Menstruation is a kind of response of the body of a healthy sexually mature woman to cyclical changes in the hormonal background and the course of the most complex physiological processes. In order for a woman to successfully produce a child, safely endure the gestation period and give birth to a healthy baby, the body of the beautiful half of humanity has the most complex system of cyclic transformations regulated by hormones.
During the next menstrual cycle, the body of a healthy woman is preparing for the onset of pregnancy. The whole cycle part is divided into several different phases (periods).
In most cases, the cycle lasts 28 calendar days. And yet, it is necessary to take into account the fact that for each individual woman the cycle duration remains sufficiently individual. It is considered the norm if this period is 21 - 35 days. It is also extremely important to pay attention to the constancy of this period throughout the entire child-bearing age of a woman. The permissible period of deviation is a period not exceeding 3 days. An important indicator is also the amount of bleeding and general well-being of the beautiful half of humanity in this period. Immediately pay attention and sign up for a consultation with a professional gynecologist for any negative changes in the previously formed rhythm or for signs of deterioration of well-being. Such careful attention to their health is extremely important. After all, even the most minor negative changes can be the first signs of the onset of a serious illness.
In the absence of physiological (or hormonal) disorders, each phase always replaces each other in a cyclical order. This helps to ensure the development of the egg and, then, to prepare the woman's body for a possible conception and subsequent pregnancy. The cycle is considered to be the period from the 1st regular hemorrhage until the next.
The cycle is divided into 3 phases:
The menstrual (follicular) phase opens the cycle, it is characterized by the onset of hemorrhage from the body of the uterus occurring due to rejection of the upper (mucous) layer of endometrial tissue. The onset of this phase suggests that the woman could not get pregnant. The first menstrual bleeding occurs in girls of the age group 11-13 years. His medical profession is usually called the "menarche." Hemorrhage is both scarce and, on the contrary, quite abundant. Most women in this period feel such ailments, such as: a general decrease in vitality and pain in the lower abdomen. If no hormonal failure has occurred, and only one follicle has matured in the woman’s body, then during the onset of menstruation, the woman cannot become pregnant, because there are no suitable conditions for fixing and dividing the fertilized egg inside the uterus. This is the longest stage and for conception it is the most important. After the menstrual hemorrhage is complete, the endometrial tissue, the lining of the uterus from the inside under the influence of estrogen can begin to appear again. In addition, follicle-stimulating hormone begins to activate the growth and subsequent development of the follicle inside the ovary. The follicle contains an egg cell and by the end of the 2nd phase it will be completely ready to fertilize the egg cell at least 1 follicle. This phase of the cycle is a preliminary stage to the occurrence of a possible pregnancy. During the course of this phase, swelling and sensitivity of the mammary glands may occur, vaginal discharges can be quite abundant, but they should be transparent. This is due to the fact that the increasing level of the hormone estrogen provides for the appearance of cervical mucous secretions necessary to accelerate the penetration of spermatozoa into the uterus.
The ovulation phase, as a rule, lasts no more than 2 days in a row. During this period, under the influence of the hormone estrogen in the woman's body comes a hormonal peak. This condition contributes to the development of luteinizing substance inside the pituitary gland. During the course of this phase, the dominant follicle breaks. Then, the egg, which is completely ready for the beginning of fertilization, passes into the abdominal cavity. During the course of the ovulation phase, a small bleeding from the vaginal discharge can occur in a woman's body. This period is considered to be the most favorable for fertilization of the egg. In addition, during the period from the 12th to the 15th day of the cycle, the woman may feel a particularly strong sexual desire.
The luteal phase proceeds from the onset of ovulation to the onset of the main menstrual hemorrhage. The follicle accumulates the luteinized hormone inside it and is converted into a yellow body, which actively releases hormones estrogen and progesterone into the blood of a woman. The woman's body is still fully prepared for the entry of a male spermatazoid and the subsequent fertilization of the egg. If the pregnancy comes, progesterone inside the corpus luteum will be released into the woman’s blood until the placenta forms. If there is no conception, the level of hormones will decrease and the next menstrual cycle will begin, consisting of 4 above the listed phases.
When can fluctuations in the menstrual cycle?
The cycle of menstruation, the normal period of which is in the range from 21 to 35 days. However, it can stray from the rhythm, either without additional reasons, or for various physiological reasons. They are considered the norm of “jumps” of the cycle in girls of the adolescent age group or during the waiting period of menopause. All other significant changes in the timing of the menstrual cycle may be a symptom of the development of a physiological disorder.
Affect the timing of the menstrual cycle can:
Infectious diseases. Moreover, among them are not only sexually transmitted diseases, sexually transmitted diseases. Poor quality hygiene procedures, the use of tampons during menstrual hemorrhage, contaminated water, contact with people suffering from infectious diseases can provoke an infection of the genital organs.
Violations of the thyroid gland and adrenal glands. These vital organs play an important role in the proper formation of hormonal levels, which directly affects the cycle duration. In such cases, in order to stabilize the menstrual cycle, you will have to undergo examination and treatment by an endocrinologist,
Psychological problems disorders in the form of prolonged stress and depression can also cause severe fluctuations in menstruation. To restore the cycle, you need to keep your psycho-emotional state in a stable state,
Long-term medication. In this case, to restore the cycle, you may have to cancel the drug and wait some time,
Strict diet or dehydration. In this case, the body will be forced to save its resources, which can also bring down the menstrual cycle or completely stop the menstrual period, causing an early menopause,
Constant poisoning of the body with alcoholic beverages, tobacco smoke, or narcotic compounds,
Hereditary predisposition In some cases, failures may occur for no apparent reason.
What else you need to know about the features of the menstrual cycle?
Having considered each phase of the menstrual cycle in the absence of irregularities, it must be remembered that in most cases, each of the phases rarely begins in exactly the time allotted to it. And this is not always connected with the presence of any disease. Even in the absence of serious violations, each woman’s body retains its individuality. In addition, each menstrual cycle is so delicate and multifaceted process that the process of its flow may depend on a number of factors.
However, serious fluctuations of the cycle will inevitably have a negative impact on the functioning of the brain, the state of the nervous system, as well as the organs that produce the necessary hormones - the main ones being the adrenal glands and the thyroid gland. Therefore, in order to maintain your well-being and to avoid the development of serious diseases, you need to make efforts to eliminate all possible factors that could adversely affect the timing and duration of menstrual hemorrhage, which could drastically change or the time interval between periods.
ADH - antidiuretic hormone
ACTH - Corticoliberin
ARG-Gn - releasing hormone agonist of gonadotropins
LH - luteinizing hormone
OP - oxyprogesterone
RG-Gn - releasing hormone gonadotropinov
STG - somatoliberin
VEGF - Vascular Endothelial Growth Factor
TSH - thyroid-stimulating hormone (thyroliberin)
FSH - follicle-stimulating hormone
FFR - fibroplastic growth factor
Normal menstrual cycle
Menses - This is a bleeding from the female genital tract, periodically resulting from the rejection of the functional layer of the endometrium at the end of a two-phase menstrual cycle.
The complex of cyclic processes that occur in the female body and externally manifest by menstruation is called the menstrual cycle. Menstruation begins as a reaction to changes in the level of steroids produced by the ovaries.
Clinical signs of a normal menstrual cycle
The duration of the menstrual cycle in the active reproductive period of a woman is on average 28 days. The cycle time from 21 to 35 days is considered normal. Large gaps are observed during puberty and menopause, which may be a manifestation of anovulation, which may occur at this time most often.
Typically, menstruation lasts from 3 to 7 days, the amount of blood lost is negligible. Shortening or lengthening of menstrual bleeding, as well as the appearance of scanty or heavy menstruation can be a manifestation of a number of gynecological diseases.
Characteristics of the normal menstrual cycle:
Duration: 28 ± 7 days
The duration of menstrual bleeding: 4 ± 2 days,
The amount of blood loss during menstruation: 20-60 ml*,
Average iron loss: 16 mg
*95 percent of healthy women with each menstruation lose less than 60 ml of blood. Blood loss of more than 60-80 ml is combined with a decrease in the level of hemoglobin, hematocrit and serum iron.
Physiology of menstrual bleeding:
Immediately before menstruation, a pronounced spasm of the spiral arterioles develops. After dilatation of the spiral arterioles, menstrual bleeding begins. Initially, the adhesion of platelets in the endometrial vessels is suppressed, but then, due to blood transudation, the damaged ends of the vessels are sealed with intravascular thrombus, consisting of platelets and fibrin. 20 hours after the onset of menstruation, when most of the endometrium has already been torn away, a pronounced spasm of the spiral arterioles develops, due to which hemo stasis is achieved. Regeneration of the endometrium begins 36 hours after the onset of menstruation, despite the fact that the endometrium rejection is not yet fully completed.
The regulation of the menstrual cycle is a complex neurohumoral mechanism, which is carried out with the participation of 5 main parts of the regulation. These include: the cerebral cortex, subcortical centers (hypothalamus), pituitary, gonads, peripheral organs and tissues (uterus, fallopian tubes, vagina, mammary glands, hair follicles, bones, adipose tissue). The latter are called target organs, due to the presence of receptors that are sensitive to the action of hormones that the ovary produces during the menstrual cycle. Cytozolreceptory - receptors of the cytoplasm, have strict specificity for estradiol, progesterone, testosterone, while nuclear receptors can be acceptors of molecules such as insulin, glucagon, aminopeptides.
Receptors for sex hormones are found in all structures of the reproductive system, as well as in the central nervous system, skin, adipose and bone tissue and the mammary gland. The free steroid hormone molecule is captured by a specific cytosolreceptor of a protein nature, the resulting complex is translocated into the cell nucleus. A new complex with a nuclear protein receptor appears in the nucleus; this complex binds to chromatin that regulates mRNA transcription, which is involved in the synthesis of a specific tissue protein. Intracellular mediator - cyclic adenosine monophosphoric acid (cAMP) regulates the metabolism in the cells of the target tissue in accordance with the needs of the body in response to the effects of hormones. The bulk of steroid hormones (about 80% is in the blood and transported in a bound form. Their transport is carried out by special proteins - steroid-binding globulins and non-specific transport systems (albumin and red blood cells). In a bound form, steroids are inactive, therefore globulins, albumin and erythrocytes can be considered as a kind of buffer system that controls the access of steroids to receptors of target cells.
Cyclic functional changes occurring in a woman's body can be divided into changes in the system of the hypothalamus-pituitary-ovaries (ovarian cycle) and the uterus, primarily in its mucous membrane (uterine cycle).
Along with this, as a rule, cyclic shifts occur in all organs and systems of a woman, in particular, in the central nervous system, cardiovascular system, thermoregulation system, metabolic processes, etc.
The hypothalamus is a part of the brain located above the optic chiasm and forming the bottom of the third ventricle. This is an old and stable component of the central nervous system, whose overall organization has changed little in the process of human evolution. Structurally and functionally, the hypothalamus is associated with the pituitary gland. Three hypothalamic areas are distinguished: anterior, posterior, and intermediate. Each region is formed by nuclei - clusters of bodies of neurons of a certain type.
In addition to the pituitary gland, the hypothalamus affects the limbic system (amygdala, hippocampus), thalamus, bridge. These departments also directly or indirectly affect the hypothalamus.
The hypothalamus secretes liberins and statins. This process is regulated by hormones that close the three feedback loops: long, short, and ultrashort. A long feedback loop is provided by circulating sex hormones that bind to the corresponding receptors in the hypothalamus, a short one: adenohypophysis hormones, ultrashort: liberins and statins. Liberin and statins regulate the activity of the adenohypophysis. Gonadoliberin stimulates the secretion of LH and FSH, corticoliberin - ACTH, somatoliberin (STH), thyroliberin (TSH). In addition to liberin and statins, antidiuretic hormone and oxytocin are synthesized in the hypothalamus. These hormones are transported to the neurohypophysis, from which they enter the blood.
Unlike the capillaries of other areas of the brain, the capillaries of the hypothalamic funnel are fenestrated. They form the primary capillary network of the portal system.
In the 70s-80s. A series of experimental work on monkeys was carried out, which allowed to reveal differences in the function of the neurosecretory structures of the hypothalamus of primates and rodents. In primates and humans, the arcuate nuclei of the mediobasal hypothalamus are the only place of formation and excretion of RH-LH responsible for the gonadotropic function of the pituitary gland. RG-LH secretion is genetically programmed and occurs in a certain pulsating rhythm with a frequency of approximately once per hour. This rhythm is called tsirkhoral (sentry). The region of arcuate nuclei of the hypothalamus is called arcuate oscillator. The circhoral nature of WG-LH secretion was confirmed by directly determining it in the blood of the portal system of the pituitary stalk and jugular vein in monkeys and in the blood of women with ovulatory cycles.
The releasing hormone LH is isolated, synthesized and described in detail. So far, it has not been possible to isolate and synthesize folliberin. RG-LH and its synthetic analogues have the ability to stimulate the release of LH and FSH from the anterior pituitary gland; therefore, one term for the hypothalamic gonadotropic liberins, the releasing hormone of gonadotropins (RG-Gn), is now adopted.
Gnadoliberin stimulates the secretion of FSH and LH. It is a decapeptide secreted by neurons of the funnel nucleus. Gonadoliberin is not secreted continuously, but in a pulsed mode. It is very rapidly destroyed by proteases (half-destruction period is 2-4 minutes), so its impulses must be regular. The frequency and amplitude of emissions of GnRH vary throughout the menstrual cycle. The follicular phase is characterized by frequent fluctuations of a small amplitude of the serum level of gonadoliberin. By the end of the follicular phase, the frequency and amplitude of oscillations increase, and then decrease during the luteal phase.
In the pituitary gland, there are two lobes: the anterior - adenohypophysis and the posterior - neurohypophysis. Нейрогипофиз имеет нейрогенное происхождение и представляет продолжение воронки гипоталамуса. Нейрогипофиз кровоснабжается из нижних гипофизарных артерий.The adenohypophysis develops from the ectoderm of the pocket of Ratke, therefore it consists of glandular epithelium and has no direct connection with the hypothalamus. The liberins and statins synthesized in the hypothalamus enter the adenohypophysis through a special portal system. This is the main source of blood supply to the adenohypophysis. The blood in the portal system mainly enters through the upper pituitary arteries. In the region of the funnel of the hypothalamus, they form the primary capillary network of the portal system, the portal veins are formed from it, which enter the adenohypophysis and give rise to the secondary capillary network. Possible reverse flow of blood through the portal system. Features of the blood supply and the absence of the blood-brain barrier in the region of the funnel of the hypothalamus provide a two-way connection between the hypothalamus and the pituitary gland. Depending on the hematoxylin and eosin staining, the secretory cells of the adenohypophysis are divided into chromophilic (acidophilic) and basophilic (chromophobic). Acidophilic cells secrete growth hormone and prolactin, basophilic cells - FSH, LH, TSH, ACTH
In the adenohypophysis form STH, prolactin, FSH, LH, TSH and ACTH. FSH and LH regulate the secretion of sex hormones, TSH - the secretion of thyroid hormones, ACTH - the secretion of adrenal hormones. STG stimulates growth, has an anabolic effect. Prolactin stimulates the growth of the mammary glands during pregnancy and lactation after delivery.
LH and FSH are synthesized by gonadotropic cells of the adenohypophysis and play an important role in the development of ovarian follicles. By structure, they are referred to as glycoproteins. FSH stimulates follicle growth, the proliferation of granulosa cells, induces the formation of LH receptors on the surface of granulosa cells. Under the influence of FSH, the aromatase content in the maturing follicle increases. LH stimulates the formation of androgens (estrogen precursors) in tech-cells, together with FSH promotes ovulation and stimulates progesterone synthesis in luteinized cells of ovulated follicle granulosis.
The secretion of LH and FSH is variable and modulated by ovarian hormones, especially estrogen and progesterone.
Thus, a low level of estrogen has a suppressive effect on LH, while a high stimulates its production by the pituitary gland. In the late follicular phase, the level of serum estrogens is quite high, the positive feedback effect is tripled, which contributes to the formation of the preovulatory peak of PH. Conversely, during therapy with combined contraceptives, the level of estrogen in the blood serum is within the limits that determine negative feedback, which leads to a decrease in the content of gonadotropins.
The mechanism of positive feedback leads to an increase in receptors concentration and production of WG-H.
In contrast to the effect of estrogen, low progesterone levels have a positive feedback reaction to the secretion of LH and FSH by the pituitary gland. Such conditions exist immediately before ovulation and lead to the release of FSH. A high level of progesterone, which is noted in the luteal phase, reduces the pituitary production of gonadotropins. A small amount of progesterone stimulates the release of gonadotropins at the pituitary level. The negative effect of progesterone feedback is manifested by reducing the production of WG-H and reducing the sensitivity to WG-H at the level of the pituitary gland. The positive feedback effect of progesterone occurs on the pituitary gland and includes an increased sensitivity to WG-H. Estrogens and progesterone are not the only hormones that affect the secretion of gonadotropins by the pituitary gland. The same effect has the hormones inhibin and activin. Inhibin suppresses pituitary FSH secretion, activin stimulates it.
Prolactin Is a polypeptide consisting of 198 amino acid residues, synthesized by lactotropic cells of the adenohypophysis. Prolactin secretion is controlled by dopamine. It is synthesized in the hypothalamus and inhibits the secretion of prolactin. Prolactin has a diverse effect on the female body. Its main biological role is the growth of the mammary glands and the regulation of lactation. It also has a fat mobilizing effect and has a hypotensive effect. Increased secretion of prolactin is one of the common causes of infertility, since an increase in its level in the blood inhibits steroidogenesis in the ovaries and the development of follicles.
Oxytocin - peptide consisting of 9 amino acid residues. It is formed in the neurons of the macrocellular part of the hypothalamus paraventricular nuclei. The main targets of oxytocin in humans are smooth muscle fibers of the uterus and myoepithelial cells of the mammary glands.
Antidiuretic hormone (ADH) is a peptide consisting of 9 amino acid residues. It is synthesized in the neurons of the supraoptic nucleus of the hypothalamus. The main function of ADH - regulation of bcc, blood pressure, plasma osmolality.
The ovaries undergo three phases of the menstrual cycle:
- follicular phase
- luteal phase.
One of the highlights of the follicular phase of the menstrual cycle is the development of the egg. The woman's ovary is a complex organ consisting of many components, the result of the interaction of which is the secretion of sex steroid hormones and the egg is prepared for fertilization in response to the cyclic secretion of gonadotropins.
Hormonal activity from the preantral to peri-ovulatory follicle is described as a “two cell, two gonadotropin” theory. Steroidogenesis occurs in two cells of the follicle: in theca- and granulosa cells. In theca-cells, LH stimulates the production of androgens from cholesterol. In granulosa cells, FSH stimulates the conversion of the resulting androgens into estrogens (aromatization). In addition to the aromatization effect, FSH is also responsible for the proliferation of granulosa cells. Although other mediators are known in the development of ovarian follicles, this theory is fundamental for understanding the processes occurring in the ovarian follicle. It was found that for a normal cycle with a sufficient level of estrogen, both hormones are needed.
The production of androgens in the follicles can also regulate the development of the preanthral follicle. A low level of androgens enhances the process of aromatization, therefore, increases the production of estrogen, and vice versa, high - inhibits the process of aromatization and causes follicle atresia. The balance of FSH and LH is necessary for the early development of the follicle. The optimal condition for the initial stage of follicle development is low LH and high FSH, which occurs at the beginning of the menstrual cycle. If the LH level is high, the theca cells produce a large amount of androgens, causing atresia of the follicles.
Selection of a dominant follicle
Follicle growth is accompanied by secretion of sex steroid hormones under the influence of LH and FSH. These gonadotropins protect the preanthral follicle group from atresia. However, normally only one of these follicles develops to preovulatory, which is then released and becomes dominant.
The dominant follicle in the middle follicular phase is the largest and most developed in the ovary. Already in the first days of the menstrual cycle, it has a diameter of 2 mm and within 14 days by the time of ovulation it increases on average to 21 mm. During this time, a 100-fold increase in the volume of the follicular fluid occurs, the number of granulosa cells lining the basement membrane increases from 0.5x10 6 to 50x10 6. Such a follicle has the highest aromatizing activity and the highest concentration of FSH-induced receptors for LH, therefore the dominant follicle secretes the highest amount of estradiol and inhibin. Further, inhibin enhances the synthesis of androgens under the influence of LH, which is a substrate for the synthesis of estradiol.
In contrast to the FSH level, which decreases with increasing estradiol concentration, the LH level continues to rise (in low concentrations, estradiol inhibits LH secretion). It is the prolonged estrogenic stimulation that prepares the ovulatory peak of LH. At the same time, the dominant follicle is being prepared for ovulation: the number of LH receptors increases on the granular cells under the local action of estrogens and FSH. The release of LH leads to ovulation, the formation of yellow body and an increase in progesterone secretion. Ovulation occurs 10–12 hours after the peak of the LH or 32–35 hours after the start of raising its level. Usually only one follicle ovulates.
During follicle selection, FSH levels decrease in response to the negative effect of estrogens, therefore the dominant follicle is the only one that continues to develop with a falling level of FSH.
The ovarian-pituitary connection is decisive in the choice of the dominant follicle and in the development of atresia of the remaining follicles.
Inhibin and activin
The growth and development of the egg, the functioning of the corpus luteum occurs when the autocrine and paracrine mechanisms interact. It should be noted two follicular hormones that play a significant role in steroidogenesis, inhibin and activin.
Inhibin is a peptide hormone produced by granulosa cells of growing follicles, which reduces the production of FSH. It also affects the synthesis of androgens in the ovary. Inhibin affects folliculogenesis as follows: reducing FSH to a level at which only the dominant follicle develops.
Activin is a peptide hormone produced in the granulosa cells of the follicles and pituitary gland. According to some authors, activin is also produced by the placenta. Activin increases the production of FSH by the pituitary gland, enhances the process of binding FSH to granulosa cells.
Insulin-like growth factors
Insulin-like growth factors (IGF-1 and IGF-2) are synthesized in the liver under the influence of growth hormone and, possibly, in the granular cells of the follicles, act as paracrine regulators. Before ovulation, the content of IGF-1 and IGF-2 in the follicular fluid is increased by increasing the amount of fluid in the dominant follicle. IGF-1 is involved in the synthesis of estradiol. IGF-2 (epidermal) inhibits the synthesis of steroids in the ovaries.
The ovulatory peak of LH leads to an increase in prostaglandin concentration and protease activity in the follicle. The ovulation process itself is a rupture of the dominant follicle basement membrane and bleeding from the destroyed capillaries surrounding the theca cells. Changes in the wall of the preovulatory follicle, ensuring its thinning and rupture, occur under the influence of the enzyme collagenase; prostaglandins contained in the follicular fluid, proteolytic enzymes formed in granular cells, oxytocin and relaxin also play a role. As a result, a small hole is formed in the wall of the follicle, through which the egg slowly leaves. Direct measurements have shown that the pressure inside the follicle does not increase during ovulation.
At the end of the follicular phase, FSH acts on LH receptors in granulosa cells. Estrogens are an essential cofactor in this effect. As the dominant follicle develops, estrogen production increases. As a result, the production of estrogen is enough to achieve secretion of the pituitary LH, which leads to an increase in its level. The increase occurs very slowly at the beginning (from the 8th to the 12th day of the cycle), then quickly (after the 12th day of the cycle). During this time, LH activates the luteinization of granulosa cells in the dominant follicle. Thus, progesterone is released. Further, progesterone enhances the effect of estrogen on the secretion of pituitary LH, leading to an increase in its level.
Ovulation occurs within 36 hours after the start of LH elevation. Determining the release of LH is one of the best methods, which determines ovulation and is carried out using the device "ovulation determinant".
The perovulatory peak of FSH probably occurs as a result of the positive effect of progesterone. In addition to increasing the levels of LH, FSH and estrogens, an increase in serum androgen levels is also noted during ovulation. These androgens are released as a result of the stimulatory effect of LH on tech-cells, especially in the non-dominant follicle.
An increase in the androgen content has an effect on libido enhancement, confirming that this period is the most fertile in women.
LH levels stimulate meiosis after the sperm enters the egg. When an oocyte is secreted from the ovary into ovulation, the wall of the follicle is destroyed. It is regulated by LH, FSH and progesterone, which stimulate the activity of proteolytic enzymes, such as plasminogen activators (which secrete plasmin, stimulating collagenase activity) and prostaglandins. Prostaglandins not only increase the activity of proteolytic enzymes, but also contribute to the appearance of an inflammatory-like reaction in the wall of the follicle and stimulate the activity of smooth muscles, which contributes to the release of the oocyte.
The importance of prostaglandins in the process of ovulation is proven by studies that determine that a decrease in the release of prostaglandin can lead to a delay in the release of the oocyte from the ovary during normal steroidogenesis (syndrome of underdeveloped luteinized follicle — SNLF). Since SNLF is often the cause of infertility, women wishing to become pregnant are advised to avoid taking prostaglandin synthesized synthesizers.
The structure of the yellow body
After the release of the egg from the ovary into the cavity of the follicle, capillaries are rapidly growing, granulose cells undergo luteinization: an increase in their cytoplasm and the formation of lipid inclusions. Granular cells and tektotsity form a yellow body - the main regulator of the luteal phase of the menstrual cycle. The cells that form the wall of the follicle accumulate lipids and yellow pigment lutein and begin to secrete progesterone, estradiol-2, inhibin. A powerful vascular network promotes the entry of yellow body hormones into the systemic circulation. A complete corpus luteum develops only in cases when an adequate number of granulosa cells with a high content of LH receptors is formed in the preovulatory follicle. An increase in the size of the corpus luteum after ovulation occurs mainly due to an increase in the size of granulosa cells, while their number does not increase due to the absence of mitoses. In humans, the corpus luteum secretes not only progesterone, but also estradiol and androgens. The mechanisms of regression of the corpus luteum are not well understood. It is known that prostaglandins have a luteolytic effect.
Fig. Ultrasound picture of the "blooming" yellow body during pregnancy 6 weeks. 4 days. Energy mapping mode.
Hormonal regulation of the luteal phase
If the pregnancy does not occur, the involution of the corpus luteum occurs. This process is regulated by a negative feedback mechanism: hormones (progesterone and estradiol) secreted by the corpus luteum act on the gonadotropic cells of the pituitary gland, inhibiting the secretion of FSH and LH. The secretion of FSH also inhibits inhibin. A decrease in FSH levels, as well as local action of progesterone, inhibits the development of a group of primordial follicles.
The existence of the corpus luteum depends on the level of LH secretion. When it decreases, usually 12-16 days after ovulation, the involution of the corpus luteum occurs. In its place a white body is formed. The mechanism of involution is unknown. Most likely, it is caused by paracrine influences. With the involution of the corpus luteum, the levels of estrogen and progesterone fall, which leads to an increase in the secretion of gonadotropic hormones. As the levels of FSH and LH increase, a new group of follicles begins to develop.
If fertilization has occurred, the existence of the corpus luteum and the secretion of progesterone support chorionic gonadotropin. Thus, the implantation of the embryo leads to hormonal changes that preserve the corpus luteum.
The duration of the luteal phase in most women is constant and is approximately 14 days.
The complex process of biosynthesis of steroids ends with the formation of estradiol, testosterone and progesterone. Steroid-producing tissues of the ovaries are granulosa cells lining the follicle cavity, cells of the internal teka and to a much lesser extent the stroma. Granulosa cells and tech-cells are synergistically involved in the synthesis of estrogens, the cells of the thecal membrane are the main source of androgens, which are also produced in small amounts in the stroma, progesterone is synthesized in the cells and granulosa cells.
In the ovary, 60-100 µg of estradiol (E2) are secreted into the early follicular phase of the menstrual cycle, 270 µg per luteal phase, at the time of ovulation, 400-900 µg per day. About 10% of E2 is aromatized in the ovary from testosterone. The amount of estrone formed in the early follicular phase is 60-100 mcg, by the time of ovulation its synthesis increases to 600 mcg per day. Только половина количества эстрона образуется в яичнике. Вторая половина ароматизируется в Е2. Эстриол является малоактивным метаболитом эстрадиола и эстрона.
Прогестерон образуется в яичнике в количестве 2 мг/сут в фолликулярную фазу и 25 мг/сут в лютеиновую фазу менструального цикла. In the process of metabolism, progesterone in the ovary is converted to 20-dehydroprogesterone, which has a relatively low biological activity.
The following androgens are synthesized in the ovary: Androstenedione (testosterone precursor) in the amount of 1.5 mg / day (the same amount of androstenedione is formed in the adrenal glands). About 0.15 mg of testosterone is formed from androstenedione, approximately the same amount of it is formed in the adrenal glands.
A brief overview of the processes occurring in the ovaries
LH stimulates the production of androgens in theca cells.
FSH stimulates the production of estrogen in granulosa cells.
The most developed follicle in the middle of the follicular phase becomes dominant.
The increasing formation of estrogen and inhibin in the dominant follicle inhibits the secretion of FSH by the pituitary gland.
A decrease in the level of FSH causes atresia of all follicles except the dominant one.
FSH induces LH receptors.
Proteolytic enzymes in the follicle lead to the destruction of its wall and the release of the oocyte.
The corpus luteum is formed from granular and tech-cells that have survived after ovulation.
Progesterone secreted by the corpus luteum is the dominant hormone. In the absence of pregnancy, luteolysis occurs 14 days after ovulation.
Endometrium consists of two layers: functional and basal. The functional layer changes its structure under the action of sex hormones and, if the pregnancy has not occurred, is rejected during menstruation.
The beginning of the menstrual cycle is considered the 1st day of menstruation. At the end of menstruation, the thickness of the endometrium is 1-2 mm. Endometrium consists practically only of the basal layer. The glands are narrow, straight and short, lined with a low cylindrical epithelium, the cytoplasm of stromal cells is almost the same. As estradiol levels increase, a functional layer forms: the endometrium prepares for implantation of the embryo. The glands lengthen and become convoluted. The number of mitoses increases. As proliferation increases, the height of epithelial cells increases, and the epithelium from single-row becomes multi-row by the time of ovulation. The stroma is swollen and loosened, the cell nuclei and the volume of the cytoplasm increase in it. Vessels moderately tortuous.
Normally, ovulation occurs on the 14th day of the menstrual cycle. The secretory phase is characterized by high levels of estrogen and progesterone. However, after ovulation, the number of estrogen receptors in endometrial cells is reduced. Endometrial proliferation is gradually inhibited, DNA synthesis decreases, the number of mitoses decreases. Thus, progesterone has a predominant effect on the endometrium during the secretory phase.
Glycogen-containing vacuoles appear in the glands of the endometrium, which are detected using the CHIC reaction. On the 16th day of the cycle, these vacuoles are rather large, are present in all cells and are under the nuclei. On the 17th day, the nuclei, pushed back by vacuoles, are located in the central part of the cell. On the 18th day, the vacuoles appear in the apical part, and the nuclei in the basal part of the cells, glycogen begins to be released into the lumen of the glands by apocrine secretion. The best conditions for implantation are created on the 6-7th day after ovulation, i.e. on the 20-21st day of the cycle, when the secretory activity of the glands is maximal.
On the 21st day of the cycle, the decidual endometrial stroma begins. The spiral arteries are sharply twisted, later due to a decrease in stromal edema, they are clearly visible. First, decidual cells appear that gradually form clusters. On the 24th day of the cycle, these clusters form perivascular eosinophilic couplings. On the 25th day, islands of decidual cells are formed. By the 26th day of the cycle, the number of neutrophils that migrate there from the blood becomes decidual. Neutrophil infiltration is replaced by necrosis of the endometrial functional layer.
If implantation has not occurred, the glands cease to produce a secret, and degenerative changes begin in the functional layer of the endometrium. The immediate cause of its rejection is a sharp drop in the content of estradiol and progesterone as a result of involution of the corpus luteum. In the endometrium, the venous outflow decreases and the vessels expand. Next, the arteries narrow, resulting in ischemia and tissue damage and functional loss of the endometrium. Then bleeding from arteriole fragments remaining in the basal layer of the endometrium occurs. Menstruation stops when the arteries are narrowed, the endometrium is restored. Thus, the cessation of bleeding in the endometrial vessels is different from hemostasis in other parts of the body.
As a rule, bleeding stops as a result of the accumulation of platelets and fibrin deposition, which leads to scarring. In the endometrium, scarring can lead to a loss of its functional activity (Asherman syndrome). To avoid these effects, an alternative hemostasis system is needed. Vascular contraction is a mechanism to stop bleeding in the endometrium. In this case, scarring is minimized by fibrinolysis, which destroys blood clots. Later restoration of the endometrium and the formation of new blood vessels (angiogenesis) leads to the completion of bleeding within 5-7 days from the start of the menstrual cycle.
The effect of estrogen and progesterone withdrawal on menstruation is well defined, but the role of paracrine mediators remains unclear. Vasoconstrictors: prostaglandin F2a, endothelium-1 and platelet-activating factor (TAF) can be produced within the endometrium and participate in the reduction of blood vessels. They also contribute to the beginning of menstruation and further control over it. These mediators can be regulated by exposure to vasodilating agents such as prostaglandin E2, prostacyclin, nitric oxide, which are produced by the endometrium. Prostaglandin F2a has a pronounced vasoconstrictor effect, increases arterial spasm and endometrial ischemia, causes contractions of the myometrium, which, on the one hand, reduces blood flow, and on the other, helps to remove the rejected endometrium.
Endometrial repair includes glandular and stromal regeneration and angiogenesis. Vascular endothelial growth factor (VEGF) and fibroplastic growth factor (PFR) are found in the endometrium and are potent angiogenic agents. It is revealed that estrogen-produced glandular and stromal regeneration is enhanced under the influence of epidermal growth factors (EGF). Growth factors such as transforming growth factor (TGF) and interleukins, especially interleukin-1 (IL-1), are of great importance.
A brief overview of the processes occurring in the endometrium
The main role at the beginning of menstruation is spasm of arterioles.
The functional layer of the endometrium (upper, constituting 75% of the thickness) is rejected.
Menstruation stops due to vasospasm and endometrial repair. Fibrinolysis prevents the formation of adhesions.
Characterized by estrogen-induced proliferation of glands and stroma.
Characterized by progesterone-induced secretion of glands.
Decidualization is induced in the late secretory phase.
Decidualization is an irreversible process. In the absence of pregnancy in the endometrium apoptosis occurs with the subsequent appearance of menstruation.
So, the reproductive system is a supersystem, the functional state of which is determined by the reverse afferentation of its constituent subsystems. Allocate: a long loop of feedback between the hormones of the ovary and the nuclei of the hypothalamus, between the hormones of the ovary and the pituitary gland, a short loop between the anterior lobe of the pituitary and the hypothalamus, ultrashort between the WG-LH and neurocytes (nerve cells) of the hypothalamus.
Feedback in a mature woman is both negative and positive. An example of a negative connection is the increased release of LH from the anterior pituitary in response to low estradiol levels in the early follicular phase of the cycle. An example of positive feedback is the release of LH and FSH in response to the ovulatory maximum of estradiol in the blood. The mechanism of negative feedback increases the formation of WG-LH with a decrease in the level of LH in the cells of the anterior pituitary gland.
Gonadoliberin is synthesized by neurons of the funnel nucleus, then enters the portal system of the pituitary gland and enters the adenohypophysis through it. Gonadoliberin secretion occurs impulsively.
The early stage of development of a group of primordial follicles does not depend on FSH.
With the involution of the corpus luteum, the secretion of progesterone and inhibin decreases and the level of FSH increases.
FSH stimulates the growth and development of a group of primordial follicles and their secretion of estrogen.
Estrogens prepare the uterus for implantation, stimulating the proliferation and differentiation of the functional layer of the endometrium and together with FSH contribute to the development of follicles.
According to the two-cell theory of the synthesis of sex hormones, LH stimulates the synthesis of androgens in techocytes, which are then transformed into estrogens in granulosa cells under the influence of FSH.
The increase in the concentration of estradiol on the mechanism of negative feedback, loop
which closes in the pituitary and hypothalamus, inhibits the secretion of FSH.
A follicle that will ovulate in a given menstrual cycle is called dominant. Unlike other follicles that have begun to grow, it carries a larger number of FSH receptors and synthesizes more estrogens. This allows it to develop, despite the decrease in the level of FSH.
Adequate estrogenic stimulation provides the ovulatory peak of LH. It, in turn, causes ovulation, the formation of the yellow body and the secretion of progesterone.
The functioning of the corpus luteum depends on the level of LH. When it decreases, the corpus luteum undergoes involution. This usually happens on the 12-16th day after ovulation.
If fertilization has occurred, the existence of the corpus luteum supports chorionic gonadotropin. The corpus luteum continues to secrete progesterone, which is necessary to preserve early pregnancy.
What phases is the cycle divided into?
All three periods ensure the proper functioning of the female reproductive system. They are divided according to certain changes that occur under the action of hormonal levels:
Most women have no idea when each of them comes, what it is typical for and what happens in the body. This knowledge is very important for planning pregnancy, timely recognition of body signals about disruptions in work and preventing the development of diseases not only of the urinary, but also the endocrine system.
The menstrual cycle, as well as its duration, varies from one woman to another, but the changes that occur during these periods are the same for all healthy women. They are usually divided into phases of the menstruation cycle by day and by the readiness of the female body for fertilization.
But also the phases of the menstrual cycle are classified according to characteristic signs and changes occurring under the influence of hormones in the uterus. Each of the phases is characterized by changes in the inner layer of the endometrium, and they are called for characteristic signs. Already from the name you can understand what exactly is happening in a month:
Those periods, which are not known to everyone, but they are definitely heard about, occur in the ovaries and end in the uterine cavity.
The first phase of the menstrual cycle begins its action from the first day of the bleeding. While the uterus rejects the unnecessary inner layer, which grew during the last cycle, a new period of the menstrual cycle begins in the ovaries, its phases gradually pass from the first day.
Endometrial dying cells come out as menstrual bleeding, these are particles of the inner lining of the uterus, as well as blood from damaged vessels. The contraction of the walls of the uterus to reject this layer occurs under the action of contraction of smooth muscles, hence the occurrence of pain and discomfort during menstruation.
The menstrual phase lasts an average of 3 to 7 days, if the bleeding does not stop after a week, this may indicate pathological disorders.
The blood itself in these secretions is not more than a third part, so the monthly discharge should not cause unpleasant effects on health and does not affect the blood formation in any way.
While the uterus rejects the lining, a new menstrual cycle is born in the ovaries. In the brain in the area of the pituitary and hypothalamus, the processes that trigger the work of the ovaries occur, under the influence of hormones in one of the appendages, several follicles start to develop at once from those stocks that nature has laid at birth. Begin their growth from 7 to 12 pieces a maximum, for a week they reach impressive sizes. At this point, the most viable follicle is determined by natural selection, and it begins to progress further, the others atrophy and gradually disappear.
The most capable follicle is called dominant, its development occurs under the action of the hormone FSH (follicle-stimulating hormone). If for some reason there is an imbalance, then the follicle may not develop to its logical end and go into the persistence stage, or, having reached the required size, it simply does not burst at the right time. Until the time of rupture of the sheath, phase 1 of the menstrual cycle continues.
When the egg is ready to go out of the shell, and hormonal changes occur in the body, the 2nd phase of the menstrual cycle starts. The uterus at this stage begins to secrete, and the endometrium begins to grow again. Under the action of luteinizing hormone, the membrane of the dominant follicle is broken, the viable cell goes outside.
With a normal cycle of 28 days, ovulation occurs on the 14-15 day of the menstrual cycle. From the beginning of the monthly period, at least 7-9 days should pass to the full maturation of the egg.
Stressful situations, various diseases, a way of life can affect the process of ovulation, so laid by nature that the body selects the optimal day for conception and ovulation can occur sooner or later. It may not occur, and such a cycle is called anovulatory cycle. They can normally be several per year, this is not considered a pathology, but a feature of the body in women.
If ovulation took place in the second part, conception is possible. Women in most cases do not feel any changes, and to determine the onset of ovulation is possible only on ultrasound or doing home tests to determine the level of LH. But you can also observe ovulation by measuring and fixing the basal temperature, a special table will help to observe the fluctuations of indicators.
The process lasts no more than 2 days, at this time, the egg, getting into the abdominal cavity, is captured by the fibers of the fallopian tube and gets inside, where she, moving into the uterus, can meet with the spermatozoon and conception occurs. The life of the egg is not more than 36 hours after the rupture of the follicle and its release from the membrane.
The final stage begins from the moment of movement completely ready for fertilization of the egg. In place of a torn follicle, a temporary gland is formed, which is called the corpus luteum. This is a complete organ of the endocrine system, which begins to produce progesterone for the successful insertion of a fertilized egg and proliferation of the endometrium.
Produced estrogen prepares the female body for pregnancy, but if it does not come, other processes occur. The body is preparing for conception, and the woman is gaining weight, there are changes in the area of the mammary glands. All indicators return to normal after menstruation.
If the egg has met in the fallopian tube with the sperm cell, and conception has occurred, it moves further, it turns out, in the uterus. There it is attached to the previously prepared endometrium and under the action of progesterone forms its own placenta. Until the appearance of a full-fledged shell, the yellow body performs a protective function for it and then dies as superfluous.
Temporary gland exists from 10 to 14 days, for all this indicator is individual. After that, the hormones to support possible pregnancy cease to be produced, and their concentration is significantly reduced compared to estrogen.
If the pregnancy has not come, the corpus luteum gradually fades away, and by 28-30 days from the beginning of the cycle the unfertilized egg together with the particles of the endometrium and the blood comes out in the form of menstruation. By the first day of the new month in the appendages there is no trace of all the processes taking place there.
The menstrual cycle enables a woman to fulfill her mission and take out and give birth to a healthy child. Observing your cycle helps in planning a pregnancy, preventing it, and in a timely manner gives you the opportunity to notice pathological changes and consult a doctor even before the appearance of unpleasant symptoms.