LM 13.1: Menstrual Cycle and Physiology of Ovulation

Question 1

what is day 1 of the menstrual cycle?

Answer 1

the first day of menstrual bleeding

this is the “beginning” of the menstrual cycle

Question 2

what is the normal length of a menstrual cycle?

Answer 2

average length of the adult menstrual cycle is 28 to 35 days

although cycles as short as 21 days (from the beginning of one menses to the next) are considered within normal

Question 3

how does the menstrual cycle vary with age?

Answer 3

most adult women between the ages of 20 and 40 years have cycles with fairly little variability in length.

variability aka less regularity is much more common in the first 5-7 years and the last 10 years of menstruation

maturity of the hypothalamic-pituitary axis, which correlates with regularity of menstrual cycle, varies with age, as well as many other factors

Question 4

which phase of the menstrual cycle has the least amount of variation?

Answer 4

the luteal phase = from the time of ovulation until menstruation begins

it is much more consistent in length; usually 14 days and has very little variation

this is because of the hormonal cascades and endometrial activity and the journey of the developing oocyte, it’s all a very precise and consistent timing

Question 5

which phase of the menstrual cycle is largely responsible for the variability of the menstrual cycle?

Answer 5

the follicular phase

this phase can vary in length by 2 to 5 days normally in an individual

Question 6

what are the 5 important hormones in the menstrual cycle?

Answer 6

1. GnRH –> hypothalamus
2. FSH –> pituitary
3. LH –> pituitary
4. estradiol –> ovaries
5. progesterone –> ovaries

Question 7

how is GnRH released during the menstrual cycle?

Answer 7

it’s a neurohormone that’s produced by neural cells in the hypothalamus

it’s released in a pulsatile manner over time which effects which hormones are released in what amounts –> pulses occur ever 1-3 hrs depending on which part of the cycle you’re in and they last 5-25 minutes

if GnRH was constant, there’s actually inhibition of the gonadotropins (FSH and LH) instead of stimulation

Question 8

how does FSH effect GnRH?

Answer 8

FSH has a negative feedback on GnRH

so as FSH rises, it changes the pulses of GnRH

Question 9

what is the function of FSH?

Answer 9

1. stimulating the follicle/maturing of the egg within the ovary
2. release of estrogen from the ovary which then has a negative feedback on FSH

Question 10

what is the function of LH?

Answer 10

release of the egg/oocyte once it’s mature so that it can be fertilized

Question 11

what is the function of progesterone?

Answer 11

it’s produced from the remnant of the mature oocyte that has left the ovary called the corpus luteum

so the corpus luteum produces progesterone

Question 12

which hormones cause the endometrium to thicken and mature?

Answer 12

the combination of estrogen (due to FSH) and progesterone (from the corpus luteum) work to change the endometrial lining as the cycle goes along

the endometrium thickens with estrogen and matures under the influence progesterone via the production of glands so that it’s ready for implantation of the mature oocyte if fertilization occurs

the corpus luteum only lasts about 14 days and then it begins to involute and becomes nonfunctional

if pregnancy does occur then the hCG begins to develop and takes the place of progesterone/estrogen in keeping the endometrium thick and healthy

Question 13

when does ovulation occur?

Answer 13

day 14 +/- 1-2 days depending on the length of the follicular phase

Question 14

how do hormone levels fluctuate throughout the menstrual cycle?

Answer 14

FSH levels under the influence of GnRH begin to rise during the follicular phase – then due to negative feedback they begin to fall

under the influence of FSH, estrodiol levels rise until mid cycle and as FSH levels fall, estradiol levels also fall –> the combination of FSH and estradiol decreases induces a big peak in LH under the influence of GnRH

because of the peak of LH, ovulation is induced and the egg that has been maturing under the influence of FSH and estradiol is released

as the oocyte leaves the ovary, it leaves behind the corpus luteum and the corpus luteum starts to produce progesterone for the next 14 days – as the corpus luteum starts to die the progesterone levels will decrease in the absence of fertilization/hCG = sloughing of the endometrium aka your period starts

Question 15

what happens during the early follicular phase of the menstrual cycle?

Answer 15

this is the “least active” time, hormonally speaking, within the ovary

estradiol and progesterone concentrations are relatively low

increased FSH concentrations are stimulated by low frequency GnRH pulses

this causes “recruitment” of a group of developing follicles

LH pulses slow down or stop completely

Question 16

what happens during the mid-follicular phase of the menstrual cycle?

Answer 16

increase in FSH secretion causes progressive growth of the primary follicles

several follicles grow and their granulosa cells hypertrophy and divide (first meiotic division has been completed)

increased FSH secretion also leads to increased serum concentrations of estradiol

subsequently, increased estradiol negatively feeds back on the HP axis, suppressing FSH and LH secretion

GnRH release begins increases, preparing for the next stage

“triple stripe” pattern can be seen on ultrasound indicating endometrial thickening

Question 17

what happens during the late follicular phase of the menstrual cycle?

Answer 17

increased release of estradiol and inhibin A from the growing follicle result in increased serum levels

FSH and LH concentrations continue to fall (negative feedback from estradiol)

a dominant follicle emerges (typically only 1 per cycle, although polyovulation does occur) – the development of this oocyte is halted at the stage of metaphase II of meiosis II until fertilization takes place –> when a sperm cell fertilizes the female sex cell the secondary oocyte rapidly completes the remaining stages of meiosis II , giving rise to an ootid and an ovum, with which the sperm cell unites.

also during this time, FSH induces LH receptors in the ovary –> ovarian secretion of intrauterine growth factors such as insulin-like growth factor-1 (IGF-1) also increase

further thickening of the endometrium (under the control of rising serum estradiol concentrations)

increase in the amount and “stringiness” (Spinnbarkeit) of the cervical mucus (increase in a mucin protein MUC5B, important for sperm transit to the uterus) –> many women are able to monitor changes in cervical mucus to detect approximate timing of ovulation

Question 18

what happens during the luteal phase of the menstrual cycle?

Answer 18

serum estradiol levels reach a peak approximately 1 day prior to ovulation

s sudden switch from negative feedback control of LH by estradiol to a sudden positive feedback occurs; A VERY UNIQUE NEUROENDOCRINE PHENOMENON! –> the switch from negative to positive feedback of LH release is poorly understood; an increase in the number of pituitary gonadotropin-releasing hormone (GnRH) receptors may contribute, but there is probably no change in GnRH input to the pituitary

a 10-fold increase in serum LH concentrations occurs (as well as a small rise in serum FSH concentrations.

other ovarian factors contribute to the LH surge (it cannot be recreated simply by administering estrogen and a progestin to women in the early to mid-follicular phase)

the frequency of LH pulses continues to be approximately one per hour, but the amplitude of the LH pulses increases dramatically.

the granulosa cells around the oocyte begin to luteinize and produce progesterone just prior to release of the oocyte

follicular rupture occurs predictably after the LH surge –> measurement of serum or urine LH can be used to estimate the timing of ovulation

Question 19

what happens in the mid and late luteal phase?

Answer 19

progesterone levels rise due to secretion from the corpus luteum

LH pulses slow down to one pulse every four hours –> inhibin A is also produced by the corpus luteum, and serum concentrations of inhibin A peak in the mid-luteal phase

in the late luteal phase, LH secretion decreases, and progesterone and estradiol production by the corpus luteum falls

if the oocyte becomes fertilized, it implants in the endometrium several days after ovulation. The early embryo begins to make chorionic gonadotropin, which maintains the corpus luteum and progesterone production

Question 20

what are the 2 layers of the endometrium?

Answer 20

1. stratum basalis

the stratum basalis attaches to myometrium, and serves as an anchor for the endometrium within the uterus and stays relatively unchanged

2. stratum functionalis

the functional layer that is the active/ dynamic layer and where a fertilized or blastocyst will implant

Question 21

which 2 hormones are required for the building of the endometrium?

Answer 21

1. estrogen
2. progesterone

you need BOTH and in the correct combination

bricks are the estrogen which helps build the thickness and lining of the endometrium over time especially during the follicular phase

in order for the endometrium to mature and become stable you need progesterone so it’s like the mortar between the bricks which serves to strengthen the endometrium

if you have excessive/unopposed estrogen that just begins to build without adequate progesterone to stabilize them, eventually the endometrium becomes unstable and can lead to breakthrough bleeding/slaughing of the endometrium in an unorganized fashion