Physiology of the Normal Menstrual Cycle

What are the phases of the menstrual cycle?

By convention, the first day of menses represents the first day of the cycle (day 1). The cycle is then divided into two phases: follicular and luteal. ●The follicular phase begins with the onset of menses and ends on the day before the luteinizing hormone (LH) surge. ●The luteal phase begins on the day of the LH surge and ends at the onset of the next menses.

What ovarian and endometrial changes occur during the late follicular phase?

By the late follicular phase, a single dominant follicle has been selected, while the rest of the growing cohort of follicles gradually stop developing and undergo atresia. The dominant follicle increases in size by approximately 2 mm per day until a mature size of 20 to 26 mm is reached. Rising serum estradiol concentrations result in gradual thickening of the uterine endometrium and an increase in the amount and "stringiness" (spinnbarkeit) of the cervical mucus. Many women are able to detect this change in mucus character.

How does the menstrual cycle change throughout a woman's lifetime?

In general, menstrual cycle length peaks at approximately age 25 to 30 years and then gradually declines so that women in their forties have slightly shorter cycles. Changes in intermenstrual interval are primarily due to changes in the follicular phase; in comparison, the luteal phase remains relatively constant

What ovarian and endometrial changes occur during the early follicular phase?

Ovarian ultrasonography has demonstrated that the ovary is quiescent in the early follicular phase, except for the occasionally visible resolving corpus luteum from the previous cycle. The endometrium is relatively indistinct during menses and then becomes a thin line once menses is complete. It is normal to see small follicles of 3 to 8 mm in diameter at this time.

What is the middle to late luteal phase?

Progesterone secretion from the corpus luteum results in gradually rising progesterone concentrations in the middle to late luteal phase. This leads to progressive slowing of luteinizing hormone (LH) pulses down to one pulse every four hours. Pulses of progesterone occur soon after these slow LH pulses. As a result, there can be significant excursions in serum progesterone concentrations during the luteal phase. Inhibin A is also produced by the corpus luteum, and serum concentrations of inhibin A peak in the mid-luteal phase. Inhibin B secretion is virtually absent during the luteal phase. Serum leptin concentrations are highest in the luteal phase. In the late luteal phase, a decrease in LH secretion results in a gradual fall in progesterone and estradiol production by the corpus luteum in the absence of a fertilized oocyte. If, however, the oocyte becomes fertilized, it implants in the endometrium several days after ovulation. The early embryo begins to make chorionic gonadotropin, which maintains the corpus luteum and progesterone production.

What is the midcycle surge (luteal phase)?

Serum estradiol concentrations continue to rise until they reach a peak approximately one day before ovulation. Then, a unique neuroendocrine phenomenon occurs: the midcycle surge. The surge represents a switch from negative feedback control of luteinizing hormone (LH) secretion by ovarian hormones (such as estradiol and progesterone) to a sudden positive feedback effect, resulting in a 10-fold increase in serum LH concentrations and a smaller rise in serum follicle-stimulating hormone (FSH) concentrations.

How long is the average menstrual cycle?

The average adult menstrual cycle lasts 28 to 35 days, with approximately 14 to 21 days in the follicular phase and 14 days in the luteal phase.

What endometrial changes occur during the middle to late luteal phase?

The decline in estradiol and progesterone release from the resolving corpus luteum results sequentially in the loss of endometrial blood supply, endometrial sloughing, and the onset of menses approximately 14 days after the LH surge. In response to falling corpus luteum steroid production, the hypothalamic-pituitary axis is released from negative feedback and follicle-stimulating hormone (FSH) levels rise, thereby beginning the next cycle.

What endometrial changes occur during the midcycle surge (luteal phase)?

The gradually increasing serum progesterone concentrations have a profound impact on the endometrial lining, leading to cessation of mitoses and "organization" of the glands. This change can be detected on ultrasonography relatively soon after ovulation; the "triple stripe" image is lost, and the endometrium becomes more uniformly bright.

What is the late follicular phase?

The serum concentrations of estradiol and inhibin A increase daily during the week before ovulation due to release from the growing follicle. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations are falling at this time due to negative feedback effects of estradiol. As the dominant follicle is selected, FSH induces LH receptors in the ovary and increases ovarian secretion of intrauterine growth factors such as insulin-like growth factor-1 (IGF-1).

What ovarian and endometrial changes occur during the mid-follicular phase?

Within approximately seven days from the onset of menses, several 9 to 10 mm antral follicles are visible on ovarian ultrasonography. The rising serum estradiol concentrations result in proliferation of the uterine endometrium, which becomes thicker, with an increase in the number of glands and the development of a "triple stripe" pattern on ultrasound.

What ovarian changes occur during the midcycle surge (luteal phase)?

The LH surge initiates substantial changes in the ovary. The oocyte in the dominant follicle completes its first meiotic division. In addition, the local secretion of plasminogen activator and other cytokines required for the process of ovulation is increased. The oocyte is released from the follicle at the surface of the ovary approximately 36 hours after the LH surge. It then travels down the fallopian tube to the uterine cavity. There is a close relation of follicular rupture and oocyte release to the LH surge; as a result, measurements of serum or urine LH can be used to estimate the time of ovulation in women. Even before the oocyte is released, the granulosa cells surrounding it begin to luteinize and produce progesterone. Progesterone acts rapidly to slow the pulse generator so that LH pulses become less frequent by the termination of the surge.

What is the early follicular phase?

The early follicular phase in humans is the time when the ovary is the least hormonally active, resulting in low serum estradiol and progesterone concentrations. Release from the negative feedback effects of estradiol, progesterone, and probably luteal phase inhibin A results in a late luteal/early follicular phase increase in gonadotropin-releasing hormone (GnRH) pulse frequency and a subsequent increase in serum follicle-stimulating hormone (FSH) concentrations of approximately 30 percent. This small increase in FSH secretion appears to be required for the recruitment of the next cohort of developing follicles, one of which will become the dominant and ultimately ovulatory follicle during that cycle. Serum inhibin B concentrations, secreted by the recruitable pool of small follicles, are maximal and may play a role in suppressing the FSH rise at this time in the cycle.

What is the mid-follicular phase?

The modest increase in follicle-stimulating hormone (FSH) secretion in the early follicular phase gradually stimulates folliculogenesis and estradiol production, leading to progressive growth of the cohort of follicles selected that cycle. As several follicles initially grow to the antral stage, their granulosa cells hypertrophy and divide, producing increasing serum concentrations of estradiol via FSH stimulation of aromatase and then inhibin A from the granulosa cells in the ovaries. The increase in estradiol production feeds back negatively on the hypothalamus and pituitary, resulting in suppression of mean serum FSH and luteinizing hormone (LH) concentrations as well as the LH pulse amplitude. In comparison, the gonadotropin-releasing hormone (GnRH) pulse generator speeds up slightly to a mean LH pulse frequency of approximately one per hour (versus one per 90 minutes in the early follicular phase).