Male Hypogonadism Flashcards

1
Q

What does kisspeptin do?

A

Stimulates the hypothalamus to release pulses of GnRH

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2
Q

What is the function of GnRH?

A

Stimulates the anterior pituitary to release LH and FSH

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3
Q

What stimulates the gonads to produce testosterone?

A

LH and FSH

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4
Q

How does testosterone contribute to the HPG axis?

A

Provides negative feedback to hypothalamus and pituitary

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5
Q

What cell produces testosterone?

A

Leydig cells (under the control of LH)

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6
Q

How is testosterone transported around the body?

A

Majority is bound to SHBG and albumin (only 0.5-2% is free)

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7
Q

What is testosterone converted into?

A

Dihydrotestosterone (highly active form) and oestradiol

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8
Q

What is male hypogonadism?

A

Low/reduced gonadal (testicular) function = more common with age (>40)

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9
Q

What is affected in primary hypogonadism?

A

The testes = spermatogenesis is more affected than testosterone production

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10
Q

Why is primary hypogonadism known as hypergonadotrophic hypogonadism?

A

Decreased testosterone = decreased negative feedback so increased production of LH/FSH

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11
Q

What is affected in secondary hypogonadism?

A

Hypothalamus or pituitary (testes capable of normal function) = spermatogenesis and testosterone production are affected equally

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12
Q

Why is secondary hypogonadism known as hypogonadotrophic hypogonadism?

A

LH/FSH low (or inappropriately normal) despite low testosterone

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13
Q

What are some congenital causes of primary hypogonadism?

A

Klinefelter’s syndrome, cryptorchidism (undescended testes), Y-chromosome microdeletions

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14
Q

What are some acquired causes of primary hypogonadism?

A

Testicular torsion/trauma, chemo/radiotherapy, varicocele (enlarged testicular vein), orchitis (mumps), infiltrative diseases (haemochromatosis), glucocorticoids/ketoconazole

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15
Q

What is the most common genetic cause of hypogonadism?

A

Klinefelter’s syndrome = not inherited (caused by nondisjunction), diagnosed by karotyping

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16
Q

What is the genetic phenotype of Klinefelter’s syndrome?

A

Usually 47XXY, but may be 46XY/47XXY mosaicism

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17
Q

What are some features of Klinefelter’s syndrome?

A

Infertile due to tubular damage, small firm testes, poor beard growth, no frontal balding, breast development, female body shape

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18
Q

What does Klinefelter’s syndrome increase the incidence of?

A

Increased incidence of cryptorchidism, learning disabilities and psychosocial issues
Increased risk of breast cancer and non-Hodgkin lymphoma

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19
Q

What are some congenital causes of secondary hypogonadism?

A

Kallmann’s syndrome, Prader-Willi syndrome

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20
Q

What are some acquired causes of secondary hypogonadism?

A

Pituitary damage, hyperprolactinaemia, obesity, diabetes, steroids/opioids, acute systemic illness, eating disorders, excessive exercise

21
Q

What is Kallmann’s syndrome characterised by?

A

Isolated GnRH deficiency and hyposmia/anosmia (loss/no sense of smell)

22
Q

What are some features of Kallmann’s syndrome?

A

Unilateral renal agenesis (only have one kidney), red-green colour blindness, cleft lip, bimanual kinesis

23
Q

What is the epidemiology of Kallmann’s syndrome?

A

More common in males, over 20 gene mutations implicated, inheritance patterns vary

24
Q

What are the symptoms of pre-pubertal hypogonadism?

A

Small male sexual organs and gynaecomastia
Decreased body hair, high pitched voice, low libido
“Eunuchoidal” habitus (tall, slim, long limbs)
Decreased bone and muscle mass

25
Q

What are symptoms of post-pubertal hypogonadism?

A

Normal skeletal proportions, penis/prostate size and voice
Decreased libido, spontaneous erections, pubic/axillary hair, testicular volume and shaving frequency
Decreased muscle and bone mass, energy and motivation
Gynaecomastia

26
Q

What should be performed if a man presents with infertility?

A

Semen analysis

27
Q

What initial investigation is done for hypogonadism?

A

Measure AM testosterone = if normal then hypogonadism unlikely

28
Q

How many times should AM testosterone be measured?

A

Twice (even if first measurement is low) = if normal on either occasion then hypogonadism unlikely

29
Q

How is primary hypogonadism diagnosed?

A

Two AM testosterone measurements that are low

Elevated LH/FSH

30
Q

How is secondary hypogonadism diagnosed?

A

Two AM testosterone measurements that are low

Low/inappropriately normal LH/FSH

31
Q

Why is measuring total testosterone misleading?

A

Only free testosterone is active and SHBG concentrations can vary widely

32
Q

When should testosterone be measured?

A

Between 8-11am

33
Q

What is used to measure testosterone?

A

Calculated free testosterone = total testosterone and SHBG measured and an algorithm is used

34
Q

What are the aims of treatment for hypogonadism?

A

Establish/maintain secondary sexual characteristics
Maintain sexual function
Improve fertility and quality of life

35
Q

What are some examples of testosterone replacement therapies?

A

Testosterone 1% and 2% gel, oral or IM testosterone undecanoate, testosterone enanthate/propionate/cipionate

36
Q

How is testosterone gel prescribed?

A

Transdermal gel applied daily, requires dose titration

37
Q

What are the advantages of testosterone gel?

A

Fast onset, convenient, mimics circadian rhythm

38
Q

What are the disadvantages of testosterone gel?

A

Skin irritation, interpersonal transfer, non-compliance long term

39
Q

How is oral testosterone undecanoate prescribed?

A

Tablets taken once or twice daily

40
Q

What are the advantages and disadvantages of oral testosterone undecanoate?

A
Advantages = convenient
Disadvantages = variable testosterone levels, nausea, non-compliance
41
Q

How is IM testosterone undecanoate (Nebido) given?

A

Injection given every 10-14 weeks

42
Q

What are the advantages of IM testosterone undecanoate (Nebido)?

A

Steady testosterone levels, convenient, good compliance

43
Q

What are the disadvantages of IM testosterone undecanoate (Nebido)?

A

Difficult to withdraw if having side effects, local pain at injection site, coughing following injection, contraindicated in bleeding disorders

44
Q

How is testosterone enanthate/propionate/cipionate (Sustanon) given

A

Intramuscular injection every 2-3 weeks

45
Q

What are the advantages of testosterone enanthate/propionate/cipionate (Sustanon)?

A

Easy to withdraw if having side effects, can be easily self-administered

46
Q

What are the disadvantages of testosterone enanthate/propionate/cipionate (Sustanon)?

A

Variable testosterone levels, coughing following injection, local pain at injection site. contraindicated in bleeding disorders

47
Q

What are some contraindications of testosterone replacement?

A

Confirmed hormone-responsive cancer (eg breast)
Possible/confirmed prostate cancer
Haematocrit > 50%
Severe sleep apnoea/heart failure

48
Q

How often should patients on testosterone replacement be seen?

A

Every 3-6 monthly whilst starting treatment, then annually thereafter

49
Q

What should be done in the review of a patient on testosterone replacement?

A

Check general health and testosterone concentration
Measure DRE and PSA
Measure haematocrit concentration