Fertility After Anabolic Steroid Use

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OBJECTIVE

To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized treatment regimen for spermatogenesis recovery.


DESIGN AND SUBJECTS

A retrospective analysis of a cohort of men with a prior history of anabolic steroid use and infertility complaints (between 2018 and 2022) was conducted.


EXPOSURE

The standardized treatment approach involved discontinuing testosterone replacement therapy and administering a combination regimen of clomiphene citrate and human chorionic gonadotropin for a minimum of 3 to 6 months. MAIN OUTCOME MEASURES: The main outcome measures included changes in sperm parameters, predominantly sperm concentration, and subsequent pregnancy outcomes.


RESULTS

A total of 45 men (median age 37 years, IQR 32-45) met inclusion criteria for this analysis. Median duration of prior T use was 4 years (IQR 1.3-10), with the two most common modalities consisting of injection therapy (43.5%) and oral therapy (34.8%). Median initial sperm concentration was 0 million/cc (IQR 0-1.15), and 23 (51.1%) men initially presented with azoospermia. The median duration of combination hCG/clomid therapy was 5 months (IQR 3-12). In initially azoospermic men (N:23), 5 were lost to follow-up, 6 (33.3%) progressed to severe oligospermia (<5 million/cc), 6 (33.3%) to oligospermia (<15 million/cc), 1 (5.6%) to normozoospermia (>15 million/cc), and 5 (27.8%) remained azoospermic following medical treatment for 6 months. Among the 24 couples who responded to the follow-up call, a total of 9 (37.5%) achieved a successful subsequent pregnancy. Of these, 33.3% (3 couples) used assisted reproductive technology (ART), while 66.7% (6 couples) conceived naturally. On logistic regression analysis, no significant predictors for improved sperm parameters or successful pregnancy were identified.


CONCLUSION

Despite appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with more than half showing limited improvement in semen parameters after six months of treatment. Only a fraction of men achieves normozoospermia following treatment. Further research is needed to explore predictors for improved sperm parameters and successful pregnancy outcomes in men with a history of anabolic steroid use.





Strengths of this study include a large study cohort relative to prior studies and the employment of a standardized treatment regimen, which allowed for proper analysis of outcomes. Furthermore, to the best of our knowledge, this is the first study to assess fertility outcomes including pregnancy rates and use of ART utilizing this standardized treatment regimen.

There are several limitations to this study to note. This was a retrospective review and subject to confounding variables which cannot be controlled for. Compliance with the treatment regimen, age of first steroid use, and recency of steroid use was not specifically evaluated and may have affected outcomes. Similarly, we do not have standard data on social history, such as alcohol use, tobacco use, occupational exposure, and exercise regimens, all of which may potentially influence outcomes. Furthermore, we found no significant predictors for improved sperm concentration on Journal Pre-proof logistic regression analysis; however, this may be in part to a small study sample which was not powered enough to detect statistically significant differences. Regarding the inclusion of BMI as a predictor, we note that BMI is not a great measure of adiposity, especially in a population of men who use steroids potentially for increasing muscle mass. Other measurements of adiposity such as waist circumference or body fat percent, data which is not available to us, would be a better indicator of adiposity. Lastly, with respect to fertility outcomes, our results may be affected by responder bias, in that those with successful fertility outcomes were more likely to respond to a follow-up call. On the same note, another limitation is not having comprehensive data on the types of ART used by the couples. We understand the value of such analysis and its implications for understanding the outcomes of men who achieved normozoospermia.

Future work should continue to investigate factors that may predict successful fertility outcomes in men with prior history of anabolic steroid use. In addition, sperm concentration was the main focus of this study; however, further analysis is required to assess effects of treatment protocols on other semen parameters, such as volume and motility. Lastly, this study evaluated one standardized treatment regimen for treatment of men with anabolic steroid use and future studies should investigate potential alternate treatment regimens with subsequent fertility outcomes.


In conclusion, our study contributes important insights into the management of infertility in men with a prior history of anabolic steroid use. Despite the implementation of appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with approximately 50% failing to demonstrate substantial improvement in their semen parameter even after undergoing a six-month treatment protocol. While the standardized treatment protocol resulted in improvements in sperm concentrations for many individuals, a substantial proportion of the men still faced challenges in achieving normozoospermia. Furthermore, the chances of achieving pregnancy through natural conception alone were found to be quite low, emphasizing the importance of ART procedures in assisting couples in this population. These findings underscore the need for comprehensive fertility counseling and personalized treatment approaches for men with a history of anabolic steroid use who are seeking to achieve parenthood.
 

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Table 1. Descriptive statistics of our cohort.
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*A significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with approximately 50% failing to demonstrate substantial improvement even after undergoing a six-month treatment protocol.
 
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