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Endocrinology of the Menstrual Cycle

The Endocrine Cycle and the Physiology of the Menstrual Cycle

The interplay between pituitary and ovarian hormones gives rise to a stereotyped pattern of hormone levels during the menstrual cycle. The graph below shows relative hormone levels in an average 28-day cycle.

The sequence of events in the menstrual cycle is determined by the relative hormone levels at each stage. Below, the major physiological effects of the predominant hormones in each phase of the menstrual cycle are discussed. The details of follicular development and the endometrial cycle will be addressed in succeeding sections.

Menstrual cycle – Follicular Phase

The follicular phase of the menstrual cycle spans the first day of menstruation until ovulation. The primary goal during the follicular phase is to develop a viable follicle capable of undergoing ovulation. The early events of the follicular phase are initiated by a rise in FSH levels at the first day of the cycle. The rise in FSH levels can be attributed to a decrease in progesterone and estrogen levels at the end of the previous cycle and the subsequent removal of inhibition of FSH by these ovarian hormones. FSH stimulates the development of 15-20 follicles each month and stimulates follicular secretion of estradiol by upregulating secretion of androgens by the theca externa and by inducing the aromatase enzyme receptor on granulosa cells. FSH further induces expression of FSH receptors by follicles. As estradiol levels increase under the influence of FSH, estradiol inhibits the secretion of FSH and FSH levels decrease.

Hormones and menstrual cycle

Under normal circumstances, one follicle evolves into the dominant follicle, destined for ovulation, while the remaining follicles undergo atresia. It is currently not known how the dominant follicle is selected; yet it has been observed that the dominant follicle always expresses an abundance of FSH receptors. As FSH levels decrease towards the end of the follicular phase, the developing follicles must compete for relatively small amounts of FSH. The dominant follicle, with its high concentration of FSH receptors, continues to acquire more FSH even as FSH levels decrease. The dominant follicle can continue to synthesize estradiol, which is essential for its complete maturation. The remaining, poorly FSH receptor-endowed follicles can not produce the requisite amount of estradiol. These follicles cease to develop and ultimately undergo atresia. The dominant follicle matures and secretes increasing amounts of estrogen. Estrogen levels peak towards the end of the follicular phase of the menstrual cycle. At this critical moment, estrogen exerts positive feedback on LH, generating a dramatic preovulatory LH surge. Estrogen can only exert positive feedback on LH at this precise stage in the menstrual cycle; if estrogen is artificially provided earlier in the cycle, ovulation will not be induced.

Endocrinology of the Menstrual Cycle

Menstrual cycle – Ovulation

The LH surge is required for ovulation. Under the influence of LH, the primary oocyte enters the final stage of the first meiotic division and divides into a secondary oocyte and the first Barr body. The LH surge induces release of proteolytic enzymes, which degrade the cells at the surface of the follicle, and stimulates angiogenesis in the follicular wall and prostaglandin secretion. These effects of LH cause the follicle to swell and rupture. At ovulation, the oocyte and corona radiata are expelled into the peritoneal cavity. The oocyte adheres to the ovary and muscular contractions of the fallopian tube bring the oocyte into contact with the tubal epithelium to initiate migration through the oviduct.

Menstrual cycle – Luteal Phase

The luteal phase is defined by the luteinization of the components of the follicle which were not ovulated and is initiated by the LH surge. The granulosa cells, theca cells, and some surrounding connective tissue are all converted into the corpus luteum, which eventually undergoes atresia. The major effects of the LH surge are the conversion of granulosa cells from predominantly androgen-converting cells to predominantly progesterone-synthesizing cells, the expression of new LH receptors which fosters increased progesterone synthesis, and reduced affinity of granulose cells for estrogen and FSH. Combined, these changes promote increased progesterone secretion with some estrogen secretion. Progesterone secretion by the corpus luteum peaks between five and seven days post-ovulation. High progesterone levels exert negative feedback on GnRH and subsequently GnRH pulse frequency decreases. As GnRH pulse frequency decreases, FSH and LH secretion also decreases. The corpus luteum further loses its FSH and LH receptors.

Endocrinology of the Menstrual Cycle

Lacking stimulation by FSH and LH, after 14 days corpus luteum undergoes atresia and begins evolving into the corpus albicans. With the decline of both estrogen and progesterone levels, an important negative feedback control on FSH is removed and FSH levels rise once again to initiate the next menstrual cycle.

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