Cholestasis in Athletes: Causes and the Link With Pharmacology
Cholestasis means that bile does not flow properly from the liver to the intestine. In the general population it has many causes, but in sport one stands out: drug-induced liver injury linked to oral anabolic steroids, unregulated "research chemicals" and some herbal products. Our editorial team explains how the condition develops, how it is recognised and why it should never be self-managed.
What cholestasis is
The liver produces bile, which carries waste products such as bilirubin and helps digest fats. Bile travels through tiny channels between liver cells, into larger ducts and finally into the small intestine. Cholestasis occurs when this flow is reduced or blocked at any point.
Doctors distinguish intrahepatic cholestasis, where the problem lies inside the liver at the level of cells and small channels, from extrahepatic cholestasis, where a larger duct is obstructed, for example by gallstones or a tumour. Drug-related cholestasis is usually intrahepatic.
When bile backs up, bilirubin and bile acids accumulate in the blood. This produces the characteristic signs: yellowing of the skin and eyes (jaundice), dark urine, pale stools and often intense itching.
The European Association for the Study of the Liver (EASL) guidelines on cholestatic liver diseases describe a systematic approach to diagnosis, beginning with blood tests and imaging to exclude obstruction before considering drug-induced causes.
Causes relevant to sport
Athletes can develop cholestasis for the same reasons as anyone else: gallstones, viral hepatitis, autoimmune liver disease, pregnancy-related cholestasis or prescribed medicines such as certain antibiotics. These causes must always be considered first.
However, sport adds specific risk factors. The best documented is the use of 17-alpha-alkylated anabolic-androgenic steroids, oral compounds chemically modified to survive passage through the liver. A study by Robles-Diaz and colleagues from the Spanish DILI Registry described a distinct pattern of liver injury in people using illicit anabolic steroids, characterised by prolonged jaundice and marked rises in bilirubin.
Unlicensed products sold online, including selective androgen receptor modulators (SARMs) and so-called "prohormones", have also been linked to cholestatic injury in published case reports. Their contents are often unknown or different from the label.
Herbal and dietary supplements are another recognised cause. A review by Navarro and colleagues from the US Drug-Induced Liver Injury Network reported that the proportion of liver injury cases attributable to supplements has risen, with bodybuilding products and multi-ingredient weight-loss products prominent.
| Category | Examples | Typical pattern |
|---|---|---|
| Oral 17α-alkylated AAS | Illicit oral steroids | Bland cholestasis, prolonged jaundice |
| Unlicensed "research" compounds | SARMs, designer prohormones | Cholestatic or mixed injury |
| Herbal and dietary supplements | Green tea extract, multi-ingredient fat burners | Hepatocellular or mixed |
| Prescribed medicines | Some antibiotics, e.g. co-amoxiclav | Cholestatic, often delayed |
How the pharmacology causes injury
Drug-induced cholestasis often results from interference with transport proteins that move bile acids out of liver cells, such as the bile salt export pump. When these transporters are inhibited, bile acids accumulate inside liver cells and become toxic.
The 17-alpha-alkyl modification that allows oral steroids to resist breakdown is closely associated with this effect. Reviews by Solimini and colleagues and others summarise links between such compounds and cholestasis, peliosis hepatis (blood-filled cysts in the liver) and liver tumours including adenomas.
Individual susceptibility plays a role. Genetic variations in transport proteins may explain why some people develop severe injury while others do not. The risk cannot be predicted reliably in advance.
A serious complication of very high bilirubin levels is kidney injury, sometimes called bile cast nephropathy, which has been reported in severe AAS-associated cholestasis. This shows that the condition can affect organs beyond the liver.
Symptoms and tests
Recognising cholestasis early is important. Typical warning signs include:
- yellowing of the eyes or skin;
- persistent, often severe itching, especially of the hands and feet;
- dark, tea-coloured urine and pale or clay-coloured stools;
- fatigue, loss of appetite, nausea and weight loss;
- discomfort in the upper right abdomen.
Blood tests typically show raised alkaline phosphatase (ALP), gamma-GT and bilirubin. Clinicians calculate a ratio between ALT and ALP to classify injury as hepatocellular, cholestatic or mixed, as described in the review of drug-induced liver injury by Andrade and colleagues.
An ultrasound scan helps exclude gallstones and duct obstruction. Further tests may screen for viral hepatitis, autoimmune liver disease and other causes. A liver biopsy is occasionally required.
Athletes should be honest with their doctor about all substances used, including supplements and non-prescribed drugs. Doctors in the UK work under confidentiality rules, and accurate information is essential for diagnosis.
Treatment and outlook
The cornerstone of management is stopping the suspected substance. In many cases of drug-induced cholestasis, liver tests gradually improve over weeks to months, but recovery can be slow, and in AAS-associated injury jaundice may persist for a prolonged period.
Specialists may prescribe medicines to relieve itching and support bile flow. Hospital admission may be needed for severe jaundice, kidney problems or signs of liver failure. Self-treatment with "liver detox" supplements is not a substitute for medical care and can add further risk.
The US National Institutes of Health LiverTox database is a reference resource that clinicians use to evaluate drug-related liver injury.
Prevention is straightforward in principle: avoid non-prescribed hormonal drugs and unregulated products, use supplements from reputable sources, and tell your GP about everything you take. In the UK, anabolic steroids are Class C controlled drugs, and SARMs are not authorised medicines.
The editorial team's conclusions
Cholestasis is a serious liver condition in which bile flow is impaired. In athletes, oral anabolic steroids, unlicensed compounds and some supplements are recognised causes.
Symptoms such as jaundice, itching and dark urine require prompt medical evaluation, as complications can affect the kidneys and other organs.
Recovery is possible after stopping the culprit, but it may be slow and should be supervised by specialists.
Further reading on our site: liver function tests explained for athletes, hepatotoxicity of oral steroids, and the risks of unregulated supplements.
References
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–267.
- Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I, Stephens C, García-Cortes M, García-Muñoz B, et al. Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther. 2015;41(1):116–125.
- Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363–373.
- Solimini R, Rotolo MC, Mastrobattista L, Mortali C, Minutillo A, Pichini S, et al. Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping. Eur Rev Med Pharmacol Sci. 2017;21(1 Suppl):7–16.
- Andrade RJ, Chalasani N, Björnsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al. Drug-induced liver injury. Nat Rev Dis Primers. 2019;5(1):58.
- National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox: clinical and research information on drug-induced liver injury. Bethesda (MD): NIDDK; 2012–.
- https://compare-steroidi.com/prodotto/genotropin-36-iu-pfizer-labs
