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RGU 1 > Polycystic ovarian syndrome > Flashcards

Polycystic ovarian syndrome Flashcards

1
Q

Is polycystic ovarian syndrome (PCOS) heterogeneous/variable phenotypic/polygenic?

A

YES

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2
Q

What are the reproductive and cardiovascular features of PCOS?

A
  • fecundity decline (monthly pregnancy rate is diminished because she’s not ovulating).
  • endocrine/metabolic consequences (dyslipidemia that could lead to T2DM)
  • vascular or endothelial damage
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3
Q

** Where do we think the problem is in PCOS? (EXAM QUESTION)

A

right at the pituitary (mostly LH).

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4
Q

What happens if the GnRH frequency is too fast or continuous (e.g. GnRH agonist)?

A

FSH/LH levels rise initially then decrease due to desensitization/down-regulation.
*Aka you need to have the right GnRH frequency to cause ovulation.

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5
Q

What happens if the GnRH frequency is too slow?

A

there is insufficient FSH/LH to drive the ovaries

*Aka you need to have the right GnRH frequency to cause ovulation.

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6
Q

What causes the LH spike from the pituitary?

A

enough of estradiol being produced in the ovary to induce the LH surge

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7
Q

What is the main problem in PCOS?

A
  • women cannot achieve the LH surge well enough.

- they get high pulse waves and pulse frequencies, but never get the surge they need for ovulation to occur.

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8
Q

What cells line the outer antral follicle?

A

theca cells (LH acts on these to induce androgen (androstenedione and testosterone) production via cAMP reaction from cholesterol).

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9
Q

What cells lie beneath the basement membrane of the theca cells?

A

granulosa cells (FSH stimulates these to convert androgens (that have crossed the theca cells basement membrane to enter the granulosa cells of the follicle) to estradiol via cAMP and aromatase reaction.

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10
Q

What is the two cell-two gonadotropin theory?

A

states that you need both theca and granulosa cells, as well as both FSH and LH in order for the ovary to work and make estrogen and progesterone.

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11
Q

What happens after the granulosa cells have made lots of estradiol (estradiol surge) due to FSH stimulation?

A

this induces an LH surge, which leads to OVULATION (marking the beginning of the secretory phase of the endometrial cycle).

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12
Q

What is a letenized granulosa cell?

A

granulosa cell that has adequate androgens to make estradiol.

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13
Q

What happens to the residual follicle after ovulation?

A
  • it becomes a corpus luteum, which primarily secretes progesterone (driving the secretory phase; preparing the endometrium for a possible pregnancy).
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14
Q

** What 2 of 3 issues should women with PCOS have related to their condition?

A
  • ovulatory disturbance (oligomenorrhea= infrequent menses). So if their menses is off their ovulation is also off.
  • androgen excess (clinical OR biochemical)
  • sonographic evidence of high density antral follicles
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15
Q

What are some other things you must rule out when diagnosing PCOS?

A
  • nonclassical adrenal hyperplasia
  • androgen-secreting tumors
  • hyperprolactinemia
  • thyroid dysfunction
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16
Q

What are some important health implications of PCOS?

A
  • impaired glucose tolerance
  • dyslipidemia
  • obesity
  • INFERTILITY
  • sleep apnea
  • fatty liver (non-alcoholic hepatic steatosis)
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17
Q

What are the important points regarding economic cost of PCOS?

A
  • screen, treat, and prevent sequelae
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18
Q

Do women with PCOS have normal ovaries and reproductive organs?

A

YES!!! They just don’t get the right signals.

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19
Q

Do the ovaries usually contain small cysts?

A

Yes usually 10 or more, but they aren’t really cysts bc they are so tiny. Really they are just follicles.

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20
Q

What does the ovary’s appearance look like?

A
  • surface area is doubled
  • same number of primordial follicles, but the number of growing and atretic follicles is DOUBLED (aka high antral follicle count).
  • increased stroma due to hyperplasia of thecal cells.
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21
Q

What does ovulatory disturbance mean in PCOS?

A
  • threshold levels of estradiol are not sustained for pre-ovulatory LH surge= no ovulation.
  • self-testing kits will show that you have LH but it’s just reading the presence of little LH spikes, and not the large LH surge required for ovulation.
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22
Q

Will women with PCOS have progesterone secretion?

A

minimal bc they aren’t ovulating and forming the corpus luteum, which is responsible for progesterone secretion.

23
Q

What is the major androgen that is elevated in women with PCOS?

A

testosterone (expressed clinically with acne or hair growth).

24
Q

What major protein is decreased in PCOS?

A

sex hormone binding globulin (SHBG). If this is low, it will not pick up free testosterone in the circulation.
*BC helps to increase SHBG :)

25
Q

Is insulin growth factor binding protein (IGFBP) increased or decreased in PCOS?

A
  • DECREASED
26
Q

Is insulin growth factor increased or decreased in PCOS?

A
  • INCREASED
27
Q

What are the major symptoms of PCOS?

A
  • menstrual irregularities (oligomenorrhea or amenorrhea). Bleeding patterns can be spotty or heavy.
  • hirsutism and acne
  • obesity (50%)
28
Q

What questions should you ask on history taking with PCOS?

A
  • how many menses do you get per year? (5= oligomenorrhea).
  • reproductive abnormalities
  • endocrine disturbances
  • mothers or sisters with PCOS
  • family hx of premature cardiac disease
29
Q

Is there a potential genetic defect or familial clustering of PCO?

A

YES!!

30
Q

Could there be an insulin receptor defect in PCOS that causes serine phosphorylation of the insulin receptor?

A

YES

31
Q

What is over-expressed in the theca cells and granulosa cells in women with PCOS?

A
  • mRNA for the LH-receptor
32
Q

How do we treat a woman with PCOS who’s BMI is elevated?

A
  • loss of 5% body weight
33
Q

What can we give a woman with PCOS to help her get pregnant?

A
  • clomiphene, letrazole, or gonadotropins to induce ovulation
34
Q

What will we give women with metabolic abnormalities (insulin resistance)?

A
  • metformin (glucophage)
35
Q

Is surgery needed for PCOS?

A

NEVER NO

36
Q

Are adolescents with PCOS treated the same as adults?

A

YES

37
Q

Why do oral contraceptives work so well in treating PCOS?

A
  • they take care of everything that PCOS is doing. Instead of having tonically high levels of LH, the birth control pills lower LH, allowing androgens to be lowered, which will in turn lower hair growth and acne. Will also increase SHBG and restores menses (not because you are restoring the HPG axis, but from the pill hormones itself).
38
Q

What will weight loss do to help PCOS?

A
  • decrease peripheral aromitization of androgens to estrogens :)
  • increase levels of SHBG :)
  • decrease already high insulin levels :)
39
Q

What is insulin resistance?

A
  • reduced glucose response to a given amount of insulin. Can occur due to peripheral target tissue resistance, decreased hepatic clearance, or increased pancreatic sensitivity.
40
Q

What causes the increased insulin (hyperinsulinemia) in PCOS?

A

increased insulin secretion secretion by beta cells of the pancreas

41
Q

Does the hyperinsulinemia or hyperandrogenism come first in these PCOS pts?

A
  • most likely the high insulin causes the high androgens.
  • insulin binds to both the insulin receptor and the IGF-I receptors (on the theca cells of the ovaries). If insulin receptors are blocked or deficient in number, then insulin binds to IGF-I receptors in the ovary causing hyperandrogenism.
42
Q

What are some other important actions of hyperinsulinemia?

A
  • inhibits hepatic synthesis of SHBG= decreased binding of free testosterone (increasing free testosterone).
  • inhibits hepatic synthesis of IGFBP-I= decreased levels lead to compensatory increased activity of the IGF-I receptor at the ovary.
43
Q

So what are the overall goals of treatment for PCOS?

A
  • reduce androgens (by giving oral contraceptives).
  • protect the endometrium against the effects of unopposed estrogen (endometrial hyperplasia; precursor for endometrial adenocarcinoma).
  • support lifestyle changes to lower body weight.
  • lower risk of cardiovascular disease by lowering insulin levels.
  • induction of ovulation for PREGNANCY :)
44
Q

What is important to remember about PCOS and estrogen?

A

you are in a constant estrogen state (aka estrogen is around all the time, but not enough to cause the LH surge leading to ovulation).

45
Q

How do we test for glucose tolerance and insulin resistance?

A
  • euglycemic clamp (BEST but impractical)
  • glucose tolerance test (2 hour glucose with 75 g glucose load). This will check both glucose and insulin in the fasting, 1 hour state, and 2 hour states. If insulin resistant then the insulin levels will be elevated at every time frame.
46
Q

How does metformin (glucophage) work?

A
  • lowers blood glucose by increasing intestinal use of glucose, enhancing peripheral glucose uptake, and stimulating insulin mediated glucose disposal.
  • also enhances insulin sensitivity at the post-receptor level.
  • decreases gluconeogenesis in the liver
47
Q

What are some ADRs of metformin?

A
  • decreased B-12 absorption
  • homocysteine elevation
  • rare cases lactic acidosis (do not give if serum creatinine is greater than 1.4 mg/dL).
48
Q

What anti-androgens are available to treat the androgen effects of PCOS?

A
  • spironolactone= potassium sparing diuretic that also blocks the androgen receptor.
  • alpha-reductase inhibitors (flutamid, finesteride) but these are hard on the liver. RARELY give these drugs.
  • ornithine decarboxylase inhibitors (eflornithine)= cream for the skin.
49
Q

Is non-medical treatment the first line therapy for PCOS?

A

YES especially in younger pts.

50
Q

What are some supplements with insulin sensitizing properties?

A
  • cinnamon, vitamin D, inositol, reservatrol, and chromium.
51
Q

*** What is the FIRST line therapy for infertility treatment in pts with PCOS?

A

Oral agens:

  • CLOMIPHENE= estrogen receptor blocker (very SAFE).
  • LETRAZOLE= aromatase inhibitor (actually breast cancer drug).
52
Q

*** What is the SECOND line therapy for infertility treatment with PCOS?

A
  • injectable gonadotropins= higher level with more risks (OHSS; ovarian hyper stimulation).
53
Q

How do we reduce the risk of ovarian hyper stimulation when using injectable gonadotropins?

A
  • in vitro fertilization

- elective frozen embryo transfer

54
Q

So, is PCOS a disease?

A

NO it is a sign that the ovary is not a culprit, but rather probably the pituitary gland. It is a problem of the high levels and overactivity of LH at the ovary.

RGU 1 (17 decks)

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