Chapter 28 Reproductive System: Menstruation & Menopause 04

Menstrual Cycle Overview

• Typical length: $18$ – $40$ days, average $28$ days.
• Comprises two inter-linked cycles working in parallel:
  • Ovarian cycle (events inside the ovary)
  • Uterine cycle (changes in the endometrium)
• Six named phases in chronological order:
  1. Menses (Uterine,
     Day\ 1\ –\ 5)
  2. Follicular phase (Ovarian,
     Day\ 5\ –\ 13)
  3. Proliferative phase (Uterine,
     Day\ 5\ –\ 13)
  4. Ovulation (Ovarian,
     Day\ 14)
  5. Luteal phase (Ovarian,
     Day\ 14\ –\ 28)
  6. Secretory phase (Uterine,
     Day\ 14\ –\ 28)

Menses (Uterine,

Day\ 1\ –\ 5)

• Sharp ↓ in progesterone causes constriction of spiral arteries → ischemia & sloughing of functional endometrium.
• Hormone milieu at onset:
  • ↓ FSH, ↓ LH, ↓ estrogen, markedly ↓ progesterone.
• Blood & tissue loss = menstrual bleeding.

Follicular Phase (Ovarian,

Day\ 5\ –\ 13)

• Trigger: ↑ GnRH (hypothalamus) → ↑ FSH & LH (anterior pituitary).
• FSH surge → cohort (~$25$) of primordial follicles begin maturation; most undergo atresia.
• Hormonal cascade:
  • Granulosa cells secrete ↑ estrogen.
  • Rising estrogen induces an LH surge (+ feedback) and small androgen/progesterone rise.
• Cytological milestone: primary oocyte ($1^\circ$) completes Meiosis I → secondary oocyte ($2^\circ$) + first polar body.

Proliferative Phase (Uterine,

Day\ 5\ –\ 13)

• Driven mainly by ↑ estrogen (ovary).
• Events:
  • Rapid regeneration of endometrial functional layer.
  • Growth of glands & spiral arteries.
  • ↑ mitosis in stromal cells → thickness restored.
• Endocrine context: simultaneous rapid ↑ FSH & LH culminates in the pre-ovulatory surge.

Ovulation (Ovarian,

Day\ 14)

• Peak estrogen levels from dominant follicle → massive LH surge.
• LH surge effects:
  • Completion of Meiosis I in $1^\circ$ oocyte.
  • Proteolytic enzymes & prostaglandins weaken follicular wall.
  • Rupture of mature (Graafian) follicle → $2^\circ$ oocyte expelled into peritoneal cavity.
• $2^\circ$ oocyte arrests at Metaphase II until fertilization.
• Peak FSH simultaneously recruits new follicles (most enter atresia).
• Occurs ~every $28$ days; body temperature often rises slightly post-ovulation (basis of BBT charts).

Luteal Phase (Ovarian,

Day\ 14\ –\ 28)

• Granulosa & theca cells luteinize → corpus luteum (CL).
• CL secretes high progesterone + moderate estrogen, which:
  • Exert negative feedback on hypothalamus/pituitary → ↓ GnRH, ↓ FSH, ↓ LH (prevents new ovulations).
• Two possible outcomes:
  1. Fertilization (within $24$ h of ovulation):
  • Trophoblast secretes hCG ≈ $8$ days post-fertilization.
  • hCG rescues CL → sustained ↑ progesterone/estrogen.
  • Maintains thick secretory endometrium; menses suppressed.
  1. No fertilization:
  • CL remains functional only $10$ – $12$ days.
  • CL involutes → corpus albicans → sharp ↓ progesterone & estrogen.
  • Loss of hormonal support initiates next menses.

Secretory Phase (Uterine,

Day\ 14\ –\ 28)

• Dominant hormone: progesterone from CL (estrogen secondary).
• Endometrial changes:
  • Further thickening via stromal edema & glycogen-rich secretions.
  • Coiled (spiral) glands enlarge → nutrient-laden uterine fluid (uterine milk).
• FSH & LH remain low.
• If implantation fails, falling progesterone → endometrial ischemia begins late in this phase.

Hormonal Regulation & Feedback Loops (Fig. $28.20$ & $28.19$)

• Hypothalamic GnRH pulses drive pituitary FSH & LH release.
• Positive feedback: Rising estrogen during late follicular phase enhances GnRH sensitivity → LH/FSH surges.
• Negative feedback:
  • Progesterone (luteal) inhibits GnRH, FSH, LH.
  • Moderately high estrogen outside the surge window also exerts inhibition.
• Overall sequence:
  1. ↑ FSH → follicle growth → ↑ estrogen.
  2. ↑ estrogen (threshold) → LH surge → ovulation.
  3. CL → ↑ progesterone/estrogen → endometrial hypertrophy & pituitary inhibition.
  4. CL demise → ↓ hormones → menses → cycle restarts.

Aging & the Female Reproductive System

• Progressive ↓ fertility beginning mid-$30$s (reduced ovarian reserve & oocyte quality).
• Decreased sexual desire often reported.
• Cancer incidence:
  • Breast cancer risk peaks $45$ – $65$ y.
  • Uterine & cervical cancer risk highest $50$ – $65$ y.

Menopause & Perimenopause

• Definition: permanent cessation of menses after $12$ consecutive months without bleeding; average age ≈ $50$ y.
• Perimenopause (“female climacteric”): transitional $40$ – $50$ y window with irregular cycles.
• Endocrine shifts:
  • Follicles become less sensitive to FSH/LH → ↓ mature follicles & corpus lutea.
  • Gradual ↓ estrogen & progesterone.
  • Resulting vasomotor instability → "hot flashes".
• Hormone Replacement Therapy (HRT): combined estrogen ± progesterone can alleviate symptoms but may ↑ risks (breast/uterine cancers, myocardial infarction, stroke, thromboembolism).

Post-Menopausal Physiological Changes

• Reproductive tract:
  • ↓ uterine size & endometrial atrophy.
  • Vaginal epithelium: ↓ thickness, ↓ secretions → ↑ infections; ↓ elasticity → ↓ contractility during intercourse; ↑ pH.
• Skin: ↓ epidermal thickness, altered collagen; paradoxical ↑ melanin synthesis (hyperpigmentation in some areas).
• Cardiovascular: ↑ prevalence of hypertension & atherosclerosis attributed partly to lost estrogenic protection.

Key Clinical & Real-World Connections

• Tracking basal body temperature & cervical mucus assists ovulation prediction for fertility or contraception.
• Oral contraceptives mimic elevated luteal hormones → suppress GnRH/FSH/LH, preventing ovulation.
• hCG detection forms the basis of home pregnancy tests; sensitivity ~$25$ mIU/mL ≈ $8$ – $10$ days post-fertilization.
• Disorders of cycle regularity (e.g., PCOS) often involve altered GnRH pulse frequency and insulin resistance.
• Understanding ischemic mechanism of menses underlies NSAID use for dysmenorrhea (↓ prostaglandins).