Endocrinology of the menstrual cycle

• Pituitary gland

  • pea size (1 cm^2)
  • weight 1 g
  • two lobes (anterior and posterior)
  • connects to the hypothalamus via the pituitary stalk
• Menstrual Cycle: Recurring cycle of events in uterus and ovaries under the influence of hormones in females
• Anatomy of Ovary

  A) Preantral follicle

  B) Antral follicle

  C) Mature follicle

  D) Primordial follicle

  E) Corpus luteum

  
• • ovaries are made of many sac like structures called ovarian follicles
  • ovarian follicles contain oocyte and cells that produce oestrogen and progesterone
  • thecal cells and granulosa cells produce oestrogen and progesterone when stimulated with FSH and LH
• Development of Ovarian Follicles

  A) Primordial

  B) Primary

  C) Secondary

  D) Graafian

  E) Ovulation

  
• Changes in ovaries

  • follicular phase
  • ovulation
  • luteal phase
• Changes in uterus

  • menstrual phase
  • proliferation phase
  • secretory phase
• Early Follicular Phase (pre-ovulation) - low levels of oestrogen mean little negative feedback on anterior pituitary and hypothalamus, therefore increased production of LH. Inhibin released by ovaries leads to negative feedback and decreased production of FSH.
• Late follicular phase (just before ovulation) - High levels of oestrogen from mature follicle in ovary have positive feedback on the hypothalamus and the anterior pituitary. This leads to a surge in FSH and LH levels. Inhibin has negative effect on FSH so the spike is not as high.
• LH Surge

  • restarts meiosis in the oocyte which becomes haploid
  • activates enzymes - dissolve follicle wall and promote vascular leakage so that antrum swells and bulges
  • follicle ruptures
  • ovulation
  • oestrogen production dives
• Corpus luteum is the source of oestrogen and progesterone in luteal phase. Progesterone

  • inhibits FSH and LH, stopping further follicle development and ovulation in current cycle
  • prepares uterus for pregnancy (should fertilisation occur)
• Luteal phase (after ovulation) - high levels of progesterone from corpus luteum have negative feedback effects on hypothalamus and anterior pituitary. Moderate levels of oestrogen have positive feedback on hypothalamus and anterior pituitary. This leads to an overall gradual decrease in FSH and LH.
• If fertilisation does not occur

  • corpus luteum degenerates spontaneously
  • progesterone falls
  • uterus loses its endocrine support
  • menstruation
  • FSH and LH work on follicles

  If fertilisation does occur

  • corpus luteum maintained by hCG from the chorion
  • becomes the corpus luteum of pregnancy
  • maintains uterine lining until placenta takes over as main producer of progesterone at 3 months
• Oestrogen

  • promotes growth of endometrium and myometrium
  • promotes formation of progesterone receptors
• Progesterone acts on the oestrogen-primed endometrium

  • loosens and softens connective tissue - makes implementation easier
  • promotes secretion of nutrients (glycogen)
  • quietens uterine activity
• Without fertilisation

  • no hCG so corpus luteum degenerates
  • progesterone (and oestrogen) support lost
  • uterine prostaglandins -> vasoconstriction -> tissue death
  • blood and endometrial debris (menses) lost through vagina
• Dysmenorrhoea - painful periods
• Menorrhagia - heavy or prolonged periods
• amenorrhoea - absence of periods (primary or secondary)
• oligomenorrhoea - light periods
• Mechanism of action of combined contraceptive pill

  • low dose of oestrogen
  • decreased FSH from anterior pituitary
  • decreased development of follicle
  • no ovulation
  • progestogens
  • makes cervical mucus sperm-unfriendly
  • decreased LH from anterior pituitary
  • decreased GnRH from hypothalamus
  • decreased motility of fallopian tube
• Progestogen-only pill

  • low dose progestogen taken continuously (either norethisterone or levonorgestrel)
  • makes cervical mucus inhospitable to sperm
  • hinders implantation through its effect on the endometrium and on the motility and secretions of the fallopian tubes
  • menstruation often ceases initially but usually returns with prolonged use
  • main adverse effects: breakthrough bleeding and irregular menses
• Name the hormones involved in regulation of menstrual cycle

  Oestrogen, progesterone, FSH and LH
• The early follicular phase (or pre-ovulation phase) is controlled by negative feedback by oestrogen. True or false?


  True
• What is the significance of positive feedback by high concentration of oestrogen during late follicular phase or just before ovulation?

  LH (and FSH) surge triggers ovulation.
• What causes the LH peak at the middle of the cycle and what is the role of LH in ovulation?

  Cause: High levels of oestrogen have positive feedback effect on anterior pituitary leading to LH surge

  Role: Follicle ruptures and mature oocyte is assisted to fallopian tube (ovulation is triggered)
• During luteal phase, there is moderate amount of oestrogen exerting positive feedback on HPA and high amount of progesterone exerting negative feedback on HPA. However, the negative feedback by progesterone dominates and reduces the production of FSH and LH by pituitary gland. Explain why it is important to keep FSH and LH low at this stage of the menstrual cycle by progesterone?

  Prevents premature ovulation, maintains corpus luteum and regulates the menstrual cycle
• A 17 year old girl visits the paediatrician because of 8 month absence of period. Physical examination shows a well-toned female athlete with minimal subcutaneous body fat, BMI 17. Pregnancy test: negative, radiography: normal hypothalamus and pituitary, LH low, prolactin normal. GnRH stimulates the release of both FSH and LH. What is the explanation for absence of periods?

  Hypothalamic suppression due to being underweight. Low GnRH leads to low LH, and dysregulation of periods.