Ovarian Changes During the Menstrual Cycle

Overview

1. Follicular phase - Days 1-14 (variable, 10-14 days)
2. Luteal phase - Days 14-28 (fixed, ~14 days)

Diagram 1: HPO Axis - Hormonal Control Flowchart

Diagram 2: Ovarian & Endometrial Cycle Timeline

Diagram 3: Complete Hormonal Changes During the Menstrual Cycle

Diagram 4: Integrated Menstrual Cycle Diagram

Phase 1: Follicular Phase (Days 1-14)

Sub-phases and Follicle Development

Follicle Developmental Stages

Hormonal Events in the Follicular Phase

Day 1:  FSH rises (corpus luteum has degenerated; estrogen + progesterone fall)
        ↓
Days 1-8: FSH stimulates granulosa & theca cells
          Granulosa: aromatase activity (androgens → estrogens)
          Theca: LH stimulates androgen synthesis
        ↓
Days 8-12: Rising estradiol → NEGATIVE FEEDBACK on FSH
           Inhibin B from granulosa cells also suppresses FSH
           LH initially falls (negative feedback)
        ↓
Days 12-13: Estradiol peaks (sustained high levels > 200 pg/mL for 48-50 hours)
            → POSITIVE FEEDBACK on LH → LH SURGE triggered
            → FSH also surges (smaller peak)
        ↓
Day 13-14: LH surge induces resumption of meiosis I in oocyte
           → Secondary oocyte formed (arrested in meiosis II metaphase)

• Negative feedback: Low-moderate estradiol + inhibin B suppress FSH and LH
• Positive feedback: High sustained estradiol (>200 pg/mL for 36-48h) triggers the LH surge - unique reversal of the usual inhibitory action

The LH Surge and Ovulation (Day 14)

• 34-36 hours after the START of the LH surge
• 10-12 hours after the PEAK of the LH surge

Events at Ovulation

1. The LH surge activates protease enzymes (collagenase, plasminogen activator) in the follicle wall
2. The follicle wall thins, and stigma (avascular spot) forms at the surface
3. The Graafian follicle ruptures
4. The secondary oocyte (with its corona radiata) is expelled into the peritoneal cavity and swept into the fallopian tube
5. Prostaglandins and oxytocin assist in follicular rupture via smooth muscle contraction

Phase 2: Luteal Phase (Days 14-28)

Corpus Luteum Formation (Luteinization)

• Blood vessels invade the previously avascular granulosa layer (vascularization is essential for LDL cholesterol delivery)
• LDL cholesterol is the main substrate for steroid synthesis in the corpus luteum
• The corpus luteum becomes the primary source of progesterone in the luteal phase

Hormonal Events in the Luteal Phase

Day 14 (Ovulation): LH surge ends; corpus luteum forms
        ↓
Days 14-21: Progesterone rises sharply (peak ~8-10 ng/mL at day 21)
            Estradiol rises again (second peak - from corpus luteum)
            Inhibin A secreted by corpus luteum
            → Together suppress FSH and LH (prevent new follicle recruitment)
        ↓
Days 21-26: If NO fertilization:
            Corpus luteum begins to degenerate (luteolysis)
            Progesterone and estradiol fall
        ↓
Day 26-28: Hormones reach nadir
           FSH begins to rise (negative feedback removed)
           Next cycle recruited
        ↓
Day 28/0: Menses begins

Corpus Luteum of Menstruation vs. Pregnancy

Summary Flowchart: Ovarian Cycle

MENSTRUATION (Day 1)
       |
       ↓ [FSH rises as CL degenerates]
PRIMORDIAL → PRIMARY → SECONDARY FOLLICLE
       |
       ↓ [FSH + LH stimulate follicle growth, Days 1-12]
DOMINANT FOLLICLE SELECTED (Days 5-7)
       |
       ↓ [Estradiol rises; negative feedback suppresses FSH]
GRAAFIAN FOLLICLE forms (Days 12-14)
       |
       ↓ [Estradiol peaks → POSITIVE FEEDBACK → LH SURGE]
OVULATION (Day 14) - Secondary oocyte released
       |
       ↓ [Luteinization of ruptured follicle]
CORPUS LUTEUM forms
       |
    ___|___
   |       |
NO fertilization   Fertilization
   |                   |
Luteolysis         hCG maintains CL
(Day 24-26)        → Corpus luteum of pregnancy
   |
Corpus albicans
   |
Menses → Cycle repeats

Key Points Summary

1. Follicular phase (Days 1-14): Variable duration; FSH drives follicle recruitment and selection; rising estradiol eventually triggers LH surge via positive feedback.
2. Ovulation (Day ~14): LH surge causes follicle rupture 34-36 hours later; a secondary oocyte arrested in metaphase II is released.
3. Luteal phase (Days 14-28): Fixed 14-day duration; corpus luteum secretes progesterone + estrogen; if no fertilization, luteolysis occurs and the cycle restarts.
4. Corpus albicans: The remnant scar left by a degenerated corpus luteum; accumulates over a woman's reproductive life.
5. The two-cell, two-gonadotropin theory: LH stimulates theca cells (androgens) and FSH stimulates granulosa cells (aromatase: converts androgens to estrogens) - the basis of follicular estrogen production.
6. Inhibins and activins: Inhibin B (follicular phase) and inhibin A (luteal phase) selectively suppress FSH; activins stimulate FSH - fine-tuning gonadotropin secretion throughout the cycle.