Understanding and managing the suppression of spermatogenesis caused by testosterone replacement therapy (TRT) and anabolic–androgenic steroids (AAS)

Abstract

Use of testosterone replacement therapy (TRT) and anabolic–androgenic steroids (AAS) has increased over the last 20 years, coinciding with an increase in men presenting with infertility and hypogonadism. Both agents have a detrimental effect on spermatogenesis and pose a clinical challenge in the setting of hypogonadism and infertility. Adding to this challenge is the paucity of data describing recovery of spermatogenesis on stopping such agents. The unwanted systemic side effects of these agents have driven the development of novel agents such as selective androgen receptor modulators (SARMs). Data showing natural recovery of spermatogenesis following cessation of TRT are limited to observational studies. Largely, these have shown spontaneous recovery of spermatogenesis after cessation. Contemporary literature suggests the time frame for this recovery is highly variable and dependent on several factors including baseline testicular function, duration of drug use and age at cessation. In some men, drug cessation alone may not achieve spontaneous recovery, necessitating hormonal stimulation with selective oestrogen receptor modulators (SERMs)/gonadotropin therapy or even the need for assisted reproductive techniques. However, there are limited prospective randomized data on the role of hormonal stimulation in this clinical setting. The use of hormonal stimulation with agents such as gonadotropins, SERMs, aromatase inhibitors and assisted reproductive techniques should form part of the counselling process in this cohort of hypogonadal infertile men. Moreover, counselling men regarding the detrimental effects of TRT/AAS on fertility is very important, as is the need for robust randomized studies assessing the long-term effects of novel agents such as SARMs and the true efficacy of gonadotropins in promoting recovery of spermatogenesis.

Spermatogenesis recovery treatment in less than four months from zero to almost 16 million sperms per milliliter after several cycles of steroids in 44‐year‐old healthy man

“…Mechanism of action related to testosterone in male body, and it is correlations with spermatogenesis, hypothalamus, and anterior pituitary, is very well known 15 . Within a very short period of only few months of anabolic steroids use major side effects can occur 13–15,23 . The purpose of this case report is focus on spermatogenesis and blood tests parameters changes due to negative effect of testosterone, stanozolol, and oxandrolone.…”

“…According to literature and practical experiences, normal production of healthy sperms after steroid's use is having recovery period of 12–14 months 15 . To speed up this process, recommendation is to use clomiphene (25 or 50 mg daily) and human chorionic gonadotropin (daily dose 500–3000 UI) as combined therapy with minimum of 3 months treatment to optimal of 6–12 months 13–15 . Since clomiphene was showing improvement in sperm quality in almost 60% of patient in previous studies, 16 and combined treatment had around 67% of improvement in the period of 6 months, decision was to use only clomiphene.…”

“…Many different approaches have been used in the past, including medications and food supplements (mostly antioxidants) to improve sperm count in healthy males. [13][14][15][16][17][18][19][20][21][22] In this paper, we report the case of the healthy, sporty, intellectual, educated (pharmacist), and very active man in his early 40th. His example was unique due to very fast and unusually successful level of spermatogenesis recovery after several steroids' cycles (4 months after last steroid use and 3.5 months after therapy and habit changes).…”

“…In any case, use of anabolic steroids has direct and negative influence on spermatogenesis which was proven long time ago. Most of the scientific data are supporting reversibility of spermatogenesis in healthy men after steroid cycles 13–15 . However, depends on the age, time that steroids have been used, amount and type of steroids, damage that has be done, and overall condition of the person, spermatogenesis can be back to normal level (above 15 million sperms per milliliter) within 12–24 months after last uptake of steroids 13–15 or to limited level (below 15 million sperms per milliliter) without further improvements.…”

Trans Dermal Testosterone Compared to Intramuscular Testosterone for Young Males with Delayed Puberty: A PRISMA Guided Systematic Review

“…8,9 The typical clinical approach for adolescent males with CDGP or hypogonadism is the prescription for Testosterone Replacement Therapy (TRT). Currently various choices of interventions for TE replacement and management for adults are available, including intramuscular (IM), subcutaneous, oral and transdermal preparations, [10][11][12][13][14][15] but the right tittered choice and mode of administration of TE for young adults are not available. [16][17][18] Pitfalls in the use of TE usages for adolescents have disclosed multitudes of risks, associated behavioral deviations in the pre pubertal group and below target height line achievement with non-advancement of one's age which has generated a warning for its usage.…”