ENDO - Androgen deficiency in men

Question 1

What are the symptoms and signs of androgen deficiency in men (general, sexual & organ specific features)?

Answer 1

General

• Low sense of well being, poor concentration
• tiredness, poor stamina
• mood change - depression, irritability

Sexual

• reduced libido is almost universal
• erectile failure (rare)

Organ specific features

• reduced muscle mass and strength
• osteoporosis and fracture
• increased fat mass
• gynaecomastia

Question 2

What are the appropriate tests to confirm the diagnosis of androgen deficiency? And what do they mean?

Answer 2

Total (TT)or free (FT) Testosterone

N.B. No age related reference ranges. T assay characteristics lack standardization; Inaccuracy in low range

• Normal serum TT = eugonadal
• Low TT: repeat – any normal level= eugonadal
• Calculated FT(cFT): if TT borderline, SHBG abnormal to rule out falsely low TT
• LH (if elevated) may indicate decreased T secretion

Question 3

What is the difference between classical androgen deficiency due to pathology of the hypothalamo-pituitarygonadal
axis and non-specific low testosterone levels due to aging and disease?

Answer 3

Non specific low testosterone levels due to ageing & disease is not powered to assess meaningful gains in important health outcomes or risk of cardiovascular disease or prostate cancer due to limited RCTs unlike pathology of HPA.

Hence risk benefit ratio therefore unknown and likely different in older men compared to young hypogonadal males

Question 4

What does clinical Px of male hypogonadism depend on? Give examples

Answer 4

Age of onset.

1st trimester:

• Partial virilisation, Ambiguous genitalia.
• Complete deficiency: Female external genitalia

3rd trimester: Micropenis, Cryptorchidism

Pre-puberty:
-Incomplete pubertal maturation -Testes

Question 5

What are the causes of androgen deficiency? (Primary & secondary)

Answer 5

Primary: LH/FSH elevated

1. Acquired:
   - testicular damage due to trauma, orchitis, toxins
   - drugs; spironolactone, ketoconazole
2. Congenital:
   - Klinefelter syndrome
   - cryptorchidism
   - LH/FSH-receptor mutations

Secondary: LH/FSH low/normal

1. Structural (Pituitary/hypothyroidism):
   - tumour
   - surgery/radiation/trauma
   - infiltration; e.g. sarcoid, iron overload
2. Genetic
   - Kallmann’s syndrome
   - idiopathic HH
   - LH/FSH beta subunit mutations

3 Functional

• Hyperprolactinemia!
• Morbid obesity!
• Cushings syndrome!!

Question 6

What are causes of partial/transient androgen deficiency?

Answer 6

• acute illness
• chronic disease e.g. ESRF, COPD, HIV, T2D
• Drugs: glucocorticoids, opioids, GnRH agonists, anabolic steroids

Question 7

Describe Klinefelter’s syndrome

Answer 7

• Prevalence 1:660, 25% diagnosed during lifetime; 90% 47, XXY
• Early Dx enables speech therapy, educational support
• Main feature testes

Question 8

Describe the approach for diagnostic evaluation of adult men suspected for having androgen deficiency

Answer 8

1. Hx & Examinations
2. Morning total Testosterone
   - if normal, follow up.
   - if low T (

Question 9

Describe non classical androgen deficiency

Answer 9

• Common in ageing and chronic disease
• RCTs limited by small numbers, short duration, different inclusion criteria, surrogate outcomes
• Risk benefit ratio unknown and likely different in older men compared to young hypogonadal males
• Safety and efficacy remains to be evaluated in randomised controlled trials

Question 10

What is the effect of testosterone replacement in hypogonadal men?

Answer 10

• increased serum TT
• increased body composition, prostate volume & haemoglobin
• increased energy & sex function

Question 11

What types of testosterone products are available?

Answer 11

• Injection (deep intramuscular): 250mg/2 weeks. (+) widely available. (-) painful. Wide moody/energy swings. Having libido like a teenager in an elderly can be disturbing for the pt and the partner
• Transdermal (patch, cream, gel): build the dose up gradually. (+) suitable in bleeding disorders. (-) irritable patches.
• Subdermal implant. 800mg 6 monthly. (+) convenience. (-) unable to terminate rapidly
• Oral:2-3 tablets/day
• Others: ointment etc

Question 12

What are the contraindications to testosterone replacement therapy?

Answer 12

•evidence of prostate cancer
–abnormal Digital Rectal Examination
–elevated PSA (> 3ng/ml)
–diagnosed prostate cancer

• breast cancer
• erythrocytosis (HCT > 52%) or hyperviscosity
• untreated obstructive sleep apnoea
• severe lower urinary tract symptoms (IPSS >19)
• class III or IV heart failure
• Desire to have child

Question 13

What are the potential SE of testosterone replacement?

Answer 13

• erythrocytosis
• acne & oily skin
• detection of subclinical prostate cancer
• growth of metastatic prostate cancer
• reduced sperm production & fertility
• gynaecomastia
• male pattern balding
• worsening of BPH symptoms
• growth of breast cancer
• induction/worsening of OSA

Question 14

Describe management of men with androgen deficiency

Answer 14

1. Lifestyle measures and treatment of comorbidities
2. Testosterone replacement therapy (consider SE & CI)

Monitor male pts on testosterone therapy with:

• Hx & examination 3/4-12 first year and then 1/12
• testosterone levels 3/12 after first initiation
• liver function 3-6/12
• prostate specific antigen 3/12 first & 6-12/12
• DRE: annually if unchanging
• lipids: 1/12
• haematocrit: baseline 3/12, and then annually
• BMD of lumbar spine, femoral neck & hip: 1-2 yrs after therapy in men w/ osteoporosis/low trauma fracture