Endocrine Infertility Flashcards
Outline the hypothalamo-pituitary-gonadal axis, including negative feedback influences in
1) Men
2) Women
1)
- Hypothalamus secretes GnRH
- GnRH stimulates LH / FSH secretion from pituitary
- LH / FSH stimulates testosterone secretion from the testes
- Testosterone and inhibin have negative feedback inhibition on the secretion of LH / FSH from the pituitary
- Testosterone has negative feedback inhibition on the secretion of GnRH
2)
- Hypothalamus secretes GnRH
- GnRH stimulates LH / FSH secretion from pituitary
- LH / FSH stimulates oestrogen secretion from the ovaries
- Oestrogen and inhibin have negative feedback inhibition on the secretion of LH / FSH from the pituitary
- Oestrogen has negative feedback inhibition effect on the secretion of GnRH from the hypothalamus
Name the 3 phases of the menstrual cycle
- Follicular phase
- Ovulation
- Luteal phase
Outline the hypothalamo-pituitary-gonadal (HPG) axis hormonal changes (i.e. excluding progesterone) in the phases of the menstrual cycle - don’t need to go into the detail like graaffian follicles, corpus luteum etc
Follicular
- Normal HPG axis - i.e. hypothalamic GnRH stimulates LH / FSH which stimulates oestrogen secretion from the ovaries and the oestrogen has negative feedback on the hypothalamus and the pituitary
- However, as the follicle enlarges, oestrogen no has a positive feedback on GnRH and LH / FSH
Ovulation
- This positive feedback that oestrogen exerts causes an LH surge - which causes the egg to be released in ovulation
Luteal phase
- If implantation does not occur - there is breakdown of the endometrium
- If it does, there is endometrial proliferation
Why is unhindered endometrial proliferation not alright, in the event there is no implantation that occurs?
- Predisposes to cancer
Define infertility in terms of at what point is there considered to be infertility problems in one of either the male or the female (or both) in a couple?
- Infertility = Inability to conceive after 1 year of unprotected sex
What would a blood test indicate in the event of primary hypogonadism…
1) In males?
2) In females?
1)
- Low testosterone
- High LH / FSH due to less negative feedback by testosterone
2)
- Low oestradiol
- High LH / FSH due to less negative feedback by testosterone
What would a blood test indicate in the event of secondary hypogonadism…
1) In males?
2) In females?
1)
- Low LH / FSH
- Low testosterone as a result of the low LH / FSH
2)
- Low LH / FSH
- Low oestradiol as a result of the low LH / FSH
What is defective in…
1) Primary hypogonadism?
2) Secondary hypogonadism?
1)
- The gonads’ (testes / ovaries) production of testosterone / oestradiol
2)
- The hypothalamus / pituitary’s production of GnRH or LH / FSH respectively which therefore loweres production of testosterone / oestradiol
Give 5 clinical features of male hypogonadism
- Loss of libido
- Impotence
- Small testes
- Decreasd muscle bulk
- Osteoporosis
Give the 4 main cause categories for male hypogonadism and then, where applicable, give the subcategories of these hypogonadism causes
- Hypothalamic-pituitary disease
- Hypopituitarism
- Kallman’s disease (inappropriate migration and development of GnRH neurones in hypothalamic development)
- Illness / underweight - appropriate nutrition is required for appropriate hypothalamo-pituitary function in regards to sex hormones
- Primary gonadal disease
- Congenital e.g. Klinefelter’s (XXY)
- Acquired e.g. Testicular torsion → necrosis
- Hyperprolactinaemia
- Androgen receptor deficiency
5.
1) What is the pathophysiology of Kallman’s syndrome and how it causes male hypogonadism?
2) What are the clinical signs?
1)
- Inappropriate migration and development of GnRH neurones in hypothalamic development - so is a hypothalo-pituitary disease causing male hypogonadism due to the resulting lack in testosterone production
2)
- Anosmia - lack of smell sense (as GnRH neurones and olfactory neurones migrate together in embryonic development)
- Pre-pubertal phenotype
- Testes originally undescended
- Stature low-normal
4 ways to investigate male hypogonadism and what findings may show?
- Check LH / FSH + Testosterone levels - if all low this indicates secondary hypogonadism and if testosterone is low but LH / FSH is high, this indicates primary hypogonadism
- Check Prolactin level - high prolactin indicates hypogonadism as a result of hyperprolactinaemia
- Check sperm count and motility - either azoospermia (absence of sperm in ejaculate) or oligospermia (reduced number of sperm in the ejaculate)
- Chromosomal analysis - e.g. if you see 47 XXY this is Klinefelter’s causing hypogonadism
3 treatments for male hypogonadism?
- Testosterone replacement therapy to preserve muscle bulk and prevent osteoporosis
- Subcutaneous gonadotrophin injections to stimulate spermatogenesis if male hypogonadism caused by hypothalamo-pituitary disease
- Dopamine agonist if male hypogonadism caused by hyperprolactinaemia because dopamine suppresses prolactin secretion
5 possible endogenous sites for androgen production?
- Interstitial Leydig cells of the testes
- Adrenal cortex
- Ovaries
- Placenta
- Tumours
Give 4 main actions of testosterone
- Development of male genital tract
- Secondary sexual characteristics
- Anabolic effects (muscle, bone)
- Maintains fertility in adulthood
1) What are the 2 things that testosterone can be converted into and outline the reaction, and the enzyme involved in each reaction. Basically express it in terms of the reaction with formula: ‘testosterone (+enzyme) → product’
2) What receptors do these products act on?
3) What type of receptors do both of them act on?
1)
- Testosterone (+5α-reductase) → DHT (dihydrotestosterone)
- Testosterone (+aromatase) → 17ß-oestradiol (E2)
2)
- DHT acts on androgen receptors
- 17ß-oestradiol (E2) acts on oestrogen receptors
3)
- Nuclear receptors
What will testosterone do in adulthood?
- Lean body mass (due to anabolic activity)
- Muscle size and strength
- Bone formation and bone mass (in young men)
- Libido and potency
Define primary amenorrhoeas
Failure to develop spontaneous menstruation by the age of 16 years
Define secondary amenorrhoeas
Absence of menstruation for 3 months in a woman who previously had cycles
Define oligomenorrhoeas
Irregular long cycles
Give 4 causes of amenorrhoea and the subcategories of the causes where applicable
- Pregnancy
- Lactation - high prolactin stops menstruation
- Ovarian failure:
- Premature ovarian failure (early menopause)
- Ovariectomy / chemotherapy
- Ovarian dysgenesis due to Turner’s syndrome (45X)
- Gonadotrophin failure:
- Hypothalo-pituitary disease
- Kallman’s syndrome (failure of GnRH secretion)
- Low BMI (leptin deficiency)
- Post-pill amenorrhoea (downregulates the hypothalamus and pituitary)
- Hyperprolactinaemia
- Androgen excess - gonadal tumour
1) How do you represent Turner’s syndrome symbolically and what is the pathophysiology?
2) What are the signs of Turner’s?
1) 45 X (missing one X chromosome)
2)
- Short stature
- Ovarian dysgenesis
- Cubitus Valgus
8 investigations into amenorrhoea?
- Pregnancy test
- Day-21 progesterone - if low then ovulation did not occur
- LH / FSH and oestrogen levels - test for hypothalamic-pituitary disease
- Androgen levels (testosterone, androstenedione, DHEAS)
- Prolactin measurement - test for hyperprolactinaemia
- Chromosomal analysis (check for Turner’s)
- U/s scan of ovaries / uterus
- Thyroid function tests (hyper- and hypothyroidism can impact menstruation)
3 ways to treat amenorrhoea?
- Treat the cause e.g. low weight
- Primary ovarian failure - HRT, infertile
- Hypothalamic / pituitary disease - HRT for oestrogen replacement (won’t improve fertility) and gonadotrophins for fertility
