The Endocrine Cycle and the Physiology of the Menstrual Cycle

Menstruation describes the female period. The menstruation cycle involves the monthly release of an egg (ovum) in a process called ovulation, with bleeding due to shedding of the uterine lining at the end of the cycle.

Normal menstruation is a highly complex interactions between a number of hormones produced by three organs of the body; the hypothalamus; the pituitary gland and the ovaries. The interactions between these organs are referred to as the hypothalamic-pituitary-ovarian axis (HPO axis). The cycle has an average duration of 28 days, but the normal range is between 21 to 35 days. Menstruation usually starts at an average age of 13 (called menarche) and lasts on average till age 51 (called menopause).

The inner lining of the uterus (the endometrium) goes through three phases during the menstrual cycle: the proliferative phase, the secretary phase and the menstrual phase. The changes in this lining is needed for provision of an optimal environment for the fertilized egg to grow, that is why needs to be shed and renewed monthly.

The ovarian cycle is divided into two phases: the follicular phase and the luteal phase, during which different levels of hormones are released.

Bleeding as a result of menstruation lasts 2 to 7 days on average, from which there is an average loss of 20 to 80mL of blood.

The Hypothalamic-Pituitary Axis

The Hypothalamus

There are five different hormones released from the hypothalamus that have an effect on the menstrual cycle. These hormones include:

Gonadotrophin Releasing Hormone (GnRH) Thyrotropin Releasing Hormone (TRH) Somatotropin Release-Inhibitory Factor (SRIF) Corticotrophin Releasing Factor (CRF) Prolactin Release-Inhibiting Factor (PIF) Each of these have a different effect on the anterior

pituitary gland, stimulating it to release or stop releasing a particular hormone.

GnRH:

Release of this hormone is responsible for the stimulation of specific cells called gonadotrophs in the pituitary gland. This stimulation results in the production of two important hormones called LH (luteinising hormone) and FSH (follicular stimulating hormone) from the pituitary.

GnRH is of great importance in the menstrual cycle. One of the most important features of GnRH release is the fact that its release occurs in a pulsatile fashion. At the start of puberty there is a marked increase in the frequency and amplitude of GnRH release. A part of the brain called the surge centre in the brain controls the timing of this increased release of GnRH. The surge centre is present in females very early in life, however it is only as puberty approaches that this centre becomes more responsive to hormonal changes.

Throughout the menstrual cycle there is pulsatile release of GnRH. Anything that interferes with the pulse frequency of GnRH can stop the menstrual cycle from occurring. Restoration of this pulsatile GnRH by administering hormones can produce a return to ovulation.

The Pituitary Gland

Anatomy:

The pituitary gland is an out pouching of the base of the brain which lies under the hypothalamus. The close proximity of these two parts of the brain is a reflection of their closely linked function.

The pituitary gland is divided into two different parts, each of which have different functions. The anterior pituitary is responsible for housing the gonadotrophs, these are the cells that release hormones important in controlling the menstrual cycle.

Physiology:

The anterior pituitary gland is composed of six different cell types and produces six different hormones. The cell type that is of importance in menstruation is the gonadotroph. These cells release follicle stimulating hormone (FSH) and luteinizing hormone (LH) and are also responsible for production and storage of these hormones.

FSH:The granulosa in the ovaries are the main target for the action of FSH. In response to FSH stimulation the granulosa cells release oestrogen. The combined effect of oestrogen and FSH is to cause growth and increased oestrogen production.

LH:LH stimulates cells in the ovary, called the theca cells, to produce hormones called androgens which are then transported to the granulosa cells in the ovary for conversion into oestrogens.

Gonadotrophin secretary patterns

The normal ovulatory cycle is divided into two phases called the follicular and luteal phases.

Follicular phase - is initiated from the day bleeding stops and finishes with a mid cycle surge of LH.

Luteal phase - this is initiated with the mid-cycle surge of LH which coincides with ovulation and ends with the first day of onset of the period.

Anatomy:

The female ovaries are paired, flat, elliptical structures which measure approximately 5cm in diameter. The ovaries are in the abdomen and are suspended by various ligaments.

The ovary itself consists of two parts, the outer cortex and the inner medulla. The cortex is where development of the eggs occurs, and the medulla carries nerves and blood vessels.

Physiology:

Females are born with approximately one million primary follicles. These fetal follicles contain a developing egg called a primary oocyte surrounded by a layer of granulosa cells. These primary oocytes are part way through a cell division. This process of division doesn't resume until the time of ovulation. With each ovarian cycle, a handful of ovarian follicles are recruited and usually only one of these ovulates, the remaining unrecruited follicles remain in an inactive state. Development of follicles occurs until menopause.

Hormones in the ovarian cycle:

Estrogen:This is low at the beginning of the menstrual cycle and peaks at the middle and then drop once again towards the end.

Progesterone:There is little production of this in the first half of menstruation but a significant increase in the second half. The progesterone remains high if pregnancy occurs. Progesterone is responsible for an increased body temperature in pregnancy as well.

Endometrium

Anatomy:

The endometrium is the inner layer of the uterus and is attached to the muscle layer of the uterus. It is functionally divided into two distinct zones. The outer part is the part that sheds during the menstrual cycle, and the inner part contains stem cells that helps to regenerate the lost cells.

Physiology:

The endometrium goes through three stages during the menstrual cycle:

Menstrual phase Proliferative phase Secretary phase

For a brief description of the endocrinology, stage of follicular development, and characteristics of the endometrium during a particular phase of the menstrual cycle, make a selection here: 

Early Follicular Phase Late Follicular Phase Pre-ovulation and Ovulation Early Luteal Phase Late Luteal Phase  

Early Follicular PhaseDays 1-6

Endocrinology At the beginning of the follicular phase,

FSH and LH levels are increased relative to baseline. Estrogen and progesterone levels are low.

Follicular Development Increased FSH levels stimulate 15-20

primordial follicles to develop into primary unilaminar follicles.

Uterine Endometrial Cycle Menstruation occurs at the beginning of

the follicular phase and the functionalis is shed.

Late Follicular PhaseDays 7-14

 Endocrinology Approximately eight days into the follicular phase,

FSH levels decrease due to negative feedback at the level of the pituitary gland and estradiol levels increase due to previous stimulation by FSH at the level of the ovary.

 Follicular Development Primary unilaminar continue to develop into

primary multilaminar follicles. With increased estrogen production, the follicles form fluid-filled vesicles which can later mature into an antrum.

 Uterine Endometrial Cycle The late follicular phase is marked by proliferation

of the functionalis and proliferation and elongation of non-secreting endometrial glans.

Pre-Ovulation and OvulationDays 13-14

 Endocrinology One day before ovulation, a surge in LH occurs and FSH levels

increase temporarily. LH and FSH both increase due to positive feedback by estrogen at the level of the pituitary gland. LH and FSH begin to decrease back to baseline levels almost immediately. By the time ovulation occurs, LH and FSH are on the decline.

 Follicular Development Before ovulation occurs, one follicle evolves into a dominant

follicle and develops an antrum while the remaining primary follicles undergo atresia. The dominant follicle, now called a Graafian follicle, completes its first meiotic division. At ovulation, the secondary oocyte and corona radiata are expelled into the peritoneal cavity and taken up by the oviduct.

 Uterine Endometrial Cycle At ovulation, the functionalis and endometrial glands have

reached their maximum sizes. The endometrial glands are still non-secretary.

Early Luteal PhaseDays 15-21

 Endocrinology Progesterone and, to a lesser extent, estrogen

are produced by the corpus luteum. The corpus luteum evolves under the influence of the pre-ovulatory surge in LH. LH and FSH are under negative feedback control by these ovarian hormones at the level of the pituitary gland.

 Follicular Development After ovulation, mural granulosa cells and

thecal cells of the dominant follicle remain in the ovary and become the corpus luteum.

 Uterine Endometrial Cycle Progesterone stimulates endometrial glands to

secrete glycogen, mucus, and other substances. The endometrial glands now have a tortuous appearance.

Late Luteal PhaseDays 22-28

Endocrinology In the absence of fertilization, the corpus luteum

degenerates and progesterone and estrogen levels subsequently fall. At day 28 of the menstrual cycle, estrogen and progesterone are at their lowest levels. Negative feedback on FSH is removed, and FSH secretion can again increase to initiate the beginning of the next cycle.

Follicular Development When fertilization does not occur, the corpus luteum

undergoes atresia. Towards the end of the cycle, the corpus luteum devolves into the corpus albicans, or white scar.

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Uterine Endometrial Cycle As progesterone and estrogen levels

decrease with the degeneration of the corpus luteum, the endometrium begins to undergo involution. At days 25-26, the spiral arteries begin to vasoconstrict. By day 28, marked ischemia causes apoptosis of the functionalis