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PCOS Flashcards

1
Q

The most commonly diagnosed endocrine disorder in women of reproductive age

A

PCOS

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2
Q

PCOS Incidence

A

10%

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3
Q

Primary issues in PCOS

A
  1. Psychological (anx, depression, sleep and eating disorders)
  2. Dermatologic (hirsutism, acanthosis nigricans, acne)
  3. Reproductive (menstrual disturbance, infertility, endometrial cancer, pregnancy complications)
  4. Metabolic features (insulin resistance, metabolic syndrome, T2DM, cardiovascular risk factors)
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4
Q

Diagnosis of PCOS

A

2 of 3 of (Rotterdam criteria):
- Oligo or amenorrhoea
- Clinical and/or biochemical signs of hyperandrogenism
- Polycystic ovaries on USS:
—> >20 follicles (2-9mm) in at least one ovary (most effective USS marker)
—> ovarian volume > 10mL (also accurate) or > 10 follicles in at least one ovary in adults if using older technology or image quality is insufficient (e.g. TA scan)
—> TVUSS most accurate

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5
Q

PCOS pathophysiology

A
  • Genetic susceptibility and pattern (autosomal dominant pattern, although no gene has been identified)
  • Caused by elevated ovarian androgens which cause polycystic ovary appearance
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6
Q

Mechanisms for high levels of androgens:

A
  1. Extraovarian production (adrenal production, CAH, steroid abuse, androgen secreting adrenal tumours)
  2. Increased levels of LH -> stimulates androgen production in ovarian theca cells
  3. Decreased levels of SHBG = increased levels of free circulating androgens.
    —> Levels are inversely proportional to BMI so obese women have low SHBG
  4. Increased insulin levels = augments the actions of LH -> increased ovarian androgen production
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7
Q

PCOS DDX

A
  • Late onset CAH
  • Cushings syndrome
  • Androgen secreting tumours
  • Steroid use
  • Drugs such as phenytoin
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8
Q

Clinical evaluation in PCOS

A

Hirsutism
Infertility
Insulin resistance and T2DM (5%)
Hyperlipidaemia
Obesity
Absent or irregular periods
Fhx PCOS
Cardiovascular health

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9
Q

PCOS - examination

A

BMI
Hirsutism
Full abdominal and pelvic exam to exclude other causes
BP

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10
Q

PCOS IX

A
  • D3 LH and FSH
  • PRL
  • Oestrogen and testosterone
  • SHBG and free androgen index (biochemical assessment if of greatest value in patients without clinical signs.
  • Pelvic USS (ideally TVUSS)
  • AMH (likely to be high)
  • BHCG
  • Morning 17 OH progesterone to rule out CAH
  • TFTs
  • Lipids and TGs
  • OGTT (fasting glucose not reliable)/HbA1c
  • May warrant pipelle/hysteroscopy D&C, depending on clinical picture
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11
Q

PCOS Management

A
  1. Lifestyle advice
    - weight loss, exercise, diet, smoking cessation, reduce ETOH
  2. Regulate menstrual cycles
    - COCP
    - Alternative is progestogen for 14 days every 3/12 to induce endometrial shedding
    - metformin
  3. Infertility (see other flash card) - anovulation = cause
  4. Hirsutism
    - Waxing, electrolysis, plucking, shaving, bleaching, laser
    - COCP, second line - cypoterone acetate containing COCP (anti-androgen)
    - Spironolactone
    - Flutamide
  5. Screening for and management of OSA
  6. Insulin resistance/metabolic risk
    - consider metformin: beneficial for cycle regulation, insulin resistance and lipid profiles.
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12
Q

Infertility in PCOS
- Metformin

A
  • Metformin
    —> biguinide in the anti-hyperglycaemia agents. Improves insulin sensitivity, glucose uptake, and prevents gluconeogenesis in the liver.
    —-> May help to regulate menstrual cycles by improved hormonal profile + lower levels of insulin leading to reduced LH action on the ovary.
    —> 8-10% conception rate
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13
Q

Infertility in PCOS - Clomiphene

A
  • SERM
  • Acts at level of hypothalamus -> blocks negative feedback from oestrogen on hypothalamus -> increased GnRH and FSH production -> oocyte maturation and release
  • Conception rates approx 40%
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14
Q

Infertility in PCOS - Letrozole

A
  • Aromatase inhibitor acting at the level of the ovary
  • Blocks oestrogen formation -> increased production of GnRH, FSH -> increased oocyte maturation and release
  • More effective than letrozole
  • Shorter half life
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15
Q

Infertility rx in PCOS - Gonadotrophin therapy with FSH and a trigger

A

Trigger = HCG or goserelin

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16
Q

Infertility in PCOS - laparoscopic ovarian diathermy or drilling

A
  • Has surpassed wedge resection
  • Thought to decrease LH levels and increase SHBG
17
Q

PCOS and infertility in high BMI

A

Ovarian stimulation and ovulation induction is not recommended for women with BMI > 35

18
Q

PCOS - long term sequelae

A
  • Cardiovascular risk: stroke, MI, hyperlipidaemia
  • Endometrial hyperplasia and cancer due to unopposed oestrogen (if amenorrhoeic/oligomenorrhoea then no luteal progesterone ride)
  • Emotional and psychological effects -> anx and depression
  • Infertility
  • Insulin resistance and T2DM
19
Q

PCOS diagnosis in young women/adolescents

A
  • USS and AMH are NOT recommended within 8 years of menarche
  • Young women “at risk” can be identified with FU assessment
20
Q

Define irregular cycles and ovulatory dysfunction

A

Irregular menses:
- normal in the first year post menarche as part of the pubertal transition
- >1 to <3 years post menarche: <21 or >45 days
- > 3 years post menarche: <21 or >35 days, or <8 cycles per year
- > 1 year post menarche: > 90 days for any one cycle

Ovulatory dysfunction: can still occur with regular cycles, if anovulation needs to be confirmed -> serum progesterone

21
Q

Evaluation of biochemical hyperandrogenism in women on the COCP

A
  • Not able to reliably assess as COCP increases SHBG and reduces gonadotropin-dependent androgen production.
  • IF necessary, pill should be withdrawn for 3/12 before testing with alternative contraception
22
Q

If androgen levels are markedly above lab reference ranges:

A

Consider other causes:
- Ovarian and adrenal neoplasm (also consider if sudden onset/rapid progression of sx).
- CAH
- Cushings syndrome
- Ovarian hyperthecosis (after menopause)
- Iatrogenic
- Syndromes of severe insulin resistance

23
Q

Clinical hyperandrogenism

A
  • Hirsutism alone = predictive of biochemical hyperandrogenism
  • female pattern hair loss and acne in isolation (without hirsutism) = relatively weak predictors
  • Recognize that some women may have undergone hair removal*
24
Q

How to assess hirsutism

A

Modified Ferriman Gallwey score of 4-6 (depending on ethnicity)

25
PCOS ethnicity
Higher prevalence in South East Asian and Eastern Mediterranean regions
26
PCOS and menopause
- should be considered a lifelong diagnosis - hyperandrogenism persists in the postmenopause
27
OSA and PCOS
- significantly higher prevalence in women with PCOS, independent of BMI
28
Endometrial CA and PCOS
- premenopausal women with PCOS have a markedly higher risk of developing hyperplasia and endometrial CA - long-standing untreated amenorrhoea, higher weight, T2DM and persistent thickened endometrium are addition to PCOS as risk factors - Prevention = weight management, cycle regulation and regular progestogen therapy - If excessive ET is detected -> biopsy + withdrawal bleeding indicated
29
COCP and PCOS
- for management of hirsutism and/or irregular menstrual cyclees - consider in adolescents at risk - natural oestrogen preparations and the lowest oestrogen doses (20-30mcg of ethinyl estradiol or equivalent) - the 35mcg ethinyl estradiol + cypoterone acetate should be considered second-line therapy over other COCPs, balancing the benefits and adverse effects - including VTE risks - consider contraindications and risks - individualized counselling
30
POPs and PCOS
May be considered for endometrial protection, evidence in PCOS specifically is limited
31
Antiandrogens in PCOS
E.g. spironolactone, cyproterone -> may cause undervirilization in male fetuses if conceive while taking => should be strongly counselled to use effective contraception. - could be considered to rx hirsutism where there are contraindications to COCP or COCP is poorly tolerated, as long as there is alternative effective contraception
32
PCOS and bariatric surgery
PCOS is a metabolic condition and could be considered an indication at a lower BMI threshold for bariatric/metabolic surgery, similar to diabetes. - Likely to cause rapid return of fertility => need effective contraception, ideally prior to surgery. - Contraception should be continued until a stable weight is achieved, usually after 1 year, to avoid significantly increased risk of FGR, prematurity, SGA, pregnancy complications, and prolonged hospitalization of the infant.
33
PCOS and pregnancy (risks):
- higher gestational weight gain - miscarriage - GDM (ideally OGTT preconception, if not then offer at first antenatal visit and repeat at 24-28 weeks) - HTN and PET - IUGR, SGA and low birth weight - preterm delivery - CS DOES NOT (alone) increase risk of LGA or instrumental delivery
34
Metformin in PCOS + pregnancy
Could be considered to reduce preterm delivery and limit excess gestational weight gain (long term impact on offspring unclear)
35
Gonadotropins vs other ovulation induction techniques
- more expensive - more expertise required - more intensive USS monitoring required - low dose step-up gonadotrophin protocol should be used to improve chance of monofollicular development - consider cancelling cycles where there is more than a total of 2 follicles >14mm and advising avoidance of unprotected intercourse - live birth rate, clinical pregnancy rate per patient and ovulation rate per cycle are higher than with clomiphene
36
PCOS and infertility
- Ovulation induction (letrozole 1st line, metformin may be considered, gonadotrophins, laparoscopic ovarian surgery 3rd line) - IVF if first or second line ovulation induction therapies have failed -->> multiple pregnancies can be minimised by use of single embryo transfer -->> increased risk of OHSS => options to reduce the risk should be offered
37
How to reduce the risk of OHSS in IVF in the context of PCOS
- the use of GnRH antagonist is recommended as it enables the use of an agonist trigger, with the freezing of all embryos generated if required, without compromising the cumulative live birth rate, to reduce the risk of significant OHSS - FSH can be used for controlled ovarian (hyper)stimulation - LH should NOT be routinely used in combination with FSH - Adjunct metformin could be used to reduce risk of OHSS and miscarriage if GnRH agonist long protocol is being used instead of GnRH agonist.
38
Pathogenesis of anovulation in PCOS
- Increased adipose = increased peripheral production of oestrogen - Obesity and Increased insulin due to insulin resistance reduces SHBG production = more free circulating androgens and oestrogen - Insulin also augments the effects of LH -> increased production of androgens in the theca cells of the ovary --> high oestrogen and androgens result in negative feedback on the hypothalamus and anterior pituitary to inhibit GnRH, FSH and LH release => there is no dominant follicle maturation and no ovulation. --> progesterone levels remain low as there is no ovulation to form the corpus luteum => proliferation of endometrium in response to oestrogen but no progesterone withdrawal to trigger menstruation

Endocrine (3 decks)

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