Nate Marquardt (above, file photo) has undergone testosterone replacement therapy. | (AP photo/Jack Dempsey)

Another elite mixed martial artist has fallen to the Catch-22 of steroid use.The allure of male androgens for fighters is as undeniable as it is understandable. Athletes can benefit from the additional strength to be gained from supplementing their natural testosterone levels with exogenous steroids. Fighters benefit particularly from increased lean muscle mass, increased endurance, more rapid healing and, crucially, aggression. Testosterone is the mother’s milk of combat.Anti-doping boards are not unaware of the appeal of illicit steroid use. Their diligence and increasing sophistication at detecting synthetic steroids has driven athletes who wish to use steroids in two directions: either towards undetectable designer steroids or into the arms of laboratory-engineered testosterone. The benefits for an athlete who chooses pharmaceutical-grade testosterone are numerous, not least of which is the ability to trade the skullduggery of the illicit drug market for the civility of a doctor’s office and prescription pad.Both Chael Sonnen and Nate Marquardt freely admit they took this path, supplementing their natural testosterone with pills and injections. However, they both claim that their steroid use is legitimate because they suffer from male hypogonadism -- the sole disease for which testosterone replacement therapy is a well-established therapy. And, in fact, they both almost certainly do.Hypogonadism is a condition in which the gonads -- ovaries in females and testes in males -- fail to produce adequate amounts of sex hormones. Clinically, hypogonadism is separated into prepubertal and late onset. Pre-pubertal hypogonadism in males can be easily missed. In the absence of informed and attentive parents and pediatricians, these boys and young men fall behind their peers in growth, muscular development, hair growth and all of the secondary sexual characteristics associated with the transition from boyhood to manhood. It is devastating.Both Marquardt and Sonnen claim to suffer the symptoms of late onset gonadal failure: lethargy, fatigue, decreased sense of well-being, reduced physical and mental activity, diminished libido, increased sweating and depressive mood. They both report blood tests showing sub-physiologic levels of testosterone. To date, neither fighter has a clear diagnosis for the cause of their hypogonadism, and this is the crux of the matter. While there are many causes for hypogonadism, statistically -- in light of the fact that both men are elite athletes in the prime of life, and that one of them has already failed an athletic commission steroid test -- one must consider the possibility that their hypogonadism may be caused by previous steroid use.All state athletic commissions allow testosterone replacement therapy for hypogonadism. They require only that the fighter obtain permission well in advance of competition and stay within certain dosing parameters. Marquardt and Sonnen appear to have forgone those requirements.Marquardt stated that he first realized there might be a problem with his testosterone regimen when the New Jersey State Athletic Control Board notified him of an “incompletion” in his TRT therapeutic exemption documentation.Counsel to the NJSACB Nick Lembo later stated that Marquardt was allowed to compete at March’s UFC 128 because he was “going through the process” of applying for a TUE. Part of the agreement that allowed him to compete included him submitting to the state's normal protocols for granting the exemption.Those guidelines, which are similar to the United States Anti-Doping Agency policy, state all applicants need to come off therapy for a minimum of two months, and preferably three, to establish a baseline level of testosterone.Another issue the NJSACB raised -- and a point backed up by Marquardt -- pinpointed the fact that he was seeing his primary-care physician rather than a board-certified endocrinologist as required by both the USADA and the NJSACB.Once Marquardt went off of the synthetic testosterone, he encountered a scenario that would be hard for any man: wrestling the emotional and physical strain of suddenly being testosterone-free. For a combat fighter training for his next fight, it would be devastating.According to his interview with Ariel Helwani on “The MMA Hour,” at the end of that eight-week period, Marquardt’s hormone levels were such that he was deemed to be hypogonadal and a candidate for TRT. The problem he then faced was that athletic commissions monitor a T/E ratio to limit how much testosterone can be taken, even for fighters who have received clearance to use synthetic hormones.When the gonads produce testosterone, they also produce epitestosterone -- a chemical in all respects identical to testosterone but for a “cis”-hydroxyl group in place of testosterone’s “trans”-hydroxyl. In both men and women, the ratio of these two chemicals -- vital testosterone and biological waste epitestosterone -- produced by the body and excreted in the urine is 1:1. Taking synthetic testosterone increases that T/E ratio.A man whose testicular function is so diminished that he meets criteria for TRT would also be faced with the difficulty of not producing sufficient natural epitestosterone. For most men, this would be of no importance -- epitestosterone plays no role on male physiology -- but for a fighter, it would mean that he could take only very small sub-physiologic doses of synthetic testosterone without going over the accepted 6:1 T/E threshold.This is the Catch-22 of steroid use. Once a person has started taking exogenous steroids, whether for legitimate reasons or not, it is nearly impossible to stop.It is possible to coax testes that have been shut off by steroid use back to life. The process is time consuming and expensive, and it would never have returned Marquardt’s testosterone to functional levels in time for his fight.The alternative Marquardt and his physician opted for was an injection of testosterone, gambling that the testosterone would help him train for the fight and drop to acceptable levels by fight day. They were close; according to his agent, Marquardt’s levels were within the acceptable range only 24 hours after weigh-ins. Perhaps the weight cutting disturbed his metabolism. Or perhaps his physician was unfamiliar with the nature of synthetic testosterone clearance.The future is uncertain for Marquardt, but his present is grim. Temporarily stripped of his career, he has fallen by the wayside of a sport rapidly ascending. Hopefully, his body and career will heal in time.