How to recognise and respond to androgen misuse and abuse

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.

Commonly abused androgenic substances^1,2: 

• Boldenone undecylenate (Equipoise, Parenabol)
• Clostebol acetate (Steranabol)
• Chlorodyhydromethyl-testosterone (CDMT)
• Dihydrotestosterone
• Drostanelone propionate (Dromostanalone, Masteron)
• Fluoxymesterone (Halotestin, Ultandren)
• Formebolone (Esiclene)
• Mesterolone (Proviron)
• Metandienone (Methandorosteneolone, Dianabol)
• Methenolone acetate (Primabolon)
• Methyltestosterone (Android, Metandren, Testred)
• 19-Nortestosterone (Nandrolone, Deca- Durabolin)
• Oxandrolone (Anavar)
• Oxymetholone (Anadrol)
• Stanozolol (Winstrol)
• Testosterone (Sustanon, Testo depot, Nebido)
• Tetrahydrogestinone (THG, The Clear)
• Trenbolone ethanate (Trenabol, Parabolan)

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

• Primary testicular failure (hypergonadotrophic hypogonadism)
  - Klinefelter syndrome and other genetic disorders
  - Testicular trauma, torsion, infection or excision (orchidectomy)​​​​​​
  - Testis atrophy
• Secondary testicular failure (hypogonadotropic hypogonadism)
  - Congenital (e.g. Kallman’s syndrome and variants)
  - Acquired (prolactinoma, pituitary disease, surgery, radiotherapy)
• Gender-affirming treatment for transgender and gender-diverse people⁵
• Delayed puberty

Pharmacological use for non-androgen deficiency

Androgens can be used to treat the following conditions (typically using synthetic androgen receptor modulators rather than testosterone):

• Osteoporosis (including corticosteroid-induced bone loss)
• Anaemia (due to bone marrow or renal failure)
• Advanced breast cancer
• Cachexia or wasting
• Burns
• Hereditary angioedema

Research

• Functional low testosterone, chronic disease and ill health
• Male contraception

When does androgen use become misuse or abuse?⁴ 

Androgen misuse

Misuse occurs when someone uses androgens without medical indication or despite contraindication. For example, for:

• Male infertility
• Sexual dysfunction (in the absence of androgen deficiency due to pathological hypogonadism)
• “Low T (testosterone)”, “late-onset hypogonadism”, “male menopause”, “andropause”, functional hypogonadism
• Non-specific symptoms (e.g. lethargy, tiredness)
• Ageing

Androgen abuse

Androgen abuse is classified as use without medical indication for:

• Physical performance (e.g. increased strength, endurance, recovery)
• Physical appearance (e.g. increased muscle mass)
• Occupational reasons (e.g. security staff, police, armed forces)

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.

The following medications are commonly used in combination with androgens. It is important to note the list below is for information only and is not an endorsement of clinical use. For each of these drugs, use in the context of androgen misuse or abuse is ‘off-label’, safety and efficacy is unproven and the rationale for their use is based on a poor understanding of complex endocrine mechanisms:

• Clenbuterol — a veterinary β2-adrenergic receptor agonist, used to increase muscle mass and reduce body fat
• Ephedrine, Synepherine — used to reduce body fat
• Growth hormone — used for its anabolic and lipolytic properties, and its potential to reduce muscle and tendon rupture
• Growth hormone releasing hormones/peptides (e.g. Modified GRF(1-29), Sermorelin, Ipomorelin, GHRP-2), HGH analogues (e.g. HGH Fragment 176-191) — falsely claimed to increase GH levels and muscle mass
• Human chorionic gonadotropin (hCG) — used to promote testicular testosterone production
• Recombinant human luteinising hormone (rLH) — may be promoted for stimulation of the testes but it is difficult to manufacture and exceedingly expensive, so marketed preparations are likely to be fake
• Insulin-like growth factor-1 (IGF-1) — used to increase muscle mass
• Clomiphene citrate and aromatase inhibitors — used to prevent gynaecomastia, promote testes growth and/or hasten recovery of the suppressed HPT axis
• Insulin — often used in combination with growth hormone to increase glucose uptake by muscle and adipose tissue, and inhibit protein breakdown
• Prohormones (e.g. androstenedione, dihydroepiandrostenedione) — used as substrate for androgen production
• Thyroid hormone (synthetic T3, T4 or natural extracts) — used to increase metabolism, thereby reducing body fat
• Prescription drugs (e.g. sedatives, analgesics, anti-inflammatories, PDE5 inhibitors, antidepressants, diuretics) — used to treat unwanted side effects of androgen abuse
• Illicit drugs (amphetamine, cocaine, cannabis, heroin) — may be used to lose or maintain weight, relax, or relieve pain

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 androgens^8,9,10 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

Social factors

• Education level
• Profession or occupation
• Sports and recreational activities (gym or other athletic activities, professional training)
• Marital and fertility status 
• Support network
• Alcohol and other drug use
• Other types of abuse

Medical and psychological factors

• Puberty
• Prior reproductive pathology
• Presenting complaint(s)
• Psychiatric health
• Sleep
• Sexual function and reproductive health
• Current diseases
• Current medications
• Current dietary supplement use
• Allergies/hypersensitivity
• Family history (especially prostate and cardiovascular disease)

Physical examination

• General appearance (height, weight, body mass index, muscularity)
• Testicular size and consistency, or cliteromegaly
• Skin (acne, stretch marks)
• Chest (gynaecomastia)
• Hair (premature baldness, body hair)
• Abdomen (hepatic enlargement)
• Heart and lungs (pulse, blood pressure, signs of heart failure, cardiac murmurs)
• Neurological assessment
• Musculoskeletal assessment

Investigations

Laboratory tests

• Reproductive hormones (testosterone, sex hormone binding globulin, luteinising hormone, follicle stimulating hormone)
• Other hormones, when considering hypothalamo-pituitary-adrenal function (insulin-like growth factor-1, thyroid stimulating hormone, T3, T4, prolactin)
• Liver function (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, bilirubin)
• Routine biochemistry and haematology (renal function, glucose, full blood count, lipids)

Imaging

• Liver scan, MRI or CT scan — rarely required unless there is a suspicion of hepatic dysfunction (fatty liver, peliosis or tumour)

Physical signs of androgen abuse

• Rapid and significant weight gain (approximately 10 kg in 2-3 months)
• Muscular physique (disproportionate muscle growth around chest, neck and shoulders)
• Preoccupation with physical fitness, diet or gym attendance
• Severe acne (mainly on back, shoulders and chest)
• Stretch marks (usually between biceps and pectoral muscles, possibly back and thighs)
• Excess body hair and/or accelerated baldness
• Hypertension
• Injection site swelling, tenderness, redness
• Tendon and muscle tears 
• Abnormal blood lipids
• Abnormal liver function

Male-specific physical signs of androgen abuse

• Gynaecomastia
• Subfertility
• Erectile dysfunction
• Testicular atrophy

Female-specific physical signs of androgen abuse

• Deeper voice
• Increased growth of facial and body hair
• Abnormal menstruation
• Clitoral enlargement

Psychological signs of androgen abuse

• Aggression
• Impulsivity
• Altered libido
• Anxiety
• Dysphoria
• Depression
• Empathy disorder
• Jealousy
• Muscle dysmorphia
• Mood instability
• Panic attack
• Psychosis
• Reduced mentalising capacity
• Sleep disorders
• Suicidal ideation
• Suicide attempt 
• Violence
• Worry

Adverse psychological effects of androgen abuse

• Irritability
• Nervousness
• Aggressiveness
• Recklessness
• Self-aggressiveness
• Dependence 
• Withdrawal syndrome 
• Depression
• Suicidal ideation

Adverse physical effects of androgen abuse

Haematological system

• Polycythaemia

Cardiovascular system

• Dyslipidaemia
• Coronary heart disease 
• Myocardial infarction
• Hypertension
• Abnormal ECG
• Arrhythmia
• Left ventricular hypertrophy
• Hypertrophic cardiomyopathy
• Dilated cardiomyopathy 
• Heart failure
• Sudden cardiac failure

Hepatic system

• Cholestasis
• Hyperbilirubinaemia
• Steatosis
• Peliosis
• Adenomas
• Hepatocellular carcinoma 
• Liver coma

Integumentary system

• Acne
• Striae distensae
• Profuse sweating
• Alopecia 
• Hirsutism

Renal system

• High creatinine
• High cystatin C
• Glomerulosclerosis
• Cholemic nephrosis (bile cast nephropathy)
• Renal failure

Reproductive system

Male:

• Decreased testis volume
• Impaired spermatogenesis
• Infertility
• Low libido
• Erectile dysfunction
• Gynaecomastia
• Hypogonadism

Female:

• Anovulation
• Amenorrhoea
• Dysmenorrhoea
• Infertility

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 studies^15,16,17.

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 months^20,21. 

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

Download the clinical summary guide as a print-ready PDF:
 
Androgen Use, Misuse and Abuse

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.