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

Hum Reprod. 2021 Mar 18;36(4):880-890. doi: 10.1093/humrep/deaa366.

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.

Keywords: anabolic steroids; androgens; bodybuilding; post-cycle therapy; semen analysis; testosterone.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens*
  • Humans
  • Male
  • Prospective Studies
  • Semen Analysis
  • Spermatogenesis*
  • Testosterone

Substances

  • Androgens
  • Testosterone