For what is the decrease in estrogen and progesterone during the menstrual cycle responsible quizlet?

The female reproductive system is a wonderfully complex system involving continuous communication between the brain centers and the ovary. Hormones secreted by the hypothalamus, the pituitary and the ovary are the messengers that regulate the monthly cycle.

The Hypothalamus and the Pituitary

The hypothalamus is located centrally in the brain and communicates by way of an exchange of blood with the pituitary gland. Several neuroendocrine agents, or hormones, are produced by the hypothalamus. The most important hormone for reproduction is called gonadotropin releasing hormone, better known as GnRH. It is released in a rhythmic fashion every 60 to 120 minutes.

GnRH stimulates the pituitary gland to produce follicle stimulating hormone (FSH), the hormone responsible for starting follicle (egg) development and causing the level of estrogen, the primary female hormone, to rise. Leutinizing hormone (LH), the other reproductive pituitary hormone, aids in egg maturation and provides the hormonal trigger to cause ovulation and the release of eggs from the ovary.

The Ovary

The main function of the ovaries is the production of eggs and hormones. At birth, the ovaries contain several million immature eggs. No new eggs will be developed. These eggs are constantly undergoing a process of development and loss. Most will die without reaching maturity. This process of egg loss occurs at all times, including before birth, before puberty and while on birth control pills. The ovary undergoes a constant process of egg depletion throughout its lifetime.

As the levels of FSH and LH in the blood increase with puberty, the eggs begin to mature and a collection of fluid — the follicle — begins to develop around each one.

The first day of menses is identified as cycle day one. Estrogen is at a low point. Therefore, the pituitary secretes FSH and LH, a process which actually begins before the onset of your menses. These hormones in turn stimulate the growth of several ovarian follicles, each containing one egg. The number of follicles in the monthly "cohort" of developing follicles is unique to each individual. One follicle will soon begin to grow faster than others. This is called the dominant follicle.

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As the follicle grows, blood levels of estrogen rise significantly by cycle day seven. This increase in estrogen begins to inhibit the secretion of FSH. The fall in FSH allows smaller follicles to die off. They are, in effect, "starved" of FSH.

Ovulation

When the level of estrogen is sufficiently high, it produces a sudden release of LH, usually around day thirteen of the cycle. This LH peak triggers a complex set of events within the follicles that result in the final maturation of the egg and follicular collapse with egg extrusion. Ovulation takes place 28 to 36 hours after the onset of the LH surge and 10 to 12 hours after LH reaches its peak.

The cells in the ovarian follicle that are left behind after ovulation undergo a transformation and become the corpus luteum. In addition to estrogen, they now produce high amounts of progesterone to prepare the lining of the uterus for implantation.

The Luteal Phase

The luteal phase, or second half of the menstrual cycle, begins with ovulation and lasts approximately 14 days — typically 12 to 15 days.

During this period, changes occur that will support the fertilized egg, which is called an embryo, should pregnancy result. The hormone responsible for these changes is progesterone, which is manufactured by the corpus luteum. Under the influence of progesterone, the uterus begins to create a highly vascularized bed for a fertilized egg.

If a pregnancy occurs, the corpus luteum produces progesterone until about 10 weeks gestation. Otherwise, if no embryo implants, the circulating levels of hormone decline with the degeneration of the corpus luteum and the shedding of the lining of the uterus (endometrium), leading to bleeding.

The Uterus

The lining of the uterus, or endometrium, prepares each month for the implantation of an embryo. This preparation occurs under the influence of estrogen and progesterone from the ovary. If no pregnancy develops, the endometrium is shed as a menstrual period, about fourteen days after ovulation.

Introduction

The reproductive system of a female, unlike men, shows regular cyclic changes that teleologically may be regarded as periodic preparation for pregnancy and fertilization. In primates and humans, the cycle is a menstrual cycle, and its most conspicuous feature is the periodic vaginal bleeding that occurs with the shedding of uterine mucose (menstruation). The length of the cycle is notoriously variable, but an average figure is 28 days from the start of one menstrual period to the start of the next. By common usage, the days of the cycle are identified by number starting with the first day of menstruation. It begins at puberty, ranging from the ages of 10 to 16, and ends at menopause at an average age of 51.[1][2][3]

Function

Hormones are secreted in a negative and positive feedback manner to control the menstrual cycle. Hormone secretion begins in the hypothalamus where gonadotropin-releasing hormone (GnRH) is secreted in an increased, pulsatile fashion once puberty starts. GnRH is then transported to the anterior pituitary, where it activates its 7-transmembrane G-protein receptor. This provides a signal to the anterior pituitary to secrete stimulating follicle hormone (FSH) and luteinizing hormone (LH). FSH and LH provide input to the ovaries. Within the ovarian follicle, there are 2 cell types responsible for hormone production, theca cells, and granulosa cells. LH stimulates theca cells to produce progesterone and androstenedione by activating the enzyme, cholesterol desmolase. Once androstenedione is secreted, the hormone diffuses to the nearby granulosa cells. Here, FSH stimulates the granulosa cells to convert androstenedione to testosterone then 17-beta-estradiol by activating the enzyme, aromatase. As levels of 17-beta-estradiol or progesterone increase based on the phases of the menstrual cycle, there is negative feedback back to the anterior pituitary to lower the levels of FSH and LH being produced and subsequently, the levels of 17-beta-estradiol and progesterone produced. An exception to this is during ovulation. In this case, once a critical amount of 17-beta-estradiol is produced, it provides positive feedback to the anterior pituitary to produce increased amounts of FSH and LH. This feedback system is represented in figure 1. Additionally, within the feedback system, the granulosa cells produce inhibin and activin, which inhibit and stimulate FSH release from the anterior pituitary, respectively. This feedback mechanism is controlled by upregulating, to increase hormone production, or downregulating to decrease hormone production, the GnRH receptors on the anterior pituitary.[4][5][6]

Mechanism

Phase 1: The Follicular, or Proliferative Phase

The first phase of the menstrual cycle is the follicular or proliferative phase. It occurs from day one to day 14 of the menstrual cycle, based on the average duration of 28 days. The variability in the length of the menstrual cycle occurs due to variations in the length of the follicular phase. The main hormone during this phase is estrogen, specifically 17-beta-estradiol. The increase in this hormone occurs by the upregulation of the FSH receptors within the follicle at the beginning of the cycle. However, as the follicular phase progresses to the end, the increased amounts of 17-beta-estradiol will provide negative feedback to the anterior pituitary. The purpose of this phase is to grow the endometrial layer of the uterus. 17-beta-estradiol achieves this by increasing the growth of the endometrial layer of the uterus, stimulating increased amounts of stroma and glands, and increasing the depth of the arteries that supply the endometrium, the spiral arteries.

Additionally, this phase is also essential to create an environment that is friendly and helpful to possible incoming sperm. 17-beta-estradiol achieves this by creating channels within the cervix, allowing for sperm entry.[7] The channels are made within the abundant, watery, and elasticity changes of the cervical mucous. During this phase, a primordial follicle begins to mature into a Graafian follicle. The surrounding follicles begin to degenerate, which is when the Graafian follicle becomes the mature follicle. This sets up the follicle for ovulation, the next step.

Ovulation

Ovulation always occurs 14 days before menses; therefore, with an average 28-day cycle, ovulation occurs on day 14. At the end of the proliferative phase, 17-beta-estradiol levels are at a high due to the follicle maturation and increased production of the hormone. During this time only, 17-beta-estradiol provides positive feedback for FSH and LH production. This occurs when a critical level of 17-beta-estradiol is reached, at least 200 picograms per milliliter of plasma. The high levels of FSH and LH present during this time is called the LH surge. As a result, the mature follicle breaks, and an oocyte is released. The changes to the cervix as initiated during the follicular phase further increase, allowing for increased, waterier cervical mucous to better accommodate the possible sperm—the levels of 17-beta-estradiol fall at the end of ovulation. 

Phase 2: The Luteal or Secretory Phase

The next phase of the menstrual cycle is the luteal or secretory phase. This phase always occurs from day 14 to day 28 of the cycle. Progesterone stimulated by LH is the dominant hormone during this phase to prepare the corpus luteum and the endometrium for possible fertilized ovum implantation. As the luteal phase ends, progesterone will provide negative feedback to the anterior pituitary to decrease FSH and LH levels and, subsequently, the 17-beta-estradiol and progesterone levels. The corpus luteum is a structure formed in the ovary at the site of the mature follicle rupture to produce 17-beta-estradiol and progesterone, which is predominant at the end of the phase due to the negative feedback system. The endometrium prepares by increasing its vascular supply and stimulating more mucous secretions. This is achieved by the progesterone stimulating the endometrium to slow down endometrial proliferation, decrease lining thickness, develop more complex glands, accumulate energy sources in the form of glycogen, and provide more surface area within the spiral arteries.

Contrary to the cervical mucous changes seen during the proliferative phase and ovulation, progesterone decreases and thickens the cervical mucous making it non-elastic since the fertilization period passed, and sperm entry is no longer a priority. Additionally, progesterone increases the hypothalamic temperature, so body temperature increases during the luteal phase. Near the end of the secretory phase, plasma levels of 17-beta-estradiol and progesterone are produced by the corpus luteum. If pregnancy occurs, a fertilized ovum is implanted within the endometrium, and the corpus luteum will persist and maintain the hormone levels. However, if no fertilized ovum is implanted, then the corpus luteum regresses, and the serum levels of 17-beta-estradiol and progesterone decrease rapidly.

Normal Menstruation

When the hormone levels decrease, the endometrium layer, as it has been changed throughout the menstrual cycle, is not able to be maintained. This is called menses, considered day 0 to day 5 of the next menstrual cycle. The duration of menses is variable. Menstrual blood is chiefly arterial, with only 25% of the blood being venous blood. It contains prostaglandins, tissue debris, and relatively large amounts of fibrinolysis from endometrial tissue. The fibrinolysis lyses the clot so that menstrual blood does not contain clots typically unless the flow is heavy. 

The usual duration of the menstrual flow is 3-5 days, but flows as shorts as 1 day and as long as 8 days can occur in a normal female. The amount of blood loss can range from slight spotting to 80 mL and the average being 30 mL. Loss of more than 80 mL of the blood is considered abnormal. Various factors can affect the amount of blood flow, including medications, the thickness of the endometrium, blood disorders, and disorders of blood clotting, etc.

Pathophysiology

Anovulatory Cycles

In some cases, ovulation fails to occur during the menstrual cycle. Such cycles are called anovulatory cycles, and they are common for the first 12-18 months after menarche (The occurrence of the first menstrual period) and again before the onset of menopause. When ovulation does not occur, usually no corpus luteum is found, and the effect of progesterone on the endometrium is absent.[8] Estrogen continues to cause the growth of the endometrium, however, and the proliferative endometrium becomes thick enough to break down and begin to slough. The time it takes for the bleeding to occur is fluctuating, but it generally occurs in less than 28 days from the previous menstrual period. The flow is also inconsistent and ranges from scanty to relatively profuse.[9]

Clinical Significance

A female has an average of 450 menses throughout her lifetime; therefore, it is important to understand the menstrual cycle and its physiology because of the various complications, consequences, and distress that it may have for a female patient. A female presenting with primary or secondary amenorrhea will need to undergo clinical testing to diagnose the reason. Still, reasonable testing from the level of the ovaries to the hypothalamus cannot be performed unless a clinician thoroughly understands the hormone feedback system. Additionally, there may be problems with her menses themselves, such as premenstrual syndrome, dysmenorrhea, or menorrhagia. Without an understanding of the female anatomy and menstrual cycle physiology, a clinician would be unable to obtain a complete history and physical to allow understanding of the underlying cause. Infertility is a prominent issue in our society, and the menstrual cycle is the basis for how a woman’s body prepares for pregnancy, so each patient’s menstrual cycle must be evaluated as a possible area of concern for her infertility. As clinicians, we must understand the menstrual cycle in its entirety to provide relevant clinical care to our female patients.[10][11][12]

Figure

Hormone secretion feedback system; Hormone variation throughout the menstrual cycle. Contributed by Dhanalakshmi Thiyagarajan

References

Rosner J, Samardzic T, Sarao MS. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Oct 9, 2021. Physiology, Female Reproduction. [PubMed: 30725817]

Coast E, Lattof SR, Strong J. Puberty and menstruation knowledge among young adolescents in low- and middle-income countries: a scoping review. Int J Public Health. 2019 Mar;64(2):293-304. [PMC free article: PMC6439145] [PubMed: 30740629]

Pan B, Li J. The art of oocyte meiotic arrest regulation. Reprod Biol Endocrinol. 2019 Jan 05;17(1):8. [PMC free article: PMC6320606] [PubMed: 30611263]

Harlow SD. Menstrual Cycle Changes as Women Approach the Final Menses: What Matters? Obstet Gynecol Clin North Am. 2018 Dec;45(4):599-611. [PubMed: 30401545]

Gibson DA, Simitsidellis I, Collins F, Saunders PTK. Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders. Int J Mol Sci. 2018 Oct 22;19(10) [PMC free article: PMC6214123] [PubMed: 30360364]

Pepe G, Locati M, Della Torre S, Mornata F, Cignarella A, Maggi A, Vegeto E. The estrogen-macrophage interplay in the homeostasis of the female reproductive tract. Hum Reprod Update. 2018 Nov 01;24(6):652-672. [PubMed: 30256960]

Herbison AE. A simple model of estrous cycle negative and positive feedback regulation of GnRH secretion. Front Neuroendocrinol. 2020 Apr;57:100837. [PubMed: 32240664]

Thomas VG. The Link Between Human Menstruation and Placental Delivery: A Novel Evolutionary Interpretation: Menstruation and fetal placental detachment share common evolved physiological processes dependent on progesterone withdrawal. Bioessays. 2019 Jun;41(6):e1800232. [PubMed: 31119755]

Carlson LJ, Shaw ND. Development of Ovulatory Menstrual Cycles in Adolescent Girls. J Pediatr Adolesc Gynecol. 2019 Jun;32(3):249-253. [PMC free article: PMC6570576] [PubMed: 30772499]

van Duursen MBM. Modulation of estrogen synthesis and metabolism by phytoestrogens in vitro and the implications for women's health. Toxicol Res (Camb). 2017 Nov 01;6(6):772-794. [PMC free article: PMC6062382] [PubMed: 30090542]

Gunn HM, Tsai MC, McRae A, Steinbeck KS. Menstrual Patterns in the First Gynecological Year: A Systematic Review. J Pediatr Adolesc Gynecol. 2018 Dec;31(6):557-565.e6. [PubMed: 30064002]

Alvergne A, Högqvist Tabor V. Is Female Health Cyclical? Evolutionary Perspectives on Menstruation. Trends Ecol Evol. 2018 Jun;33(6):399-414. [PubMed: 29778270]

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