pathogenesis of pcos
TRANSCRIPT
Year 5 Medicine
Polycystic Ovary Syndrome and Hirsutism
Stella Milsom
Overview
diagnosis of PCOS-new Rotterham Consensus
symptoms of PCOS
future health risks associated with PCOS
relevant investigation of woman with likely symptoms
management of hirsutism related to PCOS
What is polycystic ovary syndrome?
syndrome of ovarian hyperandrogenisation
associated symptoms of androgen excess
anovulation leads to menstrual irregularity
most common gynaecological condition
affecting women of childbearing age
also associated with the metabolic syndrome
POLYCYSTIC OVARIAN SYNDROMEPOLYCYSTIC OVARIAN SYNDROMEPOLYCYSTIC OVARIAN SYNDROME
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Normal ovariesvolume < 8 cm3
scattered folliclesmildly enlarged generally > 8 cm3
peripheral distribution of follicles
increased stroma
Polycystic ovariesl
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Pathogenesis of PCOS
LH insulin/IGF1 cytochrome P450
ovarian androgen production
disturbed folliculogenesis
obesity
Diagnosis of polycystic ovary syndrome
symptoms of androgen excess irregular menses acne, hirsutism
biochemical androgen excess total / free testosterone, androstenedione, LH
pelvic ultrasound 1 or both ovaries enlarged, >12 peripheral follicles
Anovulation in PCOS
presents as:absence of periodsinfrequent periods ( > 35 day
cycle)dysfunctional uterine bleedingoccasionally regular periods
risk of endometrial cancer
Biochemistry in PCOS
Raised LH or LH:FSH ratio
One or more androgen levels raisedtestosteroneandrostendioneDHEAS
Polycystic Ovaries
Normal ovaries volume < 8 cm3 scattered follicles
Polycystic OvariesGenerally >8cm3 peripheral distribution
of follicles increased stroma
2004 Consensus PCOS Definition
2 out of the following 3 features
anovulation
clinical and/or biochemical evidence of androgen excess
polycystic ovaries on ultrasound:
1 or more ovaries ≥10mls in size and ≥12 follicles
Human Reproduction, 2004
PCOS
PCOS is also associated with a characteristic metabolic syndrome that includes:
insulin resistance dyslipidemia hypertension
These features are linked with increased risks of type 2 diabetes and possibility of premature cardiovascular disease
Metabolic abnormalities in PCOS due to insulin resistance
impaired GTT 40%
Diabetes – 5x more likely than weight matched controls OGTT vs FG
gestational diabetes increased risk
dyslipidemia HDL LDL TG
potential cardiovascular risk
Associations of PCO with clinical conditions
PCO present in
75% cases of anovulatory infertility (Adams 1986, Hull 1987)
87% cases of oligomenorrhoea (Adams 1986)
80% cases of hirsutism and regular menses
(Adams 1986, Hull 1987)
83% women presenting with acne to dermatology clinic
(Bunker 1989)
30-40% women with amenorrhoea (Adams 1986)
What tests are useful?
androgens, FSH, LH, estradiol
prolactin, thyroid function, pregnancy test (causes of secondary amenorrhea)
ultrasound pelvis
What tests are useful?
remember to exclude secondary causes of PCOS
androgen secreting tumour
acromegaly
non classical CAH
Management of PCOS
symptom orientated
long term risk reduction
Management of PCOS- Current Symptoms
determine which predominates-infertility or androgen excess
then consider antiandrogen versus ovulation induction therapy
consider state of endometrium
first line medical management from diagnosis to reproduction most likely be OCP
Hirsutism and PCOS
defined as coarse terminal hair in a male distribution
do not confuse with lanugo hair
assessed by the Ferriman-Galwey score
does not always correlate with androgen levels
Management of androgen excess symptoms in PCOS
symptoms include:
hirsutism
acne
androgenic alopecia
Management of androgen excess symptoms in PCOS
First line treatment for mild hirsutism
weight loss and exercise
oral contraceptive (Estelle and Yasmin)
metformin
Effect of lifestyle in hirsute PCOS
weight gain causes an increase in insulin resistance and androgen
production in PCOS women
antiandrogen therapy is less efficacious
modest weight loss and increase in exercise e.g. 5-10% weight loss will
often improve hirsutism by reducing androgen production
OCP and hirsutism
first line treatment for hirsutes (manages endometrium and
contraception also)
synthetic E2 suppresses gonadotropin driven androgen
production
increase in SHBG decreases bioavailable T to hair follicle
addition of low dose CPA (Estelle) provides antiandrogenic
progesterone
Metformin and hirsutism
useful alternative to OCP in woman with hirsutism who also desires fertility
common to have gut side effects
commence slowly, work up to 1500mg/day
moniter with liver and renal function ( occasional hepatotoxicity, theoretical risk of
lactic acidosis)
Metformin and hirsutism
In both lean and overweight women with PCO improves insulin sensitivity and lipids
decreases hyperandrogenism
increases frequency of ovulation (40-70%) compared to placebo
Management of androgen excess symptoms in PCOS
Treatment of more severe hirsutism (refer)
OCP plus additional antiandrogen therapy: spironolactone 200mg/day cyproterone in reverse sequential regime (specialist) flutamide 250mg/day (specialist) finasteride unfunded and less effective
for the future: vaniqa cream (ornithine decarboxylase inhibitor)
Combination antiandrogen therapy
use in conjunction with OCP
specialist prescription
require monitoring (liver function)
used in more severe hirsutism or unresponsive women
course up to 36 months
require contraception
6 months before effect but may improve up to 2 years
after initiating therapy (50% reduction in FG score)
Management of PCOS-longer term
consider OCP, metformin, progestins, antiandrogens,
ovulation induction, lipid lowering agents, antihypertensives
as necessary
surveillance for diabetes, hypertension and dyslipidemia
especially if positive family history and overweight
monitor endometrium
active weight loss and exercise programme