lecture 30: disease and disorders 2: ovarian Flashcards
1
Q
What is ovarian follicle development?
A
preantral follicle growth (4 months)
- primordial follicles
- initial recruitment
- primary follicles
Antral follicle growth (2 cycles)
- antrum formation
- cyclic recruitment
- some undergo atresia
- selection and dominance
- ovulation
2
Q
What are genes involved in fertility?
A
- primordial follicles
- KITL, KIT, AMH
- primary follicle
- GDF9, KITL
- secondary follicle
- FSH, FSHR, IGF1, CCND2, TAF4B
- early antral follicle
- INHA, INHBA, CX37
- ERalpha, ERbeta
- ovulation
- LHR, COX2, PR, CEBPB, NRIP1
- COC integrity
- GDF9, BMP15, PTGER2, PTX3, AMBP
- fertilisation and pre-implantation development
- ZP1, ZP2, ZP3, MATER, DNMT1o, PMS2, HSF1
- implantation
- COX2, HOXA10, HOXA11, LIF, IL11R, HMX3, PR, ERalpha
3
Q
What are examples of people purporting bizarre reasons for ovarian disorders?
A
- women drivers could suffer damage to ovaries, says Saudi Sheikh
4
Q
What are normal levels of follicles?
A
- foetus at 20 weeks’ gestation: each ovary contains about 4 million follicles
- term: 1-2 million follicles
- puberty: 300,000 - 400,000
- 37 years: 100,000 then rapid loss
- perimenopausal threshold less than 1000 follicles?
- also decline in quality
5
Q
What is premature ovarian insufficiency (POI)?
A
- incidence and cause
- POI or premature ovarian failure (POF)
- affects ~1% of population
- genetic - Turner and Fragile X syndrome, inhibin alpha gene
- unknown - autoimmune?
- side effect of cancer/fertility issues and treatment
- symptoms
- no periods for 4 months before age 40
- FSH levels greater than 40mlU/ml on 2 occasions at least 1 month apart (never rely on one off level); day 2-6 if cycling
- abnormally low AMH and oestrogen level
- exclusion of all other causes of absent periods, chromosome test
- treatment
- no known treatment
- sometimes responsive to ovarian stimulation, donor eggs to conceive
- at risk pre-pubertal girls option of ovarian cryopreservation
- still need contraception: lifetime chance of ever conceiving 5-10%
- HRT/contraception until around 50 years
- major problem is decreased oestrogen on related health issues
- related health issues
- osteoporosis
- heart disease
- hypothyroidism
- auto-immune diseases
- support networks
6
Q
What are problems with ovulation?
A
- no ovulation = no egg = no pregnancy
- 40% of all infertile women
- symptoms
- oligomenorrhoea (infrequent period)
- amenorrhoea (absent period), more than 6 months
- causes
- hormone deficiency
- very low body weight (less than 20%) - eating disorders
- obesity (10-15%) and weight fluctuations
- diet and stress
- over exercise
- hormone resistance (insulin)
- damaged or diseases ovaries, pituitary tumour
7
Q
What is anovulation?
A
- diagnosis
- ultrasound
- abnormalities - ovarian (cysts), uterine growths, endometriosis
- blood tests
- steroids, gonadotrophins, prolactin, thyroid, AMH
- ultrasound
- treatment
- lifestyle changes?
- hormonal ovulation induction (OI)
- clomiphene citrate (Clomid/Serophene)
- pill for 5 days, side-effects
- stimulates ovulation (80%), twinning (10%)
- gonadotrophins (FSH, LH, hCG)
- injections, side-effects
- promoting follicle growth
- risk of multiples
- clomiphene citrate (Clomid/Serophene)
- IVF treatment
8
Q
What is polycystic ovary syndrome (PCOS)?
A
- affects 5-10% of women - most common endocrine disorder
- indigenous Australian women up to 21%
- issues with diagnosis, could be more?
- syndrome - multifaceted symptoms, several diseases
- symptoms
- weight gain (centralised)
- increased acne and bad skin
- hirsutism - face (male patterns)
- anovulation, irregular menstrual cycles
- subfertility - lack of pregnancy and higher miscarriage
- mood swings, decreased libido, ovulation kit useless
- variation in symptoms and how many are evident
- effects on embryo/foetus - programming?
9
Q
How is PCOS diagnosed?
A
- strict but changing criteria
- increased androgens - hirsutism (70%), increased acne
- anovulation, irregular menstrual cycles
- presence of cystic follicles – enlarged ovaries, increased small surface cysts
- must have 2 of 3 - can have PCOS and NOT have cystic ovaries (40%)!
- blood tests
- increased LH, decreased FSH, decreased SHBG, increased androgens, increased oestrogens (oestrone)
- ultrasound
- greater than 12 follicles 2-9mm (small), increased ovary size
10
Q
What is the interaction between theca and granulosa cells?
A
- interact to make oestrogens
- theca: cholesterol → androgens
- granulosa: androgens → oestrogens
11
Q
What happens to theca and granulosa in PCOS?
A
- over production of LH and androgens
- theca: cholesterol → androgens
- granulosa: androgens X oestrogens
- testosterone goes into blood → fat cell → production of oestrone → anterior pituitary
12
Q
What are causes and risk factors for PCOS?
A
- genetic factors??
- weight
- change, over/under, hard to lose (metabolic)
- loss of just 5% BW can resolve anovulation
- half of all PCOS women are NOT overweight
- insulin resistant (increased circulating insulin) 80% of women
- insulin → increased androgens
- insulin → decreased SHBG (liver)
13
Q
What is follicular development in PCOS?
A
- insulin acts on developing follicle
- responds to LH
- → final step in development
- follicular development stopped
- death of granulosa cells
- death of theca cells prevented by insulin
- cyst
- testosterone secreted
14
Q
What are factors associated with PCOS?
A
- obesity and metabolic sequelae
- type II diabetes
- cardiovascular disease
- uterine/ovarian carcinomas (increased oestrone)
15
Q
What are treatments for PCOS?
A
- OCP (+ androgen inhibitors)
- clomiphene - to boost FSH
- blockers of androgen synthesis (e.g. flutamide)
- metformin - insulin sensitiser
- need to treat underlying causes !!
- weight loss
- exercise
- dietary interventions
- low GI diet (glucose)
- vegetables and pulses
- vitamin D (deficiency - insulin resistance)
- combinations
- patient specific BUT don’t address all symptoms
- sources of advice
- diagnosis, treatments etc
- Jean Hailes
- POSAA