2.5: The Menstrual Cycle
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- 91843
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Let’s put together what we learned about ovulation, the buildup and then shedding of the endometrial lining in the uterus, and the function of the uterine tubes and vagina, to explore the three phases of the menstrual cycle.
The menstrual cycle is the series of changes in which the uterine lining is shed, rebuilt, and prepared for implantation under the effect of ovarian hormones. The timing of the menstrual cycle starts with the first day of menses, referred to as day one of a woman’s period. Cycle length is determined by counting the days between the onset of bleeding in two subsequent cycles. Because the average length of a woman’s menstrual cycle is 28 days, this is the period used to identify the timing of events in the cycle. This period is also known as the intermenstrual interval. The menstrual cycle length varies among women, and even in the same woman, from one cycle to the next, typically from 21 to 35 days. Changes in the intermenstrual interval are primarily due to changes in the follicular phase; in comparison, the luteal phase remains relatively constant.
Just as the hormones produced by the granulosa and theca cells of the ovary “drive” the follicular (14-21 days) and luteal phases (14 days) of the ovarian cycle, they also control the three distinct phases of the menstrual cycle. These are the menses phase, the proliferative phase, and the secretory phase.13
2.5.1.1 Menses Phase (Days 1-5)
The menses phase of the menstrual cycle is the phase during which the lining is shed; that is, the days that the woman menstruates (Figure 2.5.14). Although it averages approximately five days, the menses phase lasts 2 to 7 days, or longer. As shown in Figure 2.5.15, the menses phase occurs during the early days of the follicular phase of the ovarian cycle, when progesterone, FSH, and LH levels are low. Recall that progesterone concentrations decline due to the degradation of the corpus luteum, marking the end of the luteal phase. This decline in progesterone triggers the shedding of the stratum functionalis of the endometrium (Figure 2.5.14). The ischemia produced by the contraction of spiral arteries leads to degeneration and sloughing of the functional zone, leaving only the basal zone remaining at the end of menstruation. The menstrual flow contains blood, tissue fragments, and uterine fluids.14
Figure 2.5.14: Menstrual phase (days 1-5). When the ischemic tissue in the functional zone loses its integrity, it is sloughed as menstruation. (A) This image, taken from early in the menstrual phase, shows an intact surface epithelium on the right half of the image (black arrows), while tissue has already begun to slough in other areas (left half; T-shaped arrows). Sloughing of the functional zone is indicated by the lack of surface epithelium, the presence of glands at the luminal surface, and missing portions of the functional zone. The thickness of the remaining functional zone indicates that this tissue was taken during the early days of the menstrual phase. 100x. (B) This image is taken close to the end of the menstrual phase; all of the functional zone has been lost, and only the bases of glands remain, from which new glands will originate. Extravasated blood (arrows) can be seen throughout the endometrium.10x.
Image Source: Images used with permission from Digital Histology. Pakurar, Alice S. and John W. Bigbee. Carole W. Christman, Ph.D, Medical Illustrator. Digital Histology, (ND). This work is openly licensed via CC BY SA Creative Commons License. Available from Virginia Commonwealth University.
Figure 2.5.15 Hormone levels in ovarian and menstrual cycles. The correlation between hormone levels and their effects on the female reproductive system is shown in this timeline of the ovarian and menstrual cycles. The menstrual cycle begins at day one with the start of menses. Ovulation occurs around day 14 of a 28-day cycle, triggered by the LH surge.
- Image Source: Karve, Simantini. "Anatomy and Physiology of the Female Reproductive System." Human Physiology for Allied Health Professionals, (2022). This work is openly licensed via CC
2.5.1.2 Proliferative Phase (Days 6-14)
Once menstrual flow ceases, the endometrium begins to proliferate again, marking the beginning of the proliferative phase of the menstrual cycle. It occurs when the granulosa and theca cells of the tertiary follicles begin to produce increased amounts of estrogen. These rising estrogen concentrations stimulate the endometrial lining to rebuild. Recall that the high estrogen concentrations will eventually lead to a decrease in FSH because of negative feedback, resulting in atresia of all but one of the developing tertiary follicles. The switch to positive feedback—which occurs with the elevated estrogen production from the dominant follicle—then stimulates the LH surge that will trigger ovulation. In a typical 28-day menstrual cycle, ovulation occurs on day 14. Ovulation marks the end of the proliferative phase as well as the end of the follicular phase.
The endometrium in the proliferative phase is not very thick, the glands are straight, and the spiral arteries are not readily visible (Figure 2.5.16). The stroma in the basal zone is characterized by relatively smaller and closely packed cells resulting in darker staining (distinguishing features of the basal zone). The bases of the glands, located in this layer, are the source of cells that regenerate the glands and also the surface epithelium of the functional zone following menstruation. Estrogen produced by ovarian follicles induces the rapid growth of the functional zone of the endometrium during the proliferative phase. The simple branched tubular uterine glands are straight; they are non-secretory at this stage. Spiral arteries are present to support the rapidly growing and proliferating functional zone; however, they are not coiled and not prominent histologically.15
Figure 2,5.16 Proliferative endometrium. Straight, non-secretory endometrial glands (arrows). 100x..
Image Source: Images used with permission from Digital Histology. Karve, Simantini. "Anatomy and Physiology of the Female Reproductive System." Human Physiology for Allied Health Professionals, (2022). This work is openly licensed via CC
2.5.1.3 Secretory Phase (Days 14-28)
In addition to prompting the LH surge, high estrogen levels increase the uterine tube contractions that facilitate the pickup and transfer of the ovulated oocyte. High estrogen levels also slightly decrease the acidity of the vagina, making it more hospitable to sperm. In the ovary, the luteinization of the granulosa cells of the collapsed follicle forms the progesterone-producing corpus luteum, marking the beginning of the luteal phase of the ovarian cycle. In the uterus, progesterone from the corpus luteum begins the secretory phase of the menstrual cycle, in which the endometrial lining prepares for implantation (Figure 2A.17). The endometrial glands secrete a glycogen-rich fluid over the next 10 to 12 days. If fertilization has occurred, this fluid will nourish the ball of cells now developing from the zygote. At the same time, the spiral arteries develop to provide blood to the thickened stratum functionalis. If no pregnancy occurs within 10 to 12 days, the corpus luteum will degrade into the corpus albicans. Levels of both estrogen and progesterone will fall, and the endometrium will grow thinner. Prostaglandins will be secreted, which causes constriction of the spiral arteries and reduces oxygen supply. The endometrial tissue will die, resulting in menses—or the first day of the next cycle.
The histological features of the endometrium during the secretory phase (days 14-26) are demonstrated in Figure 2.5.17. The uterine glands become secretory under the effect of estrogen and progesterone. During the early portion of the secretory phase (Figure 2.5.17, A), the endometrium is thicker in comparison to the endometrium of the proliferative phase, the glands are saccular, and the spiral arteries are present, but are not highly coiled. Late in the secretory phase, the glands in the functional zone are greatly sacculated and have characteristic saw-tooth features. These glands are distended with secretory product in their lumens. The spiral arteries are coiled and can readily be seen zigzagging through the endometrium at the junction of the basal and functional zones (Figure 2.5.17, B). Around day 24, multipotential stromal cells differentiate into cells called pre-decidual cells (if there is no pregnancy) or decidual cells if implantation occurs. These cells appear first around the spiral arteries and beneath the surface epithelium, as shown in (Figure 2.5.18, C). If fertilization and implantation occur, the decidual cells provide nutrition for the implanting blastocyst and form the maternal placenta (decidua).16
Figure 2.5.17 Secretory Endometrium. (A) Early secretory phase endometrium with secretory products starting to accumulate in some glands (arrows). Glands are increasing in size and become sacculated. 100x. (B) Late secretory phase endometrium; glands are widely sacculated, with characteristic saw-tooth appearance, and lumens distended with secretions (X). The spiral arteries are coiled (arrows). 200x.
Image Source: Images used with permission from Digital Histology. Pakurar, Alice S. and John W. Bigbee. Carole W. Christman, Ph.D, Medical Illustrator. Digital Histology, (ND). This work is openly licensed via CC BY SA Creative Commons License. Available from Virginia Commonwealth University.
Very late in the secretory phase (days 26-28), also known as the pre-menstrual phase (Figure 2A.18), the endometrium demonstrates certain morphological features secondary to the decreased hormone production by the degrading corpus luteum. The endometrium shrinks and becomes less edematous. The spiral arteries undergo alternate contraction and relaxation resulting in ischemia and degeneration of the endometrial tissue supplied by these arteries; this phase is also known as the ischemic portion of the secretory phase. The degenerating endometrium shows sacculated glands with precipitated secretory products in their lumens, areas of degeneration, and extravasation of blood in the stroma (Figure 2A.18, A, B). Pre-decidual cells can be seen beneath the surface of the epithelium (Figure 2A.18, C).17
Figure 2.5.18 Pre-menstrual Phase (Days 26-28). (A, B) The functional zone is declining. The sacculated glands (arrowheads) show precipitated secretory product; areas of degeneration are obvious (X); extravasated blood (arrows) is present in the stroma. 40x. (C) The image is from an area similar to that enclosed by the rectangle in (B); pre-decidual cells (arrows) can be seen beneath the surface epithelium. 400x.
Image Source: Images used with permission from Digital Histology. Pakurar, Alice S. and John W. Bigbee. Carole W. Christman, Ph.D, Medical Illustrator. Digital Histology, (ND). This work is openly licensed via CC BY SA Creative Commons License. Available from Virginia Commonwealth University.
Kai J, Dutton B, Vinogradova Y, et al. Rates of medical or surgical treatment for women with heavy menstrual bleeding: the ECLIPSE trial 10-year observational follow-up study. Southampton (UK): National Institute for Health and Care Research; 2023 Oct. (Health Technology Assessment, No. 27.17.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK596976/ doi: 10.3310/JHSW0174
Glossary Terms
- Blastocyst
- Post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues
- Corpus luteum
- Transformed follicle after ovulation that secrets progesterone
- Decidual cells
- Hyperplastic endometrial
stromal cells - Estrogen
- Class of predominantly female sex hormones important for the development and growth of the female reproductive tract, secondary sex characteristics, the female reproductive cycle, and the maintenance of pregnancy
- Follicle-stimulating Hormone (FSH)
- Anterior pituitary hormone that stimulates the production and maturation of sex cells
- Follicular phase
- Period of the menstrual cycle representing follicular growth, increase in ovarian estrogen (estrogens) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of menstruation and ends with ovulation
- Granulosa
- Supportive cells in the ovarian follicle that produce estrogen
- Ischemia
- Insufficient blood flow to the tissues
- Luteal phase
- Period in the menstrual cycle that follows ovulation, characterized by the development of corpus luteum, increase in progesterone production by the ovary and secretion by the glandular epithelium of the endometrium. The luteal phase begins with ovulation and ends with the onset of menstruation
- Luteinizing hormone (LH)
- Anterior pituitary hormone that triggers ovulation and the production of ovarian hormones in females, and the production of testosterone in males
- Menses
- Shedding of the inner portion of the endometrium out through the vagina; also referred to as menstruation
- Oocyte
- Shedding of the inner portion of the endometrium out though the vagina; also referred to as menstruation
- Ovulation
- Release of a secondary oocyte and associated granulosa cells from an ovary
- Progesterone
- Sex hormone important in regulating the reproductive cycle in those with ovaries and the maintenance of pregnancy
- Saccular
- Having the form of a sac
- Stromal cells
- Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere
- Theca
- Estrogen-producing cells in a maturing ovarian follicle
- Uterus
- Muscular hollow organ in which a fertilized egg develops into a fetus
- Zygote
- Fertilized OVUM resulting from the fusion of a male and a female gamete
Footnotes
- Karve, Simantini. "Anatomy and Physiology of the Female Reproductive System." Human Physiology for Allied Health Professionals, (2022). This work is openly licensed via CC
BY NC SA 4.0 Creative Commons License. Available from LibreText, Skyline College. - Karve, 2022.
- Karve, 2022.
- Karve, 2022.
- Karve, 2022.
- Karve, 2022.
Image Acknowledgements
- Karve, Simantini. "Anatomy and Physiology of the Female Reproductive System." Human Physiology for Allied Health Professionals, (2022). This work is openly licensed via CC
BY NC SA 4.0 Creative Commons License. Available from LibreText, Skyline College. - Pakurar, Alice S. and John W. Bigbee. Carole W. Christman, Ph.D, Medical Illustrator. Digital Histology, (ND). This work is openly licensed via CC BY SA Creative Commons License. Available from Virginia Commonwealth University. .