Normal Menstrual Physiology

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.

⭐ 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).

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

• 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.