• Introduction to Hormones of the Menstrual Cycle
• Hypothalamic-Pituitary-Ovary Axis
• The Endocrine Cycle and the Physiology of the Menstrual Cycle
  

Introduction

The female menstrual cycle is determined by a complex interaction of hormones. The predominant hormones involved in the menstrual cycle are gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone. GnRH is secreted by the hypothalamus, the gonadotropins FSH and LH are secreted by the anterior pituitary gland, and estrogen and progestin are secreted at the level of the ovary. GnRH stimulates the release of LH and FSH from the anterior pituitary, which in turn stimulate release of estrogen and progestin at the level of the ovary.

Gonadotropin Releasing Hormone (GnRH)

Gonadotropin releasing hormone (GnRH) is secreted from the hypothalamus in a pulsatile manner throughout the menstrual cycle. In order for the menstrual cycle to proceed normally, GnRH must be released in pulses. On average, the frequency of GnRH secretion is once per 90 minutes during the early follicular phase, increases to once per 60-70 minutes, and decreases with increased amplitude during the luteal phase. GnRH induces the release of both FSH and LH; however, LH is much more sensitive to changes in GnRH levels.

Follicle Stimulating Hormone (FSH)

Follicle stimulated hormone (FSH) is secreted by the anterior pituitary gland and is essential for follicular growth until the antrum develops. FSH secretion is highest and most critical during the first week of the follicular stage the menstrual cycle. FSH induces estrogen and progesterone secretion at the level of the ovary by activating aromatase and p450 enzymes and exerts negative feedback on GnRH secretion. FSH further induces the proliferation of granulosa cells and expression of LH receptors on granulosa cells.

Luteinizing Hormone (LH)

Luteinizing hormone (LH) is secreted by the anterior pituitary gland and is required for both growth of preovulatory follicles and luteinization and ovulation of the dominant follicle. During the follicular phase of the menstrual cycle, LH induces androgen synthesis by theca cells; stimulates proliferation, differentiation, and secretion of follicular thecal cells; and increases LH receptors on granulosa cells. The preovulatory LH surge drives the oocyte into the first meiotic division and initiates luteinization of thecal and granulosa cells. The resulting corpus luteum produces high levels of progesterone and some estrogen.

Estrogen

Estrogen is produced at the level of the ovary and is crucial for the development of the antrum and maturation of the Graafian follicle. Estrogen is predominant at the end of the follicular phase, directly preceding ovulation. Estradiol, the most potent and abundant estrogen, is primarily derived from androgens produced by thecal cells. The androgens migrate from the thecal cells to the granulosa cells, where they are converted into estradiol by aromatase enzyme. Some estradiol can also be produced via de novo synthesis by thecal cells. The actions of estradiol include induction of FSH receptors on granulosa cells, proliferation and secretion of follicular thecal cells, induction of LH receptors on granulosa cells, and proliferation of endometrial stromal and epithelial cells. At low circulating levels, estrogens exert negative feedback on LH and FSH secretion; however, at very high levels estrogens exert positive feedback on LH and FSH secretion. Estrogen further induces proliferation of estrogen-converting granulosa cells and synthesis of estrogen receptors, establishing a positive feedback loop on itself. In the uterine endometrial cycle, estrogen induces proliferation of the endometrial glands.

Progestin

Progestin is secreted at the level of the ovary, primarily by luteinized follicles. Progestin levels increase just prior to ovulation and peak five to seven days post-ovulation. The first step in progestin synthesis requires p450 enzyme and the two circulating forms of progestin are progesterone and 17-hydroxy-progesterone. Progestins stimulate the release of proteolytic enzymes from thecal cells that ultimately prepare for ovulation. Progestins further induce migration of blood vessels into the follicle wall and stimulate prostaglandin secretion in follicular tissues. During the luteal phase, progestins induce swelling and increased secretion of the endometrium.