Clinical summary guide

Androgen use, misuse and abuse

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The GP’s role

General practitioners have a role in identification of androgen abuse and the management of its cessation, usually under the guidance of an experienced endocrinologist.

Overview

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 women.

Two percent of Australian secondary-school students report using performance and image enhancing drugs (including androgens).

Androgen abuse often involves massive doses and multiple drugs taken simultaneously that provide a vastly higher level of androgen action than required for physiological replacement in legitimate androgen deficiency.

Commonly abused androgenic substances

Table: Commonly abused androgenic substances

Legitimate androgen uses

Androgen misuse

Androgen abuse

Compounds commonly used in combination with androgens

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 impact; 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 in attempt to reduce the risk or extent of androgen abuse-induced gynaecomastia but 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 attempt to reverse the androgen-induced suppression of sperm and testosterone production.

However, there is no evidence that these regimens restart the reproductive system. From a theoretical perspective, accelerated recovery of testicular function would require ongoing treatment of yet more drugs and would have additional adverse effects.

In reality, cessation of androgen abuse is the only effective approach to recovery, which takes 6-18 months and clearly requires a doctor’s support, as for other behavioural disorders.

The list below, of medications commonly used in combination with androgens is for information only, not as an endorsement of clinical use.

Table: Compounds commonly used in combination with androgens

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 online. People who misuse or abuse androgens may attempt to obtain prescriptions from doctors, whose compliance would constitute professional misconduct.

Dietary supplements

Contamination of protein supplements with biologically active androgens can result in an identical clinical and biochemical picture to androgen abuse. Close examination of products acquired through gyms or online 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 products.

Patients should be advised to eat healthy food rather than use supplements. Supplements do not contain all the nutrients contained in whole foods and cannot compensate for a poor diet.

Diagnosis of androgen abuse

An effective means of knowing if a patient is abusing androgens is to ask them, after establishment of a trusting, non-judgemental relationship.

For patients suspected of androgen abuse, or who seek treatment for androgen abuse or its side-effects, an appropriate medical history, physical examination and laboratory tests should be undertaken.

Typically, serum LH, FSH and SHBG will be supressed. 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 signs of androgen abuse

Psychological signs of androgen abuse

Adverse effects of androgen abuse

Management of androgen abuse

There are no clinical trials of managing patients from the public who abuse androgens, so information to guide practice is limited to that from observational studies.

Treatment usually requires a multidisciplinary approach involving the combined efforts of the general practitioner, endocrinologist and psychologist.

A formal care plan could facilitate this approach and would also facilitate patient education for long term behaviour change. The focus of care should be for the expeditious and permanent cessation of this dangerous lifestyle choice.

A supportive approach that is analogous to that used for other licit and illicit social drugs (e.g., alcohol, caffeine, cocaine) and behavioural disorders (e.g. anorexia nervosa, muscle dysmorphia) is the best option. Encouragement and advice that reproductive function will recover with time, and that patience is necessary, may be helpful.

Referral for psychological assessment and possible therapy may benefit patients who abuse androgens because of body image issues. 

Patients who are unwilling to cease androgen abuse should be advised of the adverse effects of continued use, focussing on the potential consequences for their fertility and long-term cardiovascular health.

They should be counselled about the health risks associated with the use of potentially unknown substances and self-injecting.

Medical practitioners should not allow themselves to become resources for ongoing drug supply, including medications used in this subculture (e.g., anti-oestrogens, hCG), or to facilitate continuation of androgen abuse.

The development of a trusting clinician-patient relationship may facilitate discontinuation of androgen abuse. A care plan should be established, aimed at cessation, ideally performed by a supportive team with endocrine and psychological expertise.

Discontinuing androgen abuse

People who abuse androgens develop psychological and physical dependence. Withdrawal symptoms from discontinuation of androgen abuse include decreased sexual drive and a flu-like syndrome consisting of fatigue, headache, musculoskeletal pain and insomnia, followed by depression.

These features are like those from withdrawal from caffeine or benzodiazepines, less severe than those from withdrawal from nicotine, and without the potential fatality of withdrawal from alcohol, amphetamines or opiates.

There is no legal pathway for the prescription of testosterone or synthetic androgens without a legitimate medical indication. In fact, consistent prescriptions for androgens to abusers constitutes professional misconduct.

Therefore, general practitioners should offer supportive care and health monitoring aimed at cessation of androgen abuse, in the context of an agreed and active understanding of the goals of treatment within the limits of medical services for the patient. Referral to an experienced endocrinologist is advised.

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.

Recovery of endogenous gonadotrophins, testosterone and spermatogenesis, may take many months, with the duration of recovery depending mainly on the time since cessation. The outlook for recovery of fertility and testosterone production is generally very good but prolonged.

Ad hoc treatment with anti-estrogens, aromatase inhibitors or hCG lacks any sound evidence basis for safety and efficacy.

If there is claimed urgency for restoration 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.

This resource was produced in response to requests from Australian General Practitioners, for information to help them respond to androgen abuse.

Clinical review

Prof Mathis Grossmann, University of Melbourne

Androgen use, misuse and abuse

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