The initial phase of the monthly menstrual cycle is known as the follicular phase. It involves the development and growth of a large antral follicle, selection of the dominant follicle, and its growth until ovulation. The dominant follicle must have a fully matured oocyte and follicle cells that produce high levels of estrogen.

The second phase of the menstrual cycle is called the luteal phase. During this phase, the corpus luteum secretes hormones, mainly progesterone and estradiol, which are essential for the progression of the normal cycle.

The late stages of follicular development, ovulation, and luteinization are regulated by the hypothalamus and pituitary gland. Similar to males, the hypothalamus releases GnRH in pulses, stimulating the production of LH and FSH by the pituitary gland. A higher frequency of GnRH pulses promotes LH production, while a slower frequency promotes FSH production. The unique aspect of the female reproductive system is the midcycle gonadotropin surge, which depends on a continuous high level of estrogen from the dominant follicle.

The interaction between the ovary, pituitary gland, and hypothalamus is a dynamic process that orchestrates the events of the menstrual cycle. It starts with the ovary at the end of the luteal phase of the previous nonfertile cycle. Subsequent events are numbered according to a specific diagram.

Event 1: If fertilization and implantation do not occur, the corpus luteum regresses and ceases to function (luteolysis). This leads to a significant decrease in progesterone, estrogen, and inhibin levels by day 24 of the menstrual cycle.

Event 2: The pituitary gland perceives the end of luteal function as a release from negative feedback. This results in an increase in FSH approximately 2 days before menstruation begins. The precise reason for the selective increase in FSH is not completely understood, but it may be related to the slow frequency of GnRH pulses during the luteal phase, which is influenced by high progesterone levels.

Event 3: The rise in FSH levels leads to the recruitment of a group of large antral follicles (2-5 mm in diameter). These follicles undergo rapid growth, which is highly dependent on gonadotropins. They produce low levels of estrogen and inhibin B.

Event 4: As estrogen and inhibin B levels slowly rise, the gonadotrope (pituitary cells that produce gonadotropins) responds by reducing FSH secretion. The absence of progesterone promotes an increase in the frequency of GnRH pulses, selectively increasing LH synthesis and secretion by the gonadotrope. As a result, the LH:FSH ratio gradually increases during the follicular phase.

Event 5: Declining FSH levels prompt the ovary to undergo follicular atresia, causing all the recruited follicles, except for the dominant follicle, to regress. The selection process is driven by the follicles' strong dependency on FSH despite declining FSH secretion. Typically, only the largest follicle with the highest number of FSH receptors and optimal blood supply can survive. This dominant follicle produces increasing amounts of estradiol-17β and inhibin B. At this stage, FSH plays a critical role in inducing the expression of LH receptors in the mural granulosa cells of the dominant follicle.
The first half of the monthly menstrual cycle is referred to as the follicular phase of the ovary and is characterized by recruitment and growth of a large antral follicle, selection of the dominant follicle, and growth of the dominant follicle until ovulation. The dominant follicle must contain a fully developed oocyte and somatic follicle cells that secrete high levels of estrogen.
The second half of the monthly menstrual cycle is referred to as the luteal phase of the ovary and is dominated by hormonal secretions of the corpus luteum. The corpus luteum must secrete both progesterone and estradiol for progression of the normal cycle.
Regulation of Late Stages of Follicular Development, Ovulation, and Luteinization: The Human Menstrual Cycle
As stated earlier, late stages of follicular development and luteal function are absolutely dependent on normal hypothalamic and pituitary function. As in the male, hypothalamic neurons secrete GnRH in a pulsatile manner. GnRH in turn stimulates LH and FSH production by pituitary gonadotropes. A high frequency of GnRH pulses (1 pulse per 60–90 minutes) selectively promotes LH production, whereas a slow frequency promotes FSH production. A major difference between the male and female reproductive axes is the midcycle gonadotropin surge, which is dependent on a constant high level of estrogen coming from the dominant follicle.
A highly dynamic “conversation” occurs among the ovary, pituitary, and hypothalamus in which the events of the menstrual cycle are orchestrated, beginning with the ovary at the end of the luteal phase of a previous nonfertile cycle (
Fig. 44.23 ). Events that follow are numbered according to
Fig. 44.24 : Event 1: In the absence of fertilization and implantation, the corpus luteum regresses and dies (called luteolysis). This leads to a dramatic decline in levels of progesterone, estrogen, and inhibin by day 24 of the menstrual cycle.
Event 2: The pituitary gonadotrope perceives the end of luteal function as a release from negative feedback (see
Fig. 44.23B , Late Luteal Phase). This leads to an increase in FSH about 2 days before the onset of menstruation. The basis for the selective increase in FSH is incompletely understood, but it may be due to the slow frequency of GnRH pulses during the luteal phase, which in turn is due to high progesterone levels.
CHAPTER 44 The Male and Female Reproductive Systems
Event 3: The rise in FSH levels recruits a crop of large (2–5 mm in diameter) antral follicles to begin rapid, highly gonadotropin-dependent growth. These follicles produce low levels of estrogen and inhibin B.
Event 4: The gonadotrope responds to the slowly rising levels of estrogen and inhibin B by decreasing FSH secretion (see
Fig. 44.23A , Early Follicular Phase). The absence of progesterone promotes an increase in the frequency of GnRH pulses, thereby selectively increasing LH synthesis and secretion by the gonadotrope. Thus the LH:FSH ratio slowly increases throughout the follicular phase.
Event 5: The ovary’s response to declining FSH levels is follicular atresia of all of the recruited follicles except for one dominant follicle (see
Fig. 44.23A , Early Follicular Phase). Thus the process of selection is driven by an extreme dependency of follicles on FSH in the face of declining FSH secretion. Usually only the largest follicle with the most FSH receptors and best blood supply can survive. This follicle produces increasing amounts of estradiol-17β and inhibin B. A critical action of FSH at this time is induction of the expression of LH receptors in the mural granulosa cells of the dominant follicle (see