Normal Menstrual Physiology

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Menstrual Cycle: Definitions & Phases - Cycle Rhythms

  • Normal Menstrual Cycle (Eumenorrhea):
    • Interval: 21-35 days (average 28 days).
    • Duration of flow: 2-7 days (average 4-5 days).
    • Volume of blood loss: 20-80 mL (average 35 mL). >80 mL is menorrhagia.
  • Cycle Phases (Interlinked):
    • Ovarian Cycle:
      • Follicular Phase (variable): Follicle growth, estrogen ↑.
      • Ovulation: LH surge, oocyte release (Day 14 in 28-day cycle).
      • Luteal Phase (fixed 14 days): Corpus luteum, progesterone ↑.
    • Uterine (Endometrial) Cycle:
      • Menstrual Phase: Endometrial shedding.
      • Proliferative Phase: Endometrial regrowth (estrogen-driven).
      • Secretory Phase: Endometrial maturation (progesterone-driven).
  • Rhythm: Infradian (cycle >24h), orchestrated by HPO axis. Ovarian and Uterine Cycles with Hormone Levels

⭐ The luteal phase is consistently 14 days; variations in cycle length are primarily due to follicular phase duration.

HPO Axis: Regulation & Feedback - Brain-Ovary Chat

  • Orchestration: Hypothalamus-Pituitary-Ovarian (HPO) axis governs menstrual cycle.
  • Hypothalamus: Pulsatile Gonadotropin-Releasing Hormone (GnRH).
    • Slow pulses favor FSH release.
    • Fast pulses favor LH release.
  • Anterior Pituitary: GnRH stimulates secretion of:
    • FSH: Ovarian follicle growth, estrogen (E2) production.
    • LH: Ovulation, corpus luteum, progesterone (P4) production.
  • Ovarian Hormones & Feedback:
    • Estrogen (E2):
      • Low/moderate levels: Negative feedback on Hypothalamus/Pituitary (↓GnRH, ↓FSH, ↓LH).
      • Sustained high levels (pre-ovulatory): Positive feedback on Pituitary → LH surge.
    • Progesterone (P4): Negative feedback on Hypothalamus/Pituitary.
    • Inhibin (from granulosa cells): Selectively ↓FSH secretion from pituitary.
    • Activin (from granulosa cells): Stimulates ↑FSH secretion from pituitary.

⭐ LH surge (for ovulation) needs sustained high E2 (>200 pg/mL for ~48-50 hrs).

HPO axis, ovarian, endometrial, and hormonal changes

Ovarian Cycle: Folliculogenesis & Luteinization - Egg's Big Show

  • Folliculogenesis (FSH-driven):
    • Primordial follicle → Primary → Secondary → Graafian (mature) follicle.
    • Granulosa cells: convert androgens (from LH-stimulated theca cells) to estrogen (E2).
    • One dominant follicle emerges.
  • Ovulation (LH surge-triggered):
    • Caused by sustained ↑E2 from dominant follicle (positive feedback).
    • Oocyte released ~10-12 hrs post-LH peak, 24-36 hrs post-E2 peak.
    • ⭐ > The LH surge is essential for final oocyte maturation (meiosis I completion) and ovulation.
  • Luteinization (LH maintains):
    • Corpus Luteum (CL) forms from follicle remnants.
    • Produces progesterone (P4; dominant) & estrogen. P4 prepares endometrium.
    • CL lifespan: ~14 days. If no pregnancy → luteolysis (corpus albicans) → ↓P4, E2 → menses.
    • If pregnancy: hCG rescues CL.

Endometrial Cycle: Proliferation & Secretion - Monthly Makeover

Uterus H&E Secretory Phase Histology

  • Cyclical endometrial changes driven by ovarian hormones. Two main phases post-menstruation:

  • 1. Proliferative Phase (Days ~5-14; Follicular Phase)

    • Hormone: ↑ Estrogen.
    • Endometrium: Regenerates stratum functionalis; thickness ↑ to 3.5-5 mm.
    • Glands: Straight, tubular; mitoses.
    • Arteries: Spiral arteries lengthen.
  • 2. Secretory Phase (Days ~15-28; Luteal Phase)

    • Hormone: ↑ Progesterone (Estrogen present).
    • Endometrium: Thickens to 5-6 mm (up to 14 mm).
    • Glands: Tortuous ("saw-tooth"), dilated; secrete glycogen.
    • Stroma: Edematous; predecidual changes.
    • Arteries: Spiral arteries coil.
    • 📌 Progesterone = Prepares for Pregnancy.

    ⭐ Peak endometrial receptivity for implantation: days 20-24 (6-10 days post-ovulation).

  • Menstruation: If no implantation, ↓ Estrogen & Progesterone → spiral artery spasm → ischemia → shedding of stratum functionalis (superficial 2/3rds).

High‑Yield Points - ⚡ Biggest Takeaways

  • The Hypothalamic-Pituitary-Ovarian (HPA) axis orchestrates the menstrual cycle.
  • Pulsatile GnRH from hypothalamus stimulates pituitary FSH and LH.
  • FSH promotes follicular maturation and estrogen synthesis, causing endometrial proliferation.
  • A mid-cycle LH surge is the critical trigger for ovulation.
  • The corpus luteum, post-ovulation, secretes progesterone for secretory endometrium.
  • Menstruation results from progesterone withdrawal if no pregnancy.
  • Normal cycle: 21-35 days; menses: 2-7 days; blood loss: <80 mL.

Practice Questions: Normal Menstrual Physiology

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