9. Endocrine Infertility Flashcards
Male Hypothalamo-Pituitary-Gonadal Axis
- GnRh pulses from the hypothalamus, stimulating the release of LH and FSH from the pituitary
- Lh then stimulates testosterone production in the testes- Leydig cells
- Testosterone aids spermatogenesis and secondary sexual characteristics
- FSH -> sertoli cells -> Sperm + Inhibin A,B
THREE phases of the menstrual cycle
- Follicular phase
- Ovulation
- Luteal phase
Female Hypothalamo-Pituitary-Gonadal Axis in FOLLICULAR PHASE
LH stimulates production of oestrodiol and progesterone
FSH stimulates follicular development and inhibin
- Leading follicle becomes the GRAFFIAN FOLLICLE after around day 10
- Oestrogen initially inhibits LH and FSH secretion
Female Hypothalamo-Pituitary-Gonadal Axis in LUTEAL PHASE
Once the oestrogen reahces a threshold, it switches from negative feedback to positive feedback
It increases GnRH release and increases LH sensitivity to GnRH
This leads to a mid-cycle LH surge which triggers ovulation
Infertility definition
Inability to concieve after 1 year of regular unprotected sex
1/6 couples affected
Primary Gonadal Failure features
A defecit of the gonads
The testes or ovaries are not producing sex steroids so there is no feedback on the HPG axis SO you get high GnRH, LH and FSH
Clinical features of male hypogonadism
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoperosis (testosterone has an anabolic effect in the bones)
Causes of male hypogonadism
- Hypothalamic-Pituitary Disease
- Hypopituitarism
- Kallmann Syndrome (anosmia and low GnRH) presents as a failure to go through puberty and coincident anosmia (GnRH and olfactory neurones migrate forwards together
- Underweight (due to low levels of leptin)
- Primary Gonadal Disease
- Congenital= Klinefelters Syndrome (XYY)
- Acquired= Testicular torsion, chemotherapy
- Hyperprolactinoma
- Androgen Receptor Deficiency (very RARE)
Investigations for Male Hypogonadism
- LH, FSH and Testosterone serum test- if low should be followed up by MRI of the pituitary
- Prolactin test- checking for hyperprolactinaemia
- Sperm count
- Chromosomal analysis- cheking for klinefelters (XYY
Azoospermia definition
Abscence of sperm in the ejaculate
Oligospermia definition
Reduced numbers of sperm in the ejaculate
Treatment of Male Hypogonadism
- Replacement testosterone for all patients (will increase muscle bulk and protect against osteoperosis)
If hypothalamic/ pituitary disease:
- Gonadotrophins to stimulate testosterone release- subcutaneous gonadotrophin
If Hyperprolactinaemia:
- Dopamine agonist (prolactin inhibitor)
Main actions of testosterone
- Development of the male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects (muscle, bone)
Circulating testosterone binding
Heavily protein bound (98%)
Tissue specific processing of testosterone
In different tissues you get testosterone being converted to other things:
- 5 a-reductase converts testosterone to dihydrotestosterone (DHT) which acts on androgen receptors
- Aromatase converts testosterone to 17B-oestradiol (E2) which acts via Oestrogen receptors
Both of these variants act on nuclear receptors
Testosteone in adulthod will increase
- Lean body mass
- Muscle size and strength
- Bone formation and bone mass (in young men)
- Libido and potency
- It will NOT restore fertility, which requires treatment with gonadotrophins to restore normal spermatogenesis
Characteristics of Amenorrhoea
Abscence of periods
Primary Amenorrhoea= failure to develop spontaneous menstruation by the age of 16 years
Secondary Amenorrhoea= abscence of menstruation for 3 months in a woman who has had previous cycles
Oligomenorrhoea
Irregular long cycles
Causes of amenorrhoea
- PREGNANCY
- Lactation
-
Ovarian Failure:
- Early menopause
- Oophorectomy
- Ovarian dysgenesis (Turner’s syndrome)
-
Gonadotrophin failure:
- Hypothalamic/ Pituitary disease
- Kallmann’s syndrome
- Low BMI
- Post pill
- Hyperprolactinaemia
Investigations to identify causes of Amenorrhoea
Pregnancy test
LH, FSH and Oestradiol serum test (to identify gonadotrophin failure)
Day 21 Progesterone test:
- Progesterone rises over a long time over the second half of the cycle
- Should be a rise to indicate ovulation
Prolactin test
Thyroid function test- Hyper and hypo can cause problems with periods
Chromosomal analysis (turner’s)
Ultrasound
Treatment of Amenorrhoea
Treat the cause:
Primary ovarian failure- HRT
Hypothalamic/ pituitary disease- HRT
Polycystic Ovarian syndrome characteristics
- Affects 1 in 12 women of reproductive age
- Associated with:
- Increased cardiovascular risk
- Insulin resistence
Criteria needed to diagnose Polycyctic Ovarian syndrome
Require TWO of the following:
- Polycystic ovaries on the ultrasound scan
- Oligoovulation/ anovulation
- Clinical/ biochemical androgen excess
Clinical features of polycystic syndrome
- Hirtuism
- Menstrual cycle disturbance
- Increased BMI
Treatment of PCOS- Fertility
- Metiformin- Insulin sensitiser used in type II diabetes
- Clomiphene- Anti-oestrogenic effect in the hypothalamo-pituitary axis- binds to O receptors therby blocking negative feedback- results in increased GnRH and gonadotrophin secretion
- Gonadotrophin therapy
Clinical features of Hyperprolactinaemia
- Galactorhoea
- Reduced GnRH secretion/ LH action leads to hypogonadism
-
Prolactinoma:
- Headache
- Visual field defect
Treatment of Hyperprolactinaemia
Treat the cause - e.g. stop the drugs if that’s what’s causing it
- Dopamine Agonists:
- Bromocriptine
- Cabergoline
- This will also cause a decrease in the size of the tumour if it is being caused by a prolactinoma
- Prolactinoma:
- Dopamine agonist therapy
- Pituitary surgery rarely needed (because drugs usually work)
