Ovulatory dysfunction

Question 1

Ovarian steroids are derived from ______

Answer 1

cholesterol

Question 2

What is the rate limiting step of ovarian steroid synthesis?

Answer 2

movement of cholesterol into mitochondria

Question 3

Describe the importance of GnRH pulse frequency on HPO axis function

Answer 3

• rapid pulses favor LH, slower pulses favor FSH
• if the frequency is too low there is inadequate stimulation of pituitary and decreased gonadotropin function
• if the frequency is too high or constant, expression of GnRH receptor is down regulated and gonadotropin release is decreased

Question 4

Estradiol tends to ______ GnRH pulse frequency and progesterone tends to ______ pulse frequency

Answer 4

estradiol increases, progesterone decreases

Question 5

Differentiate the roles of theca cells vs granulosa cells

Answer 5

LH stimulates theca cells to produce androgens from cholestrol

FSH stimulates aromatization of androgens into estrogens in the granulosa cells

Question 6

Developing follicles will undergo atresia if not rescued by _____ in the late luteal phase of the previous menstrual cycle

Answer 6

FSH

Question 7

Describe the events that occur in the follicular phase of the ovulatory cycle

Answer 7

• increase in FSH causes granulosa cells to produce more estrogen which exerts negative feedback on FSH release
• over the course of the follicular phase, FSH levels begin to decline
• larger follicles produce more FSH receptors so are more sensitive to the declining FSH levels
• a single dominant follicle produces androgens that inhibit growth of neighboring follicles
• rising estrogen eventually causes in increase in GnRH pulse frequency leading to an LH surge

Question 8

After ovulation, remaining follicular cells form the _______, which is supported by LH

Answer 8

corpus luteum

Question 9

Describe the events in the luteal phase

Answer 9

• high progesterone from the CL exerts negative feedback on GnRH, LH, FSH and begin to favor FSH over LH
• the CL regresses after 14 days unless pregnancy occurs and hCG continues to stimulate the CL
• CL demise causes drop in estrogen and progesterone, so there are slower GnRH pulses which favors FSH
• FSH rescues the next group of follicles

Question 10

Decline in ______ triggers menses

Answer 10

progesterone

Question 11

List hypothalamic/ pituitary causes of ovulatory dysfunction

Answer 11

• hypopituitarism
• hyperprolactinemia
• functional hypothalamic amenorrhea

Question 12

How can infertility due to hypopituitarism be treated?

Answer 12

exogenous gonadotropins to stimulate ovarian function

Question 13

How is infertility due to hyperprolactinemia treated?

Answer 13

• remove causative medications
• treat hypothyroidism
• use dopamine agonists

Question 14

Functional hypothalamic amenorrhea is characterized by _____ GnRH pulsatility

Answer 14

slow or absent

Question 15

List causes of functional hypothalamic amenorrhea

Answer 15

under nutrition
excessive exercise
chronic disease

Question 16

What are the clinical features of PCOS

Answer 16

 clinical or biochemical hyperandrogenism,
 oligo/anovulation
 polycystic ovaries by ultrasound

Question 17

PCOS is a diagnosis of ________

Answer 17

exclusion

Question 18

List the major clinical features of PCOS

Answer 18

hyperandrogenism
insulin resistance
arrest of follicular development and lack of regular ovulation

Question 19

Hyperandrogenism in PCOS seems to be due to an intrinsic abnormality in the ______ cells

Answer 19

theca

Question 20

Insulin resistance in people with PCOS leads to compensatory ___________

Answer 20

hyperinsulinemia

Question 21

What pathways in PCOS do NOT demonstrate insulin resistance?

Answer 21

ovarian steroidogenesis

Question 22

High insulin in PCOS leads to:

Answer 22

increased ovarian androgen production

suppression of SHBG–> more free testosterone

Question 23

The absence of ovulation means that uterine estrogen exposure is unopposed by cyclic _______, leading to lack of regular endometrial shedding. This increases risk of endometrial hyperplasia and carcinoma.

Answer 23

progesterone

Question 24

Should PCOS be considered an estrogen deficient state?

Answer 24

NO

• small follicles do produce some estrogen
• ovarian androgens are aromatized to estrogen peripherally

Question 25

What is the best approach to PCOS?

Answer 25

weight loss

Question 26

How can irregular menses due to PCOS be treated?

Answer 26

combination OCPs

- progestins stabilize endometrium

Question 27

How can hirsutism due to PCOS be treated?

Answer 27

combination OCPs

• suppress LH/ FSH, decrease ovarian androgen production
• increase production of SHBG

Question 28

An anti-androgen like _______ can be used to treat hirsutism due to PCOS

Answer 28

spironolactone

Question 29

How can fertility be achieved in patients with PCOS?

Answer 29

• medications that interrupt negative feedback by estrogen and boost FSH production, ex clomiphene or letrozol

Question 30

Patients with ________ present identically to patients with PCOS

Answer 30

nonclassic CAH
- function of enzyme is only mildly impaired so cortisol is sufficient but occurs at the expense of increased ACTH and steroid hormone precursors that are shunted into androgen production pathways

Question 31

In premature ovarian failure, estrogen deficiency causes serum ______ levels to rise

Answer 31

FSH

loss of negative feedback on FSH release