Position Statement
Use and Misuse of Androgens

introduction

Androgens are hormones based on the structure of testosterone, the major male sex hormone. The main medical use of androgens is for androgen replacement therapy in patients with established androgen deficiency. Androgen deficiency occurs in 5 out of 1000 men and is caused by either testicular or hypothalamic-pituitary disease. The diagnosis may easily be missed, denying patients simple and effective medical treatment. The diagnosis of androgen deficiency involves recognising appropriate clinical features with confirmation by hormonal measurements (FSH, LH and testosterone.). In men with features suggestive of androgen deficiency this diagnosis is unlikely with testis volume > 20 ml without atrophy, and with a plasma testosterone consistently > 18 nmol/L. In men presenting with erectile dysfunction and no clinical evidence of hypogonadism the diagnosis of androgen deficiency is very unlikely if the plasma testosterone is consistently > 8 nmol/L. When the diagnosis is not clear, referral to an experienced clinical endocrinologist is recommended.

Extension of the indication for testosterone therapy to partial androgen deficiency remains to be fully evaluated for safety and efficacy. These potential indications include ageing in men, apparent androgen deficiency secondary to chronic disease. These areas remain suitable for carefully monitored clinical research.

Absolute contra-indications to androgen therapy are prostate and breast cancer. Screening of men on androgen replacement therapy for cardiovascular and prostate disease should be comparable to that of men of similar age.

Misuse of androgens (no acceptable medical indication) includes male infertility, male impotence without proven androgen deficiency, and "male menopause." There is no evidence at present that the modest decrease of circulating blood testosterone commencing in mid-life has any clinical significance. The risks and benefits of androgen therapy in this setting is being evaluated but no firm conclusions are yet available. Promotion of androgen therapy for ‘male menopause" is based on inadequate evidence and is inappropriate.

The ESA endorses the source document for this position statement, "Use, misuse and abuse of androgens, Conway et al. (Submitted for publication).

Key Messages

1. Androgen deficiency is a clinical diagnosis confirmed by hormone assays.
   
   
2. Androgen replacement therapy is usually life-long and should only be started after proof of established androgen deficiency. 
   
   
3. Testosterone rather than synthetic androgens should be used for androgen replacement therapy. 
   
   
4. Oral 17a -alkylated androgens are hepatotoxic and should not be use for standard androgen replacement therapy. If used, they require monitoring for hepatotoxicity. 
   
   
5. The therapeutic goal of androgen replacement therapy is to maintain physiological testosterone concentrations. 
   
   
6. Contraindications to androgen therapy are prostate and breast cancer. Precautions include lower starting doses may be required for older men and induction of puberty, avoiding parenteral administration for men with bleeding disorders, warning competitive athletes about risks of disqualification, and androgen-sensitive epilepsy, migraine, sleep apnea, polycythemia or fluid overload. 
   
   
7. Androgen replacement therapy should be initiated with intramuscular injections of testosterone esters, 250 mg per 2 weekly. 
   
   
8. Maintenance of ART requires tailoring treatment modality to the patient's convenience to ensure long-term therapeutic compliance. Modalities currently available include testosterone injections, implants or capsules. Choice depends on convenience, cost, availability and familiarity.
   
   
9. Androgen deficiency protects against prostate disease and men receiving androgen replacement therapy are not at higher risk of prostate disease than eugonadal men of comparable age.
   
   
10. Screening for cardiovascular and prostate disease among men on ART should be similar to, but no more intensive than, among eugonadal men of similar age.
11. Androgen administration may invoke placebo effects. In the absence of significant androgen deficiency, this can create transient symptomatic benefits that may subsequently wane causing confusion and dissatisfaction for patients and management difficulties for doctors. 
    
    
12. There is no indication for androgen therapy in male infertility. 
    
    
13. Androgen deficiency is an uncommon presenting cause of erectile dysfunction. All men presenting with erectile dysfunction should be evaluated for androgen deficiency. If androgen deficiency is confirmed, an underlying pathological cause needs further investigation.
    
    
14. At present, there is no convincing evidence that, in the absences of proven androgen deficiency, androgen therapy is effective and safe treatment for (a) older men per se, (b) men with chronic non-gonadal disease or (c) for treatment of non-specific symptoms. Until further placebo-controlled clinical trials are available, such treatment cannot be recommended. 
    
    
15. There is no a priori age limit for ART where androgen deficiency is established. With appropriate monitoring, ART may be continued indefinitely.

Table 1 - Use, Misuse and Abuse of Androgens

* indications that remain to be fully evaluated by controlled clinical trials for safety and efficacy

Table 2 - Biochemical Evaluation of the Diagnosis of Androgen Deficiency in Men with Clinical Features Consistent with Hypogonadism

Notes

1. Blood sample classification based on at least 2 separate morning blood samples
2. "High" LH level is defined as >1.5 x upper limit eugonadal reference range for young men
3. Elevated testosterone is defined as above the upper limit of the eugonadal reference range for young men
4. Hypergonadotrophic and hypogonadotrophic hypogonadism are also referred to as primary and secondary hypogonadism, respectively.
5. Compensated Leydig cell failure is a form of partial androgen deficiency in which androgen replacement is often beneficial