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Users of illicit anabolic steroids may have impaired testicular function even years after they stop using the performance-enhancing drugs, a cross-sectional study suggested.

Median levels of serum insulin-like factor 3 (INSL3), a biomarker of Leydig cell capacity, were significantly lower in men who reported current anabolic steroid use compared with those who never used anabolic steroids (0.04 µg/L vs 0.59 µg/L, P<0.001), reported Jon Rasmussen, MD, PhD, of Rigshospitalet in Copenhagen, Denmark.

INSL3 levels were also significantly lower in a group of former anabolic steroid users with an average of 2.6 years since they stopped using the drugs (0.39 µg/L, P>0.001), even after adjusting for serum total testosterone and other potential confounders, according to the study online in the .

Furthermore, in a linear regression analysis, longer duration of anabolic steroid use in the former users was also significantly associated with lower INSL3 levels (P=0.022). And INSL3, but not testosterone or inhibin B, was significantly linked with testicular size (P=0.030), the study found. The researchers did not assess sperm function.

"The present clinical study provides novel data suggesting persistently impaired Leydig cell capacity in many illicit AAS [anabolic androgenic steroid] users," the study authors wrote. "Furthermore, we noted that the accumulated duration of AAS use was associated with lower serum INSL3 levels in former AAS users, indicating that a clinically relevant dose-response relationship may play a role."

Illicit anabolic steroid use, which has been common among body builders and elite athletes for decades, is becoming more frequent in the general population, the researchers noted. One study put the prevalence at 18% of individuals involved in recreational sports and 1% among non-athletes. Another study estimated the prevalence among U.S. men in general to be approximately 2%, Rasmussen and co-authors added.

Hypogonadotropic hypogonadism, caused by high levels of circulating androgens inhibiting the hypothalamus-pituitary-gonadal axis, is a known consequence of illicit anabolic steroid use. However, the extent to which the body can recover from this condition if the drugs are stopped is not known, the researchers explained.

A conducted by Rasmussen's group found lower testosterone levels and reduced testicular size after more than 2 years after the drugs were stopped. Another , however, reported normalized testosterone levels in previous steroid users, although their testicles remained smaller.

Asked for his perspective, Shalender Bhasin, MD, director of Research in Men's Health: Aging and Metabolism at Harvard Medical School in Boston, who was not involved with the study, said anabolic steroid use is more prevalent than people realize: "The vast majority of anabolic steroid users are not elite athletes. In fact they're not athletes at all -- they are recreational body builders," he told 乌鸦传媒.

Some of these men have been using large quantities of the steroids for decades, and when they stop they go through a period of withdrawal hypogonadism, Bhasin explained. Some never recover testicular function, and some only recover partially.

"This paper confirms, using a different marker of Leydig cell function, that some of the long-term anabolic steroid users, even after 3 years of withdrawal, have impaired Leydig cell function, and that is consistent with our clinical experience," Bhasin said. As many as 20% of men getting testosterone prescriptions at men's health clinics may be former anabolic steroid users, which has become a common cause of testosterone deficiency, he added.

"Testosterone use is associated with dependence, similar to many other substances of abuse," he continued. "And so many of these people will relapse, and we need to be cognizant of that, and treat it not just as a problem of testosterone deficiency but as a body-image disorder with some elements of dependence, which could lead to relapse and continued seeking behavior."

Rasmussen's group conducted a community-based cross-sectional study that included 132 men ages 18 to 50 who were involved in recreational strength training. Approximately one-third of the men (46) were current anabolic steroid users; 42 were former users, and a control group of 44 had never used the drugs.

Each man participated in one study visit, during which blood was drawn and medical history and anabolic steroid use were assessed with a structured interview. Blood was analyzed for INSL3 and total serum testosterone with liquid chromatography mass spectrometry.

Limitations of the study, the team noted, included its cross-sectional design, which could not assess testicular function before, during, and after anabolic steroid use. In addition, the study relied on self-reports of illicit steroid use. However, none of the men who reported being non-users or former users showed any biochemical signs of ongoing anabolic steroid use, the researchers said.

"In conclusion, serum INSL3 levels are lower in former AAS users than in never-users of AAS even years after AAS cessation, suggesting that impaired Leydig cell secretory capacity could persist for years in former AAS users," Rasmussen and co-authors wrote. "The implications of these findings need further investigation such as a trial investigating the effect of stimulation therapy to recover Leydig cell capacity in past AAS users."

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