Male Hypogonadism

Question 1

how does the male HPG axis work?

Answer 1

hypothalamus - is stimulated by kisspeptin to release pulses of GnRH
anterior pituitary - is stimulated by GnRH to release LH and FSH
gonads (testes) - stimulated by LH/FSH to produce testosterone
testosterone provides negative feedback to the hypothalamus and pituitary

Question 2

what do testicles produce?

Answer 2

sperm
produce testosterone
dihydrotestosterone is the very active form of testosterone

Question 3

what is testosterone production?

Answer 3

testosterone is produced by leydig cells under the influence of LH,
the majority is bound to SHBG and albumin (only 0.5-2% is free),
it’s converted into dihydrotestosterone and oestradiol.
[Oestradiol is the most active form of oestrogen, oestrogen (and therefore oestradiol) is cardio-protective.

Question 4

what is male hypogonadism?

Answer 4

reduced gonadal (testicular) function

Question 5

who gets testosterone deficiency?

Answer 5

Most commonly affects men aged 40-79 (more common with age).

Question 6

what is primary hypogonadism

Answer 6

the testes are primarily affected,
there is decreased testosterone which causes decreased negative feedback causing increase in LH and FSH secreted by the anterior pituitary = hypergonadotrophic hypogonadisim
spermatogenesis affected more than testosterone production

Question 7

what is secondary hypogonadism

Answer 7

hypothalamus/pituitary are affected,
testes are capable of normal function,
LH/FSH are low (or inappropriately normal) despite having low testosterone = hypogonadotrophic hypogonadism
spermatogenesis and testosterone are equally affected

Question 8

congenital causes of primary hypogonadism

Answer 8

Klinefelter’s syndrome
cryptorchidism
Y-chromosome microdeletions

Question 9

acquired causes of primary hypogonadism

Answer 9

• Testicular trauma/torsion
• Chemotherapy/radiation
• Varicocele (enlarged veins into the scrotum)
• Orchitis (mumps infection)
• Infiltrative diseases (e.g. haemochromatosis)
• Medications (glucocorticoids, ketoconazole)

Question 10

What is Klinefelter’s syndrome?

Answer 10

most common cause of genetic hypogonadism
NOT inherited - caused by nondisjunction
usually 47XXY but can have 46XY or 47 XXY mosaicism

Question 11

how does Klinefelter’s syndrome present?

Answer 11

variable therefore diagnosis can be late/missed

• affected men are usually infertile due to tubular damage, and have small firm testes
• increased incidence of cryptorchidism (one/both testes fail to descend from the abdomen in the scrotum) - learning disability and psychosocial issues
• increased risk of breast cancer and non-hodgkin lymphoma

Question 12

how is Klinefelter’s syndrome diagnosed?

Answer 12

karyotyping

Question 13

congenital causes of secondary hypogonadism?

Answer 13

• Kallmann’s syndrome (‘isolated hypogonadotrophic hypogonadism’)
• Prader-Willi syndrome

Question 14

acquired causes of secondary hypogonadism?

Answer 14

• Pituitary damage (tumours, infiltrative disease, infection [TB], apoplexy (unconsciousness/ incapacity due to brain haemorrhage or stroke), head trauma
• Hyperprolactinaemia
• Obesity, diabetes
• Medications (steroids, opioids)
• Acute systemic illness
• Eating disorders, excessive exercise

Question 15

what is Kallmann’s syndrome?

Answer 15

genetic disorder characterised by isolated GnRH deficiency and hyposmia (reduced ability to smell) or anosmia (loss of sense of smell)

Question 16

what is the presentation of hypogonadism with pre-pubertal onset?

Answer 16

onset (puberty only occurs with treatment…?)
• Small male sexual organs e.g. small testes (volume <5 mL), penis and prostate
• Decreased body hair, high-pitched voice, low libido
• Gynaecomastia
• Eunuchoidal habitus (tall, slim, long arms and legs)
• Decreased bone and muscle mass
May also have symptoms of cause (e.g. anosmia with Kallmann’s syndrome)

Question 17

what is the presentation of hypogonadism with post-pubertal onset?

Answer 17

• Normal skeletal proportions, penis/prostate size and voice
• Decreased libido, decreased spontaneous erections
• Decreased pubic/axillary hair, reduced shaving frequency
• Decreased testicular volume
• Gynaecomastia
• Decreased muscle and bone mass
• Decreased energy and motivations
May also have symptoms of cause (e.g. pituitary lesion causing visual field defect)

Question 18

how is testosterone measured?

Answer 18

• Total testosterone can be misleading as only the free portion is biologically active
• SHBG conc. can vary widely (can be affected by many things e.g. ageing, androgens etc.)
• So total testosterone and SHBG are measured and an algorithm is used to give ‘calculated free testosterone’
• Testosterone should be measured between 8-11am (peaks in the morning)

Question 19

what is the aim of management of hypogonadism?

Answer 19

establish/maintain secondary sexual characteristics, 
maintain sexual function, 
improve fertility (where possible), 
improve body composition, 
improve quality of life

Question 20

what is the management of hypogonadism?

Answer 20

testosterone replacement therapy

- testosterone therapy started by endocrinologists, once it is stable it can be monitored in primary care

Question 21

methods of testosterone replacement?

Answer 21

gel: risk of interpersonal transfer
nebido: long-acting (every 10-14 weeks) IM injection
sustanon: short-acting (every 2-3 weeks) IM injection
oral capsules - not commonly used

Question 22

what are the contraindications of testosterone replacement therapy?

Answer 22

confirmed hormone responsive cancer (e.g. prostate/breast),
possible prostate cancer (e.g. raised PSA, suspicious prostate on DRE) ,
haematocrit >50% and severe sleep apnoea/heart failure

Question 23

how is testosterone replacement monitored?

Answer 23

3-6 monthly whilst starting treatment - after that checked annually,
general health and testosterone concentration,
DRE [digital rectal exam] and PSA [prostate-specific antigen],
haematocrit (testosterone stimulates the bone marrow to produce red blood cells),
symptoms of sleep apnoea