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
