206/207 - Endocrine Control of Female Reproduction I & II Flashcards

1
Q

When during the menstrual cycle does progesterone peak?

A

7 days after ovulation

(When the corpus luteum is chugging along making progesterone)

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2
Q

How will levels of the following hormones change in ovarian failure?

  • Estradiol:
  • LH/FSH:
A
  • Estradiol: low
  • LH/FSH: high

Vs. hypothalamic amenorrhea, will have low estradiol AND low LH/FSH

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3
Q

Which ovarian cells aromatize androgen to estrogen?

Which gonadotropin stimulates the development of these cells?

A

Granulosa cells

FSH

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4
Q

How will levels of the following hormones change in hypothalamic amenorrhea?

  • Estradiol:
  • LH/FSH:
A
  • Estradiol: low
  • LH/FSH: low

Vs. ovarian failure, will have low estradiol and HIGH LH/FSH

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5
Q

How is PCOS diagnosed?

A

Requires 2/3 of:

  • Oligo and/or anovulation
  • Signs of hyperandrogenism
  • 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

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6
Q

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
A
  • 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
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7
Q

List 3 things that increase levels of sex hormone binding globulin

A
  • Hyperthyroidism
  • Pregnancy
  • Estrogen treatment (OCPs)

All will decrease the effect of sex hormones; bound to SHBG = not biologically active

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8
Q

Which gonadotropin supports the corpus luteum?

Which hormone is produced as a result?

A

LH

Progesterone

  • Corpus luteum produces progesterone*
  • Note: LH also stimulates theca cells to produce androgens*
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9
Q

Which ovarian cells secrete androgens?

Which gonadotropin stimulates these cells?

A

Theca cells

LH

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10
Q

Which hormone supports early pregnancy?

A

Progesterone from the corpus luteum

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11
Q

[hormone] stimulates proliferation of the uterine lining

[hormone] stimulates differentiation of the uterine lining

A

Estrogen stimulates proliferation of the uterine lining

Progesterone stimulates differentiation of the uterine lining

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12
Q

After ovulation, what happens to the granulosa cells and theca cells that are left in the follicle?

A

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

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13
Q

List 2 causes of gonadal dysgenesis

A

Turner syndrome (45, XO)

Fragile X carrier

Swyer syndrome (46XY)

Thank you @Ben Gastevich!

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14
Q

Describe the positive feedback loop that triggers ovulation

A
  • Sustained high estrogen + progesterone bump
    • Beginning of progesterone rise increases the pituitary response
  • -> LH surge
    • Normally, LH is inhibited by increased estrogen/progesterone
  • -> Ovulation!
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15
Q

How does hypothyroidism affect menstruation?

(Describe the pathway)

A

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
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16
Q

What is the most common cause of secondary amenorrhea?

A

Pregnancy

Secondary amenorrhea = used to have normal menstruation, but it stopped

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17
Q

Before treating a patient with PCOS, what diagnostic evaluation must be done?

A

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
18
Q

How is hypothalamic amenorrhea treated?

A
  • 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

19
Q

Which gonadotropins are favored by the following GnRH secretion patterns?

  • High frequency:
  • Low frequency:
  • Continuous:
A
  • High frequency: LH secretion
  • Low frequency: FSH secretion
  • Continuous: No secretion
    • Desensitization inhibits both LH and FSH
20
Q

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?

A

PCOS = unopposed estrogen

  • > incresed risk of endometrial cancer
  • Must induce ovulation (or theoretically give periodic progesterone?) to protect the endometrium
21
Q

Will people with PCOS have a positve or negative progestin challenge?

A

Positive

  • Estrogen is present, but abnromalities in hormone signaling prevent progesterone production, LH surge
22
Q

Which hormone suppresses prolactin?

A

Dopamine

  • Dopamine tonically inhibits prolactin release
  • Decreased dopamine -> increased prolactin*
23
Q

What does a positive progestin challenge imply about the cause of a patient’s secondary amenorreha?

A

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

24
Q

How is menopause diagnosed?

(lab test, assuming consistent clinical picture)

A

High FSH

  • Due to lack of inhibin, lack of estrogen negative feedback
25
Q

List 2 causes of hypothalamic amenorreha

A
  • Genetic defect: Kallman syndrome
    • GnRH neurons fail to igrate
    • -> Primary amenorrhea
  • Functional hypothalamic amenorrhea
    • May cause primary or secondary amenorrhea
    • Usually associated with increased stress
      (Nutritional, environmental, behavioral)
26
Q

Why are estrogen-progestin challenges rarely done?

A

We can pretty easily measure estrogen levels in the blood

If normal and no bleed after progestin challenge, implies abnormal outflow tract

27
Q

How does prolactin affect ovulation?

How is this adaptive (evolutionarily)?

A

Prolactin inhibits ovulation

  • Prolactin suppresses GnRH pulses
  • -> No LH/FSH
  • -> No positive feedback loop from estrogen
  • -> No ovulation

Prolactin triggers lactation - adaptive to not be able to have another bably while breastfeeding a new one

28
Q

What causes polyglandular autoimmune disease?

A

Auto-antibodies to endocrine organs

Can target ovaries -> premature ovarian failure

29
Q

What is the most common cause of anovulation in teh setting of normal estrogen?

A

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
30
Q

What defines menopause?

A

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

31
Q

Which gonadotropin is required to maintain the corpus luteum?

A

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

32
Q

What is the difference between menstrual bleeding and the bleeding that people on birth control pills experience during the placebo pills?

A
  • 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

33
Q

How is the dominant follicle selected during oocyte maturation?

A

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
34
Q

What is the most common endocrine disorder of reproduction?

A

Polycystic Ovarian Syndrome (PCOS)

35
Q

How does kisspeptin affect GnRH release?q

A

Kisspeptin stimulates GnRH

36
Q

List 4 symptoms of hyperprolactinemia

A
  • 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
37
Q

List 3 ovarian peptide hormones synthesized in the granulosa cell and their functions

A
  • Inhibin - inhibits FSH
    • Secretion stimulated by LH
  • Activin - stimulates FSH, increases FSH receptors in ovary
  • Follistatin - inhibits activin -> less FSH
38
Q

At what stage of follicular development is a dominant follicle selected

A

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*
39
Q

Which gonadotropin promotes follicle development (egg maturation) in the ovary?

Which hormone is elevated as a result?

A

FSH

Estrogen

Granulosa cells proliferate in resonse to FSH; then they aromatize androgens (from theca cells) to estrogen

40
Q

Which dopamine agonist is most effective for treating hyperprolactinemia AND producing ovulation?

A

Cabergoline