Endocrinology 9 - Endocrine Infertility Flashcards
Draw the male and female hypothamus-pituitary testis/ovary axis
- Male GnRH is positive, LH/FSH positive at testes. Inhibin is negative as is testosterone
- In females, GnRH and LH/FSH are positive, oestradiol, progesterone and inhibin are negative in follicular phase, during ovulation oestradiol is positive
What is primary gonadal failure?
- No testosterone or oestradiol production despite high LF/FSH
- Less negative feedback so also high GnRH
List the clinical features of male hypogonadism
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoporosis
List the causes of male hypogonadism
- Hypothalamic-pituitary disease (hypopituitarism, Kallmans syndrome, illness/underweight due to leptin deficiency)
- Primary gonadal disease (congenital klinefelters, or acquired tersticular torsion (ischaemia)/ chemotherapy)
- Hyperprolactinaemia
- Androgen receptor deficiency
What is Kallmans syndrome?
- Failure GnRH secretion
- Often occurs with a failure of smell (due to olfactory nerves migrating with GnRH in development) - Anosmia
- Lack of secondary sexual characteristics and puberty
What investigations are done in male hypogonadism?
- LH, FSH and testosterone levels measured, if all are low an MRI pituitary is performed
- Prolactin
- Sperm count (azoospermia is absence and oligospermia is reduced numbers)
- Chromosomal analysis
How is male hypogonadism treated?
- Replacement testosterone
- For fertility (if hypopituitary disease) give subcutaneous gonadotrophins
- Dopamine agonist to treat hyperprolactinaemia
List the endogenous sites of production of androgens
- Intersitital leydig cells of the testes
- Adrenal cortex
- Ovaries
- Placenta
- Tumours
List the main actions of testosterone
- Development of the male genital tract
- Maintains fertility in adults
- Control of secondary sexual characteristics
- Anabolic effects
List the clinical uses of testosterone
- In adulthood, increases lean body mass, muscle size and strength, bone formation and mass, libido and potency
- It wont restore fertility, this requires gonadotrophins
List the infertility disorders in females
- Amenorrhoea
- Polycystic ovarian syndrome
- Hyperprolactinaemia
List the types of amenorrhea
Amenorrhoea - absence of periods
Primary amenorrhoea - failure to begin spontaneous menstruation by age 16 years
Secondary amenorrhoea - absence of menstruation for 3 months in a woman who has previously had cycles
Oligomenorrhoea - irregular long cycles
List the causes of amenorrhoea
- Pregnancy or lactation
- Premature ovarian insufficiency (early menopause)
- Chemotherapy/ ovariectomy
- Ovarion dysgenesis (turners)
- Gonadotrophin failure (hypothalamus or pituitary disease, Kallmanns, low BMI, post pill)
- Hyperprolactinaemia
- Androgen excess (gonadal tumour)
List the investigations of amenorrhoea
- Pregnancy test
- LH, FSH, oestradiol
- Day 21 progesterone (measure day 18, 21 and 24)
- Prolactin, thyroid function tests
- Androgens
- Chromosomal analysis
- Ultrasound
How is amenorrhoea treated?
- Treat the cause
- Primary ovarian failure (HRT, infertile)
- Hypothalamic/pituitary disease (HRT for oestrogen, LH/FSH)
What is PCOS associated with?
- Increased cardiovascular risk and insulin resistance
- Affects 1 in 12 women
How is PCOS diagnosed?
Need two out of:
- Polycystic ovaries on ultrasound
- Oligo/anovulation
- Clinical/biochemical androgen excess
List the clinical features of PCOS
- Hirsutism
- Menstrual cycle disturbance
- Increased BMI
How is PCOS treated?
- Metformin (for diabetes)
- Clomiphene (anti-oestrogenic, blocks normal negative feedback resulting increase of GnRH and LH/FSH)
- Gonadotrophin therapy in IVF
What causes hyperprolactinaemia?
- Dopamine antagonist drugs (antiemetics like metoclopramide and anti-psychotics like phenothiazines)
- Prolactinoma
- Stalk compression due to pituitary adenoma
- PCOS
- Hypothyroidism
- Oestrogens, pregnancy, lactation
- Idiopathic
List the clinical features of hyperprolactinaemia
- Galactorrhea
- Reduced GnRH secretion/LH action resulting in hypogonadism
- Headache and visual field defect
How is hyperprolactinaemia treated?
- Treat the cause
- Dopamine agonist (bromocriptine or cabergoline)
- Prolactinoma (dopamine agonist or pituitary surgery)
What can testosterone be converted to?
- Testosterone to dihydrotestosterone (binds to nuclear receptors) via 5-alpha reductase (active in males)
- Testosterone to 17 beta oestradiol via aromatase in females
How is dopamine released to inhibit prolactin?
- Dopaminergic neurones release dopamine into the median eminance
- Tuberoinfundibular pathway in the arcuate nucleus
How should you monitor a pregnant woman with a prolactinoma who is not taking her medication?
- Assess visual field regularly
- If necessary, she can take cabergoline as it does not affect the baby
Why is it difficult to measure prolactin during pregnancy?
Prolactin levels rise during pregnancy anyway due to hyperplasia of lactotrophs
How can you assess premature menopause?
- Blood test (oestrogen levels)
- Bone density scan (osteoporosis)
Interpret these three hormone test results:
a) High oestrogen, Low LH and FSH
b) Low LH and FSH and low oestrogen
c) High LH and FSH and low oestrogen
a) Pregnant - high oestrogen, low LH and FSH
b) Pituitary or hypothalamus problem - prolactinoma, stress, exercise (hypothalamic amennorhea)
c) Ovarian problem (premature menopause)
