Explain the menstrual cycle with hormonal changes and diagram

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The Menstrual Cycle: Hormonal Changes and Phases

Diagram

Menstrual cycle - hormonal fluctuations, ovarian and endometrial histology across 28 days

The diagram shows body temperature, FSH, LH, estradiol, and progesterone curves across days 1-28, alongside ovarian follicle development (top) and endometrial thickness changes (bottom). - Rosen's Emergency Medicine

Overview

The menstrual cycle averages 28 days (range: 21-35 days) and is a coordinated interaction among the hypothalamus, anterior pituitary, ovary, and uterus. By convention, Day 1 is the first day of menstrual bleeding. The cycle is divided into two major phases:

Follicular phase (Days 1-14): also called the proliferative phase
Luteal phase (Days 14-28): also called the secretory phase

Level 1: Hypothalamic Control - GnRH

The entire cycle is driven by GnRH (gonadotropin-releasing hormone), a decapeptide produced by neurons in the arcuate nucleus of the hypothalamus. GnRH must be released in a pulsatile fashion - continuous infusion causes downregulation of pituitary GnRH receptors and suppresses gonadotropins (this is the principle behind GnRH agonist therapy).

Follicular phase: frequent, small-amplitude GnRH pulses → favors LH secretion
Late follicular phase: increased pulse frequency and amplitude
Luteal phase: longer intervals between pulses, higher amplitude → favors FSH secretion

GnRH has a very short half-life (2-4 minutes) due to rapid proteolytic cleavage. - Berek & Novak's Gynecology, p. 270

Phase 1: Follicular Phase (Days 1-14)

Menstruation (Days 1-5)

At the start of the cycle, estrogen and progesterone levels are at their nadir. The withdrawal of hormonal support causes:

Vasospasm of the spiral arteries (mediated by prostaglandin F2α)
Necrosis and shedding of the stratum functionale of the endometrium
Menstrual bleeding (approximately 50-80 mL blood loss)

The stratum basale (supplied by short, straight basilar arteries) is preserved and serves as the regenerative layer.

Follicle Recruitment and Growth (Days 1-13)

At the start of each cycle, FSH rises slightly (due to low estrogen/progesterone feedback from the previous cycle)
FSH stimulates several primordial follicles to enlarge and develop an antrum (cavity filled with follicular fluid)
By Day 6, one dominant follicle is selected - the one best able to produce intrafollicular estrogen for final maturation
The theca interna cells of the follicle produce androgens, which are aromatized to estrogen (17β-estradiol) by the granulosa cells (the two-cell theory)
Rising estradiol exerts negative feedback on FSH, causing FSH to fall, which leads to atresia of all non-dominant follicles

Endometrial Changes (Proliferative Phase)

Estradiol stimulates:

Rapid growth of the endometrium (Days 5-14)
Lengthening and straightening of uterine glands (not yet secretory)
Elongation of spiral arteries
Cervical mucus becomes copious, watery, elastic, and shows "ferning" on a glass slide - channels in the mucus help sperm penetrate the cervix

The LH Surge and Ovulation (Day 14)

As the dominant follicle matures, estradiol rises to a critical threshold (~200 pg/mL sustained for ~50 hours). This triggers a switch from negative to positive feedback, producing the massive LH surge (and a smaller FSH surge). This is the most dramatic hormonal event of the cycle.

The LH surge triggers resumption of meiosis I in the oocyte (previously arrested in prophase I since fetal life)
The follicle ruptures approximately 36 hours after the LH surge peak
The secondary oocyte is released and picked up by the fimbriated ends of the fallopian tube
The secondary oocyte immediately begins meiosis II, but arrests again at metaphase II - it only completes meiosis II if fertilized by a sperm

Minor intraperitoneal bleeding at ovulation may cause brief lower abdominal pain known as Mittelschmerz ("middle pain"). - Ganong's Review of Medical Physiology, 26e, p. 404

Phase 2: Luteal Phase (Days 14-28)

Corpus Luteum Formation

After ovulation, the ruptured follicle fills with blood (corpus hemorrhagicum), then the granulosa and theca cells luteinize under continued LH stimulation, becoming the corpus luteum (yellow body, rich in lipid-laden luteal cells). VEGF drives its vascularization.

The corpus luteum secretes both estrogen and progesterone in large amounts.

Hormonal Profile

Hormone	Level	Effect
Progesterone	Rises sharply, peaks ~Day 21	Dominant hormone of luteal phase
Estradiol	Second smaller peak	Supports endometrium
LH & FSH	Suppressed by negative feedback	Fall to basal levels
Inhibin A	Rises	Selectively suppresses FSH

Endometrial Changes (Secretory Phase)

Under progesterone + estrogen:

Endometrial proliferation slows; thickness decreases slightly
Uterine glands become tortuous and coiled, accumulate glycogen in vacuoles, and increase mucus secretion
Stroma becomes edematous
Spiral arteries elongate and become coiled, ready for implantation
Cervical mucus becomes thick, scant, non-elastic - does not fern (sperm penetration is no longer needed)

Progesterone also has a thermogenic effect - basal body temperature rises by ~0.2-0.5°C in the luteal phase (the basis of the rhythm method for contraception). - Costanzo Physiology 7e, p. 479

Luteal Regression (Without Pregnancy)

If fertilization does not occur:

The corpus luteum degenerates around Day 24-26 (luteolysis)
Estrogen and progesterone levels fall sharply
Loss of hormonal support causes endometrial ischemia and necrosis
The cycle restarts on Day 1 (next menstruation)

If Pregnancy Occurs

The trophoblast of the implanting embryo secretes hCG (human chorionic gonadotropin) by Day 8-10, which rescues the corpus luteum from degeneration. The corpus luteum continues producing progesterone to maintain the endometrium until the placenta takes over at ~8-10 weeks (luteo-placental shift).

Hormone Summary Table

Phase	Days	Dominant Hormone	FSH	LH	Estradiol	Progesterone
Menstruation	1-5	-	Low-rising	Low	Low	Low
Early follicular	1-7	FSH	Rising	Low	Rising	Low
Late follicular	8-13	Estradiol	Falling	Low	Peak (1st)	Low
Ovulation	14	LH surge	Small surge	Massive surge	Slight drop	Low
Early luteal	15-20	Progesterone	Suppressed	Falling	Rising (2nd peak)	Rising
Mid-luteal	21-23	Progesterone	Low	Low	2nd peak	Peak
Late luteal	24-28	-	Rising (for next cycle)	Low	Falling	Falling

Feedback Mechanisms

Signal	Effect on Pituitary	Timing
Low estrogen	Negative feedback - allows FSH rise	Menstruation / early follicular
High estrogen (sustained)	Positive feedback - triggers LH surge	Late follicular (Day 13)
Progesterone + estrogen	Negative feedback - suppresses FSH & LH	Luteal phase
Inhibin B (from granulosa cells)	Selectively suppresses FSH	Follicular phase
Inhibin A (from corpus luteum)	Selectively suppresses FSH	Luteal phase

Clinical Correlations

Anovulatory cycles: No LH surge, no corpus luteum, no progesterone rise - common at menarche and perimenopause; causes irregular or heavy bleeding
GnRH agonists: Continuous administration desensitizes the pituitary, suppressing gonadotropins - used in endometriosis, fibroids, IVF protocols
Clomiphene: Blocks estrogen receptors at the hypothalamus, preventing negative feedback, leading to increased FSH release and follicular recruitment - used for ovulation induction
Basal body temperature charting: Rise in BBT confirms ovulation (progesterone thermogenic effect)
Cervical mucus monitoring: Spinnbarkeit (elasticity) peaks at ovulation

Sources:

Berek & Novak's Gynecology, Chapter 7 (Menstrual Cycle Physiology), pp. 264-270
Ganong's Review of Medical Physiology, 26th Edition, Chapter 22, pp. 404-406
Costanzo Physiology, 7th Edition, p. 479

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