Diagnosing and treating androgen deficiency in men

Androgen deficiency affects between 1 in 20 and 1 in 200 men^1,2. 

GPs are typically the first point of contact for men with symptoms of androgen deficiency. This article outlines what GPs need to know about diagnosing and treating androgen deficiency — including clinical and laboratory assessments, appropriate referrals and ongoing patient management.

What is androgen deficiency?

Androgen deficiency is a syndrome characterised by low testosterone and accompanying signs and symptoms^{3, 4, 5}.

It’s estimated that approximately 5 in 1000 men have androgen deficiency warranting treatment with testosterone⁶.

A low testosterone level alone does not constitute androgen deficiency⁷, and neither does the normal age-related decline in testosterone of approximately 1% per year⁸. 

What causes androgen deficiency?

Androgen deficiency is caused by poor testicular function (hypogonadism). There are two types of hypogonadism: primary (originating from a problem in the testes) and secondary (a result of hypothalamic-pituitary disease).

Causes of primary hypogonadism

Klinefelter syndrome — which results in primary hypogonadism — is the most common cause of androgen deficiency. See our clinical summary guide on Klinefelter syndrome for further information about this condition.

Other causes of primary hypogonadism:

• Undescended testes
• Trauma
• Infection e.g. mumps orchitis
• Systemic disease e.g. haemochromatosis, thalassaemia, myotonic dystrophy
• Medical or surgical procedures e.g. radiotherapy, chemotherapy, surgery (bilateral orchiectomy), medication (spironolactone, ketoconazole)

Causes of secondary hypogonadism

• Hypogonadotropic  hypogonadism e.g. Kallmann’s syndrome
• Pituitary micro- or macro-adenoma: typically macroprolactinoma
• Pituitary trauma or disease
• Medical or surgical procedures e.g. pituitary radiotherapy or surgery

How to diagnose androgen deficiency

Androgen deficiency may have subtle effects on health and wellbeing, which can make diagnosis challenging. 

Here’s what to look for in a patient’s medical history, as well as clinical and laboratory examinations and assessments to assist diagnosis. 

Medical history

• Undescended testes
• Testicular surgery
• Pubertal development or virilisation
• Fertility
• Genitourinary infection
• Coexistent illness e.g. pituitary disease, thalassaemia, haemochromatosis
• Sexual function (all men presenting with erectile dysfunction should be assessed for androgen deficiency, even though it is an uncommon cause)
• Drug use (medical or recreational)

Clinical examination and assessment

Prepubertal onset

• Micropenis
• Small testes.

Peripubertal onset

• Delayed or incomplete sexual and somatic maturation 
• Small testes
• Attenuated penile enlargement
• Attenuated pigmentation of scrotum
• Attenuated laryngeal development
• Attenuated growth of facial, body and pubic hair
• Poor muscle development
• Gynaecomastia
   

Postpubertal onset

• Regression of virilisation
• Small testes
• Mood changes (low mood and/or irritability)
• Poor concentration
• Lethargy
• Hot flushes and sweats
• Low libido
• Reduced growth of facial or body hair
• Low semen volume
• Gynaecomastia
• Reduced muscle mass and strength
• Increased fat mass
• Bone fracture (resulting from low bone mineral density)

Laboratory examinations and assessment

At least two measurements of serum testosterone, LH and FSH (from samples collected on separate days) are required for diagnosis of androgen deficiency.

PBS criteria require androgen deficiency to be confirmed by serum testosterone below 6 nmol/l, or 6-15 nmol/l with LH 1.5 times higher than reference range (or above 14 IU/l).

Serum total testosterone

Measure serum total testosterone in the morning, after fasting. Accurate serum testosterone measurements require mass spectrometry. Values from immunoassays are less reliable.

Reference range: 

• Men aged 19-22 years, 7.4-28.0 nmol/l⁹
• Men aged 21-35 years, 10.4-30.1 nmol/l¹⁰
• Healthy men aged 71-87 years, 6.6-26.7 nmol/l¹¹

Serum FSH 

Reference range:

• Men aged 19-22 years, 1.3-12 IU/l⁹
• Men aged 21-35 years, 1.2-9.5 IU/ml¹⁰
• Men aged 74-84 years, mean 10.11, 95% confidence intervals 9.27-11.02 IU/l¹²

Serum LH 

Reference ranges:

• Men aged 19-22 years, 5.1-18.7 IU/l⁹
• Men aged 21-35 years, 1.5-8.1 IU/l¹⁰ 
• Men aged 74-78 years, median 4.1, interquartile range 3.0-6.1¹³
• Men aged 84-87 years, median 6.8, interquartile range 4.3-10.4¹³

Subsequent investigations for treatable causes of androgen deficiency

• Serum prolactin (for prolactinoma and macroadenoma)
• Iron studies and full blood count (for haemochromatosis and thalassaemia)
• Anterior pituitary function (for hypopituitarism and/or hyperfunctioning adenoma)
• Karyotyping (for suspected Klinefelter syndrome)
• Y chromosome microdeletion analysis
• Magnetic Resonance Imaging (for various hypothalamic or pituitary lesions)

How to manage patients with androgen deficiency

Testosterone replacement therapy (TRT)

TRT aims to relieve the signs and symptoms of androgen deficiency using convenient and effective (intramuscular or transdermal) testosterone preparations14.

See our clinical summary guide on androgen deficiency for a list of common TRT products and dosage. 

Contraindications and clinical considerations for TRT

TRT should not be given until all investigations are complete. 

Absolute contraindications for TRT are:

• Known or suspected breast or prostate cancer
• Haematocrit above 55%

Relative contraindications for TRT are:

• Haematocrit above 52%
• Untreated sleep apnoea
• Severe urinary obstructive symptoms of benign prostatic hyperplasia (international prostate symptom score above 19)
• Advanced congestive heart failure

Exogenous testosterone suppresses spermatogenesis in eugonadal men. Men with secondary hypogonadism who wish to preserve fertility should be managed using gonadotrophin therapy.

Monitoring TRT

Alleviating a patient’s leading symptom is the best clinical measure of effective management.

Blood sampling for serum testosterone, LH and FSH measurement should be timed to allow estimation of steady-state testosterone levels. This is feasible by sampling during the trough (immediately before next dose) for men using injectable and transdermal preparations. Timing the sampling for accurate measurement in men taking oral testosterone is more difficult.

Random sampling of blood for measurement of serum testosterone, without consideration of dosage timing, is effectively useless.

Other monitoring considerations: 

• Persistently elevated LH levels during TRT may indicate inadequate dosing
• Monitoring bone mineral density every one to two years may assist in monitoring TRT
• Haematology profile should be assessed three months after initiating TRT and annually thereafter
• Monitoring for prostate disease in men using TRT should occur as for eugonadal men of the same age

Specialist referral

The treatment and long-term management of androgen deficiency may require working with, or referring to, specialists:  

• A PBS-subsidised prescription of TRT requires treatment by, or consultation with, a specialist endocrinologist, urologist or registered member of the Australian Chapter of Sexual Health Medicine
• Long-term management of androgen deficiency is best planned in consultation with a specialist endocrinologist
• Refer men aged over 14.5 years with delayed puberty to a paediatric endocrinologist
• Refer to a fertility specialist as needed

Free clinical resource

Download the clinical summary guide as a print-ready PDF

Androgen Deficiency