9. Endocrine Infertility Flashcards
Describe the hypothalamo-gonadotrophin axis during the follicular and ovulation phase
Follicular phase: Same as men - FSH/LH stimulates the ovaries to release oestradiol + progesterone which have NEGATIVE feedback on hypothalamus + pituitary
Ovulation phase: High oestradiol levels has POSITIVE feedback on the hypothalamus, causing a SURGE in LH/FSH
What happens in the luteal phase?
If implantation doesn’t occur, endometrium is shed -> menstruation
If implantation occurs -> pregnancy
Definition of infertility?
Inability to conceive after 1 year of regular unprotected sex
1:6 couples affected Male abnormalities (30%) Female abnormalities (45%) Unknown abnormalities (25%)
What is primary gonadal failure?
Failure of the testes/ovaries -> LOW testosterone/oestradiol
So LESS negative feedback onto hypothalamus ->
HIGH GnRH -> High FSH/LH
What is secondary gonadal failure? (hypothalamus/pituitary disease)
Failure of hypothalamus/pituitary to release GnRH
LOW FSH/LH -> Low testosterone/oestradiol
Features of male hypogonadism
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoporosis
Causes of male primary hypogonadism?
Congenital: Klinefelter’s syndrome (XXY)
Acquired: Testicular torsion, chemotherapy
Causes of male secondary hypogonadism?
Hypo/pituitary disease:
- Hypopituitarism
- Kallman’s syndrome - genetic disorder (anosmia + low GnRH)
- Illness/underweight
Other causes of male hypogonadism?
Hyperprolactinaemia
Congenital Androgen receptor deficiency (rare)
Investigations for male hypogonadism?
- FSH, LH, testosterone - if ALL LOW -> MRI pituitary
If FSH/LH are high, problem with gonads - Prolactin levels
- Sperm count:
Azoospermia = absence of sperm in ejaculate
Oligospermia = reduced sperm - Chromosomal analysis (Klinefelters XXY)
Treatment for male hypogonadism?
Testosterone replacement
To reactivate spermatogenesis (fertility) -> sc gonadotrophins (FSH/LH) injection
Hyperprolactinaemia - D2 agonist
Where are the endogenous sites of androgen production?
- Leydig cells (testes)
- Adrenal cortex
- Ovaries
- Placenta
- Tumours
What are the main actions of testosterone?
- Development of male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects (muscle, bone)
What is tissue-specific processing of testosterone?
In muscle/bone:
Converted by 5a-reductase into DHT (Dihydrotestosterone)
DHT acts via Androgen receptors
In brain/adipose tissue:
Converted by aromatase into 17b-oestradiol (E2)
E2 acts via oestrogen receptors
What are the clinical uses of testosterone?
Increases:
- Lean body mass
- Muscle strength/size
- Bone formation/mass
- Libido/potency
It does NOT restore fertility - that can be achieved by gondaotrophin treatment which will activate spermatogenesis
What are the 3 causes of infertility in females?
- Amenorrhoea
- Polycystic Ovarian Syndrome (PCOS)
- Hyperprolactinaemia
What are the types of amenorrhoea?
- Primary amenorrhoea = failure to begin spontaneous menstruation by 16yrs
- Secondary amenorrhoea = no menstruation for 3 months in woman who’s previously had normal cycles
- Oligomenorrhoea = irregular long cycles
Causes of amenorrhoea at the level of gonads?
Pregnancy/lactation Ovarian failure - Premature ovarian failure - Ovariectomy/chemo - Ovarian dysgenesis (Turner's 45 XO, missing X chromosome)
Clinical features of Turners syndrome?
Short stature
Gonadal dysgenesis
Wide carrying angle
Causes of amenorrhoea at the level of hypo/pituitary?
Gonadotrophin failure:
- Hypo/pit disease
- Kallmann’s syndrome (XXY)
- Low BMI
- Post pill
Hyperprolactinaemia
Gonadal tumour -> androgen excess (RARE)
Investigations for amenorrhoea?
- Pregnancy test
- FSH/LH/oestradiol
- Day 21 progesterone (should be high if ovulating. If not, that means no LH surge -> no ovulation -> low day 21 progesterone)
- Prolactin, thyroid function tests
- Androgen levels (testosterone, DHEAS)
- Chromosomal analysis (Turners 45 XO)
- Ultrasound ovaries/uterus
Treatment for amenorrhoea?
Treat the cause (e.g. low weight)
Primary ovarian failure - HRT to treat infertility
Hypo/pit disease: HRT if not interested in fertility, for fertility give FSH/LH (part of IVF treatment)
Incidence of PCOS?
1 in 12 women of reproductive age
What is PCOS associated with?
Increased risk of CVD and insulin resistance
