Stages of the Menstrual Cycle

Why This Matters

The menstrual cycle is one of the most elegant examples of hormonal feedback regulation you'll encounter in anatomy and physiology. You're being tested on your ability to trace how the hypothalamic-pituitary-ovarian axis coordinates a precise sequence of events—from follicle development to ovulation to endometrial preparation—all through shifting hormone levels and feedback loops. This topic connects directly to broader course concepts like negative and positive feedback mechanisms, target tissue responses, and the interplay between the nervous and endocrine systems.

Don't just memorize that ovulation happens around day 14. Know why the LH surge triggers egg release, how estrogen switches from negative to positive feedback, and what happens to the corpus luteum when pregnancy doesn't occur. Exam questions—especially FRQs—will ask you to explain the mechanism behind each phase, predict what happens when hormones are disrupted, and compare the roles of FSH, LH, estrogen, and progesterone throughout the cycle.

---

Hormonal Control: The Hypothalamic-Pituitary-Ovarian Axis

The entire menstrual cycle is orchestrated by a three-tier hormonal command system. The hypothalamus releases GnRH, which triggers the anterior pituitary to secrete FSH and LH, which then act on the ovaries to produce estrogen and progesterone.

Gonadotropin-Releasing Hormone (GnRH)

• Released in pulses from the hypothalamus—pulse frequency and amplitude change throughout the cycle to favor either FSH or LH release
• Acts on the anterior pituitary to stimulate gonadotropin secretion; this is the master signal that initiates each cycle
• Subject to feedback regulation—estrogen and progesterone from the ovaries modulate GnRH release to fine-tune the cycle

Follicle-Stimulating Hormone (FSH)

• Dominates the follicular phase—stimulates growth of ovarian follicles and promotes estrogen production by granulosa cells
• Levels decline mid-cycle due to negative feedback from rising estrogen; this ensures only the dominant follicle continues developing
• Essential for follicle recruitment—without adequate FSH, follicles cannot mature and ovulation fails

Luteinizing Hormone (LH)

• Triggers ovulation through a dramatic mid-cycle surge; this is the most testable hormonal event of the cycle
• Stimulates corpus luteum formation—after ovulation, LH supports the ruptured follicle's transformation into a progesterone-secreting structure
• Works synergistically with FSH—LH acts on theca cells to produce androgens that granulosa cells convert to estrogen

---

The Follicular Phase: Building Toward Ovulation

This phase spans from day 1 of menstruation until ovulation. Rising FSH recruits a cohort of follicles, but increasing estrogen creates negative feedback that allows only the dominant follicle to survive.

Menstruation (Days 1-5)

• Marks cycle day 1—the shedding of the endometrial lining signals the start of a new cycle and occurs due to withdrawal of progesterone and estrogen
• Average blood loss is 30-80 mL—the functional layer of the endometrium (stratum functionalis) sloughs off while the basal layer remains intact
• Hormone levels are at their lowest—this removes negative feedback, allowing FSH to rise and recruit new follicles

Follicular Development (Days 1-13)

• FSH recruits 6-12 primordial follicles—these begin maturing, with granulosa cells proliferating and secreting estrogen
• Dominant follicle selection occurs around day 7—the follicle with the most FSH receptors produces the most estrogen, suppressing competitors through negative feedback
• Estrogen drives endometrial proliferation—the stratum functionalis regenerates and thickens from ~1 mm to ~5 mm in preparation for potential implantation

Estrogen's Dual Feedback Role

• Negative feedback at low-to-moderate levels—estrogen suppresses FSH and LH release during early-to-mid follicular phase
• Positive feedback at high sustained levels—when estrogen exceeds ~200 pg/mL for 50+ hours, it triggers the LH surge (this switch is heavily tested)
• Prepares the body for ovulation—estrogen also thins cervical mucus, making it more permeable to sperm

---

Ovulation: The Mid-Cycle Event

Ovulation is the brief but critical release of a mature oocyte. The LH surge causes enzymatic breakdown of the follicle wall and resumption of meiosis in the oocyte.

The LH Surge

• Peaks 24-36 hours before ovulation—this surge is triggered by sustained high estrogen from the dominant follicle (positive feedback)
• Causes follicular rupture—LH activates proteolytic enzymes (collagenases) that weaken the follicle wall, allowing the oocyte to escape
• Resumes meiosis I—the oocyte completes its first meiotic division, becoming a secondary oocyte arrested in metaphase II

Oocyte Release (Day 14 in a 28-Day Cycle)

• The secondary oocyte is released into the peritoneal cavity—fimbriae of the fallopian tube sweep it into the ampulla, where fertilization typically occurs
• Viability window is only 12-24 hours—if sperm are not present, the oocyte degenerates; this narrow window is clinically important for fertility
• Accompanied by physical signs—slight rise in basal body temperature (due to progesterone) and thin, stretchy cervical mucus (spinnbarkeit)

---

The Luteal Phase: Preparing for Implantation

This phase spans from ovulation to menstruation (~14 days). The corpus luteum produces progesterone, which transforms the endometrium into a secretory tissue capable of supporting an embryo.

Corpus Luteum Formation

• Forms from the ruptured follicle—granulosa and theca cells undergo luteinization, becoming large, lipid-rich cells that produce progesterone and some estrogen
• Progesterone is the dominant hormone—levels rise dramatically, stabilizing the endometrium and preventing further follicle development
• Has a fixed lifespan of ~14 days—without hCG from an implanting embryo, the corpus luteum degenerates into the corpus albicans

Secretory Endometrium

• Progesterone converts proliferative endometrium to secretory—glands become coiled and begin secreting glycogen, lipids, and proteins to nourish a potential embryo
• Endometrial thickness reaches 6-8 mm—spiral arteries develop to supply blood to the functional layer
• "Window of implantation" opens days 20-24—the endometrium is maximally receptive to blastocyst attachment during this narrow period

Corpus Luteum Regression

• Without hCG, luteolysis occurs—the corpus luteum loses LH receptor sensitivity and undergoes apoptosis
• Progesterone and estrogen levels plummet—this withdrawal causes spiral artery constriction, endometrial ischemia, and ultimately menstruation
• Removal of negative feedback restarts the cycle—falling steroid hormones allow FSH to rise again, recruiting a new cohort of follicles

---

Clinical Markers: Tracking the Cycle

Physical changes throughout the cycle provide non-invasive ways to identify fertile windows and confirm ovulation. These markers reflect the underlying hormonal environment.

Cervical Mucus Changes

• Estrogen thins mucus; progesterone thickens it—this pattern creates a predictable progression from sticky/opaque to clear/stretchy and back
• Peak fertility mucus resembles raw egg white—this "spinnbarkeit" mucus facilitates sperm transport and survival in the reproductive tract
• Post-ovulation mucus becomes hostile to sperm—progesterone creates a thick, acidic barrier that blocks sperm entry

Basal Body Temperature (BBT)

• Progesterone is thermogenic—it raises the hypothalamic set point by 0.3-0.5°C after ovulation
• BBT remains low during the follicular phase—the rise confirms ovulation has occurred (retrospectively, not predictively)
• Sustained elevation beyond 16 days suggests pregnancy—continued corpus luteum function maintains elevated BBT

---

Quick Reference Table

---

Self-Check Questions

1. Which two hormones are both produced by the anterior pituitary in response to GnRH, and how do their primary targets and functions differ?

2. Explain why estrogen has opposite effects on LH secretion during the early follicular phase versus the late follicular phase. What determines whether feedback is negative or positive?

3. Compare the corpus luteum and the dominant follicle: what structure gives rise to each, what hormones does each produce, and what determines their lifespan?

4. If a patient's BBT chart shows no temperature rise mid-cycle, what does this suggest about ovulation, and which hormone would you expect to be deficient?

5. FRQ-style: A woman's luteal phase consistently lasts only 8 days instead of the typical 14. Describe the hormonal cause, the effect on the endometrium, and why this pattern might cause infertility.