Menstrual Cycle

The menstrual cycle is primarily controlled by the hypothalamus-pituitary axis in the brain.
Various hormonal secretions influence the cycle:
- Gonadotrophic hormones: Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) produced by the anterior pituitary gland
  - Related to hypothalamus-pituitary axis in the brain
- Ovarian hormones: Estrogen, Progesterone, and Inhibin
  - Related to ovarian follicles within the ovary

If fertilization does not occur, the corpus luteum transforms into corpus albicans

The corpus luteum is a yellowish endocrine structure in the ovary formed from the merging of follicular thecal cells and granulosa cells → these transform into luteal cells after oocyte discharge
- Process known as luteinization
- It regresses into corpus albicans if no fertilization occurs, and stops producing estrogen and progesterone
- decrease in estrogen and progesterone levels allows the hypothalamus to resume its production of gonadotropin-releasing hormone (GnRH) → causing the release of LH and FSH by the anterior pituitary gland

Endometrial cycle - 3 phases
- Menstrual phase (menses)
- Proliferative phase
- Secretory phase

First half of the menstrual cycle (average 14 days of a 28-day cycle):
- Marked by a decline in 3 hormone levels post-ovulation, (no fertilization occurs)
  - Progesterone (by granulosa cells)
  - Estrogen & Inhibin (by corpus luteum)
Ovarian cycle begins at the start of the follicular phase - if fertilization has not occurred from previous cycle -
- Regression of corpus luteum
- Decrease in estrogen and progesterone production
- Removal of inhibition for the production of GnRH by the decrease in estrogen and progesterone levels
- Resuming FSH production and increasing FSH levels in the late luteal phase
- FSH is essential for the recruitment and development of ovarian follicles

Granulosa folliculi → under influence of FSH
Theca folliculi → under the influence of LH
- Granulosa and theca folliculi of the recruited follicles begin steroid hormone production:
  - Granulosa cells increase estrogen production
  - Androgens synthesized by theca cells diffuse into granulosa cells and are converted to estrogen by aromatase
  - LH stimulates the theca cells to synthesize and secrete progesterone and testosterone

Elevated estrogen levels initially exert negative feedback on FSH and LH secretion by the anterior pituitary gland:
- Decreased FSH levels prevent the development of another cohort of ovarian follicles in the same cycle
- This also causes a slight drop in estrogen production
- Decrease in FSH prevents recruitment and development of another cohort of ovarian follicles within the same cycle
Estrogen levels steadily rise due to granulosa cell proliferation
High estrogen stimulates additional estrogen production via positive feedback:
- Estrogen production normally requires FSH
- Estrogen usually exerts negative feedback on the release of FSH
  - Effects of estrogen on the hypothalamus and pituitary switch from negative to positive feedback, causing a surge in LH levels and a small increase in FSH before ovulation

During the late follicular phase:
- With a surge of estrogen, the endometrium undergoes rapid growth/maturation - known as proliferative phase of the endometrial cycle
- Granulosa cells secrete inhibin, progesterone, and estrogen → effectively regulating FSH and LH levels
- Adequate levels of LH, FSH, and estrogen are necessary for progesterone production by granulosa cells

High estrogen for a minimum of 2 days → positive feedback for the production of GnRH and LH
- GnRH induces more FSH and LH production by the anterior pituitary
- High estrogen levels condition the hypothalamus.
- Rising progesterone levels increase LH production due to positive feedback mechanisms
  - Known as LH surge

High estrogen at late follicular phase stimulates growth of endometrium (3-4mm in thickness) - preparing the uterus for possible pregnancy
- Estrogen also induces mucous glands of the cervix to produce watery mucous to facilitate sperm entry
- LH surge causes primary oocyte to complete first meiotic division after ovulation

The LH surge results in:
- Mature follicle secretes collagenase
- Collagenase dissolves collagen enclosing the follicle
- Break-down products of collagen induce inflammatory response
- Inflammatory response attracts leukocytes that secrete prostaglandins

Prostaglandins cause outer theca layer of follicle to contract → rupturing the follicular wall
Antral fluid together with secondary oocyte spurts
Oocyte is then expelled into peritoneal cavity
Oocyte is then swept into Fallopian tube
- Oocyte is either fertilized and turned into a zygote or dies

Inhibin secretion increases under the influence in FSH and estrogen just prior to ovulation
Inhibin decreases GnRH release post-ovulation → reduced levels of LH and FSH:
- Subsequently, the level of LH & FSH starts decreasing after ovulation
The second half of the menstrual cycle follows:
- Aka the luteal phase
- After ovum release, the follicle transforms into corpus luteum
  - Follicular cells remain as granulosa cells
  - Theca cells transform into luteal cells and begin secreting progesterone

Produces estrogen and inhibin
Progesterone and estrogen together stimulate further endometrial growth
The increasing levels of estrogen, inhibin, and progesterone suppress the hypothalamic-pituitary system
- Resulting a drop in LH and FSH secretion after ovulation

Drop in LH impacts the corpus luteum’s ability to produce estrogen and progesterone causing:

Drop in estrogen and progesterone levels, diminishes the negative feedback on the hypothalamic-pituitary axis: