Androgen Deficiency Diagnosis and Management
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4 Clinical Summary Guide Androgen Deficiency Diagnosis and management Androgen deficiency (AD) * Pituitary disease, thalassaemia, haemochromatosis. • Androgen deficiency is common, affecting 1 in 200 men under ** AD is an uncommon cause of ED. However, all men presenting 60 years with ED should be assessed for AD • The clinical presentation may be subtle and its diagnosis Examination and assessment of clinical features of AD overlooked unless actively considered Pre-pubertal onset – Infancy The GP’s role • Micropenis • GPs are typically the first point of contact for men with • Small testes symptoms of AD • The GP’s role in the management of AD includes clinical Peri-pubertal onset – Adolescence assessment, laboratory investigations, treatment, referral • Late/incomplete sexual and somatic maturation and follow-up • Small testes • Note that it in 2015 the PBS criteria for testosterone • Failure of enlargement of penis and skin of scrotum becoming prescribing changed; the patient must be referred for a thickened/pigmented consultation with an endocrinologist, urologist or member of • Failure of growth of the larynx the Australasian Chapter of Sexual Health Medicine to be eligible for PBS-subsidised testosterone prescriptions • Poor facial, body and pubic hair • Gynecomastia Androgen deficiency and the ageing male • Poor muscle development • Ageing may be associated with a 1% decline per year in serum Post-pubertal onset – Adult total testosterone starting in the late 30s • Regression of some features of virilisation • However, men who remain in good health as they age may not • Mood changes (low mood, irritability) experience a decline in testosterone • Poor concentration • The decline may be more marked in obese men • Low energy (lethargy) • Some estimates suggest that AD affects up to 1 in 10 men over • Hot flushes and sweats 60 years • Decreased libido • Acute and chronic illnesses result in decreased serum • Reduced beard or body hair growth testosterone and may present with AD-like symptoms • Low semen volume • The role of testosterone replacement therapy (TRT) in older men with modest declines in serum testosterone remains • Gynecomastia controversial • Reduced muscle strength • The most consistent effects of TRT are on: • Fracture (osteoporosis) - body composition and bone • Erectile dysfunction (uncommon) - selected aspects of mood and cognition Refer to Clinical Summary Guide 6: Testicular Cancer - libido Laboratory assessment of AD • Most studies of men with age-related AD have not shown any significant improvement in sexual function (erectile function) • Normal range serum total testosterone 8-27 nmol/L (but may with TRT vary according to the assay used) • The use of TRT for ageing men who do not meet the established • Two morning fasting samples of serum total testosterone*, criteria (PBS guide) is not recommended taken on different mornings • Older men treated outside of guidelines should be informed Guidelines for the diagnosis of AD (PBS criteria): that long-term risks/benefits are not yet documented 1. AD in a patient with an established pituitary or testicular disorder Diagnosis 2. For men aged 40+: - Testosterone < 6 nmol/L** Medical history OR • Undescended testes - Testosterone between 6 and 15 nmol/L and LH greater than • Surgery of the testes 1.5 times the upper limit of the eugonadol reference range for • Pubertal development young men** • Previous fertility * If a second total testosterone sample is indicated, a LH level • Genito-urinary infection should also be ordered. • Co-existent medical illness* ** These criteria apply to men without underlying pituitary or • Change in general well-being or sexual function** testicular pathology, to be eligible for PBS subsidy. • Degree of virilisation • Prescription or recreational drug use Other investigations Management • SHBG/calculated free testosterone (selected cases - obesity, liver disease) Assessment of treatment indications • Semen analysis (if fertility is an issue) PBS-approved indications for the prescription of testosterone • Karyotype (if suspicion of Klinefelter syndrome, 47,XXY) are: Investigations if low total testosterone with normal or • Micropenis, pubertal induction, or constitutional delay of growth low LH/FSH: or puberty, in males <18 years • Serum prolactin (prolactinoma) • AD in males with established pituitary or testicular disorders • Iron studies (haemochromatosis) • AD (confirmed by at least 2 morning fasting samples, both < 6 nmol/L) in males aged 40+ who do not have established • MRI (various lesions) pituitary or testicular disorders other than ageing • Olfactory testing (Kallmann’s syndrome) Testosterone replacement therapy (TRT) Causes of hypogonadism (AD) Clinical note: Dosing ranges are provided below as dosage should be titrated according to clinical response and serum Testicular (primary) testosterone levels • Chromosomal: Klinefelter syndrome (most common cause) T formulation Usual (starting) Dosage range • Undescended testes dosage • Surgery: bilateral orchidectomy Injections (IM) • Trauma Sustanon®, 250 mg every 2 weeks 10 to 21-day • Infection: mumps orchitis Primoteston® intervals Reandron® 1000 mg every 12 weeks Longer term: 8 to • Radiotherapy/chemotherapy/drugs (spironolactone, following loading dose at 16-week intervals ketoconazole) 6 weeks (i.e. 0, 6, 18, 30 • Systemic disease: haemochromatosis, thalassaemia, myotonic weeks) dystrophy Transdermal patch Hypothalamo-pituitary (secondary) Androderm® 2.5 mg and 5.0 mg preps: 2.5 to 5 mg daily • Idiopathic hypogonadotrophic hypogonadism: Kallmann’s 5 mg applied nightly syndrome Transdermal gel • Pituitary microadenoma (<1 cm) or macroadenoma (>1 cm) Testogel® 1%: 50 mg in 5 g sachet 2.5 to 10 g gel (25 - functional or non-functional: in men typically or pump pack dispenser; mg to 100 mg T) macroprolactinoma applied daily daily • Other causes of hypothalamic pituitary damage: surgery, Transdermal cream radiotherapy, trauma, infiltrative disease such as AndroForte®5 5% (50 mg/mL): 2 mL (100 Review levels in 1 haemochromatosis mg) applied to the torso month, up to 4 mL once daily daily Klinefelter syndrome Oral undecanoate • Is the most common genetic male reproductive disorder Andriol 40 mg capsule: 160 to 240 80 to 240 mg daily (1 in 550 men) Testocaps® mg in 2 to 3 doses daily • Is the most common cause of hypogonadism * Sustanon® is not available on the Australian Pharmaceutical • Reproductive features: small testes <4 mL, infertility, failure Benefits Scheme (PBS) to progress through puberty, gynecomastia, eunuchoidal proportions, diminished or absent body hair, decreased skeletal Follow-up muscle mass Monitoring TRT is essential • Other: learning difficulties & behavioural problems, particularly • Testosterone levels: results should be interpreted in context of in adolescence the treatment modality being used Refer to Clinical Summary Guide 10: Klinefelter Syndrome • Prostate: PSA, as per standard guidelines • Cardiovascular risk factors: blood pressure, diabetes, lipids, as Clinical notes and contraindications per guidelines • Osteopaenia/osteoporosis (fractures): bone density-DEXA • Absolute contraindications to TRT are known or suspected • Polycythaemia: haemoglobin and haematocrit, pre-treatment, hormone-dependent malignancies (prostate or breast) or at 3 and 6 months, and annually thereafter haematocrit >55% • Sleep apnoea: clinical assessment for presence of sleep apnoea • Relative contraindications include haematocrit >52%, (polysomography) untreated sleep apnoea, severe obstructive symptoms of BPH and advanced congestive heart failure Specialist Referral • Fertility: Exogenous testosterone results in suppression of • It is a requirement for PBS-subsidised testosterone that the spermatogenesis in eugonadal men. For men with secondary patient is referred for a specialist consultation (endocrinologist, causes of AD, and in whom fertility is desired, gonadotropin urologist or member of the Australasian Chapter of Sexual therapy should be instituted Health Medicine) and the name of the specialist must be • Low-normal serum testosterone common in obesity or other included in the authority application illness may not reflect AD. Address underlying disorders first • Refer to an endocrinologist to plan long-term management • Withhold treatment until all investigations are complete of AD • Certain adverse effects must be prospectively sought, • Refer to a fertility specialist as needed especially in older men, including polycythaemia and sleep • Refer to a paediatric endocrinologist if >14.5 years old with apnoea, however the testosterone preparations discussed do delayed puberty not cause abnormal liver function Date reviewed: March 2018 © Healthy Male (Andrology Australia) 2007.