198/199: Endocrine Control of Female Reproduction I & II Flashcards
When during the menstrual cycle does progesterone peak?
7 days after ovulation
(When the corpus luteum is chugging along making progesterone)
How will levels of the following hormones change in ovarian failure?
- Estradiol:
- LH/FSH:
- Estradiol: low
- LH/FSH: high
Pituitary is trying to get the ovaries to work, sending a strong signal, but the ovaries are not responding.
Vs. hypothalamic amenorrhea, will have low estradiol AND low LH/FSH
Which ovarian cells convert androgen to estrogen?
Which gonadotropin stimulates the development of these cells?
Granulosa cells, using aromatase
FSH
How will levels of the following hormones change in hypothalamic amenorrhea?
- Estradiol:
- LH/FSH:
- Estradiol: low
- LH/FSH: low
Entire HPG axis is down-regulated. Due to head lesions, genetic defects, or behavioral/environmental (stress, anorexia, etc)
Vs. ovarian failure, will have low estradiol and HIGH LH/FSH
How is PCOS diagnosed?
Requires 2/3 of:
- Oligo and/or anovulation
- Oligo-ovulation= irregular or infrequent periods
- Signs of hyperandrogenism (acne, hirsuitism)
- Ultrasound with ≥12 2-9 mm follicles in each ovary OR increased ovarian volume
- The immature follicles look like cysts
Note: criteria has historically been 12 follicles, but I think she mentioned that now with improved imaging techniques we can see follicles better so we may actually see a lot more, and if someone has 12 follicles but no sx of PCOS probably do not need to diangose
List the phase of follicular development and predominant hormone that loosly aligns with the following phases of the endometrial cycle:
- Menses:
- Proliferative phase:
- Transition between proliferative and secretory:
- Secretory phase
- Menses
- Follicular phase
- Low estradiol and progesterone
- Proliferative phase:
- Follicular phase
- High estrogen
- Transition between proliferative and secretory:
- Ovulation
- High estrogen, progesterone beginning to rise
- Secretory phase
- Luteal phase
- High progesterone, estrogen falls
List 3 things that increase levels of sex hormone binding globulin
- Hyperthyroidism
- Pregnancy
- Estrogen treatment (OCPs)
All will decrease the effect of sex hormones; bound to SHBG = not biologically active
Which gonadotropin supports the corpus luteum?
Which hormone is produced as a result?
LH
Progesterone
- Corpus luteum produces progesterone (supports a pregnancy for first 7 weeks until placenta can produce its own)*
- Note: LH also stimulates theca cells to produce androgens*
Which ovarian cells secrete androgens?
Which gonadotropin stimulates these cells?
Theca cells
LH
Which hormone supports early pregnancy?
Progesterone from the corpus luteum
[hormone] stimulates proliferation of the uterine lining
[hormone] stimulates differentiation of the uterine lining
Estrogen stimulates proliferation of the uterine lining
Progesterone stimulates differentiation of the uterine lining
After ovulation, what happens to the granulosa cells and theca cells that are left in the follicle?
They re-organize to become luteal cells
- Angiogenesis! Blood supply needed for delivery of cholesterol precursors for steroid synthesis
- More smooth ER and mito!
This forms the corpus luteum -> progesterone production
List 2 causes of gonadal dysgenesis
Turner syndrome (45, XO)
Fragile X carrier
Thank you @Ben Gastevich!
Describe the positive feedback loop that triggers ovulation
- Sustained high estrogen + progesterone bump
- Beginning of progesterone rise increases the pituitary response
- -> LH surge
- Normally, LH is inhibited by increased estrogen/progesterone, but switch to positive feedback at high levels
- -> Ovulation!
How does hypothyroidism affect menstruation?
(Describe the pathway)
Hypothyroidism = low thyroid horomone
- -> Upregualted TRH secretion from hypothalamus
- -> High TRH increases TSH and prolactin secretion
- Prolactin inhibits GnRH pulses
- -> No FSH/LH
- -> No ovulation
- -> No menstrual cycles
What is the most common cause of secondary amenorrhea?
Pregnancy
Secondary amenorrhea = used to have normal menstruation, but it stopped
Before treating a patient with PCOS, what diagnostic evaluation must be done?
Rule out other causes of high androgens
- Very high testosterone => Testosterone-secreting tumor
- High DHEAs => adrenal source
- High 17-OH-progesterone => Congenital adrenal hyperplasia
- Elevated free cortisol in urine => Cushing syndrome
How is hypothalamic amenorrhea treated?
- To relieve symptoms (ex: low bone mineral density)
- Hormone replacement
- To induce fertility
- Injectable gonadotropins
- Pulsatile GnRH
Also, behavioral therapy
Note: Leptin is NOT currently a therapeutic option
Which gonadotropins are favored by the following GnRH secretion patterns?
- High frequency:
- Low frequency:
- Continuous:
- High frequency: LH secretion
- Low frequency: FSH secretion
- Continuous: No secretion
- Desensitization inhibits both LH and FSH
Why is it important to treat patients with PCOS, even if they don’t want to become pregnant and are unbothered by hirsutism and/or acne?
PCOS = unopposed estrogen
→ endometrium always proliferating
→increased risk of endometrial cancer
- Must protect the endometrium (either with ovulation or OCPs that include progestin)
Will people with PCOS have a positve or negative progestin challenge?
Positive (will have bleeding, proves that estrogen is present)
- Estrogen is present, but abnormalities in hormone signaling prevent progesterone production, LH surge
Which hormone suppresses prolactin?
Dopamine
- Dopamine tonically inhibits prolactin release
- Decreased dopamine -> increased prolactin*
What does a positive progestin challenge imply about the cause of a patient’s secondary amenorreha?
Implies normal outflow tract, adequate estrogen
=> Cause of amenorreha is not enough progesterone to induce ovulation
Progestin challenge mimics little rise in progesterone before ovulation
How is menopause diagnosed?
(lab test, assuming consistent clinical picture)
High FSH with low estrogen
- Due to lack of inhibin, lack of estrogen negative feedback
List 2 causes of hypothalamic amenorreha
- Genetic defect: Kallman syndrome
- GnRH neurons fail to migrate
- -> Primary amenorrhea
-
Functional hypothalamic amenorrhea
- May cause primary or secondary amenorrhea
- Usually associated with increased stress
(Nutritional, environmental, behavioral)
Why are estrogen-progestin challenges rarely done?
We can pretty easily measure estrogen levels in the blood
If normal and no bleed after progestin challenge, implies abnormal outflow tract
How does prolactin affect ovulation?
How is this adaptive (evolutionarily)?
Prolactin inhibits ovulation
- Prolactin suppresses GnRH pulses
- -> No LH/FSH
- -> No positive feedback loop from estrogen
- -> No ovulation
Prolactin is high during lactation - adaptive to not be able to have another bably while breastfeeding a new one
What causes polyglandular autoimmune disease?
Auto-antibodies to endocrine organs
Can target ovaries -> premature ovarian failure
What is the most common cause of anovulation in the setting of normal estrogen?
PCOS
- Ovary is “stuck” in the follicular phase
- Theca cells are making andorgens, but granulosa cannot keep up with aromatization
- High estrogen AND androgens, but androgens interfere with signaling
- Cannot select dominant follicle
What defines menopause?
1 year has gone by since last menstrual period
Technically it’s the last menstrual period, but hard to know if it *really* is the last one until a year has gone by
Which gonadotropin is required to maintain the corpus luteum?
Continous LH secretion
Since LH drops after ovulation, the corpus luteum will die unles hCG takes over (if a pregnancy occurs)
No pregnancy -> corpus luteum dies -> no progestrerone to support endometrial lining -> ovulation
What is the difference between menstrual bleeding and the bleeding that people on birth control pills experience during the placebo pills?
- Menstrual bleeding = bleeding 14 days after ovulation
- When the corpus luteum dies and there is no progesterone to support the endometrial lining
- Bleeding on placebo pills = hormone withdrawal bleeding
- OCPs suppress ovulation
- Stopping the estrogen/progesterone in the pills has a similar effect as the corpus luteum dying, but this bleeding is not in response to ovulation
How is the dominant follicle selected during oocyte maturation?
At the pre-antral stage, follicles develop FSH receptors
- Basically, the first follicle that develops FSH receptors becomes dominant
- FSH helps the follicle grow
- Induces more FSH receptors -> this follicle responds best to FSH
- Causes **granulosa cell proliferation and more estrogen
- > follicle grows rapidly, becomes an antral follicle**
- The granulosa cells will also develop LH recetpors -> can make progesterone too (required for ovulation)
- When FSH levels fall (2/2 estrogen secretion from the dominant follicle), the other follicles will become atretic
What is the most common endocrine disorder of reproduction?
Polycystic Ovarian Syndrome (PCOS)
How does kisspeptin affect GnRH release?
Kisspeptin stimulates GnRH
List 4 symptoms of hyperprolactinemia
- Galactorrhea
- Infertility
- Can be present even w/o menstrual distrubances
- Menstrual disturbances
- Oligomenorrhea, amenorrhea
- Hypogonadism
- Low estrogen sx: hot flashes, vaginal dryness, decreased bone density
List 3 ovarian peptide hormones synthesized in the granulosa cell and their functions
-
Inhibin - inhibits FSH
- Secretion stimulated by LH
- Activin - stimulates FSH, increases FSH receptors in ovary
- Follistatin - inhibits activin -> less FSH
At what stage of follicular development is a dominant follicle selected
Pre-antral -> antral
- There can be many pre-antral follicles, but then a dominant one is selected and there is only 1 antral follicle*
- The rest become atretic follicles*
Which gonadotropin promotes follicle development (egg maturation) in the ovary?
Which hormone is elevated as a result?
FSH
Estrogen
Granulosa cells proliferate in resonse to FSH; then they aromatize androgens (from theca cells) to estrogen
Which dopamine agonist is most effective for treating hyperprolactinemia AND producing ovulation?
Cabergoline
