Menstrual Cycle Regulation

The menstrual cycle is the recurring sequence of ovarian and endometrial changes produced by coordinated signalling along the hypothalamic-pituitary-ovarian axis. A follicular phase of follicle growth and rising estrogen is followed by an ovulatory luteinizing hormone (LH) surge and a luteal phase dominated by progesterone; if no pregnancy occurs, falling steroids lead to menstruation and a new cycle begins.

Definition

Menstrual cycle regulation is the integrated hypothalamic-pituitary-ovarian control of the recurring follicular, ovulatory, and luteal phases, driven by gonadotropins and by estrogen and progesterone feedback, and reflected in cyclic endometrial change.

Scope

The topic covers the phases of the cycle, the feedback switch from negative to positive estrogen feedback that produces the ovulatory LH surge, the hormonal events of the follicular and luteal phases, and the corresponding endometrial changes. It is a physiology reference topic and does not provide clinical guidance.

Core questions

• What hormonal events define the follicular, ovulatory, and luteal phases?
• How does estrogen feedback switch from negative to positive to generate the LH surge?
• How do ovarian steroids drive the endometrial cycle?
• What ends the luteal phase and initiates menstruation?

Key concepts

• Follicular phase
• Ovulatory LH surge
• Luteal phase and progesterone dominance
• Negative-to-positive estrogen feedback switch
• Proliferative and secretory endometrium
• Luteolysis and menstruation

Key theories

Estrogen feedback switch driving ovulation

Through most of the cycle estrogen exerts negative feedback on gonadotropins, but sustained high estrogen from the dominant follicle switches to positive feedback, triggering the mid-cycle LH surge that causes ovulation.

Mechanisms

In the follicular phase, rising FSH supports cyclic recruitment and growth of follicles (McGee & Hsueh, 2000), and the dominant follicle secretes increasing estrogen via the two-cell, two-gonadotropin pathway (Hillier et al., 1994). Estrogen initially restrains gonadotropins by negative feedback, but once it is high and sustained, feedback switches to positive, producing the mid-cycle LH surge that triggers ovulation (Knobil, 1980; Mihm et al., 2011). The ruptured follicle luteinizes into the corpus luteum, whose progesterone defines the luteal phase and converts the proliferative endometrium to a secretory one. In the absence of pregnancy the corpus luteum regresses; estrogen and progesterone fall, the endometrium is shed as menstruation, and the loss of steroid feedback allows FSH to rise and begin the next cycle (Mihm et al., 2011).

Clinical relevance

Understanding the hormonal phases of the cycle provides the physiological basis for appreciating ovulation, fertility timing, and the cyclic endometrium. The entry is educational reference on cycle physiology; it is non-prescriptive and is not a basis for diagnosis or treatment.

History

The neuroendocrine framework of the menstrual cycle was synthesized by Knobil, who integrated pulsatile GnRH, gonadotropin secretion, and ovarian steroid feedback into a coherent account of cyclic ovulation (Knobil, 1980). Subsequent reviews consolidated the hormonal and follicular events of the normal cycle (Mihm et al., 2011).

Key figures

• Ernst Knobil
• Stephen Hillier
• Aaron Hsueh

Seminal works

• knobil-1980
• mihm-2011

Frequently asked questions

What triggers ovulation?

Sustained high estrogen from the dominant follicle switches estrogen feedback from negative to positive, producing a mid-cycle surge of LH that triggers ovulation.

Why does menstruation occur if there is no pregnancy?

Without pregnancy the corpus luteum regresses and estrogen and progesterone fall; withdrawal of this steroid support causes the secretory endometrium to be shed as menstruation.