week 1 lec 3 Flashcards
PCOS is characterized by (3)
irregular menstrual periods
high androgen levels
polycystic ovaries
most common endocrine disorder in reproductive age people with uterus/ovaries
PCOS
3 hormonal imbalances in PCOS
inappropriate gonadotropin secretion
insulin resistance with hyperinsulinemia
excessive androgen production
wk 1 lec 3 pathophysiology chart of PCOS on page 6 and slide 10
:)
causes of PCOS?
unknown but… genetic, environment and fetal exposure to high androgen levels
LH to FSH ratio is PCOS
increased
GnRH in PCOS
increased pulsatile release
progesterone and estrogen and androgens in PCOS
anovulation causes decreased progesterone release and increased estrogen
increased androgens
acanthuses ingrains in PCOS
from insulin resistance
hirsutism, acne, alopecia in PCOS from
androgen excess
altered GnRH pulsaility leads to increase ___ compared to ___
LH increases (increase pulse frequency and amplitude)
compared to FSH (remains the same)
FSH vs LH function
FSH- stimulates growth of ovarian follicles
LH- stimulates ovulation and ovarian hormone production (i.e. stimulates androgen production)
LH to FSH ration in PCOS
above 2:1
lower FSH in PCOS leads to
reduction in aromatase activity, less conversion of testosterone to estrogen in the granulosa cells
dominant follicles in PCOS?
dominant follicle doesnt develop bc LH secretion occurs before it can
so theres several immature follicles (difficult to ovulate)
which phase is missing since no ovulation in PCOS
effect on hormones
no luteal phase
no progesterone, leaving estrogen unopposed –> endometrial neoplasia risk
increased LH leads to
increased steroid hormone proaction in ovary –> excess androgen production
high androgen levels cause
dyslipidemia, hirsutism, acne
peripherally converted into estrongen in adipose tissue (augmented in obese people)
androgens turn into what peripherally
estrogen (in adipose tissue)
cause high estrogen levels all cycle (no longer fluctuate) and impacts feedback loop at hypothalamus and pituitary
risk of endometrial hyperplasia in PCOS
from chronically elevated estrogen stimulating endometrial cells
follicular atresia from
insulin resistance and hypersecretion
diabetes and PCOS
from insulin resistance and hypersecretion and elevated blood glucose
compensatory hyperisulinemia
reduced glucose uptake from target cells in response to insulin
insulin resistance in both lean and obese PCOS patients
insulin stimulates what from the pituitary
LH and FSH
insulin increases release of what from theca cells
androgens
insulin decreases production of what in the liver
Decreases the production of SHBG in the liver→increased circulating androgens
androgens get stimulated by 2 things
elevated LH and insulin
where are androgens mainly produced
ovarian theca cells (testosterone and androstenedione)
elevated male hormones in PCOS
free testosterone and DHEAS
sex hormone binding globulin (SHBG) is made
in the liver
SHBG production is suppressed by
insulin production
less circulating SHBG causes what effect on androgens
more androgens are unbound and free to circulate and bind with end-organ receptors (hair follicles, sebaceous glands→acne)→clinical hyperandrogenism
anovulation from many things…
-altered GnRH pulsailty
-insulin resistance (i.e. metformin helps with oligo-ovulation)
-androgens produced by large # of astral follicles
short term vs long term consequences of PCOS and hyperandrogenism
short term: obesity, infertility, sleep apnea, irregular menses, anxiety, depression, abnormal lipid levels, ANFLD, hirsutism/acne/androgen alopecia, insulin resistance/ acathosis nigricans
long term: T2DM, endometrial cancer, cardiovascular disease
obesity and PCOS`
insulin resistance etc
PCOS and infertility
from anovulatory cycles
menstural dysfunction in PCOS
amenorrhea, oligomenorrhea and heavy bleeds (lead to iron deficiency)
result of anovulation
lack of progesterone production
chronic estronge exposure (that unopposed by progesterone) leads to
chronic exposure of the endometrium→instability of thickened endometrium can lead to unpredictable bleeding
oligomenorrhea vs amenorrhea
Oligomenorrhea (less than 9 menstrual periods in a year) and amenorrhea (absence of menses for 3 or more months) usually begins with menarche in people with PCOS
what menstural intervals warrant further investigation
<20 or >45 days > 2 years after menarche or an interval >90 days at any time
aging and PCOS and menstural dysfunction
As people with PCOS age, regular cycles may resume (due to lower antral follicle count, and decrease in follicular androgen production)
obstructive sleep apnea
PCOS and obesity
dyslipidemia and PCOS
high LDL and triglyceride
lower HDL
high cholesteroll: HDL ratio
–> CVD
3 parts of hyperandrogenism
hirsutism
acne
alopecia
what signs of rapid increase in androgens are not related to PCOS and should be investigated to see if have androgen secreting tumor
increased muscle mass, deepening voice, and cliteromegaly
hirsutism- what causes the hair follicle changes
in the hair follicle testosterone is converted by 5 alpha reductase to DHT (dihydrotestosterone)
testosterone and DHT convert short vellus hair to terminal hair (DHT is more effective) [[permanent and irreversible]]
what turns testosterone into dihydrotestosterone in hair follicle
5 alpha reductase
most common areas of hirsutism (androgen sensitive areas)
upper lip, chin, sideburns, chest, and linea alba of the lower abdomen
racial impacts on hirsutism
Mediterranean individuals have a greater concentration than Northern Europeans, and a much higher concentration than Asians.
alopecia (less common) in PCOS is caused by
excessive 5 alpha reductase activity in hair follicle –> increase DHT levels
terminal hairs that aren’t dependent on androgens transform to a vellus hair follicle- leading to alopecia
alopecia in PCOS
In certain hair-bearing areas, androgens activate sebaceous glands and transform vellus follicles (A) into terminal follicles (B), causing hirsutism. Conversely, under androgen influence, terminal hairs that were previously not androgen-dependent (C) shrink and revert to vellus-like hairs, leading to balding (D).
4 factors involved in pathogensis of acne
- Blockage of the follicular opening by hyperkeratosis
- Sebum overproduction
- Proliferation of commensal bacteria (Propionibacterium acnes)
- Inflammation
what causes an increase in sebum formation which leads to inflammation and comedones formation and scarring [acne]
testosterone –> DHT in sebaceous gland
treat acne in PCOS
- Minimizing inflammation
- decreasing keratin production
- lowering colonization of P. acnes (bacteria)
- reducing androgen levels to diminish sebum production
acanthuses nigricans and insulin resistance and hyperinsulinemia can lead to
keratinocyte growth
impaired glucose tolerance metrics
fasting glucose of 6.1-6.9 mmol/L or Hb A1c of 6.0-6.4% or 2 hour post oral glucose tolerance test with 75 grams of glucose 7.8-11 mmol/L
what further increases degree of insulin resistance in PCOS
anovulation
how to test for impaired glucose tolerance (IGT) and T2DM
75 grams oral glucose tolerance test
fasting and 2 hour post glucose load
OR HbA1c too…
recommend oral glucose tolerance test for T2DM and impaired glucose tolerance if
high-risk women BMI > 25 kg/m2 or BMI > 23 kg/m2 in Asian women, history of abnormal glucose tolerance or family history of diabetes, hypertension, or high risk ethnicity and those planning pregnancy or seeking fertility treatment.
endometrial neoplasia/cancer
mitogenic changes increase with involution and unopposed estrogen
endometrial neoplasia from
hyperandrogenism, hyperinsulinemia and obesity decrease circulating SHBG and increase circulating estrogen
develop endometrial neoplasia if
> 40 yrs old
obese and chronic anovulation
metabolic syndrome 4 characteristics
insulin resistance, obesity, dyslipidemia, and hypertension.
pregnancy and PCOS
miscarriage, gestational diabetes, hypertesnion, preterm birth
esp if obese
how do increased use of fertility intervention in those with PCOS cause an increased risk of
multi-fetal gestations risk increases→increases risk of maternal and neonatal complications
cutaneous marker of insulin resistance
acanthuses nigricans
where is acathosis nigricans
A thick grey-brown velvety plaque in flexure areas such as back of neck, axillae, waist, groin, infra-mammary crease (below the breast).
