POLYCYSTIC OVARY SYNDROME
EXAM REVIEW QUESTIONS AND
ANSWERS
Pathophysiology - ANSWER-As you can guess from the phenotypic heterogeneity....
Despite decades of research, the pathogenesis of PCOS is still not fully undrestood.
Genetics and Lifestyle/obesity can lead to hormonal changes. Genetics can lead to:
Early evidence of identified abnormal gonadotropin secretion.
Evidence supports a defect in ovarian and adrenal steroidogenesis in PCOS with higher
basal and LH stimulated androgen levels leading to acne as well.
Obesity leads to the metabolic components
It increases insulin stimulates theca cells in the same fashion as LH leading to diabetes
and ovarian follicle problems.
Pathogenesis: gonadotropin abnormalities - ANSWER-1) HPO Axis - FSH makes the
small follicles grow and LH makes androgens and is supposed to be low so that
increased leads to ovulation.
2) Neuroendocrine - LH pulse abnormalities suggest an abbert pattern of GnRH
secretion, variation in its frequency affects gonadotropin gene expression. If there is a
rapid frequency, it leads to increased LH mRNA and increased Follistatin mRNA which
decreases FSH. EFFECT: elavated ratio of LH:FSH.
3) Hypothalamic sensativity to negative feedback on LH secretion: progesterone
negative feedback is blunted and androgen excess is involved in reducing negative
feedback (making it worse).
4) increase gnrh, leads to increased LH (androgen synthesis increase) and decreased
FSH (inhibition of folliculogenesis)
5) STATS: LH/FSH ratios are elevated in 70-80% of women with PCOS.
Pathophysiology - Androgen excess - ANSWER-1) lh receptors in theca cells which
make androgens
2) Sex hormone binding globulin (SHBG) = binding protein for androgens. Bound
androgen is not active. Increase of SHBG - less activity and vise versa.
3) increased LH and hyperinsulinemia leads to increased androgens leading follicular
arrest (irregular menses, infertility, pco). Increased androgens inhibit aromatase and
insulin leads to premature luetinization (higher effects of LH).
Elevated A and I leads to decreased SHBG leading to acne, hirsutism (hairs).
Pathophysiology - Insulin resistance - ANSWER-- affects 50-70%
- Insulin - tyrosine kinase receptor - phosphorylates specific proteins, but abnormalities
in the process may not make them work correctly, both for taking up glucose and the
other downstream effects of insulin
- affects glucose transport, metabolic pathways and preserves ovarian steriodogenesis.
, - insulin stimulates ovarian androgen production, may contribute to premature arrest of
follicle growth and premature responsiveness to LH, decreases SHBG.
- in study: 31% of pcos women had impaired glucose tolerance and 7.5% had type2 dm,
significantly higher than age, weight, and ethnic comparable controls.
pathophysiology: obesity/adopose tissue dysfunction - ANSWER-1) greater than 50% of
PCOS women are obese and have increased waist/hip ratio
2) obese PCOS have increased abdominal fat compared with controls.
3) adipose leads to insulin resistance which leads to increased hyperinsulin and
increased androgens, decreased SHBG, increased LH.
4) increased adipocyte size in lean and obese women with PCOS and size correlates
with insulin sensativity. increase of fat cells in lean PCOS and visceral fat content.
pathogenesis: intrauterine environment - ANSWER-1) in rhesus monkey, sheep and
mouse: testosterone excess in intrauterine environment leads to PCOS phenotype, in
humans, increased androgen exposure intrauterine leads to PCOS phenotype
2) in monkeys, early prenatal androgens program body fat distribution and glucose
metabolism whilst late prenatal androgens do not.
3) PRO to prenatal programming: newborns of PCOS women had increased umbilical
vein T, and difference between these girls and control boys was not significant, also
pregnant PCOS women had higher androgen levels.
4) CON: cord blood of infants of PCOS did not show higher androgens, prenatal
androgen exposure does not correlate with PCOS diagnosis in teens.
pathogenesis: genetics - ANSWER-- Twin studies - heritability 0.79
- RR 3 - 7 for siblings of PCOS women
- First degree relative affected = 15-40%
- Complex disorder - genetic variants (multiple loci and epigenetic modifications)
combined with risk-increasing lifestyle and environmental factors
pathogenesis: environment - ANSWER-- factors - nutrition - obesity may unmask or
amplify symptoms of hyperinsulinemia and hyperandrogenism in suseptible individuals
- graphs of differences between obese and normal weight girls (through puberty), T and
Free T higher in obese, SHBG is decreased and insulin is higher.
- vitamin d insufficenciy is associated with metabolic syndrome and CDV, obesity
promotes insufficiency because vit D is sequester in adipose, 82% of PCOS women are
VIT D deficient.
origins of PCOS: the two hit hypothesis - ANSWER-- Genetic or epigenetic factors: set
reproductive and metabolic trajectories in early life
- Factors later in life: influence the severity of adult phenotype
Nutrition
Exposures
Pregnancy complications of PCOS - ANSWER-- Subfertility
- Miscarriage risk (contreversial)
EXAM REVIEW QUESTIONS AND
ANSWERS
Pathophysiology - ANSWER-As you can guess from the phenotypic heterogeneity....
Despite decades of research, the pathogenesis of PCOS is still not fully undrestood.
Genetics and Lifestyle/obesity can lead to hormonal changes. Genetics can lead to:
Early evidence of identified abnormal gonadotropin secretion.
Evidence supports a defect in ovarian and adrenal steroidogenesis in PCOS with higher
basal and LH stimulated androgen levels leading to acne as well.
Obesity leads to the metabolic components
It increases insulin stimulates theca cells in the same fashion as LH leading to diabetes
and ovarian follicle problems.
Pathogenesis: gonadotropin abnormalities - ANSWER-1) HPO Axis - FSH makes the
small follicles grow and LH makes androgens and is supposed to be low so that
increased leads to ovulation.
2) Neuroendocrine - LH pulse abnormalities suggest an abbert pattern of GnRH
secretion, variation in its frequency affects gonadotropin gene expression. If there is a
rapid frequency, it leads to increased LH mRNA and increased Follistatin mRNA which
decreases FSH. EFFECT: elavated ratio of LH:FSH.
3) Hypothalamic sensativity to negative feedback on LH secretion: progesterone
negative feedback is blunted and androgen excess is involved in reducing negative
feedback (making it worse).
4) increase gnrh, leads to increased LH (androgen synthesis increase) and decreased
FSH (inhibition of folliculogenesis)
5) STATS: LH/FSH ratios are elevated in 70-80% of women with PCOS.
Pathophysiology - Androgen excess - ANSWER-1) lh receptors in theca cells which
make androgens
2) Sex hormone binding globulin (SHBG) = binding protein for androgens. Bound
androgen is not active. Increase of SHBG - less activity and vise versa.
3) increased LH and hyperinsulinemia leads to increased androgens leading follicular
arrest (irregular menses, infertility, pco). Increased androgens inhibit aromatase and
insulin leads to premature luetinization (higher effects of LH).
Elevated A and I leads to decreased SHBG leading to acne, hirsutism (hairs).
Pathophysiology - Insulin resistance - ANSWER-- affects 50-70%
- Insulin - tyrosine kinase receptor - phosphorylates specific proteins, but abnormalities
in the process may not make them work correctly, both for taking up glucose and the
other downstream effects of insulin
- affects glucose transport, metabolic pathways and preserves ovarian steriodogenesis.
, - insulin stimulates ovarian androgen production, may contribute to premature arrest of
follicle growth and premature responsiveness to LH, decreases SHBG.
- in study: 31% of pcos women had impaired glucose tolerance and 7.5% had type2 dm,
significantly higher than age, weight, and ethnic comparable controls.
pathophysiology: obesity/adopose tissue dysfunction - ANSWER-1) greater than 50% of
PCOS women are obese and have increased waist/hip ratio
2) obese PCOS have increased abdominal fat compared with controls.
3) adipose leads to insulin resistance which leads to increased hyperinsulin and
increased androgens, decreased SHBG, increased LH.
4) increased adipocyte size in lean and obese women with PCOS and size correlates
with insulin sensativity. increase of fat cells in lean PCOS and visceral fat content.
pathogenesis: intrauterine environment - ANSWER-1) in rhesus monkey, sheep and
mouse: testosterone excess in intrauterine environment leads to PCOS phenotype, in
humans, increased androgen exposure intrauterine leads to PCOS phenotype
2) in monkeys, early prenatal androgens program body fat distribution and glucose
metabolism whilst late prenatal androgens do not.
3) PRO to prenatal programming: newborns of PCOS women had increased umbilical
vein T, and difference between these girls and control boys was not significant, also
pregnant PCOS women had higher androgen levels.
4) CON: cord blood of infants of PCOS did not show higher androgens, prenatal
androgen exposure does not correlate with PCOS diagnosis in teens.
pathogenesis: genetics - ANSWER-- Twin studies - heritability 0.79
- RR 3 - 7 for siblings of PCOS women
- First degree relative affected = 15-40%
- Complex disorder - genetic variants (multiple loci and epigenetic modifications)
combined with risk-increasing lifestyle and environmental factors
pathogenesis: environment - ANSWER-- factors - nutrition - obesity may unmask or
amplify symptoms of hyperinsulinemia and hyperandrogenism in suseptible individuals
- graphs of differences between obese and normal weight girls (through puberty), T and
Free T higher in obese, SHBG is decreased and insulin is higher.
- vitamin d insufficenciy is associated with metabolic syndrome and CDV, obesity
promotes insufficiency because vit D is sequester in adipose, 82% of PCOS women are
VIT D deficient.
origins of PCOS: the two hit hypothesis - ANSWER-- Genetic or epigenetic factors: set
reproductive and metabolic trajectories in early life
- Factors later in life: influence the severity of adult phenotype
Nutrition
Exposures
Pregnancy complications of PCOS - ANSWER-- Subfertility
- Miscarriage risk (contreversial)
