Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

reproduction > PCOS > Flashcards

PCOS Flashcards

1
Q

What is PCOS?

A
  • the ovary contains increased numbers (>20) of small Antral follicles (2-9mm) visible in a necklace shape on high quality transvaginal transducers
  • there is a disorder of follicle growth at all stages
  • in some cases there is a failure of dominant follicle selection and therefore anovulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the different stages of follicle growth where disorder can occur in PCOS?

A
  1. Possibly increased proportion of primordial follicles and increased number of activated primary follicles
  2. Arrested in antral follicle growth before they mature
  3. Lower rates of atresia > antral follicles persist (visible in US)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are multiple symptomatology with PCOS

A
  • endocrine , gynaecological, diabetic, dermatological, earring disorders, psychiatry.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are systematic metabolic manifestations with PCOS?

A

-Insulin resistance
-obesity has a bigger impact on PCOS population compared to normal, especially regarding IR
-Annual economic cost of diagnosis and treatment of PCOS in USA was calculate d$4.36 billion and 40% of this was IR/ T2D related

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is PCOS diagnosed?

A

darker regions which indicates fluid
NOT CYST but follicles that have stopped growing
> 20 follicles arranged in necklace like way around the ovary indicates PCOS
< 20 follicles isn’t diagnostic of PCOS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some disorders that mimic PCOS so must be excluded in diagnosis?

A

-non classical adrenal hyperplasia
-hyoerprolactinemia, thyroid disease , Cushing syndrome
-ovarian hyper the oasis - nests of luteinized theta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the diagnose criteria?

A

Rotterdam criteria
- 2/3 criteria’s met means PCOS positive
1. hyperandrogenism
2. Ovulatory dysfunction
3. PCO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the issue with identifying polycystic ovaries?

A

Techniques and equipment dependent
Transvaginal imaging not always appropriate (eg in adolescence girls)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Hyperandrogenism and limitations (criteria 1)

A

too much androgen levels
-Clinical and biochemical evidence
-assays not standardised across labs
-normative data not clearly defined
-clinical hyperandrogenism difficult to quantify
-ethnicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is ovulatory dysfunction and it’s limitations (criteria 2)

A

=>oligomenorrhea and anovulation
-frequent bleeding <21days or infrequent bleeding > 35days.
-to confirm ovulation serum progesterone level at mid luteal phase of cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are 3 polycystic ovary morphology (PCOM) (criteria 3)?

A
  1. Normal = 5 or less follicles in an ovary with a small amount of stroma
  2. Anovulatory = 20 or more follicles, 2-9mm diameter arranged peripherally around an enlarged core dense stroma, ovarian volume >10ml with NO dominant follicle
  3. Ovulatory PCO = early follicular, mid follicular and ovulation, dominant follicle present, but instead of other ovaries dying small follicles persist.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the different phenotypes and their diagnostic criteria that match (alphabetical -H,O,P)?

A

Phenotype A = criteria 1/2/3
Phenotype B = criteria 1/2
Phenotype C = criteria 1/3
Phenotype D = criteria 2/3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are features of phenotype A and B (classic PCOS)?

A

Phenotype A = HOP , phenotype B = HO
caused by:
- BMI syndrome
-metabolic syndrome
- Most common 2/3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the features of phenotype C (ovulatory PCOS)?

A

phenotype C = HP
BMI is often normal but BMI increases can alter phenotypic presentation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are features of phenotype D (normandrogenic PCOS)?

A

-chronic anovulation and PCOM but normal serum androgens and no HA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do you know a woman has ovulated at some point?

A

corpus luteum or albican present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Most PCOS women have …

A

oligomenorrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are different factors that are involved in follicles arrest, which annovulatory PCOS women have?

A
  1. androgens
  2. intra- follicular inhibitors, eg. AMH
  3. Defect in apoptosis
  4. dysregulated gonadotrophin (both FSH and LH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is a key factor that distinguishes ovulatory and anovulatory women?

A
  • insulin resistance level
    study: adult rhesus monkey fed western style diet (high fat/sugars) and exposed to chronically elevated T from puberty to menopause => altered small AF numbers, morphology and transcriptome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

oligomenorrhoea

A

infrequent periods, fewer than 6-8 periods per year

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

amenorrhea

A

absence of periods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the prevalence of PCO?

A
  • 32% patients have amenorrhea
  • 87% patients have oligomenorrhea
  • 87% patients have hirsutism and regular cycle
  • 22% of ‘ normal’ population - no signs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The most common cause of anovulatory infertility is …

A

PCOS
73% of women with anovulatory infertiltiy have PCOS

24
Q

What is PCOS prevalence in the world

A

PCOS presentation in European population differs
from US population
* Within US – variability seen between Hispanic ,
African-American and White populations
* East Asian population with PCOS have ↓ BMI and hirsutism compared to other population
* South Asian populations have greater insulin
resistance; metabolic sequelae and obesity cf to other populations

25
Q

What is the aetiology of PCOS?

A
  1. 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

  1. Monozygotic twins twice as likely to both have PCOS than dizygotic.
  2. common finding of raised androgen led to belief that PCOS is caused by an inherited disorder -most likely in the steroid biosynthetic pathway
  3. Many candidate genes were investigated: all ‘obvious’ ones ruled out
  4. Complex polygenic disease – involves subtle interaction with environmental factors (intra- & extra-uterine)
26
Q

Chinese studies on PCOS

A

1st Genome-wide association study (GWAS) identified causative
genes in Han Chinese women (2011)
– 744 women with PCOS & 895 controls

GWAS confirmed variants in DENND1A, THADA, FSHR & INSR => Confirming the biological relevance of PCOS-associated variants by
molecular analysis.

27
Q

What are 3 candidate genes seen in PCOS?

A
  • LHCGR and FSHR genes = involved in making LH and FSH , so variation in these genes causes dysregulation of gonadotrophins

– THADA = linked to Type 2 diabetes

– DENND1A = linked with obesity

28
Q

What is the link between expression of DENND1A.V2 in normal theca cells and PCOS?

A
  • DENND1A. V2 transfected in normal theca cells results in augmented androgen and progestin production
    (high androgen levels are involved in follicle arrest seen in PCOS (anovulatory))
    DENND1A is linked to obesity = obese woman have more DENND1A = more DENND1A = high levels of androgen bc of DENND1A
29
Q

PCOS & Gonadotrophins I

A
  • consistent feature of PCOS is disordered gonadotrophin, secretion leading to downstream ovarian consequences
    -high LH , low FSH or vice versa = basically LH: FSH ratio is altered
    Rapid GnRH frequency -> favoring rapid LH pulse secretion
30
Q

Studies on PCOS and Gonadotrophins I

A

In PCOS women there is an increase in LH secretion regardless of body weight when lean and obese PCOS women were compared to lean and obese control women.

31
Q

Why does dysregulated gonadotrophin secretion occur?

A

In normal ovaries - CL releases progesterone - negative feedback in HPG - decreased FSH and LH (regulated)

In PCOS = high testosterone levels = impairs progesterone ability to provide negative feedback to decrease levels of gonadotrophins = increased LH /FSH

32
Q

Evidence for increased testosterone impacting progesterone’s ability to cause negative feedback comes from ..

A
  1. Flutamide = an androgen antagonist = binds to androgen decreasing levels = progesterone negative feedback not impaired = less FSH and LH
  2. oral contraceptive pills:
    normal ovaries OC pill = high levels of progesterone and oestrogen = negative feedback = decreased levels of FSH and LH
    PCO OC pill = high levels of progesterone = negative feedback impaired by androgen = high levels of LH and FSH
33
Q

What does high levels of LH in PCOS lead to?

A
  • thecal hyperplasia and the hyper-androgenemia, but high androgens (HA) is also intrinsic and can be independent of LH (so woman without high LH can still have HA)
34
Q

hyperandrogenism

A
  • increased/hypersecretion of androgen is the most consistent biochemical abnormality in women with PCOS
35
Q

How do you measure increased androgen (testosterone)?

A
  • measure free testosterone, measure sex hormone binding globulin (SHBG) which binds to testosterone and total testosterone, work out free T by total T - SHBG T
    -increased LH leads to increased androgen production
    >7 nmol/L then need to screen for androgen producing tumour
36
Q

What are clinical signs of high androgen?

A
  • androgenic alopecia
    -hirustism (excess terminal hair)
  • acne
  • distressed
37
Q

Testosterone levels and symptoms in PCOS

A
  • higher the T the more the symptoms
  • anovulatory with hirustism has the most severe symptoms
  • anov - h > anov> ov-h > PCO> normal
38
Q

More than what level of androgen is indicative of tumour and need to screen for it?

A

> /= 7nmol/L

39
Q

Androgen and hirsutism

A

T converted to DHT in hair follicle - hirtuism
PCOS women
- high T levels = more hirtusism
-5 alpha-reductase may be higher = DHT conversion
- sensitivity to androgen may be higher

The excess testosterone comes from theca cell dysfunction in PCOS not from adrenals , increase in testosterone and progesterone is seen in PCOS

40
Q

How can we test where the excess androgen is coming from?

A

Dexomathosone (cortisol)- suppresses the adrenals by negative feedback to HPA so if the levels are still high then androgen must be coming from ovary.
- inhibitor can be used to reduce excess androgen from ovaries

41
Q

Where are androgens produced in women?

A
  • adrenal glands
  • ovaries
  • peripheral tissue
  • androgen target tissue : ie hair follicles,skin which explains hirsutism in PCOS
42
Q

When there is intrinsic dysfunction in theca cells we look at androgen and progesterone production - why is progesterone also measured?

A

-same biosynthetic pathway for androgen and progesterone so shows inherent disorder
-both 17 alpha- hydroxylase and C17-20 lyase reside on a single protein and are encoded by a single gene, CYP17

43
Q

increased androgen doesnt always mean increased oestrogen

A
  • oestrogen is not elevated in PCOS, increased androgens doesn’t always mean its converted to oestrogen bc aromatase levels are still normal (not elevated)
  • due to increase in number of arrested follicles will see a slight increase E2 but not DF levels even when T increases.
  • levels of AR may not be increased in GC even if androgen levels increased
44
Q

How is CYP17 involved in increased steroid production by theca which is common in PCOS?

A
  • CYP17 promoter is more active - more steroids
  • CYP17 mRNA degrades more slowly - more steroids
    so we have more androgen and progesterone in the theca.
45
Q

Biosynthetic pathway

A
  • insulin is co - gonadotrophin with LH so hyperinsulinemia will lead to increased hyper andogenemia via cross talk on pathways

-women with T1D have to take exogenous insulin - develop hyperinsulinemia - leads to hyperandrogenism - develop secondary PCOS

46
Q

Morphometric studies

A

Hughesden 1982 : counted follicle numbers in sections from 17 PCOS and 17 normal ovaries
-found 2x all of the growing stages in PCO,

Webber et al(2003)…Lancet
-counted follicles in biopsies
-six times more primary follicles
-no significant increase in primordials

Maciel GA et al (2004), CEM
-counted follicles in sections
-‘stockpiling’ of primary follicles
(PCOS increased follicles numbers in early stage of folliculogenesis)

47
Q

Why do we see increased follicles in PCO?

A

Androgens seem likely candidate for increasing follicles number in early folliuculogenesis
– Androgens involved in stimulating primordial follicle initiation and increasing
number of small antral follicles
– LH hypersecretion amplifies androgen production by theca
– AR expression found in GC at all follicle stages

48
Q

If we see increased follicles in PCOS then why anovulation common?

A
  • increased follicle activation and recruitment but growth of follicles (at primary stage) arrested before they mature due to high levels of AMH in PCOS women
49
Q

What causes arrest before the follicles at primary stage proceed to antral stage?

A
  • altered ratio of FSH : LH , bc there is low FSH : LH (due to LH hypersecretion) ratio normal maturation is reduced, lower rates of atresia.
50
Q

What are the intra-ovarian factors involved in follicular recruitment & growth that also contribute to arrest?

A
  • AMH and other TGF- beta superfamily members
  • AMH production is higher from granulosa cells of PCO
  • Reflected in AMH serum levels which is 2-3x higher in PCO compared to normal.
51
Q

Androgen in utero as a cause of PCOS

A
  • excess foetal T (exposure of female animals to elevated androgens in the utero) induces PCOS like traits that manifest in offspring during adulthood:
  • sheep models had increased LH pulsatility and impaired E2/ P feedback
  • offspring of T exposed monkey mothers after puberty => LH hypersecretion, ovulatory dysfunction, hyper- androgenism and IR
    => 50% have enlarged ovaries and increased follicles counts
  • Adolescent girls with high androgen have similar pattern of rapid LH pulse secretion before menarche
  • obesity in pubertal girls also alters LH pulses
52
Q

Pregnant women with PCOS? maternal T raised but is fetus exposed to HA?

A

High levels of SHBG and aromatase activity in placenta, prevent maternal T crossing over, so female foetus is not androgenised.
=> aromatase converts the high androgens to oestrogen
so excess secretion may be coming from fetus itself?

53
Q

Androgens and hypothesis of PCOS origin

A

Exposure of developing hypothalamus to excess androgen before final programming of steroids feedback and other regulatory mechanisms alters GnRH pulsatility and feedback.

54
Q

AMH & hypothesis of PCOS origin

A
  • Excess AMH in utero may affect development of female fetus
  • AMH arises from mother and not the fetus
  • in women with normal fertility AMH levels would drop during pregnancy
  • in pregnant women with PCOS AMH levels are elevated leading to follicle arrest.

Treated pregnant mice with AMH → altered neuroendocrine phenotype (affects GnRH neurones) of female offspring and induced PCOS-like phenotype

55
Q

Summary

A

Polycystic ovaries are genetically acquired
and may have a foetal origin
* There is a defect in the way follicles grow
* There is a basic defect in steroid
metabolism
* The gene/s causing this are becoming
known
* Endocrine disturbances result in
miscarriage, anovulation, infertility and hyper-
androgenism

reproduction (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions