Ovulatory dysfunction Flashcards
Ovarian steroids are derived from ______
cholesterol
What is the rate limiting step of ovarian steroid synthesis?
movement of cholesterol into mitochondria
Describe the importance of GnRH pulse frequency on HPO axis function
- 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
Estradiol tends to ______ GnRH pulse frequency and progesterone tends to ______ pulse frequency
estradiol increases, progesterone decreases
Differentiate the roles of theca cells vs granulosa cells
LH stimulates theca cells to produce androgens from cholestrol
FSH stimulates aromatization of androgens into estrogens in the granulosa cells
Developing follicles will undergo atresia if not rescued by _____ in the late luteal phase of the previous menstrual cycle
FSH
Describe the events that occur in the follicular phase of the ovulatory cycle
- 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
After ovulation, remaining follicular cells form the _______, which is supported by LH
corpus luteum
Describe the events in the luteal phase
- 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
Decline in ______ triggers menses
progesterone
List hypothalamic/ pituitary causes of ovulatory dysfunction
- hypopituitarism
- hyperprolactinemia
- functional hypothalamic amenorrhea
How can infertility due to hypopituitarism be treated?
exogenous gonadotropins to stimulate ovarian function
How is infertility due to hyperprolactinemia treated?
- remove causative medications
- treat hypothyroidism
- use dopamine agonists
Functional hypothalamic amenorrhea is characterized by _____ GnRH pulsatility
slow or absent
List causes of functional hypothalamic amenorrhea
under nutrition
excessive exercise
chronic disease
What are the clinical features of PCOS
clinical or biochemical hyperandrogenism,
oligo/anovulation
polycystic ovaries by ultrasound
PCOS is a diagnosis of ________
exclusion
List the major clinical features of PCOS
hyperandrogenism
insulin resistance
arrest of follicular development and lack of regular ovulation
Hyperandrogenism in PCOS seems to be due to an intrinsic abnormality in the ______ cells
theca
Insulin resistance in people with PCOS leads to compensatory ___________
hyperinsulinemia
What pathways in PCOS do NOT demonstrate insulin resistance?
ovarian steroidogenesis
High insulin in PCOS leads to:
increased ovarian androgen production
suppression of SHBG–> more free testosterone
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.
progesterone
Should PCOS be considered an estrogen deficient state?
NO
- small follicles do produce some estrogen
- ovarian androgens are aromatized to estrogen peripherally
What is the best approach to PCOS?
weight loss
How can irregular menses due to PCOS be treated?
combination OCPs
- progestins stabilize endometrium
How can hirsutism due to PCOS be treated?
combination OCPs
- suppress LH/ FSH, decrease ovarian androgen production
- increase production of SHBG
An anti-androgen like _______ can be used to treat hirsutism due to PCOS
spironolactone
How can fertility be achieved in patients with PCOS?
- medications that interrupt negative feedback by estrogen and boost FSH production, ex clomiphene or letrozol
Patients with ________ present identically to patients with PCOS
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
In premature ovarian failure, estrogen deficiency causes serum ______ levels to rise
FSH
loss of negative feedback on FSH release
