2010: Describe the hormonal changes that occur across the ovarian (menstrual) cycle.

The menstrual cycle promotes the generation of a suitable environment for the implantation of a fertilized embryo. The average female menstrual cycle lasts between 28 and 35 days. It can be subdivided into two distinct phases; the follicular phase and the luteal phase. The follicular phase begins with the onset of menses (period) for 3 to 6 days and the entire follicular phase can last between 14 and 21 days until ovulation occurs. The luteal phase follows ovulation and lasts about 14 days. The entire cycle is controlled by two main steroid hormones known as oestrogen and progesterone produced by the ovaries. The HypothalamicPituitary-Ovarian Axis plays a central role in the regulation of circulating levels of these hormones. In the presence of a pulsatile release of Gonadotrophin releasing hormone (GnRH) from the peptidergic neurons in the hypothalamus every 90 mins or so, the anterior lobe of the pituitary gland will produce Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). In the early follicular phase the ovaries are hormonally inactive and there is no progesterone and only a little oestrogen. There is a pulsatile release of GnRH will stimulate the release of FSH and LH. This in turn acts on the ovaries to promote development of ovarian follicles. FSH stimulates the development of about 145-20 follicles each month. One follicle will develop faster and is more dominant than the others and is known as the Graafian follicle. This follicle contains an ovum in a fluid-filled centre surrounded by granulosa cells and theca cells and is destined for ovulation. Only the follicle with the most granulosa cells is selected for ovulation. These cells are responsible for secreting oestrogen when properly stimulated by LH and FSH. (LH stimulates theca cells to produce androgens and testosterones which are the building blocks for these steroid hormones. The granulosa cells, under the action of FSH convert these building blocks to oestrogen. Therefore both cell types are required to act as a unit.) There will be a rise in serum oestrogen levels from day 6 until approximately half way through the cycle during which time the lining of the uterus will proliferate becoming thicker and more vascularised in preparation for implantation of a fertilised oocyte. This oestrogen along with Inhibin A produced by the granulosa cells will suppress the release of gonadotrophs from

the anterior pituitary via a negative feedback system. Approximately 48 hours before ovulation there will be a switch from a negative feedback to a positive feedback at the level of the pituitary. This will trigger a surge in LH. Oestorgen can onlyexert positive feedback on LH at this precise stage in the menstrual cycle. This usually occurs around day 9 and causes the graafian follicle to rupture and release its oocyte. 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 is expelled into the peritoneal cavity. The oocyte adheres to the ovary and muscular contractions of the smooth muscle of the fallopian tube bring the oocyte into contact with the tubal epithelium to initiate migration through the oviduct. The luteal phase follows ovulation and is always constant at 14 days despite the length of the overall cycle. The ruptured cells develop into the corpus luteum and produce progesterone and, to a lesser extent, oestrogen. This steroid hormone primes the endometrium for fertilisation and negatively feeds back on the hypothalamus and the anterior pituitary to decrease the release of LH. 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 oestrogen and progesterone levels, an important negative feedback control on FSH is removed and FSH levels rise once again to initiate the next menstrual cycle. Extra notes:

*Only oestrogenic mucous is penetrable by sperm so there is only a short window of 4-5 days in which sperm can pass through the cervical mucousa. This is the reason why women with a shorter cycle, say ~24 days find it harder to conceive. *Most twin pregnancies are double ovulation but we are designed to only ovulate once at ~day 14.