E2= estradiol LH=Luteinizing hormone P=progesterone FSH=Follicle Stimulating Hormone
Basically, the reproductive cycle is divided into three phases:
Menstruation and the follicular phase
Ovulation
Luteal phase
These three phases refer to the status of the ovary during the reproductive cycle.
Key Players:
GnRH-Gonadotropin releasing hormone- is released from the hypothalamus in a pulsatile fashion, stimulating the anterior pituitary gland to secrete LH and FSH accordingly.
FSH- follicle stimuating hormone- secreted pulsatiley from the anterior pituitary. Stimulates cells in the ovaries called granulosa cells.In charge of developing and maturing follicles in the ovary, one of which will become dominant and detach from the egg during ovulation. The granulosa cells is where estradiol (estrogen) is made.
LH- Luteinizing hormone- secreted pulsatiley from the anterior pituitary. Stimulates cells in the ovaries called theca cells. The surge of LH at the middle of the cycle is what triggers ovulation. The theca cells surround the granulosa cells. They secrete androgens which serve as precursors for the estradiol production by the granulosa cells.
Estradiol - Secreted by the ovaries. In the female, estradiol acts as a growth hormone for tissue of the reproductive organs, supporting the lining of the vagina, the cervical glands, the endometrium and the lining of the fallopian tubes. It enhances growth of the myometrium ( the muscle of the uterus). Estradiol appears necessary to maintain oocytes in the ovary. During the menstrual cycle estradiol that is produced by the growing follicle triggers, the hypothalamic-pituitary events that lead to the LH surge, inducing ovulation. In the luteal phase estradiol, in conjunction with progesterone prepares the endometrium for implantation. During pregnancy, estradiol increases due to placental production.
Progesterone- Secreted by the ovaries. Progesterone is sometimes called the "hormone of pregnancy", and it has many roles relating to the development of the fetus: Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation. At the same time, progesterone affects the vaginal epithelium (epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body) and cervical mucus, making the mucus thick and impermeable to sperm. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to menstruation. Normal menstrual bleeding is progesterone withdrawal bleeding. During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy. Progesterone decreases contractility of the uterine smooth muscle In addition progesterone inhibits lactation during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production. A drop in progesterone levels is possibly one step that facilitates the onset of labor.
Phase I: Menstruation and the Follicular phase:
The first day of menstrual bleeding is considered day 1 of the menstrual cycle.
Menstruation marks the beginning of the follicular phase of the cycle.
The endometrium (innermost lining of the uterus) is sloughed off in response to withdrawal of progesterone
Development of a new follicle with renewal of the endometrial lining
At the beginning of menstruation, concentrations of estradiol, progesterone and LH reach their lowest point.
This causes the levels of FSH to increase because usually, higher levels of the above hormones, cause the pituitary gland to secrete less FSH.
So: FSH is increased at the beginning of menstruation. This increase begins about 2 days before onset of menstruatiuon and is involved in the maturation of another group of ovarian follicles with selection of a dominant follicle for ovulation in the next cycle. It also stimulates the granulosa cells which surround the individual egg (oocyte) to increase in number and secrete estradiol.
Estradiol begins to rise by day 4.
Stimulates LH receptors on theca cells to increase their secretion of androgen precursors even more, so that the granulosa cells can continue to make more estradiol. This increase in estradiol causes the pituitary gland to secrete less FSH and also tells the pituitary gland to secrete more LH
*** NOTE: as the follicles enlarge, they secrete both androgens and estrogens. However, if the estradiol:androgen ratio is less than 1, the follicle shrinks and never becomes dominant. The dominant follicle is the one that has follicular fluid estradiol:androgen ratio of more than 1
This is why the levels of FSH, estradiol, testosterone and LH, are checked around the 3rd day of the cycle when testing a woman's fertility status.
Phase II: Ovulation:
As the dominant follicle secretes more and more estradiol, there is more stimulation of the pituitary gland to secrete more and more LH.
by Day 11 to 13- LH surge occurs which triggers ovulation within 30-36hrs after that. The oocyte is expelled from the follicle and the follicle is converted into the corpus luteum to facilitate progesterone production during the remainder of the cycle.
*** it is this LH surge that is detected in home ovulation tests
A woman is most fertile within 24-48 hours after this LH surge.
Phase III: Luteal phase:
Characterized by a change in secretion of sex steriod hormones from estradiol predominance to progesterone predominance. Now that there is a lot of LH, that LH stimulates the granulosa cells and theca cells to produce progesterone now, instead of estradiol. Production of progesterone begins about 24hrs before ovulation and rises rapidly thereafter, with max production 3 to4 days after ovulation and is maintained for about 11 days post ovulation. If fertilization and implantation do not occur, progesterone diminshes rapidly, initiating the events leading to the beginning of a new cycle.
**** adequate progesterone is necessary to facilitate implantation of the fertilized oocyte into the endometrium and to sustain pregnancy into the early first trimester
If initial rise in FSH is inadequate and if the LH surge does not achieve max amplitude, an "inadequate luteal phase" can occur, resulting in progesterone production that is inadequate to facilitate implantation of a fertilized oocyte or to sustain pregnancy.
Corpus Luteum
measures about 2.5cm wide and has a characteristic deep yellow color. As it fails, it decreases in volume and loses its yellow color. After a few months, it becomes a white fibrous streak within the ovary and is called the corpus albicans Has a fixed life span of 13-14 days unless pregnancy occurs. If oocyte is fertilized and implants within the endometrium, the early pregnancy begins secreting hCG- human chorionic gonadotropin, which sustains the corpus luteum for another 6-7wks.
*** hCG is the hormone that home pregnancy tests look for
Progesterone causes the pituitary gland to decrease the secretion of both FSH and LH, so, during the luteal phase, both FSH and LH are suppressed to low levels.
As corpus luteum fails and progesterone secretion diminishes, FSH begins to rise to prepare a woman for the next reproductive cycle.
Note, that as all of these changes are occuring in the ovaries, drastic corresponding changes are occuring in the vagina, endometrium and cervix as well. These changes serve to facilitate either menstruation or fertilization and implantation depending on which stage of the cycle it is.
So:
Menstruation is governed by FSH and estradiol
Ovulation is governed by LH
Luteal phase/pregnancy is governed by progesterone
Obstetrics and Gynecology 5th edition, Charles R.B. Beckmann and co-authors.
Thanks, Dr D. You're awesome, this is great.
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