The hypothalamic-pituitary-ovarian axis is central to female reproductive function. It regulates the cyclic secretion and feedback mechanisms of a hierarchy of hormones from the pituitary gland and the ovary that (i) result in the cyclic production of the steroid hormones, estrogen and progesterone, and (ii) promote endometrial growth in preparation for conception, with resulting menstrual cyclicity and endometrial shedding in the absence of conception. The cyclic production of these hormones ensures that a mature ovum is released from the ovaries approximately once a month and that the endometrium is concurrently receptive to the implantation of a fertilized ovum (embryo) should fertilization occur. If fertilization does not occur, the endometrium is shed in an orderly fashion, menstruation ensues, and the cycle proceeds anew. In adult women, the average cycle lasts 28 days, but ranges from 21 to 35 days; cycles shorter or longer are statistically uncommon (1,2).
The hierarchy of hormones that governs the menstrual cycle is produced by the hypothalamus, the pituitary gland, and the ovary, as follows:
1. Gonadotrophin-releasing hormone (GnRH), secreted by the hypothalamus, stimulates production of the gonadotrophic hormones, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), by the anterior pituitary gland.
2. FSH and LH modulate ovarian function to promote follicular growth, follicular maturation, and release of the ovum (ovulation).
3. Estrogen (secreted by the ovaries in response to the gonadotrophic hormones) and progesterone (produced by the corpus luteum that develops at the site of a ruptured ovarian follicle) stimulate the proliferation and secretory development of the endometrium. Along with non-steroidal factors such as inhibin, estrogen and progesterone also modulate pituitary production of the gonadotrophic hormones through feedback inhibition.
Concentrations of these gonadotrophic and ovarian hormones vary cyclically in a characteristic pattern over the course of the menstrual cycle (Fig. 1, top and center panels). Convention dictates that the first day of menstruation is considered day 1. Modulation of ovarian function by FSH and LH, leading to follicular maturation and ovulation, is known as the ovarian cycle. Concurrent phases of endometrial development to sustain an embryo, induced by estrogen and progesterone, are known as the endometrial cycle (Fig. 1, bottom panel).
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