Introduction to PCOS (Need to complete )

Question 1

What are polycystic ovaries ?

Answer 1

The ovary contains increased numbers (more than 12 ) of small antral follicles (2-9mm wide ) visible on an ultrasound.

Additionally there is sometimes a failure of dominant follicle selection which means anovulation

Question 2

What are some of the things which lead to so the polycystic ovaries ?

Answer 2

Increased proportion of primordial follicles and increased number of activated primary follicles

Arrested antral follicle growth before they have matured

Lower rates of atresia (breakdown of follicles) - antral follicles persist (visible on ultra sound )

Question 3

What are some differences between normal ovary and polycystic ovary on ultra sound ?

Answer 3

In PCO there will be an thickened stroma and whole ovary surface enlarged ,more follicles arranged in ‘necklace’ arrangement around the periphery.

Question 4

What are some disorders which can mimic PCOS?

Answer 4

Non -classical adrenal hyperplasia
(Most common is deficiency of 21 hydroxylase = Increases 17-hydroxyprogesterone and androgens

Hyperprolactinemia
Thyroid disease
Cushings syndrome
Ovarian hyperthecosis -nests of luteinised theca cells + produce lots of androgens

Question 5

What is the Rotterdam criteria ?

Answer 5

There needs to be two of these for a PCOS diagnosis :

Polycystic ovaries
Ovulatory dysfunction
Hyperandrogenism

Question 6

Under the Rotterdam Criteria what are polycystic ovaries ?

How is this detected ?

Answer 6

(either 12 or more follicles measuring 2-9mm diameter and/or increased ovarian volume >10ml in either ovary & no DF >10mm)

Technique and equipment dependent. T/V imaging not always appropriate

Question 7

Under the Rotterdam Criteria what are Hyperandrogenism?

How is this detected ?

Answer 7

(clinical/biochemical evidence)
Assays not standardized across labs; normative data not clearly defined; clinical hyperandrogenism difficult to quantify; ethnicity

Clinical hyperandrogenism includes hirsutism, acne, or male pattern alopecia or biochemical signs of hyperandrogenism i.e. elevated levels of total or free testosterone.

Question 8

Under the Rotterdam Criteria what are Ovulatory dysfunction?

How is this detected ?

Answer 8

(Oligomenorrhea/anovulation)

Frequent bleeding <21d or infrequent bleeding >35d. To confirm ovulation serum progesterone level at mid-luteal phase (d21-22) of cycle (values ≥7ng/ml needed for regular luteal function)

Anovulation is either frequent bleeding at intervals <21d or infrequent bleeding at intervals of >35d. Normal ovulation is hard to define – mid-luteal Progesterone <3-4ng/ml indicates oligo-anovulatory.

Question 9

What are the definitions of PCO?

Using an ultrasound

Answer 9

By Ultrasound:
Normal
no more than 5 follicles in an ovary with a small amount of stroma in a woman with regular cycles
PCO
In at least one ovary ≥ 12 follicles of 2-9mm diameter arranged peripherally around an enlarged core of dense stroma - ovarian volume >10mls, without a dominant follicle
PCOS
PCO on scan plus one or more symptoms

Question 10

What is the difference in morphology between normal and anovulatory PCO ?

Answer 10

In an anovulatory ovary in the early mid follicular and ovulation , the follicles will look the same throughout.
There will be no dominant follicle and there will be lots of antral follicles around the edge with thickened stroma

Question 11

What is the difference in morphology between a normal and ovulatory PCO?

Answer 11

There will be a dominant follicle at the mid-follicular phase. Which will go on to ovulate however the remaining antral follicles will remain as cysts.

Question 12

What is the difference between PCO and PCOS ?

Answer 12

Women with PCO will have regular/almost regular cycles whereas women with PCOS and cycle problems have oligomenorrhoea.

Question 13

What are some contributing factors to follicle arrest ?

Answer 13

Androgens
Intra-follicular inhibitors e.g. AMH
Defect in apoptosis -prevents normal apoptosis
Dysregulated gonadotrophin secretion (FSH and LH )

Question 14

What is one of the main differences between ovulatory and anovulatory ?

Answer 14

Insulin resistance
The level of insulin resistance
Women with PCOS who gain a lot of weight is usually linked with insulin resistance.

Most women with PCO have regular menstrual cycles

Most women with PCOS and cycle problems have oligomenorrhoea

Question 15

What is the prevalence of PCOS ?

Answer 15

32% of patients with amenorrhoea -do not ovulate
87% with oligomenorrhoea-irrregular cycles
87% with hirsutism and regular cycles
75% of bulimics?
22% of ‘normal’ population

One of the most common causes of anovulatory infertility -73%

Question 16

Outline the aetiology of PCOS

Answer 16

Familial aggregation
Sisters more likely to be affected
first-degree relatives have higher rates of metabolic abnormalities (including insulin resistance, decreased beta-cell function etc)
Male relatives of women with PCOS increased prevalence of metabolic syndrome & obesity compared to general US male population
Monozygotic twins twice as likely to both have PCOS than dizygotic.
common finding of raised androgen led to belief that PCOS is caused by an inherited disorder -most likely in the steroid biosynthetic pathway
Many candidate genes were investigated: all ‘obvious’ ones ruled out
Complex polygenic disease – involves subtle interaction with environmental factors (intra- & extra-uterine)

Question 17

What is a monozygotic twin ?

Answer 17

This is when twins form from one embryo

Question 18

What loci linked and canditate genes within those loci have been linked to PCOS through the chinese GWAS?

Answer 18

LHCGR
FSHR
THADA….linked to T2D
DENND1A …linked with obesity

Question 19

How does PCOS affect gonadotrophins ?

How does it disorder androgens?

Answer 19

A consisted feature of PCOS is disordered gonadotropin secretion which can cause downstream ovarian consequences

Elevated/upper-normal mean LH
Low/low-normal FSH

The PCOS patients will have an altered ratio of LH and FSH

Rapid GnRH frequency → favouring rapid LH pulse secretion

Elevated LH pulse frequency and increased LH:FSH ratio impairs downstream ovarian folliculogenesis and alters steroid hormone production. In PCOS the “FSH threshold” that is required for follicle maturation is not reached (due to this dysregulated gonadotrophins and also increased AMH, which alters FSH sensitivity) causing follicles to arrest in antral stages.

Question 20

What will actually cause the deregulated gonadotropin secretion?

Answer 20

Impaired negative regulation of GnRH pulse generator
High Testosterone which is intrinsic impairs negative feedback by Progesterone in presence of oestradiol (in luteal phase )

Proof: block AR with flutamide → progesterone then able to↓ LH & FSH
Also see that in late puberty girls without HA respond to progesterone with ↓LH pulse frequency o/n, which did not occur in HA girls at same pubertal stage

Question 21

How does the LH levels vary in PCOS ?

Answer 21

In woman with PCOS they will have high LH

The higher LH will drive thecal cell hyperplasia and the hyper-androgenemia, but HA is also intrinsic and can be independent of LH.

LH binds to the LH receptor in theca and drives androgen growth and theca growth

Question 22

What effect will PCOS have on androgens ?

Answer 22

Most consistent biochemical abnormality in women with PCOS is hyper secretion of androgens

Ideal to measure free (T) i.e. SHBG (sex hormone binding globulin ) and total testosterone to work out free T.It will prevent it from acting when it is bound to SHBG.

anov> ov>normal
increased androgen production by the ovary, even in ovPCO
Increased LH leads to increased androgen production

Hirsutism and acne