Hypogonadism

Question 1

Define Hypogonadism

Answer 1

Clinical syndrome that comprises symptoms and/or sign + biochemical evidence of testosterone or oestradiol deficiency

Question 2

Define the following in females:
Primary hyogonadism 
Secondary hypogonadism 
Amenorrhoea
Oligomenorrhoea

Answer 2

Primary hyogonadism: Defect in the ovaries → low oestradiol → less -ve feedback → High GnRH → High LH /FSH

Secondary hypogonadism:
Hypothalamic dysfunction → Reduced LH/FSH production → Reduced oestradiol → less negative feedback

Amenorrhoea: absence of periods (primary = failure to begin by 16, secondary = absence for 3 months)

Oligomenorrhoea: irregular, long, cycles

Question 3

Define the following in males:
Primary hyogonadism
Secondary hypogonadism

Answer 3

Primary hyogonadism: defect at the level of testes - testicular failure
Associated with low testosterone and elevated gonadotrophins

Secondary hypogonadism:
Defect at the level of the hypothalamic-pituitary axis
Associated with low testosterone and low (or inappropriately normal) gonadotrophins

Question 4

Aetiology of Hypogonadism in females

Answer 4

Primary: 
Premature ovarian insufficiency 
Autoimmune
Iatrogenic (ovariectomy, chemo)
Turner's syndrome (lacking 1 X chromosome)

Secondary:
Pregnancy and lactation (most common cause of secondary)
Kallman’s syndrome
Low BMI, stress, weight loss, eating disorder, excessive exercise
Post-pill amenorrhoea
Hyperprolactinaemia
Androgen excess (gonadal tumour, PCOS)

Question 5

Aetiology of Hypogonadism in males

Answer 5

Primary:
Klinefelter syndrome (47XXY)
Noonan syndrome 
Cryptorchidism 
Infections (mumps -> orchitis)
Drugs (cyclophosphamide + chlorambucil)
Testicular trauma, torsion, irradiation
Auto-immune orchitis 

Seconadry:
Hyperprolactinaemia
Combined pituitary hormone deficiency 
Isolated hypogonadotrophic hypogonadism 
Pituitary tumours 
Parasellar tumours 
Empty/partial empty sella syndrome 
Durgs e.g. opioids, glucocorticoids, GnRH analogues
Irradiation
Head injury, trauma, surgery

Question 6

Symptoms of Hypogonadism in males and females

Answer 6

Males:
Decreased libido
Loss of spontaneous morning erections + erectile dysfunction
Gynaecomastia 
Infertility 
Decreased energy and fatigue

Females:
Amenorrhoea/oligmenorrhoea 
Night sweats, hot flush 
Vaginal dryness, dyspareunia
Reduced libido
Infertility (oestrogen deficiency)
Pre-pubertal: absent breast development, no secondary sexual characteristics 
Post-pubertal: Loss of sexual hair, breast atrophy

Question 7

Signs of Hypogonadism in men and women

Answer 7

Men:
Gynaecomastia
Bitemporal hemianopia
Delayed puberty 
Decreased muscle mass and strength 
Lack of hair

Women:
Vaginal dryness
Pre-pubertal: absent breast development, no secondary sexual characteristics

Question 8

Investigations for Hypogonadism in men

Answer 8

Serum total testosterone: Reduced (<10.4)

Semen analysis: low sperm count if infertile

Serum SHBG: increased or decreased
Serum LH/FSH: Elevated (primary) or decreased/normal (secondary)
Serum free testosterone: reduced (<0.2)
Serum bioavailable testosterone: reduced (<2.4)
Serum prolactin: elevated (>7.83)
Iron studies: rule out haemochromatosis

MRI pituitary: may reveal pituitary adenoma or empty sella

Genetic testing: Klinefelter’s

Question 9

Investigations for Hypogonadism in women

Answer 9

Pregnancy test: negative
Oestradiol: reduced
FSH/LH: elevated (primary), reduced (secondary)

Day 21 progesterone: increase if ovulation
Prolactin: raised
TFTs: raised
Androgens: ?PCOS

Chromosomal analysis: ?Turner’s
USS scan ovaries/uterus: ?PCOS