T2 L6: Disorders of Ovulation Flashcards
(45 cards)
what does GnRH stimulate FSH to do
Act on the primary follicle granulosa cells which start producing oestrogren & Inhibin
FSH increases the LH receptors but in which cells
granulosa cells
when does oestrogen act positively on Kisspeptin & (KNDy neurones )
At critically high levels
what are the 2 potent stimulators of GnRH
Kisspeptin-( KNDy neurones )
what stimulates the kisspeptin and GnRH neurons
High oestrogen and LH production (via stim of GnRH)
what is the function of LH and FSH
FSH causes the follicle to produce oestrogen and inhibin both of which negatively feedback to the hypothalamus and pitutary to decrease FSH.
LH triggers ovulation, resumption of oocyte meiosis and changes the granulosa cells into luteal cells
what is a key concept to understand with the regulation of LH and FSH
FSH causes the follicle to produce oestrogen and inhibin both of which negatively feedback to the hypothalamus and pitutary to decrease FSH.
However as the oestrogen levels rise there is an effect of high levels of oestrogen on the Kisspeptin and KNDy neurones that stimulates the production of GnRH which stimulates the production of LH, (due to increased frequency and amplitude of the pulse from GnRH)
.
Its release occurs in a pulsatile fashion and triggers ovulation, oocyte meiosis & changes the granulosa cells into luteal cells ( small rise in FSH at this time).
describe the first half of the ovulation cycle
First half of cycle: FSH falls as oestrogen and inhibin rises. At a critical level oestrogen positively feeds back to Kisspeptin and in turn causes an increas in freq and amplitude of GnRH which causes the LH surge.
Second half of cycle: As LH now converts the granulosa cells to luteal cells hormone production swaps from oestrogen to progesterone. Progesterone peaks at Day 21 ( 7 days before the period). Progesterone, oestrogen and inhibin inhibit FSH and LH.
when taking a history, what important features of the menstrual cycle must you take into account
Regular cycle is 28 days
Bleeding begins from day 1-5
fertility is from day 11-15
mid cycle pain at ovulation
vaginal discharge alters (increased mucus post ovulation)
what is ovulation pain
leakage of follicle fluid at the time of ovulation irritates the peritoneum and causes pain
how do you diagnose ovulation
Biochemistry :
- Day 21 progesterone blood test
LH detection kits:
-urinary kits bought over the counter
Transvaginal pelvic ultrasound (done from day 10)
what can’t you do to diagnose ovulation
not: Basal temperature, cervical mucus change, vaginal epithelium changes nor endometrial biopsies
what are the 2 groups and possible causes of ovulation problems
Hypothalamus (lack of GnRH)
- Kiss1 gene deficiency- rare
- GnRH gene deficiency - rare
- weight loss/stress related/excessive exercise
- anorexia/bulimia
Pituitary (lack of FSH and LH)
- pituitary tumours (prolactinoma/other tumours)
- post pituitary surgery /radiotherapy
Causes of ovulation problems
Ovary (lack of oestrogen/progesterone)
-Premature ovarian insufficiency
Developmental or genetic causes eg Turner’s syndrome
Autoimmune damage and destruction of ovaries
Cytotoxic and radiotherapy
Surgery
-Polycystic Ovarian Syndrome: commonest cause
Define :
Amenorrhoea
oligomenorrhoea
polymenorrhoea
Amenorrhoea - lack of a period for more than 6 months
- Primary Amenorrhoea - never had a period (never went through menarche)
- Secondary Amenorrhoea -has menstruated before
Oligomenorrhoea - irregular periods
-usually occurring more than 6 weeks apart
Polymenorrhoea - periods occurring less than 3 weeks apart
Define hirsutism
Androgen-dependent’ hirsutism
Excess body hair in a male distribution
-NOT
-Androgen-independent hair growth
Hypertrichosis
-Familial / racial hair growth
what are the clinical features of PCOS Polycystic Ovarian syndrome (PCOS)
- Hyperandrogenism
- –Hirsutism, acne
Chronic oligomenorrhoea / amenorrhoea
-9 periods / year
-Subfertility
Obesity (but 25% of women with PCOS are “lean”)
what are the 3 elements in the diagnosis of PCOS
Polycystic ovaries
Androgen excess
Oligo/anovulation
(need at least 2 of these to diagnose PCOS)
what is the relationship that PCOS has with the metabolic syndrome
Insulin resistance with + insulin
- androgen production by ovarian theca cells
- +SHBG production by the liver
Impaired glucose tolerance
-+ risk gestational DM and T2 DM
- Dyslipidaemia
- Vascular dysfunction
- ? +risk cardiovascular disease ?
what is the mechanism between insulin resistance and PCOS
Insulin resistance is the underlying problem ( genetic factors also important).
High levels of Insulin and androgens cause granulosa cells to become less functional ( less oestrogen) and the follicle to arrest=anovulation,
also causes increased LH levels which drives thecal cells to increase androgens. leading to hirsutism
what is the USS appearance of Polycystic Ovaries
10 subcapsular follicules 2-8 mm in diameter,
arranged around a thickened ovarian stroma
( not all women with PCOS will have USS appearance & technically Not cysts – definition of cyst is a mass > 3cms. Wrong name for the condition! Should be poly small follicles disease!
)
what are the hormonal abnormalities in PCOS
Raised baseline LH and normal FSH levels. Ratio LH:FSH 3:1
Raised androgens and free testosterone
Reduced Sex Hormone Binding Globin (SHBG)
Oestrogen usually low but can be normal
Describe the sex hormone binding globulin SHBG
- Produced by the liver
- Binds testosterone and oestradiol
- If testosterone bound - not converted to active component dihydrotestosterone ie not “free”
- SHBG increased by oestrogens
- SHBG decreased by testosterone thus releasing more free testosterone
what are the reproductive effects of PCOS
PCOS is maybe associated with varying degrees of infertility
- 15% of all causes of infertility is lack of ovulation
- 80% of lack of ovulation due to PCOS
- Associated with increased miscarriages
- Increased risk of Gestational Diabetes