Menstrual Physiology Flashcards
What is the most common cause of secondary amenorrhea?
PREGNANCY!
If a woman gets her period regularly (aka every month), what does this mean?
She is ovulatory!
What is the normal menstrual cycle length?
- every 24-35 days and lasts less than 8 days
What brings on the period?
release of an egg from the ovary!
What will happen 2 weeks after ovulation?
EITHER:
- pregnancy (fertilization)
- period
** What is the 1st half of the menstrual cycle called from an OVARY perspective?
the FOLLICULAR phase
** What is the 2nd half of the menstrual cycle called from an OVARY perspective?
the LUTEAL phase (bc there is a corpus luteum in the ovary producing progesterone).
** What is the 1st half of menstrual cycle called from a UTERINE perspective?
PROLIFERATIVE phase
** What is the 2nd half of the menstrual cycle called from a UTERINE perspective?
SECRETORY phase
** From a steroid perspective, is the 1st half of the menstrual cycle dominated by estrogen or progesterone?
ESTROGEN
** From a steroid perspective, is the 2nd half of the menstrual cycle dominated by estrogen or progesterone?
PROGESTRONE
** Withdrawal of which hormone brings on the menstrual cycle? (TEST QUESTION)
PROGESTERONE!
*so when this goes away, a woman gets her period.
What is the variable phase of the ovarian cycle?
follicular phase (aka as you are growing the follicle) *the second phase (luteal) is FIXED between 12 and 14 days.
So a person with a 35 day ovarian cycle, how long is the luteal phase?
still 12-14 days because it is FIXED
** What is the HPG axis? (MUST MEMORIZE)
hypothalamic-pituitary-gonadal/adrenal axis:
- gonadotropin releasing hormone (GnRH) is produced in the hypothalamus (10 amino-acid peptide hormone) and secreted from 4 different nuclei in the hypothalamus.
- GnRH goes into the portalhypophaseal system, which stimulates the gonadotropes (cells in the ANTERIOR PITUITARY).
- anterior pituitary cells (gonadotropes) produce FSH and LH (both peptide hormones)!
- FSH and LH stimulate the FOLLICULAR growth of the ovary!
- In response to FSH, the ovary will produce ESTROGEN, which will stimulate the lining of the uterus (the endometrium to thicken in preparation for possible embryo).
- Ovulation stimulates PROGESTERONE production, and if she becomes pregnant, she will continue to make progesterone!
- If she does not get pregnant, progesterone goes away and she gets her period.
What does follicle mean in laymen’s terms?
just a fancy word for egg “sack”
*each follicle has 1 egg in it, and responds to follicle stimulating hormone (FSH).
In the 1st phase of the menstrual cycle (follicular phase), what happens to GnRH pulsatility?
- a spurt of GnRH occurs every 60-90 mins.
* in the middle it increases to about every 15 mins, which leads to the LH surge.
In the 2nd phase of the menstrual cycle (luteal phase), what happens to GnRH pulsatility?
- a spurt of GnRH occurs every 3-5 hours (aka down-regulated bc it is the embryo driving the process and not the pituitary at this point).
What makes up FSH and LH peptide hormones molecularly?
glycosylated polypeptides composed of an alpha subunit and a beta subunit, each transcribed from different genes.
** What are the 4 hormones that share the alpha subunit?
- TSH
- FSH
- LH
- hCG
*** What is the difference between LH and hCG?
B unit differs by 30 amino acids (this is clinically important)!
*** With respect to LH, when does ovulation occur?
- 36 hours after LH surge (around day 14 of 28 day cycle)!!!
*** So, where is the fertile window?
4 days in the middle of the month!! (days 12-16)!!!!
** What 4 things does FSH do?
- stimulates GROWTH of a cohort of antral follicles and granulosa cell proliferation.
- upregulates FSH and LH RECEPTORS.
- stimulates AROMATASE activity in granulosa cells, stimulating conversion of androstenedione to estradiol.
- stimulates INHIBIN secretion from GC, which functions in negative feedback.
How long does it take to develop an egg (from a primoridal follicle to antral follicle)?
3 months (90 days)!
What is found inside the follicle?
granulosa cells
*FSH stimulates release of ESTROGEN from these cells.
What is found around the follicles?
theca cells
What does the LH surge do?
- causes continuation of MEIOSIS of the occyte and release of 1st polar body.
- release of oocyte from the follicle 36 hours after beginning of LH surge.
- leads to luteinization of the granulosa cells (aka they make more progesterone).
How many follicles are available each month for say a 25 year old pt?
- 20-25 follicles, which are stimulated to grow by FSH. Only 1 will grow, and the rest will undergo atresia by day 4 of her cycle.
- AKA when she gets her period, 20-25 of those follicles are dying, except for 1 lucky oocyte (egg) which will continue to grow.
*** Where are all eggs arrested in development at birth, and up until ovulation?
PROPHASE I of MEIOSIS I
How does birth control work?
it inhibits the LH surge. Thus you will not ovulate and release a mature egg.
So what is the role of the ovary?
regulates the development of primary oocytes within their follicles, into mature eggs capable of fertilization.
What important numbers do we have to know about size of the follicle when ovulation occurs, and the amount of estrogen it secretes?
20 mm follicle secreting 200 of estrogen
What ovarian hormone dominates the 1st half (follicular phase) of the menstrual cycle?
ESTROGEN
What ovarian hormone dominates the 2nd half (luteal phase) of the menstrual cycle?
PROGESTERONE
Is a female infant born with her entire cohort of oocytes for life?
YES
How many eggs will a woman have a puberty?
- 300,000
Can you see an early antral follicle or a graafian follicle on ultrasound?
YES
Do we know what recruits the early follicles to be selected for development?
NO, (in other words, they are FSH and LH independent)
At what stage of development do eggs become FSH and LH responsive?
early antral (secondary) follicle.
What happens to the egg after the LH surge causes the release of the first polar body?
egg arrests at metaphase II (aka metaphase of meiosis II)
What is required for completion of meiosis and expulsion of the second polar body?
fertilization!
*** What is necessary for acrosomal activation of sperm and thus fertilization of an egg?
Zona pellucida
What do the somatic cells of the ovary (theca cells; on the outside of the follicle) produce?
androgens (testosterone, androstenedione), estrogens, and progesterone.
** What enzyme converts androstenedione to estradiol? (TEST QUESTION)
aromatase
*important because we have medications called aromatase inhibitors that are used for fertility and cancer treatment.
From what are steroid hormones produced?
- CHOLESTEROL (in response to LH). It is first converted to progesterone, which is then converted to androstenedione and testosterone in the THECA cells.
- These are then transported to the GRANULOSA cells where aromatase converts them to estradiol (in response to FSH)!
How do you remember the basic structure of a steroid hormone?
“3 diamonds and a house”
What does estrogen do?
- causes proliferation of the endometrial glands (up to 8 mm).
What does progesterone do to the endometrium?
causes secretory changes that allow for implantation
*think “pro-gestational”
On what day of the cycle does implantation occur?
day 21 (peak progesterone levels)
What is a clinical scenario in which we give progesterone to prevent pregnancy?
Plan B (aka emergency contraception). *this prevents a possibly fertilized embryo from attaching to the uterine lining. It does this by shifting the window, by which implantation could occur.
How is the early follicular phase of the ovarian cycle regulated?
- because progesterone and estrogen DECREASED at the end of the menstrual cycle leading to menses, there is no longer negative feedback effects to the hypothalamus. Thus GnRH pulse frequency increases.
- GnRH increased pulsations leads to increased FSH.
- FSH (from anterior pituitary) stimulates growth of a cohort of antral follicles.
- ovary increases secretion of estrogen (which along with inhibin) result in negative feedback to the pituitary, preventing further release of FSH.
When does serum estradiol concentrations peak?
around day 14; about 1 day before ovulation.
What happens once estradiol reaches a threshold concentration?
it becomes stimulatory to LH causing the LH surge (via increased GnRH pulse frequency).
What happens in response to this LH surge?
- oocyte in the dominant follicle completes 1st meiotic division.
- increase in local secretion of plasminogen activator and cytokines required for ovulation.
- oocyte released from follicle at ovarian surface (36 hrs after start of LH surge).
What do the granulosa cells around the oocyte begin to do, even before the oocyte is released?
“luteinize” and produce progesterone (slowing LH pulses).
Are the ovaries connected to the fallopian tubes?
actually no!
How long does it take for the ovum (egg) to travel down the fallopian tube to the uterus?
3-4 days
Within what window must fertilization occur after ovulation?
24 hours or the ovum degenerates.
What happens to the follicle after ovulation?
- the granulosa and theca interna cells lining it form the CORPUS LUTUM (stimulated by LH). This synthesizes estrogen and a lot of PROGESTERONE= endometrium to become more glandular/secretory (in preparation for implantation).
What happens to the corpus luteum if fertilzation does not occur?
it dies, thus decreasing estrogen and progesterone, which leads to the sloughing off of the secretory endometrium.
*as estrogen falls, FSH is allowed to rise again, restarting the cycle.
When is inhibin most active?
early in the menstrual cycle
