Androgens have valid medical uses but they can also be misused or abused.
This article supports GPs to understand and diagnose androgen abuse in their patients. GPs have a role in managing the cessation of androgen abuse, usually under the guidance of an experienced endocrinologist.
What is androgen abuse?
Androgen abuse is when androgens are used for a purpose (or purposes) that has no medical indication.
It often involves large doses (and multiple other drugs taken simultaneously) which provide a vastly higher level of androgen action than is required for physiological replacement in legitimate androgen deficiency1.
What is the prevalence of androgen abuse?
The extent of androgen abuse is unknown. However, it is estimated that lifetime use in the general population is probably 1-5% globally, with prevalence at least 50 times higher in men than women1.
Two per cent of Australian secondary school students report using androgens and other performance and image-enhancing drugs3.
When is the use of androgens appropriate?4
Legitimate androgen uses include testosterone replacement for androgen deficiency due to pathological hypogonadism, pharmacological use for non-androgen deficiency, and research.
Testosterone replacement for androgen deficiency
Pharmacological use for non-androgen deficiency
When does androgen use become misuse or abuse?4
Androgen misuse
Androgen abuse
Compounds commonly used in combination with androgens2
Androgen abuse often involves administration of multiple substances (“stacking”) and various dosing regimens.
Cycles of use, lasting for several weeks or months (interspersed with periods of abstinence, for “recovery”) are usual, with an entrenched but incorrect belief that it is possible to maximise anabolic effect while minimising androgenic impact2.
This is biologically implausible given the action of androgens through a single type of androgen receptor.
Antiestrogens (clomiphene, tamoxifen) and aromatase inhibitors (letrozole, anastrozole, exemestane) are used to reduce the risk or extent of androgen-induced gynaecomastia.
This is often unsuccessful, and these drugs have inherent adverse effects such as bone loss and increased thromboembolic risk.
These drugs, together with injectable hCG, are also used as “post-cycle therapy” in an attempt to reverse the androgen-induced suppression of sperm and testosterone production.
However, there is no evidence these regimens restart the reproductive system.
Sources of androgens and other substances
The internet is a common source of androgens and other drugs used in combination, but there is concern about the actual content, purity and safety of any agents obtained in this way6.
People who misuse or abuse androgens may attempt to obtain prescriptions from doctors7, whose compliance would constitute professional misconduct.
Dietary supplements
Contamination of protein supplements with biologically active androgens8,9,10 can result in an identical clinical and biochemical picture to androgen abuse. Close examination of products acquired through gyms or the internet is required.
The Australian Institute of Sport classifies dietary supplements according to scientific and practical considerations related to safety, efficacy and permissibility, and provides guidance for choosing safe products11.
GPs should advise patients to eat healthy food rather than use supplements. Supplements do not contain all the nutrients in whole foods and cannot compensate for a poor diet12.
Diagnosing androgen abuse
An effective way to know if a patient is abusing androgens is to ask them1, after establishing a trusting, non-judgemental relationship.
For patients with suspected androgen abuse, or who seek treatment for androgen abuse or its side effects, GPs should undertake an appropriate medical history, physical examination and laboratory tests.
Typically, serum LH, FSH and SHBG will be suppressed. Serum testosterone levels will vary. High levels will be obtained if testosterone administration is recent.
Low levels will occur if synthetic androgens (which are not detected by testosterone immunoassays) are used, or during the withdrawal phase when hypogonadotrophic hypogonadism is induced.
Medical history
Physical examination
Investigations
Physical signs of androgen abuse
Psychological signs of androgen abuse
Adverse psychological effects of androgen abuse
Adverse physical effects of androgen abuse
Managing androgen abuse
Practice guidance for ceasing androgen abuse
There are no clinical trials of managing patients from the public who abuse androgens13, so information to guide practice14 is limited to that from observational studies15,16,17.
Treatment usually requires a multidisciplinary approach involving a GP, endocrinologist and psychologist. A formal care plan could facilitate this approach and would also aid patient education for long-term behaviour change.
The focus of care should be the efficient and permanent cessation of the androgen abuse.
The best option is a supportive approach analogous to that used for other social drugs (e.g. alcohol, caffeine, cocaine) and behavioural disorders (e.g. anorexia nervosa, muscle dysmorphia).
It may be helpful to provide encouragement and advice that reproductive function will recover with time, and patience.
Referral for psychological assessment and possible therapy may benefit patients who abuse androgens because of body image issues18.
GPs should advise patients who are unwilling to cease androgen abuse of the adverse effects of continued use, focusing on the potential consequences for their fertility and long-term cardiovascular health.
This includes counselling about the health risks associated with using potentially unknown substances and self-injecting.
There is no legal pathway for the prescription of testosterone or synthetic androgens without a legitimate medical indication. Medical practitioners should not continue to supply drugs and medications that facilitate androgen abuse.
Developing a trusting clinician-patient relationship may help the discontinuation of androgen abuse.
Withdrawal symptoms
People who abuse androgens develop psychological and physical dependence. Withdrawal symptoms include decreased sexual drive and a flu-like syndrome comprising fatigue, headache, musculoskeletal pain and insomnia, followed by depression19.
These features are like those from caffeine or benzodiazepine withdrawal, less severe than those from nicotine withdrawal, and without the potential fatality of withdrawal from alcohol, amphetamines or opiates.
Fertility recovery
Many men who abuse androgens seek assistance with discontinuation because of infertility. Cessation of androgen abuse often allows recovery of fertility within 6-18 months20,21.
Recovery of endogenous gonadotrophins, testosterone and spermatogenesis may take many months. The duration of recovery depends mainly on the time since cessation.
Ad hoc treatment with anti-estrogens, aromatase inhibitors or hCG lacks any sound evidence for safety and efficacy.
If there is claimed urgency for recovery of spermatogenesis (e.g. restoration of fertility for a man with a female partner of advanced age), consultation with an experienced endocrinologist is essential because potential treatment may be subject to restrictions based on ‘off-label’ uses and/or uncertain safety considerations.
Free clinical resource
This resource was produced in response to requests from Australian GPs for information to help them respond to androgen abuse. Healthy Male supports GPs in their goal of helping patients to cease this damaging behaviour.