Male Hypogonadism Flashcards
What does kisspeptin do?
Stimulates the hypothalamus to release pulses of GnRH
What is the function of GnRH?
Stimulates the anterior pituitary to release LH and FSH
What stimulates the gonads to produce testosterone?
LH and FSH
How does testosterone contribute to the HPG axis?
Provides negative feedback to hypothalamus and pituitary
What cell produces testosterone?
Leydig cells (under the control of LH)
How is testosterone transported around the body?
Majority is bound to SHBG and albumin (only 0.5-2% is free)
What is testosterone converted into?
Dihydrotestosterone (highly active form) and oestradiol
What is male hypogonadism?
Low/reduced gonadal (testicular) function = more common with age (>40)
What is affected in primary hypogonadism?
The testes = spermatogenesis is more affected than testosterone production
Why is primary hypogonadism known as hypergonadotrophic hypogonadism?
Decreased testosterone = decreased negative feedback so increased production of LH/FSH
What is affected in secondary hypogonadism?
Hypothalamus or pituitary (testes capable of normal function) = spermatogenesis and testosterone production are affected equally
Why is secondary hypogonadism known as hypogonadotrophic hypogonadism?
LH/FSH low (or inappropriately normal) despite low testosterone
What are some congenital causes of primary hypogonadism?
Klinefelter’s syndrome, cryptorchidism (undescended testes), Y-chromosome microdeletions
What are some acquired causes of primary hypogonadism?
Testicular torsion/trauma, chemo/radiotherapy, varicocele (enlarged testicular vein), orchitis (mumps), infiltrative diseases (haemochromatosis), glucocorticoids/ketoconazole
What is the most common genetic cause of hypogonadism?
Klinefelter’s syndrome = not inherited (caused by nondisjunction), diagnosed by karotyping
What is the genetic phenotype of Klinefelter’s syndrome?
Usually 47XXY, but may be 46XY/47XXY mosaicism
What are some features of Klinefelter’s syndrome?
Infertile due to tubular damage, small firm testes, poor beard growth, no frontal balding, breast development, female body shape
What does Klinefelter’s syndrome increase the incidence of?
Increased incidence of cryptorchidism, learning disabilities and psychosocial issues
Increased risk of breast cancer and non-Hodgkin lymphoma
What are some congenital causes of secondary hypogonadism?
Kallmann’s syndrome, Prader-Willi syndrome
What are some acquired causes of secondary hypogonadism?
Pituitary damage, hyperprolactinaemia, obesity, diabetes, steroids/opioids, acute systemic illness, eating disorders, excessive exercise
What is Kallmann’s syndrome characterised by?
Isolated GnRH deficiency and hyposmia/anosmia (loss/no sense of smell)
What are some features of Kallmann’s syndrome?
Unilateral renal agenesis (only have one kidney), red-green colour blindness, cleft lip, bimanual kinesis
What is the epidemiology of Kallmann’s syndrome?
More common in males, over 20 gene mutations implicated, inheritance patterns vary
What are the symptoms of pre-pubertal hypogonadism?
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
What are symptoms of post-pubertal hypogonadism?
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
What should be performed if a man presents with infertility?
Semen analysis
What initial investigation is done for hypogonadism?
Measure AM testosterone = if normal then hypogonadism unlikely
How many times should AM testosterone be measured?
Twice (even if first measurement is low) = if normal on either occasion then hypogonadism unlikely
How is primary hypogonadism diagnosed?
Two AM testosterone measurements that are low
Elevated LH/FSH
How is secondary hypogonadism diagnosed?
Two AM testosterone measurements that are low
Low/inappropriately normal LH/FSH
Why is measuring total testosterone misleading?
Only free testosterone is active and SHBG concentrations can vary widely
When should testosterone be measured?
Between 8-11am
What is used to measure testosterone?
Calculated free testosterone = total testosterone and SHBG measured and an algorithm is used
What are the aims of treatment for hypogonadism?
Establish/maintain secondary sexual characteristics
Maintain sexual function
Improve fertility and quality of life
What are some examples of testosterone replacement therapies?
Testosterone 1% and 2% gel, oral or IM testosterone undecanoate, testosterone enanthate/propionate/cipionate
How is testosterone gel prescribed?
Transdermal gel applied daily, requires dose titration
What are the advantages of testosterone gel?
Fast onset, convenient, mimics circadian rhythm
What are the disadvantages of testosterone gel?
Skin irritation, interpersonal transfer, non-compliance long term
How is oral testosterone undecanoate prescribed?
Tablets taken once or twice daily
What are the advantages and disadvantages of oral testosterone undecanoate?
Advantages = convenient Disadvantages = variable testosterone levels, nausea, non-compliance
How is IM testosterone undecanoate (Nebido) given?
Injection given every 10-14 weeks
What are the advantages of IM testosterone undecanoate (Nebido)?
Steady testosterone levels, convenient, good compliance
What are the disadvantages of IM testosterone undecanoate (Nebido)?
Difficult to withdraw if having side effects, local pain at injection site, coughing following injection, contraindicated in bleeding disorders
How is testosterone enanthate/propionate/cipionate (Sustanon) given
Intramuscular injection every 2-3 weeks
What are the advantages of testosterone enanthate/propionate/cipionate (Sustanon)?
Easy to withdraw if having side effects, can be easily self-administered
What are the disadvantages of testosterone enanthate/propionate/cipionate (Sustanon)?
Variable testosterone levels, coughing following injection, local pain at injection site. contraindicated in bleeding disorders
What are some contraindications of testosterone replacement?
Confirmed hormone-responsive cancer (eg breast)
Possible/confirmed prostate cancer
Haematocrit > 50%
Severe sleep apnoea/heart failure
How often should patients on testosterone replacement be seen?
Every 3-6 monthly whilst starting treatment, then annually thereafter
What should be done in the review of a patient on testosterone replacement?
Check general health and testosterone concentration
Measure DRE and PSA
Measure haematocrit concentration
