T2 L6 Disorders of ovulation Flashcards
Describe the supra-chiasmic nuclei
Master circadian clock which interacts with kisspeptin neurons and KNDy neurons
Where are kisspeptin neurons located?
In arcuate nucleus and ateroventral peri ventricular area
What does LH trigger?
Ovulation
Resumption of oocyte meiosis
Changes granulosa cells into luteal cells
Why do some women get mid cycle pain during ovulation?
Due to leakage of follicle fluid at the time of ovulation irritating the peritoneum
What shouldn’t be used to diagnose ovulation?
Basal body temperature
Cervical mucus change
Vaginal epithelium changes
Endometrial biopsies
What are some hypothalamic causes of ovulation problems?
Kiss1 gene deficiency
GnRH gene deficiency
Weight loss / stress related / excessive exercise
Anorexia / bulimia
What are some pituitary causes of ovulation problems?
Pituitary tumours - prolactinoma / other tumours
Post pituitary surgery / radiotherapy
What are some ovarian causes of ovulation problems?
Premature ovarian syndrome
- developmental or genetic causes e.g. Turner’s syndrome
- autoimmune damage and destruction of ovaries
- cytotoxic and radiotherapy
- surgery
What is the commonest cause of ovulation problems?
PCOS
What is amenorrhoea?
Lack of a period for > 6 months
What is primary amenorrhoea?
Never had a period (never went through menarche)
What is secondary amenorrhoea?
Has menstruated before but hasn’t had a period for 6 months
What is polymenorrhea?
Periods occurring less than 3 weeks apart
What is androgen-dependent hirsutism?
Excess body hair in a male distribution
What is hypertrichosis?
Excess hair growth that doesn’t follow the male pattern
What are the 3 clinical features of PCOS?
Hyperandrogenism
- hirsutism
- acne
Chronic oligomenorrhoea / amenorrhoea
- ≤9 periods a year
- subfertility
Obesity
-25% are lean
When is PCOS diagnosed?
When 2 of these 3 symptoms are met:
- polycystic ovaries
- androgen excess
- oligo/anovulation
Describe the link between metabolic syndrome and PCOS
Insulin resistance with increasing insulin
- increase in androgen production by ovarian theca cells
- decrease in SHBG production by liver
Impaired glucose tolerance
Dyslipidaemia
Vascular dysfunction
Increased risk of cardiovascular disease
Describe the ultrasound appearance of PCOS
≥ 10 subcapsular follicles, 2-8mm diameter
Arranged around thickened ovarian storm
Not all women with PCOS will have ultrasound appearance
Describe the hormone levels in PCOS
Raised baseline LH and normal FSH levels
Raised androgens and free testosterone
Reduced sex hormone binding globulin
Oestrogen is usually low but it can be normal
What are the reproductive effects of PCOS?
Associated with varying degrees of infertility
Associated with increased miscarriages
Increased risk of gestational diabetes
What is the link between PCOS and endometrial cancer?
Increased endometrial hyperplasia and cancer
Lack of progesterone on the endometrium
Endometrial cancer is associated with type 2 diabetes and obesity
What are the treatment options for PCOS?
Lifestyle modifications Combined oral contraceptives Anti-androgens Metformin Hair removal
What lifestyle modifications are advised in PCOS?
Diet and exercise
Stop smoking
High frequency eating disorders
What are the effects of making lifestyle modifications?
Decreases insulin resistance
Increases SHBG concentration
Improved fertility / pregnancy outcomes
Improved metabolic syndrome risk factors
Describe how COCP can help with PCOS?
Increase SHBG to decrease free testosterone
Decrease FSH and LH to stimulate ovaries
Regulates cycle to decrease endometrial hyperplasia
Describe the use of anti-androgens for PCOS
Taken with COCP / other form of secure contraception
Cyproterone acetate inhibits binding of testosterone and 5 alpha dihydrotestosterone to androgen receptors
Spironolactone has anti-mineralocorticoid and anti-androgen properties
How does metformin help with PCOS?
Decrease insulin resistance and insulin levels
Decrease ovarian androgen production
May help with weight loss / diabetes prevention
Increase ovulation
Less helpful for hirsutism and oligomenorrhoea
What are the options for hair removal?
Photoepilation / electrolysis
Eflomithine cream
What are the differential diagnoses for hirsutism?
95% is PCOS or idiopathic hirsutism
1% of non-classical congenital adrenal hyperplasia
<1% Cushing’s syndrome
<1% adrenal / ovarian tumour
What is primary ovarian insufficiency?
Premature ovarian failure / premature menopause
Loss of normal function of ovaries
What is the aetiology of primary ovarian insufficiency?
Autoimmunity
X chromosomal abnormalities - Turner syndrome, fragile X
Genetic predisposition - premature menopause
Iatrogenic - surgery, radiation, chemo
What investigations should be done when considering primary ovarian insufficiency?
History / examination Increased LH and FSH Possible karyotype Consider pelvic ultrasound Consider screening for other autoimmune endocrine disease
What is the management for primary ovarian insufficiency?
Psychological support
HRT
Monitor bone density
Fertility - IVF with donor egg
What is Turner’s syndrome?
Complete / partial X monosomy in some / all cells
What are some problems associated with Turner’s syndrome?
Short stature CV system - coarctation of aorta - bicuspid aortic valve - aortic dissection - hypertension Renal Metabolic syndrome Hypothyroidism Ears / hearing problems Osteoporosis
What is congenital adrenal hyperplasia?
Disorders of cortisol biosynthesis
Defect in cortisol biosynthesis –> raised CRH / ACTH –> excess adrenal androgen production
How is congenital adrenal hyperplasia diagnosed?
High concentration of 17-hydroxyprogesterone
Can confirm with synacthen test
What is the presentation of congenital adrenal hyperplasia in adulthood?
Hirsutism
Oligo/amenorrhoea
Acne
Subfertility
What is the treatment for congenital adrenal hyperplasia?
Glucocorticoid and mineralocorticoid replacement
Supraphysioloical glucocorticoid doses may be needed to suppress adrenal androgen production
Surgical management for ambiguous genitalia
Can treat in the same was as PCOS
