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Female Reproductive Hormones and Menstrual Cycle

FSH and LH Actions

  • FSH (follicle stimulating hormone) stimulates follicles to grow and mature.
  • LH (luteinizing hormone) augments FSH and is responsible for ovulation and corpus luteum production.
  • Gonadotropin releasing hormone stimulates FSH and LH release from the anterior pituitary gland.

Hormone Production in Thecal and Granulosa Cells

  • LH stimulates androgen production (like DHEA) in thecal cells (in females) and testosterone production in Leydig cells (in male testis).
  • Thecal cells secrete androgens, which granulosa cells convert to estrogen via aromatization.
  • Androgens are chemically more like male hormones, but aromatase converts them into estrogens, which are typically female hormones.

Luteinizing Hormone Surge

  • A surge of LH triggers ovulation.
  • The tertiary follicle is ready to release the secondary oocyte into the cavity for fimbriae to sweep it up.
  • These events occur in one place in the ovary; the illustration of changes doesn't imply physical movement around the ovary.

Corpus Luteum

  • The corpus luteum is the main hormone producer after ovulation, producing estrogens, progesterone, relaxin, and inhibin.

Estrogens

  • There are various types of estrogens, but for simplicity, they are referred to as estrogen.
  • Pharmaceutical companies fine-tune hormone replacement therapy and birth control by mixing different estrogens.
  • Estrogen is lipid-based and made from cholesterol in the ovaries.
  • Estrogens are responsible for female breast tissue enlargement.
  • Estrogen promotes protein anabolism (protein synthesis), working with human growth hormone during pregnancy.
  • Estrogen lowers blood cholesterol, offering a protective effect against cardiovascular disease in females until menopause.
  • Estrogen stimulates the endometrium to proliferate, creating the functional layer of the uterus.

Hormone Feedback Systems

  • Negative feedback system: High levels of hormone A inhibit the release of hormone A releasing hormone; low levels stimulate its release.
  • Estrogen levels have an inhibitory effect on gonadotropin releasing hormone and the anterior pituitary gland.
  • Low estrogen levels stimulate the hypothalamus and anterior pituitary to release FSH and LH.
  • Moderately high estrogen levels exert negative feedback, reducing GnRH, FSH, and LH.
  • Inhibin, produced by follicles and the corpus luteum, provides negative feedback, inhibiting FSH and LH production.
  • High estrogen levels can create a positive feedback loop.

Progesterone

  • Progesterone is primarily produced by the corpus luteum.
  • Combined estrogen and progesterone prepare the endometrium for implantation.
  • High progesterone levels inhibit the release of gonadotropin releasing hormone, FSH, and LH.

Relaxin

  • Relaxin is initially produced by the corpus luteum and later by the placenta during pregnancy.
  • Relaxin inhibits myometrial contractions, allowing the uterus to remain still for potential implantation.
  • During pregnancy, relaxin relaxes the cervix and connective tissue, including the pubic symphysis, preparing the pelvis for childbirth.

Inhibin

  • Inhibin's main job is negative feedback, specifically inhibiting FSH.

Menstrual Cycle Phases

The main phases are:

  • Menstrual phase
  • Preovulatory phase
  • Ovulation (an event)
  • Postovulatory phase.

Menstrual Phase

  • The onset of menstruation (blood and sloughed-off endometrial lining) marks the start.
  • Lasts about five days (assuming a 28-day cycle for simplicity).
  • Progesterone and estrogen levels decline.
  • The body starts making more gonadotropin releasing hormone from the hypothalamus, resulting in increased LH and FSH.
  • FSH stimulates follicles to mature.

Uterine Changes During Menstruation

  • Declining progesterone and estrogen levels cause the endometrial lining to slough off.
  • Prostaglandins constrict spiral arterioles in the uterine lining, causing hypoxia and tissue death.
  • Prostaglandins also cause uterine contractions.
  • Prostaglandins augment pain signals, increasing sensitivity to pain.
  • Ibuprofen and Naprosyn inhibit prostaglandin production, reducing cramping and pain.
  • Prostaglandins cause constriction of spiral arterioles, leading to the sloughing off of the endometrial lining and menstrual flow.
  • The endometrium is reduced to the basal layer.

Preovulatory Phase

  • Days 6-13; most variable part of the cycle.
  • Secondary follicles mature and start making estrogens and inhibin.
  • By day 6, one follicle becomes dominant and will ovulate.
  • The dominant follicle's estrogen and inhibin production reduces FSH, preventing other follicles from maturing.
  • If more than one follicle becomes dominant, fraternal twins can occur.

Follicular Phase

  • In the ovary, the follicular phase is when follicles are the primary source of estrogen.

Uterine Changes in Preovulatory Phase

  • Estrogen thickens the endometrium, more than doubling its thickness, with glands and arterioles developing.
  • The endometrium continues to grow, and arterioles spiral and grow longer throughout the functional layer.

Ovulation

  • Estrogen at moderate levels inhibits FSH.
  • High estrogen levels stimulate the hypothalamus and anterior pituitary to release FSH and LH (positive feedback loop).
  • The surge in LH triggers ovulation about a day later.
  • The oocyte is surrounded by the zona pellucida and corona radiata.
  • High estrogen without progesterone triggers the LH spike.
  • Tests for LH (luteinizing hormone) can predict ovulation.

Postovulatory Phase

  • Most consistent phase (14 days).
  • After the tertiary follicle collapses, it transforms into the corpus luteum.
  • LH is still high and convinces the follicle to become the corpus luteum.
  • The corpus luteum produces progesterone, estrogen, inhibin, and relaxin.
  • After ovulation, the ovary is in the luteal phase because the corpus luteum is producing hormones.
  • Corpus luteum lasts about two weeks.
  • If no fertilization occurs, the corpus luteum degenerates into the corpus albicans.
  • If fertilization occurs, the corpus luteum is rescued by HCG (human chorionic gonadotropin) produced by the trophoblast.

Fertilization and HCG

  • If fertilization occurs, around the eighth day post-fertilization, the embryo (blastocyst) starts producing human chorionic gonadotropin (HCG).
  • HCG is like LH, sustaining the corpus luteum.
  • HCG rescues the corpus luteum, allowing it to continue producing hormones to maintain the pregnancy.
  • HCG is detectable in blood and urine (basis of home pregnancy tests).

Uterine Changes in Postovulatory Phase

  • The endometrium continues to grow thicker with more blood vessels, and glands start producing mucus and glycogen.
  • The endometrium is preparing for implantation, with glycogen as a source of energy.
  • This is known as the secretory phase.

Hormone Level Feedback

  • Moderate estrogen levels inhibit hormones from the hypothalamus, follicle-stimulating hormone, fluidizing gluteinizing hormone from the anterior pituitary.
  • Inhibin has a negative feedback effect on the anterior pituitary as well.
  • High estrogen levels cause a stimulating release from the hypothalamus and the anterior pituitary, thereby triggering ovulation.
  • Low levels of hormones from corpus albicans cause increased release of gonadotropin releasing hormone, follicle stimulating hormone, and luninizing hormone.

Menstrual Cycle - Hormone Level Chart

  • Low estrogen and progesterone trigger follicles to start maturing.
  • Maturing follicles produce more estrogen alone.
  • A spike in LH is the trigger for ovulation.
  • Corpus luteum is the primary progesterone and estrogen generator.
  • A drop in progesterone and estrogen is the trigger for menstruation.

Disorders

Female Athlete Triad

  • High-intensity athletes, especially in sports with weight concerns, may experience: early onset of osteoporosis, amenorrhea (lack of cycle).
  • Not enough gonadotropin releasing hormone then leads to low LH and FSH.
  • Dramatic drop in estrogen then leads to bone density loss.

Endometriosis

  • Endometrial tissue develops outside the uterus, such as in the ovaries, intestines, or pelvic cavity.
  • Ectopic endometrial tissue responds to hormone cycles, causing bleeding and pain.
  • Pregnancy can sometimes resolve endometriosis.
  • Certain birth controls can reduce the likelihood of developing endometriosis. Sometimes a hysterectomy may be the only solution.