Endocrine regulation of female fertility Flashcards
(24 cards)
What is primary amenorrhoea?
Never had a period
What is secondary amenorrhoea?
No periods for 6 months
What are the causes of primary amenorrhoea?
•Genitourinary abnormalities - absence of uterus, cervix or vagina - Rokitansky syndrome - Androgen insensitivity syndrome •Chromosomal abnormalities - turners syndrome •Secondary hypogonadism (pituitary/hypothalamic cause) - Kallmann syndrome - pituitary disease - hypothalamic amenorrhoea (low BMI, stress, illness)
What are the causes of secondary amenorrhoea relating to the axis?
- Hypothalamic: weight loss, stress, drugs e.g. opiates
- Pituitary: prolactinoma, pituitary tumour
- Ovarian: PCOS, premature ovarian failure
- Uterine: ashermans syndrome
Explain the Hormonal axis
- Hypothalamus releases GNRH
- GNRH stimulates the pituitary to release LH and FSH
- LH and FSH act on the ovary and the ovary releases oestrogen and progesterone which acts on the uterus
What are the physiological causes of amenorrhoea?
- Pregnancy
* Lactation
What are the iatrogenic causes of amenorrhoea?
- OCP
* Other hormonal contraceptives
What are the other causes of amenorrhoea?
•Thyroid dysfunction •Hyperandrogenism - Cushing's - Congenital adrenal hyperplasia - Adrenal or ovarian tumour
What is hirsutism?
Excess hair growth in a male pattern due to increased androgens and increased sensitivity to androgens
What is the leading cause of hirsutism?
PCOS
What is the presentation of PCOS?
- Anovulation- amenorrhoea, oligomenorrhoea (infrequent), irregular cycles
- Symptoms of hyperandrogegism: hirsutism, acne, alopecia
- Typically presents during polycystic ovaries
What are the typical endocrine features of PCOS?
- Raised testosterone
* Raised LH
What metabolic abnormalities are PCOS associated with?
- Hypertension
* hyperglycaemia due to insulin sensitivity -> T2DM
Explain the gonadotrophin component of the pathophysiology of PCOS
- Increased LH concentration, there are increased LH receptors in PCOS ovaries
- LH supports the ovarian theca cells which are responsible for ovarian androgen production
- Decreased FSH- constant low level resulting in continuous stimulation of follicles without ovulation
- Low FSH means there is a decreased conversion of androgens to oestrogen in granulosa cells
Explain the androgen component of the pathology of PCOS
- Increased androgen production from theca cells under the influence of LH
- May also be due to disordered enzyme action
- Decreased Sex hormone binding globulin (SHBG) which is produced in the liver and binds to testosterone. Only free testosterone is biologically active -> hyperandrogegism and hyperinsulinaemia
Explain the insulin component of the pathophysiology of PCOS
- Increased insulin in response to glucose load
- Increased insulin resistance
- Insulin stimulates the theca cells of the ovaries, reduces hepatic production of SHBG resulting in increased circulating androgens
What are the investigations for PCOS?
•Confirm the profile of PCOS: - testosterone - androstenedione - DHEAS - SHBG - FSH/LH •Assess for other features: type 2 diabetes and abnormal lipids •Exclude other pathologies e.g. cushings
Explain reversal of PCOS by weight loss
- Losing weight decreases amount of insulin
- This increases the amount of SHBG produced and decreases the androgens produced
- This results in lowered free testosterone and therefore increased ovulation and decreased hirsutism
Explain the use of metformin in PCOS
- Improves insulin sensitivity
- Leads to decreased LH and increased SHBG
- not useful for treatment of infertility
- Not very effective for treatment of hirsutism
- useful for those at risk of developing type 2 DM and allowing for more frequent cycles
What is the mechanism of the oral contraceptive?
Ovarian androgen suppression
What is the mechanism of corticosteroids?
Adrenal androgen suppression
What is the mechanism of action of spironolactone?
Androgen receptor antagonist
What is the mechanism of action of finasteride?
5 alpha reductase inhibition
What is the effect of calorie restriction on insulin and fertility in obese women with PCOS?
improves ovulation and fertility
