Is thyroid replacement a performance-enhancing drug?

For example, whether “banned drugs” are interpreted as including the widely used (but non-banned) nutritional supplements which athletes are urged to avoid for fear of adulteration with unlabeled banned substances. Detection of EPO in urine synthroid kairos is difficult because of the prevailing low concentrations and need to distinguish exogenous recombinant from endogenous EPO. Although further refined (165) and extended to other EPO analogs (166), the immune-electrophoresis test is sensitive but relatively laborious and provides only a short window of detection of up to a week post-administration (167). More sensitive methods based on proteomics (for EPO analogs with differences in primary structure) together with glycomics (for biosimilars and analogs which have host-cell specific variations in side-chain glycosylation but unchanged natural EPO primary structure (168)) are possible but not yet approved. Similarly, preliminary investigations have proposed a EPO-induced gene expression signatures as a biomarker to detect EPO administration but specificity relative to exercise and other physiological effects remain to be clarified (170).

Data Availability

In 2017, at the WADA accredited antidoping laboratory of Rome, the athletes declaring to consume this kind of substances, was ten times higher compared to the prevalence of hypothyroidism in Italy. This high incidence of their consumption among the athletes in conjunction with their metabolic actions and the consequences of their intake over the health, impose to investigate which is the real use of these compounds and to start to investigate a new potential doping practice. Indirect methods to increase hemoglobin include administration of recombinant human EPO or its analogs as well as hypoxia-mimetic drugs (hypoxia-inducible factor stabilizers, iron chelation, cobalt, 2,3 diphosphoglycerate analogs) or artificial oxygen carriers (perfluorocarbons, hemoglobin-based oxygen carriers). Related but non-banned methods include altitude training or its simulation by sleeping in hypoxic rooms which are less effective than hemoglobin doping (129).

Regarding to Endogenous Steroid Profile in urine, differences in the markers of the ABP steroidal module were found considering samples of athletes declaring and not declaring the supplementation with TH in the Doping Control Form. Although not all assessed parameters showed significant differences, there was observed a tendency to decrease steroid concentrations in the group of athletes who declared the consumption of levothyroxine. The information on TH therapy by athletes may be helpful for the correct interpretation of the ABP as happens for other markers considered confounding factors of the urinary steroid profile in the current WADA documents. However, the high efficiency of the HTP axis (which proved to be, throughout the study, the most strict, refined, and exquisite) does not allow us to observe differences between athletes who do not declare and those who declare having used TH supplementation.

While MS is highly effective for detecting specific androgens, it requires knowledge of the chemical structure to be detected and otherwise cannot be applied. This principle applies to never-marketed designer or nutraceutical androgens sold over the internet or in unregulated over-the-counter nutritional supplements with unlabeled steroid content. A potential solution is the modern in vitro androgen bioassay that incorporates the human androgen receptor together with a convenient transactivation chemical read-out signal into a host yeast or mammalian cell (79). This has the generic capacity to detect all bioactive androgens regardless of structure due to their direct activation of the androgen receptor.

Thyroid Medication Will Remain Legal for Elite Athletes

• Increased metabolic rate as a consequence of endogenous or exogenous excess thyroxine could theoretically lead to a situation of unintentional low energy availability and the adverse clinical sequalae of RED-S.
• Important caveats on interpreting these few well designed studies are that the effects of higher GH and T doses, as used in doping, have not been studied so that more potent higher dose and/or interactive effects cannot be excluded in the absence of well controlled, high dose, placebo-controlled studies.
• However, little is still known of the genotype-phenotype correlations that underlie beneficial genetic endowments for sports performance.
• One had a high serum T4 (153 nmol/L) and FT4 (24.8 pmol/L) with normal serum T3 and FT3, and the remainder had normal serum T4, T3, FT4, and FT3.
• Other than its proper medical use in diabetics, the use of insulin and its analogs for doping is based solely on its easy availability coupled with anecdotal information from other drug users.

While notionally sold solely for laboratory research, these unregulated products are available for purchase over the internet. Promoted by speculative fantasies on their mode of action coupled with testimonials to their efficacy but without objective testing or assurance of safety in humans, they are believed to be widely used by gullible and/or desperate athletes and their trainers. As unregistered drugs, this growing range of peptides appears to constitute a greater threat to athlete’s health than a risk of effective cheating.

While every sport requires an acquired skill, some are largely or solely based on skill and concentration (e.g. board games, target shooting, car driving, and motor-cycle riding) and may benefit from drugs that reduce anxiety, tremor, inattention or fatigue. Sports that are highly dependent on explosive, short-term anaerobic power (sprinting, throwing, boxing, wrestling), typically ones which favor a stocky, muscular build, are most susceptible to androgen-induced increases in muscle mass and strength. Other sports with an emphasis on aerobic effort and endurance (e.g. long distance or duration events), characteristically favored by a lean build, may be boosted by hemoglobin doping (blood transfusion, erythropoietin (EPO) and its analogs or mimetics. Finally, sports that depend on recovery from major injury or recurrent minor injury during intensive training, notably contact sports, may benefit from tissue proliferative and remodeling effects of growth hormone and various growth factors. Administration of exogenous GH suppresses endogenous pituitary GH secretion leading to a predominance of circulating 22 kD GH. This ratio test then serves to detect administration of exogenous recombinant human 22kD GH analogous to detection of exogenous T by the urine T/E ratio and exogenous insulin by analysis of serum C peptide (224).

Constructed in vitro androgen bioassays feature a sensitive dose-response signal proportional to the potency of the bioactive androgen (80-83). Yeast host cells have high specificity for detecting androgens but are less sensitive than mammalian cells, which express native steroid mechanisms including steroidogenic enzymes and/or other steroid receptors. Mammalian in vitro androgen bioassays can also detect pro-androgens, steroids lacking intrinsic androgenic bioactivity but which are converted into androgens within the mammalian cell. Hence, while mammalian host cells sacrifice specificity for higher sensitivity, they can also detect pro-androgens (79).

Data Analysis

It could continue to be treated like inhaled anti-asthma medications, where asthmatic athleteswho require treatment would otherwise be at a serious disadvantage in athletic competitions. Or it could be that thyroid replacement could be scrutinized even more closely, perhaps requiring better documentation to justify use in an athlete, requiring clearly-demonstrated medical need based on a specific set of parameters, recognizing that there’s thyroid replacement, and then there’s unnecessary supplementation. From my personal perspective, I’m skeptical of medical mavericks who haven’t yet produced enough evidence to convince their peers and change the medical consensus. Direct androgen doping involves administration of testosterone, natural or synthetic androgens whereas indirect androgen doping includes a variety of non-androgenic drugs which increase endogenous T. Direct androgen doping originally involved all pharmaceutically marketed natural (T, DHT, nandrolone) and synthetic androgens but has extended to non-marketed designer and nutraceutical androgens as well as pro-androgens (androstenedione, DHEA) and the new class of non-steroidal androgens (selective androgen receptor modulators, SARM (40)). Indirect androgen doping involves use of hCG, LH, anti-estrogens (estrogen receptor blockers, aromatase inhibitors), opioid antagonists, and neurotransmitters involved in neuroendocrine regulation of endogenous LH and T secretion (41-44).

• This approach was simplified by a second generation algorithm using only routine hematological parameters (hemoglobin, reticulocytes) (154), and was subsequently combined with the concept of a sequential development of individual-specific reference ranges (155) into a third generation algorithms (156,157) which were refined for the ABP (148,149).
• The empirical reference range for serum FT4 and FT3 was only minimally higher than the manufacturer’s recommended expected range, though the origins of those reference ranges are not disclosed.
• As with all biological homeostatic mechanisms, there is some physiological variation within the normal range for an individual.
• Serum TSH (left panel), T4 (upper middle panel), T3 (lower middle panel) and T3 to T4 ratio (right panel).
• Anti-Doping Agency and its British counterpart, the World Anti-Doping Agency will continue to allow elite athletes to take thyroid medication.

But among those who have publicly acknowledged being treated for thyroid problems by Brown or unnamed other physicians are American runners Ryan Hall, Galen Rupp, Amy Yoder Begley, Bob Kennedy and Patrick Smyth. “I knew hypothyroidism was kind of like something that was being diagnosed more among elite runners,” said Smyth, a marathoner who in 2011 started feeling chronically tired. When a physician near his California home found no evidence of thyroid dysfunction, Smyth flew to Houston to see Brown, who conducted some blood tests and diagnosed him with the condition. Two of 500 serum samples (184 females, 316 males) were unusable due to severe hemolysis so the analysis included 498 samples from 27 sporting discipline groups with the most frequent comprising football codes 127, aquatic sports (swimming) 76, cycling 75, weightlifting 66, and athletics 38.

REFERENCES

• The biological basis of ergogenic effects of GH have been tested in these two different scenarios with largely inconclusive findings.
• This claim is difficult to evaluate and no well controlled studies of recovery from sports injuries or tolerance of training intensity in elite athletes are reported.
• Another study of long-term storage at −80 °C demonstrated inconsistent serum TSH, FT4, and FT3 measurements using different assays.
• These include measuring urinary excretion of phthalates, plasticizers that leach out from the polyvinylchloride blood packs used to store venesected blood (141).
• Nevertheless, ergogenic effects of GH remain unproven and largely speculative as discussed in excellent recent reviews ( ).

Naïve arguments are made that deny doping is cheating, or unsafe or violates the spirit of sport and asserting that drugs should be freely available or under medical supervision (4-6). However, removing prohibition on doping would immediately render drug taking as pervasive as training in elite sport extending to promising underage and sub-elite athletes. Ensuing demands on doctors to prescribe excessive, often massive, drug doses without medical indications would be unprofessional, unethical, and unsafe. This could convert sporting participation into a potentially dangerous rather than a healthful activity.