic Androgenic Steroids

Abstract

Background and objective No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AAS) usage on the myocellular properties of human skeletal muscle in previous AAS users. We hypothesized former AAS users would demonstrate smaller myonuclei domains (i.e., higher myonuclei density) compared to matched controls. Methods A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. Results Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101–206) and 140 (24–260) weeks in current and former AAS users, respectively (P = 0.482). Geometric mean (95%CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA-to-cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = 0.013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users, beta-coefficient (95%CI), -94 (-169; -18), P = 0.024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = 0.031) compared to controls. Conclusion Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA-to-cytoplasm ratio four years after AAS cessation suggestive of enhanced retraining capacity.

Early Life Androgen Administration Attenuates Aging Related Declines in Muscle Protein Synthesis

“…An additional limitation was that our D 2 O integration period was only 24 h, which is just snapshot over a 7-month period. However, this provides strong evidence that the effects of early AAS use are long-lived and are in agreement with the idea of a potential muscle memory mechanism (15,25). Although previous research supports an androgen-induced muscle memory, more work is required to fully understand the mechanisms involved and to develop effective interventions to prevent or treat age-related declines in protein synthesis rates.…”

“…Previous work has demonstrated that brief exposure to androgens has a lasting effect on muscle size and myonuclear number resulting in a higher myonuclei density (15). Recent work observed similar findings in humans (25) whereby former AAS users have an increased transcriptional capacity as represented by a higher myonuclei density and DNA-to-cytoplasm ratio. The increased capacity for mRNA transcription provides a plausible rationale for our observed effects of ND increasing muscle protein synthesis long after cessation of use.…”

“…However, the present article presents a subset analysis of a larger study (32) wherein ND-treated animals increased body mass by 3.5% and P-treated animal decreased by 3.6%, which was significantly ( P = 0.041) different between groups. Furthermore, previous work has indicated that early androgen use has positive effects on these outcomes long after androgen cessation (15,25). Our work implicates an increase in muscle protein synthesis as a mechanism for these improved functional outcomes.…”

Effect of Testosterone on the Thyroarytenoid Muscle and Lamina Propria of Female Rat Vocal Folds

“…This persistence may be linked to the concept of “muscle memory,” wherein the muscle remains hypertrophied or retains the ability to hypertrophy rapidly for years, even after serum testosterone levels have returned to normal 38 . Muscle biopsies from the vastus lateralis muscle demonstrated persistently elevated myonuclei density and DNA to cytoplasm ratio 4 years after discontinuing the use of AAS 39 . A potential pathway involving irreversible epigenetic methylation, which could be mediated by ARs, has been under investigation, although conclusive evidence is still lacking 40–42 …”

“…38 Muscle biopsies from the vastus lateralis muscle demonstrated persistently elevated myonuclei density and DNA to cytoplasm ratio 4 years after discontinuing the use of AAS. 39 A potential pathway involving irreversible epigenetic methylation, which could be mediated by ARs, has been under investigation, although conclusive evidence is still lacking. [40][41][42] Despite ARs were found in the LP, there was no effect of testosterone on HA concentration.…”