T2 L6 Disorders of ovulation

Question 1

Describe the supra-chiasmic nuclei

Answer 1

Master circadian clock which interacts with kisspeptin neurons and KNDy neurons

Question 2

Where are kisspeptin neurons located?

Answer 2

In arcuate nucleus and ateroventral peri ventricular area

Question 3

What does LH trigger?

Answer 3

Ovulation
Resumption of oocyte meiosis
Changes granulosa cells into luteal cells

Question 4

Why do some women get mid cycle pain during ovulation?

Answer 4

Due to leakage of follicle fluid at the time of ovulation irritating the peritoneum

Question 5

What shouldn’t be used to diagnose ovulation?

Answer 5

Basal body temperature
Cervical mucus change
Vaginal epithelium changes
Endometrial biopsies

Question 6

What are some hypothalamic causes of ovulation problems?

Answer 6

Kiss1 gene deficiency
GnRH gene deficiency
Weight loss / stress related / excessive exercise
Anorexia / bulimia

Question 7

What are some pituitary causes of ovulation problems?

Answer 7

Pituitary tumours - prolactinoma / other tumours

Post pituitary surgery / radiotherapy

Question 8

What are some ovarian causes of ovulation problems?

Answer 8

Premature ovarian syndrome

• developmental or genetic causes e.g. Turner’s syndrome
• autoimmune damage and destruction of ovaries
• cytotoxic and radiotherapy
• surgery

Question 9

What is the commonest cause of ovulation problems?

Answer 9

PCOS

Question 10

What is amenorrhoea?

Answer 10

Lack of a period for > 6 months

Question 11

What is primary amenorrhoea?

Answer 11

Never had a period (never went through menarche)

Question 12

What is secondary amenorrhoea?

Answer 12

Has menstruated before but hasn’t had a period for 6 months

Question 13

What is polymenorrhea?

Answer 13

Periods occurring less than 3 weeks apart

Question 14

What is androgen-dependent hirsutism?

Answer 14

Excess body hair in a male distribution

Question 15

What is hypertrichosis?

Answer 15

Excess hair growth that doesn’t follow the male pattern

Question 16

What are the 3 clinical features of PCOS?

Answer 16

Hyperandrogenism

• hirsutism
• acne

Chronic oligomenorrhoea / amenorrhoea

• ≤9 periods a year
• subfertility

Obesity
-25% are lean

Question 17

When is PCOS diagnosed?

Answer 17

When 2 of these 3 symptoms are met:

• polycystic ovaries
• androgen excess
• oligo/anovulation

Question 18

Describe the link between metabolic syndrome and PCOS

Answer 18

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

Question 19

Describe the ultrasound appearance of PCOS

Answer 19

≥ 10 subcapsular follicles, 2-8mm diameter
Arranged around thickened ovarian storm
Not all women with PCOS will have ultrasound appearance

Question 20

Describe the hormone levels in PCOS

Answer 20

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

Question 21

What are the reproductive effects of PCOS?

Answer 21

Associated with varying degrees of infertility
Associated with increased miscarriages
Increased risk of gestational diabetes

Question 22

What is the link between PCOS and endometrial cancer?

Answer 22

Increased endometrial hyperplasia and cancer
Lack of progesterone on the endometrium
Endometrial cancer is associated with type 2 diabetes and obesity

Question 23

What are the treatment options for PCOS?

Answer 23

Lifestyle modifications
Combined oral contraceptives
Anti-androgens
Metformin
Hair removal

Question 24

What lifestyle modifications are advised in PCOS?

Answer 24

Diet and exercise
Stop smoking
High frequency eating disorders

Question 25

What are the effects of making lifestyle modifications?

Answer 25

Decreases insulin resistance Increases SHBG concentration Improved fertility / pregnancy outcomes Improved metabolic syndrome risk factors

Question 26

Describe how COCP can help with PCOS?

Answer 26

Increase SHBG to decrease free testosterone Decrease FSH and LH to stimulate ovaries Regulates cycle to decrease endometrial hyperplasia

Question 27

Describe the use of anti-androgens for PCOS

Answer 27

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

Question 28

How does metformin help with PCOS?

Answer 28

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

Question 29

What are the options for hair removal?

Answer 29

Photoepilation / electrolysis | Eflomithine cream

Question 30

What are the differential diagnoses for hirsutism?

Answer 30

95% is PCOS or idiopathic hirsutism 1% of non-classical congenital adrenal hyperplasia <1% Cushing's syndrome <1% adrenal / ovarian tumour

Question 31

What is primary ovarian insufficiency?

Answer 31

Premature ovarian failure / premature menopause | Loss of normal function of ovaries

Question 32

What is the aetiology of primary ovarian insufficiency?

Answer 32

Autoimmunity X chromosomal abnormalities - Turner syndrome, fragile X Genetic predisposition - premature menopause Iatrogenic - surgery, radiation, chemo

Question 33

What investigations should be done when considering primary ovarian insufficiency?

Answer 33

``` History / examination Increased LH and FSH Possible karyotype Consider pelvic ultrasound Consider screening for other autoimmune endocrine disease ```

Question 34

What is the management for primary ovarian insufficiency?

Answer 34

Psychological support HRT Monitor bone density Fertility - IVF with donor egg

Question 35

What is Turner's syndrome?

Answer 35

Complete / partial X monosomy in some / all cells

Question 36

What are some problems associated with Turner's syndrome?

Answer 36

``` Short stature CV system - coarctation of aorta - bicuspid aortic valve - aortic dissection - hypertension Renal Metabolic syndrome Hypothyroidism Ears / hearing problems Osteoporosis ```

Question 37

What is congenital adrenal hyperplasia?

Answer 37

Disorders of cortisol biosynthesis | Defect in cortisol biosynthesis --> raised CRH / ACTH --> excess adrenal androgen production

Question 38

How is congenital adrenal hyperplasia diagnosed?

Answer 38

High concentration of 17-hydroxyprogesterone | Can confirm with synacthen test

Question 39

What is the presentation of congenital adrenal hyperplasia in adulthood?

Answer 39

Hirsutism Oligo/amenorrhoea Acne Subfertility

Question 40

What is the treatment for congenital adrenal hyperplasia?

Answer 40

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