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.