Menstrual cycle

The menstrual cycle is genetically determined, cyclically repetitive changes in a woman’s body, especially in the links of the reproductive system, the clinical manifestation of which is blood discharge from the genital tract (menstruation).

The menstrual cycle is established after the menarche (first menstruation) and lasts for the reproductive (childbearing) period of a woman’s life before menopause (last menstruation). Cyclic changes in the woman’s body are aimed at the possibility of reproduction of offspring and are biphasic: the 1st (follicular) phase of the cycle is determined by the growth and maturation of the follicle and egg in the ovary, after which the follicle breaks and the egg leaves it – ovulation; 2nd (luteal) phase is associated with the formation of the corpus luteum. At the same time in a cyclic mode, successive changes occur in the endometrium: regeneration and proliferation of the functional layer, followed by secretory transformation of the glands. Changes in the endometrium end with desquamation of the functional layer (menstruation).

The biological significance of the changes that occur during the menstrual cycle in the ovaries and endometrium, is to ensure the reproductive function after the maturation of the egg, its fertilization and implantation of the embryo in the uterus. If the fertilization of the egg does not occur, the functional layer of the endometrium is rejected, blood secretions appear from the genital tract, and in the reproductive system again and in the same sequence processes occur, aimed at ensuring the maturation of the egg.

Menstruation is a blood discharge from the reproductive tract that repeats at regular intervals throughout the reproductive period, excluding pregnancy and lactation. Menstruation begins at the end of the luteal phase of the menstrual cycle as a result of rejection of the functional layer of the endometrium. The first menstruation (menarhe) occurs at the age of 10-12 years. During the next 1–1.5 years, menstruation may be irregular, and only then a regular menstrual cycle is established.

The first day of menstruation is conventionally taken as the 1st day of the menstrual cycle, and the cycle duration is calculated as the interval between the first days of two successive menstruations.

External parameters of the normal menstrual cycle: Duration – from 21 to 35 days (60% of women have an average cycle duration of 28 days); the duration of menstrual flow is from 3 to 7 days; the value of blood loss in menstrual days is 40-60 ml (on average 50 ml).

The processes that ensure the normal flow of the menstrual cycle are regulated by a single, functionally connected neuroendocrine system, including central (integrating) divisions, peripheral (effector) structures, as well as intermediate links.

The functioning of the reproductive system is ensured by a strictly genetically programmed interaction of five basic levels, each of which is regulated by the overlying structures according to the principle of direct and inverse, positive and negative interconnection.

The first (highest) level of regulation of the reproductive system are the cerebral cortex and extrahypothalamic cerebral structures.
(limbic system, hippocampus, amygdala). Adequate state of the central nervous system ensures the normal functioning of all the lower parts of the reproductive system. Various organic and functional changes in the cortex and subcortical structures can lead to menstrual disorders. The possibility of stopping menstruation under severe stress (loss of close people, wartime conditions, etc.) or without obvious external influences with general mental imbalance (“false pregnancy” – delay of menstruation with a strong desire for pregnancy or, on the contrary, with its fear ).

Specific neurons of the brain receive information about the state of both the external and internal environment. Internal exposure is carried out using specific receptors for ovarian steroid hormones (estrogen, progesterone, androgen), located in the central nervous system. In response to the impact of environmental factors on the cerebral cortex and extrahypothalamic structures, the synthesis, release and metabolism of neurotransmitters and neuropeptides occur. In turn, neurotransmitters and neuropeptides affect the synthesis and secretion of hormones by the neurosecretory nuclei of the hypothalamus.

To the most important neurotransmitters, i.e. nerve impulse transmitters include norepinephrine, dopamine, γ-aminobutyric acid (GABA), acetylcholine, serotonin, and melatonin. Noradrenaline, acetylcholine and GAM K stimulate the release of gonadotropic releasing hormone (GnRH) by the hypothalamus. Dopamine and serotonin reduce the frequency and reduce the amplitude of GnRH production during the menstrual cycle.

Neuropeptides (endogenous opioid peptides, neuropeptide U, galanin) are also involved in regulating the function of the reproductive system. Opioid peptides (endorphins, enkephalins, dinorphins), by binding to opiate receptors, lead to the suppression of GnRH synthesis in the hypothalamus.

The second level of regulation of reproductive function is the hypothalamus. Despite its small size, the hypothalamus is involved in the regulation of sexual behavior, monitors vegetovascular reactions, body temperature and other vital functions of the body.

The pituitary gland of the hypothalamus is represented by groups of neurons constituting the neurosecretory nuclei: ventromedial, dorsomedial, arcuate, supraoptic, paraventricular. These cells have properties like neurons (reproducing electrical impulses) and endocrine cells that produce specific neurosecretes with diametrically opposite effects (liberins and statins). JIu- berins, or releasing factors, stimulate the release of the corresponding tropic hormones in the anterior lobe of the pituitary gland. Statins have an inhibitory effect on their secretion. Currently, seven liberins are known, which by their nature are decapeptides: thyreoliberin, corticoliberin, somatoliberin, melanoliberin, folliberin, luliberin, prolactoliberin, as well as three statins: melanostatin, somatostatin, prolactostatin, or prolactin inhibitor factor.

Luliberin, or luteinizing hormone releasing hormone (HLHH), is isolated, synthesized and described in detail. So far, it has not been possible to isolate and synthesize follicle-stimulating releasing hormone. However, it has been established that RHLG and its synthetic analogs stimulate the release of gonadotrophs of not only LG, but also FSH. In this regard, one term for gonadotropic liberins is adopted – “gonadotropin-releasing hormone” (GnRH), which is essentially a synonym for lyuliberin (RHLG).

The main site of GnRH secretion is arcuate, supraoptic and paraventricular nuclei of the hypothalamus. Arcuate nuclei reproduce a secretory signal with a frequency of approximately 1 pulse of 1-3 h, i.e. in the pulsating or tsirkhoralny mode (circhoral – around an hour). These impulses have a certain amplitude and cause a periodic flow of GnRH through the portal system of blood flow to the cells of the adenohypophysis. Depending on the frequency and amplitude of GnRH pulses in the adenohypophysis, the primary secretion of LH or FSH occurs, which, in turn, causes morphological and secretory changes in the ovaries.

The hypothalamic-pituitary region has a special vascular network, which is called the portal system. A feature of this vascular network is the ability to transfer information from the hypothalamus to the pituitary and back (from the pituitary to the hypothalamus).

Regulation of the release of prolactin to a greater extent is under the influence of statins. Dopamine, which is formed in the hypothalamus, inhibits the release of prolactin from the lactotrophs of the adenohypophysis. An increase in secretion of prolactin is promoted by thyroliberin, as well as serotonin and endogenous opioid peptides.
In addition to liberin and statin, in the hypothalamus (supraoptic and paraventricular nuclei) two hormones are produced: oxytocin and vasopressin (antidiuretic hormone). The granules containing these hormones migrate from the hypothalamus along the axons of the large-cell neurons and accumulate in the posterior lobe of the pituitary (neurohypophysis).

The third level of regulation of reproductive function is the pituitary gland; it consists of the anterior, posterior, and intermediate (middle) lobes. The anterior lobe (adenohypophysis) is directly related to the regulation of reproductive function. Under the influence of the hypothalamus, gonadotropic hormones are secreted in the adenohypophysis: FSH (or follitropin), LH (or lutropin), prolactin (Prl), ACTH, somatotropic (STH), and thyrotropic (TSH) hormones. Normal functioning of the reproductive system is possible only with a balanced allocation of each of them.

Gonadotropic hormones (FSH, HG) of the anterior pituitary are controlled by GnRH, which stimulates their secretion and release into the bloodstream. The pulsating nature of the secretion of FSH, LG is the result of “direct signals” from the hypothalamus. The frequency and amplitude of GnRH secretion pulses varies depending on the phases of the menstrual cycle and affects the concentration and ratio of FSH / LH in the blood plasma.

FSH stimulates follicle growth and egg cell maturation, granular cell proliferation, the formation of FSH and LH receptors on the surface of granular cells, aromatase activity in the maturing follicle (this increases the conversion of androgens to estrogens), production of inhibin, activin and insulin-like factors.

LH promotes the formation of androgens in the cells, provides ovulation (in conjunction with FSH), stimulates progesterone synthesis in luteinized granulosa cells (yellow body) after ovulation.
Prolactin has a diverse effect on the female body. Its main biological role is stimulation of breast growth, regulation of lactation; it also has a fat mobilizing and hypotensive effect, controls the secretion of progesterone by the corpus luteum by activating the formation of receptors in it in the LG. During pregnancy and lactation, the level of prolactin in the blood increases. Hyperprolactinemia leads to impaired growth and maturation of follicles in the ovary (anovulation).

The posterior lobe of the pituitary (neurohypophysis) is not an endocrine gland, but only deposits the hormones of the hypothalamus (oxytocin and vasopressin), which are found in the body as a protein complex.

The ovaries belong to the fourth level of regulation of the reproductive system and perform two main functions. Cyclic growth and maturation of follicles, egg maturation, i.e. generative function is carried out, as well as the synthesis of sex steroids (estrogens, androgens, progesterone) – hormonal function.

The main morphofunctional unit of the ovary is the follicle. At birth, there are approximately 2 million primordial follicles in the girl’s ovaries. Their main mass (99%) during life undergoes atresia (reverse development of follicles). Only a very small part of them (300–400) goes through the full cycle of development — from the primordial to the preovulatory, with the subsequent formation of the corpus luteum. By the time of the menarche, the ovaries contain 200-400 thousand primordial follicles.

The ovarian cycle consists of two phases: follicular and luteal. The follicular phase begins after menstruation, is associated with the growth and maturation of the follicles and ends in ovulation. The luteal phase occupies a period after ovulation before the onset of menstruation and is associated with the formation, development and regression of the corpus luteum, whose cells secrete progesterone.

Depending on the degree of maturity, four types of follicles are distinguished: primordial, primary (preantralic), secondary (antral) and mature (preovulatory, dominant).

The primordial follicle consists of an immature egg cell (oocyte) in the prophase of the 2nd meiotic division, which is surrounded by one layer of granular cells. In the preantral (primary) follicle, the oocyte increases in size. The granular epithelium cells proliferate and round, forming a granular layer of the follicle. A connective tissue is formed from the surrounding stroma — a non-woven sheath — theca.

The antral (secondary) follicle is characterized by further growth: the proliferation of cells of the granular layer that produce follicular fluid continues. The resulting fluid pushes the egg to the periphery, where the cells of the granular layer form an egg-bearing tubercle (cumulus oophorus). The connective tissue sheath of the follicle is clearly differentiated into the outer and inner. The inner shell (theca interna) consists of 2-4 layers of cells. The outer sheath (theca externa) is located above the inner and is represented by a differentiated connective tissue stroma.

In the pre-ovulatory (dominant) follicle, the egg cell located on the egg-bearing tubercle is covered with a membrane called a shiny membrane (zona pellucida). In the oocyte of the dominant follicle, the process of meiosis resumes. During maturation in the preovulatory follicle, a 100-fold increase in the volume of the follicular fluid occurs (the follicle diameter reaches 20 mm). During each menstrual cycle, from 3 to 30 primordial follicles begin to grow, transforming into preantral (primary) follicles. In the subsequent menstrual cycle, folliculogenesis continues and only one follicle develops from the preantral to the preovulatory. In the process of growth of the follicle from preantral to antral granulosa cells, an antimuller hormone is synthesized, which contributes to its development. The remaining follicles that initially entered growth undergo atresia (degeneration).

Ovulation is the rupture of the preovulatory (dominant) follicle and the release of the egg cell from it into the abdominal cavity. Ovulation is accompanied by bleeding from the destroyed capillaries surrounding the cells.

After the release of the egg into the remaining cavity of the follicle, capillaries formed are rapidly growing. Granulosa cells undergo lyutherapy and —nazation, morphologically manifested in an increase in their volume and the formation of lipid inclusions — a yellow body forms.

The corpus luteum is a transient hormone-active formation that functions for 14 days, regardless of the total duration of the menstrual cycle. If the pregnancy has not come, the corpus luteum regresses, if fertilization occurs, it functions until the formation of the placenta (12th week of pregnancy).

local_offerevent_note January 29, 2019

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