The menstrual cycle is a complex series of physiological changes that occur in women of reproductive age on a monthly basis. The end result is the production of an ovum and thickening of the endometrium to allow for implantation, should fertilisation should occur. The menstrual cycle is orchestrated by the endocrine system through the complex interaction of the hypothalamus, pituitary and gonads (hypothalamic-pituitary-gonadal axis). The entire menstrual cycle lasts around 28 days, with the cycle beginning on the first day of menstruation and ovulation occurring at approximately day 14.
Hypothalamic-pituitary-gonadal axis (HPG Axis)
1. The hypothalamus secretes GnRH.
2. GnRH travels down to the anterior pituitary gland and binds to receptors on the gland.
3. This promotes the release of LH (luteinizing hormone) and FSH (follicle-stimulating hormone).
4. LH and FSH travel in the bloodstream to the ovaries.
5. When LH and FSH bind to the ovaries they stimulate the production of oestrogen and inhibin:
Oestrogen helps to regulate the menstrual cycle and is an essential component in many other physiological processes
Inhibin causes inhibition of activin which is usually responsible for stimulating GnRH production
FSH also stimulates the development of ovarian follicles, with the follicle most sensitive to FSH becoming the dominant Graafian follicle
LH causes the Graafian follicle to change into the corpus luteum, which begins to produce progesterone
Progesterone stimulates the endometrium to become receptive to the implantation of a fertilised ovum
6. Increasing levels of oestrogen, progesterone and inhibin have a negative feedback effect on the pituitary and hypothalamus.
7. This leads to the decreased production of GnRH, LH and FSH.
8. This, in turn, results in decreased production of oestrogen and inhibin.
9. If a woman becomes pregnant, GnRH, FSH and LH remain inhibited, causing menstruation to cease.
Phases of the menstrual cycle
1. At the beginning of the menstrual cycle, levels of FSH rise causing stimulation of a few ovarian follicles.
2. As follicles mature they compete with each other for dominance.
3. The first follicle that becomes fully mature begins to produce large amounts of oestrogen.
4. Oestrogen inhibits the growth of the other competing follicles.
5. The single follicle that reaches full maturity during this process is referred to as the Graafian follicle (the oocyte develops within this).
6. The Graafian follicle continues to secrete increasing amounts of oestrogen.
7. Increasing amounts of circulating oestrogen results in:
thinning of the cervical mucus to allow easier passage of sperm
inhibition of LH production by the pituitary gland
8. As oestrogen levels rise, they eventually surpass a threshold level, at which point they conversely stimulate LH production, resulting in a spike in LH levels around day 12.
9. The high amounts of LH cause the membrane of the Graafian follicle to become thinner.
10. Within 24-48 hours of the LH surge, the follicle ruptures releasing a secondary oocyte.
11. The secondary oocyte quickly matures into an ootid and then into a mature ovum.
12. The mature ovum is then released into the peritoneal space and is taken into the fallopian tube via fimbriae (finger-like projections).
13. Once ovulation has occurred LH and FSH stimulate the remaining Graafian follicle to develop into the corpus luteum.
14. The corpus luteum then begins to produce the hormone progesterone.
15. Increased levels of progesterone result in:
the endometrium becoming receptive to implantation of the blastocyst
negative feedback causing decreased LH and FSH (both needed to maintain the corpus luteum)
an increase in the woman’s basal body temperature
16. As the levels of FSH and LH fall, the corpus luteum degenerates.
17. Degeneration of the corpus luteum results in loss of progesterone production.
18. The subsequent falling level of progesterone triggers menstruation and the entire cycle begins again.
However, if fertilisation occurs…
19. If an ovum is fertilised it produces hCG which is similar in function to LH.
20. hCG prevents degeneration of the corpus luteum (resulting in the continued production of progesterone).
21. Continued production of progesterone preventsmenstruation.
22. The placenta eventually takes over the role of the corpus luteum (from 8 weeks gestation).
The uterine cycle
The uterus has its own cycle which is driven by the cyclical release of hormones by the ovaries which we’ve previously covered. The inside lining of the uterus is known as the endometrium and is composed of two layers:
Functional layer: this grows thicker in response to oestrogen and is shed during menstruation
Basal layer: this forms the foundation from which the functional layer develops (i.e. it is not shed)
Phases of the uterine cycle
The uterine cycle has three phases known as the proliferative, secretory and menstrual phases.
During the proliferative phase, the endometrium is exposed to increasing levels of oestrogen as a result of FSH and LH stimulating its production.
Oestrogen stimulates repair and growth of the functional endometrial layer allowing recovery from the recent menstruation (increasing endometrial thickness, vascularity and the number of secretory glands).
The secretory phase begins once ovulation has occurred.
This phase is driven by progesterone produced by the corpus luteum and results in the secretion of various substances by the endometrial glands, making the uterus a more welcoming environment for an embryo to implant.
At the end of the luteal phase, the corpus luteum degenerates (if no implantation occurs).
The loss of the corpus luteum results in decreased progesterone production.
The decreasing levels of progesterone cause the spiral arteries in the functional endometrium to contract.
The loss of blood supply causes the functional endometrium to become ischaemic and necrotic.
As a result, the functional endometrium is shed and exits through the vagina as menstruation.