Male Hypogonadism

Question 1

What does kisspeptin do?

Answer 1

Stimulates the hypothalamus to release pulses of GnRH

Question 2

What is the function of GnRH?

Answer 2

Stimulates the anterior pituitary to release LH and FSH

Question 3

What stimulates the gonads to produce testosterone?

Answer 3

LH and FSH

Question 4

How does testosterone contribute to the HPG axis?

Answer 4

Provides negative feedback to hypothalamus and pituitary

Question 5

What cell produces testosterone?

Answer 5

Leydig cells (under the control of LH)

Question 6

How is testosterone transported around the body?

Answer 6

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

Question 7

What is testosterone converted into?

Answer 7

Dihydrotestosterone (highly active form) and oestradiol

Question 8

What is male hypogonadism?

Answer 8

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

Question 9

What is affected in primary hypogonadism?

Answer 9

The testes = spermatogenesis is more affected than testosterone production

Question 10

Why is primary hypogonadism known as hypergonadotrophic hypogonadism?

Answer 10

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

Question 11

What is affected in secondary hypogonadism?

Answer 11

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

Question 12

Why is secondary hypogonadism known as hypogonadotrophic hypogonadism?

Answer 12

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

Question 13

What are some congenital causes of primary hypogonadism?

Answer 13

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

Question 14

What are some acquired causes of primary hypogonadism?

Answer 14

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

Question 15

What is the most common genetic cause of hypogonadism?

Answer 15

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

Question 16

What is the genetic phenotype of Klinefelter’s syndrome?

Answer 16

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

Question 17

What are some features of Klinefelter’s syndrome?

Answer 17

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

Question 18

What does Klinefelter’s syndrome increase the incidence of?

Answer 18

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

Question 19

What are some congenital causes of secondary hypogonadism?

Answer 19

Kallmann’s syndrome, Prader-Willi syndrome

Question 20

What are some acquired causes of secondary hypogonadism?

Answer 20

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

Question 21

What is Kallmann’s syndrome characterised by?

Answer 21

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

Question 22

What are some features of Kallmann’s syndrome?

Answer 22

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

Question 23

What is the epidemiology of Kallmann’s syndrome?

Answer 23

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

Question 24

What are the symptoms of pre-pubertal hypogonadism?

Answer 24

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

Question 25

What are symptoms of post-pubertal hypogonadism?

Answer 25

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

Question 26

What should be performed if a man presents with infertility?

Answer 26

Semen analysis

Question 27

What initial investigation is done for hypogonadism?

Answer 27

Measure AM testosterone = if normal then hypogonadism unlikely

Question 28

How many times should AM testosterone be measured?

Answer 28

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

Question 29

How is primary hypogonadism diagnosed?

Answer 29

Two AM testosterone measurements that are low | Elevated LH/FSH

Question 30

How is secondary hypogonadism diagnosed?

Answer 30

Two AM testosterone measurements that are low | Low/inappropriately normal LH/FSH

Question 31

Why is measuring total testosterone misleading?

Answer 31

Only free testosterone is active and SHBG concentrations can vary widely

Question 32

When should testosterone be measured?

Answer 32

Between 8-11am

Question 33

What is used to measure testosterone?

Answer 33

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

Question 34

What are the aims of treatment for hypogonadism?

Answer 34

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

Question 35

What are some examples of testosterone replacement therapies?

Answer 35

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

Question 36

How is testosterone gel prescribed?

Answer 36

Transdermal gel applied daily, requires dose titration

Question 37

What are the advantages of testosterone gel?

Answer 37

Fast onset, convenient, mimics circadian rhythm

Question 38

What are the disadvantages of testosterone gel?

Answer 38

Skin irritation, interpersonal transfer, non-compliance long term

Question 39

How is oral testosterone undecanoate prescribed?

Answer 39

Tablets taken once or twice daily

Question 40

What are the advantages and disadvantages of oral testosterone undecanoate?

Answer 40

``` Advantages = convenient Disadvantages = variable testosterone levels, nausea, non-compliance ```

Question 41

How is IM testosterone undecanoate (Nebido) given?

Answer 41

Injection given every 10-14 weeks

Question 42

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

Answer 42

Steady testosterone levels, convenient, good compliance

Question 43

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

Answer 43

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

Question 44

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

Answer 44

Intramuscular injection every 2-3 weeks

Question 45

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

Answer 45

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

Question 46

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

Answer 46

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

Question 47

What are some contraindications of testosterone replacement?

Answer 47

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

Question 48

How often should patients on testosterone replacement be seen?

Answer 48

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

Question 49

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

Answer 49

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