L6 - Disorders of Ovulation Flashcards
Describe the process of ovulation
Starts at hypothalamus with the supra chiasmic nuclei (SCN) which interacts with kisspeptin and KNDy neurons. These neurons are stimulated by high oestrogen they stimulate GnRH which drives LH production. GnRH stimulates FSH which acts on primary follicle granulosa cells which produce oestrogen and inhibin. FSH also increases LH receptors in the granulosa cells. when oestrogen too high they positively act on kisspeptin and KNDY neurons further stimulating GnRH – LH produced in a pulsatile fashion to trigger ovulation
How do you diagnose ovulation?
HISTORY Regular menstruation? Check not on hormonal contraception Mid cycle pain at ovulation vaginal discharge alters - inc mucus post ovulation
BIOCHEMISTRY
Day 21 progesterone test - 7 days before next period. LH detection kids OTC
TRANSVAGINAL PELVIC ULTRASOUND
- Done from day 10, alternate days to demonstrate the developing follicle size and corpus luteum.
What can cause ovulation problems?
- Problems with hypothalamus (lack of GnRH) maybe due to Kiss 1 gene or GnRH gene deficiency, weight loss/stress/excessive exercise/anorexia/bulimia
-Problems with Pituitary (lack of FSH and LH)
Pituitary tumours - prolactinoma
post pituitary surgery
-Problem with Ovary
(lack of oestrogen/prog)
Premature ovarian insufficiency
Polycystic ovarian syndrome - commonest
What is amenorrhoea?
Lack of period for more than 6 months
primary - never had a period before
secondary - has menstruated before
What is oligomenorrhoea?
Irregular periods usually more than 6 weeks apart
What is polymenorrhoea?
periods occurring less than 3 weeks apart
What is hirsutism?
Androgen dependant hirsutism - Excess body hair in a male distribution
What are the clinical features of polycystic ovarian syndrome?
- Hyperandrogenism (acne, hirsutism)
- Chronic oligomenorrhoea / ameno (infertility)
- obesity
What is the relationship between PCOS and metabolic syndrome?
- Increased insulin resistance with increased insulin. Raised androgen production by ovarian theca cells, reduced SHBG production by the liver
High insulin and androgens causes granulosa cells to become less functional and follicle arrests. Also causes raised LH levels which drives thecal cell to increase androgens - Impaired glucose tolerance
- Dyslipidemia
- Vascular dysfunction
What does polycystic ovaries look like on ultrasound?
More than 10
- subcapsular follicules 2-8mm diameter
- Arranged around a thickened ovarian stroma
- Not all women with PCOS show this on USS
What hormonal abnormalities will you see in PCOS?
- Raised baseline LH and normal FSH
- LH:FSH ratio 3:1
- Raised androgens and free testosterone
- Reduced SHBG
- oestrogen usually low but can be normal
What is sex hormone binding globulin? SHBG
A protein made by your liver that binds testosterone and oestradiol. If bound to testosterone it is not converted to active component dihydrotestosterone so it is not free. Decreased by testosterone thus releasing more free testosterone
SHBG is increased by oestrogens
What are the reproductive effects of PCOS?
varying degrees of infertility
80% of lack of ovulation is due to PCOS
increased miscarriage
increased risk of gestational diabetes
PCOS and endometrial cancer
Increased endometrial hyperplasia and cancer
Lack of progesterone on the endometrium
endometrial cancer associated with T2D and obesity
What is the treatment for PCOS?
- Diet/excerise
- stop smoking
- Combined oral contraceptives (increases SHBG thus decreases free testosterone decreases FSH/LH and therefore ovarian stimulate regulate cycle and decreases endometrial hyperplasia but may cause weight gain, venous thrombosis
- Anti androgens - With COCP, Cyproterone Acetate (oral tablet) inhibits binding of testosterone and 5 alpha dihydrotestosterone to androgen receptors, spironolactone - anti androgen properties
- Hair removal - photoepilation, eflornithine cream)