Neuroendocrinal regulation of women’s reproductive organs.

1.Relevance The investigation methods of has a great value for studying subject. Modern knowledge about the menstrual function, neuroendocrinological regulation of the female reproductive system function, role of hormones and biological active substances are at the heart of gynecology. The knowledge of normal menstrual cycle and neuroendocrine regulation of functions of genitals can enables to understand of dyshormonal diseases. 2. Objectives (are described in the terminology of professional activity, taking into account the system of classification of the objectives of the respective levels of cognitive, emotional and psychomotor spheres): -To analyze the results of main methods of functional diagnostics in gynecology -To explain The levels of regulation of woman`s genital functions -To suggest tactics of management of patients with hormonal imbalance of female reproductive system. -To classify mestrual disordes (irregularities) -To interpret the results of laboratory and instrumental examinations of the , , , depending with fazes of MC, the clinical and biochemical, hormonal studies of blood, results of colpocytologycal examination -To draw a diagram scheme of menstrual cycle --To make the analysis of the methods of functional diagnosis in gynecology -To make up the models of clinical cases with various hormanal pathology in women of reproductive and premenopausal age.

3. The basic level of expertise, skills, abilities, required for learning the topic

(interdisciplinary integration ) The name of the previous Acquired skills disciplines Normal Anatomy Structure of female genital organs. Topography of abdominal organs and pelvic organs. Histology Histological structure of the cervix, and endometrium in normal and in pathological conditions. Notmal Physiology Physiological changes occurring in the hypothalamic- pituitary-ovarian system of women and target organs of the sex hormones action at different ages. Pathological Physiology Hormonal changes in the body during the menstrual cycle and disorders of the microbiota of the female reproductive system. Pharmacology Groups of medications that affect the function of the hypothalamus, pituitary gland, ovaries, adrenal glands; mechanism of pharmacological action of hormonal, hemostatic, anti-inflammatory, antiviral drugs.

4. Tasks for independent work in preparation for the lesson and in class.

4.1. The list of the major terms, parameters, characteristics to be acquired by a student to be prepared for the lesson The term Definition The levels of regulation of V level is suprahypothalamic cerebral genital functions structures. IV level — hypothalamus Ш level — anterior pituitary. II level — ovaries. I level — target organs (, vagina and breasts).

Female Sex steroid hormones luteonizing hormone (LH) prolactin follicle-stimulating hormone (FSH) estrogens progesterone

- Characteristics of normal - -The modal interval when menstrual cycle occurs is considered to be 27-29 days and may vary from 21 till 35 days. - -The duration of menstrual flow is 3-4 days (from 2 till 7 days). - -The amount of blood lost is about 50- 150 (80) ml per cycle. - -The menstruation must be regular, painless. - -The reproductive cycle has two phases. - Ovarian cycle An ovarian cycle consists of two phases. The first one —, the second — . Uterine cycle the endometrial lining of the uterus builds up under the influence of increasing levels of estrogen (labeled as estradiol in the image) There are four main stages of the endometrial cycle: desquamation that is menstruation, regeneration, proliferation, and secretion phases. Menstrual cycle Determination is complex of complicated biological processes in all organism of women, witch characterized cyclical changes in all reproductive organs and provided conception and pregnancy

Ovulation is the process when the membrane of mature follicle is ruptured and oocyte is expelled from the follicle

4.2 Theoretical questions for the lesson:

1. Determination of the normal menstrual cycle 2. and physiology of pubertaty 3. Regulation of the normal menstrual cycle 4. Phase of the normal menstrual cycle 5. Change of ovarian during menstrual cycle 6. Change of endometrium during menstrual cycle 7. Characteristic of normal menstrual cycle 8. Abnormal menstruation and definitions of terms 4.3 Practical activities (tasks) to be performed on the lesson:  To Describe the proposed changes in organs of women during menstrual cycle.  To Evaluate proposed by instructor menstrual cycle, amount of blood loss during normal and pathologic menstrual cycle (anovulatory cycle, luteine phase insuffi-ciency).  To analyze the results of main methods of functional diagnostics in gynecology  To suggest tactics of management of patients with hormonal imbalance of female reproductive system.  To classify mestrual disordes (irregularities)  To interpret the results of laboratory and instrumental examinations of the cervix, endometrium, ovaries, depending with fazes of MC, the clinical and biochemical, hormonal studies of blood, results of colpocytologycal examination  To draw a diagram scheme of menstrual cycle and chart of basal temperature  To make up the models of clinical cases with various hormanal pathology in women of reproductive and premenopausal age. 4.4 Topic content

Neuroendocrinal regulation of women’s reproductive organs.

Eumenorrhea – is a menstruation with the duration of mensis is about 4-5 days (up to 7 days) and the amount of blood loss is 20-80 ml, the duration of the MC is 21- 35 days with a mean of 28 days.

NORMAL MENSTRUAL CYCLE The normal menstrual cycle has important significance in obstetrical and gynecological practice. The normal changes of menstrual cycle cause ovulation and induce changes in the endometrium that prepare it for implantation should fertilization occur. Towards the end of puberty, girls begin to release eggs as part of a monthly period called the female reproductive cycle, or menstrual cycle (menstrual referring to "monthly"). Approximately every 28 days, during ovulation, an sends a tiny egg into one of the fallopian tubes. Unless the egg is fertilized by a sperm while in the fallopian in the two to three days following ovulation, the egg dries up and leaves the body about two weeks later through the vagina. This process is called menstruation. Blood and tissues from the inner lining of the uterus (the endometrium) combine to form the menstrual flow, which generally lasts from four to seven days. The first period is called menarche. During menstruation arteries that supply the lining of the uterus constrict and capillaries weaken. Blood spilling from the damaged vessels detaches layers of the lining, not all at once but in random patches. Endometrium mucus and blood descending from the uterus, through the liquid creates the menstruation flow. Menstrual cycle The reproductive cycle can be divided into an ovarian cycle and a uterine cycle (compare ovarian histology and uterine histology in the diagram on the right). During the uterine cycle, the endometrial lining of the uterus builds up under the influence of increasing levels of estrogen (labeled as estradiol in the image). Follicles develop, and within a few days one matures into an ovum, or egg. The ovary then releases this egg, at the time of ovulation. After ovulation the uterine lining enters a secretory phase, or the ovarian cycle, in preparation for implantation, under the influence of progesterone. Progesterone is produced by the corpus luteum (the follicle after ovulation) and enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus. If fertilization and implantation occur, the embryo produces Human Chorionic Gonadotropin (HCG), which maintains the corpus luteum and causes it to continue producing progesterone until the placenta can take over production of progesterone. Hence, progesterone is "pro gestational" and maintains the uterine lining during all of pregnancy. If fertilization and implantation do not occur the corpus luteum degenerates into a corpus albicans, and progesterone levels fall. This fall in progesterone levels cause the endometrium lining to break down and sluff off through the vagina. This is called menstruation, which marks the low point for estrogen activity and is the starting point of a new cycle.

Common usage refers to menstruation and menses as a period. This bleeding serves as a sign that a woman has not become pregnant. However, this cannot be taken as certainty, as sometimes there is some bleeding in early pregnancy. During the reproductive years, failure to menstruate may provide the first indication to a woman that she may have become pregnant. Menstruation forms a normal part of a natural cyclic process occurring in healthy women between puberty and the end of the reproductive years. The onset of menstruation, known as menarche, occurs at an average age of 12, but is normal anywhere between 8 and 16. Factors such as heredity, diet, and overall health can accelerate or delay the onset of menarche. Menstruation is also called menstrual bleeding, menses, or a period. This bleeding normally serves as a sign that a woman has not become pregnant. (However, this cannot be taken as certainty, as sometimes there is some bleeding in early pregnancy.) During the reproductive years, failure to menstruate may provide the first indication to a woman that she may have become pregnant. A woman might say that her "period is late" when an expected menstruation has not started and she might have become pregnant. Eumenorrhea denotes normal, regular menstruation that lasts for a few days (usually 3 to 5 days, but anywhere from 2 to 7 days is considered normal). The average blood loss during menstruation is 35 millilitres with 10-80 mL considered normal; Follicular phase Through the influence of a rise in follicle stimulating hormone (FSH), five to seven tertiary-stage ovarian follicles are recruited for entry into the next menstrual cycle. These follicles, that have been growing for the better part of a year in a process known as , compete with each other for dominance. Under the influence of several hormones, all but one of these follicles will undergo atresia, while one (or occasionally two) dominant follicles will continue to maturity. As they mature, the follicles secrete increasing amounts of estradiol, an oestrogen. The oestrogens that follicles secrete, initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. The estrogen also stimulates crypts in the cervix to produce fertile cervical mucus, which may be noticed by women practicing . When the egg has matured, it secretes enough estradiol to trigger the acute release of luteinizing hormone (LH). In the average cycle this LH surge starts around cycle day 12 and may last 48 hours. The release of LH matures the egg and weakens the wall of the follicle in the ovary. This process leads to ovulation: the release of the now mature ovum, the largest cell of the body (with a diameter of about 0.5 mm). The needs to capture the egg and provide the site for fertilization. In some women, ovulation features a characteristic called mittelschmerz (German term meaning 'middle pain') which may last a few hours. The sudden change in hormones at the time of ovulation also causes light mid- cycle bleeding for some women. An unfertilized egg will eventually disintegrate or dissolve in the uterus. Luteal phase The corpus luteum is the solid body formed in the ovaries after the egg has been released from the fallopian tube which continues to grow and divide for a while. After ovulation, the residual follicle transforms into the corpus luteum under the support of the pituitary hormones. This corpus luteum will produce progesterone in addition to estrogens for approximately the next 2 weeks. Progesterone plays a vital role in converting the proliferative endometrium into a secretory lining receptive for implantation and supportive of the early pregnancy. It raises the body temperature by one-half to one degree Fahrenheit (one-quarter to one-half degree Celsius), thus women who record their temperature on a daily basis will notice that they have entered the luteal phase. If fertilization of an egg has occurred, it will travel as an early blastocyst through the fallopian tube to the uterine cavity and implant itself 6 to 12 days after ovulation. Shortly after implantation, the growing embryo will signal its existence to the maternal system. One very early signal consists of human chorionic gonadotropin (hCG), a hormone that pregnancy tests can measure. This signal has an important role in maintaining the corpus luteum and enabling it to continue to produce progesterone. In the absence of a pregnancy and without hCG, the corpus luteum demises and inhibin and progesterone levels fall. This will set the stage for the next cycle. Progesterone withdrawal leads to menstrual shedding (progesterone withdrawal bleeding), and falling inhibin levels allow FSH levels to rise to raise a new crop of follicles.

Hormonal control Extreme intricacies regulate the menstrual cycle. For many years, researchers have argued over which regulatory system has ultimate control: the hypothalamus, the pituitary, or the ovary with its growing follicle; but all three systems have to interact. In any scenario, the growing follicle has a critical role: it matures the lining, provides the appropriate feedback to the hypothalamus and pituitary, and modifies the mucus changes at the cervix. Gonadal Two sex hormones play a role in the control of the menstrual cycle: estradiol and progesterone:

 Estrogen peaks twice, during follicular growth and during the luteal phase.

 Progesterone remains virtually absent prior to ovulation, but becomes critical in the luteal phase and during pregnancy. Many tests for ovulation check for the presence of progesterone. After ovulation the corpus luteum which develops from the burst follicle and remains in the ovary secretes both estradiol and progesterone. Only if pregnancy occurs do hormones appear in order to suspend the menstrual cycle, while production of estradiol and progesterone continues. Abnormal hormonal regulation leads to disturbance in the menstrual cycle. Hypothalamus and pituitary These sex hormones come under the influence of the pituitary gland, and both FSH and LH play necessary roles:

 FSH stimulates immature follicles in the ovaries to grow.

 LH triggers ovulation. The gonadotropin-releasing hormone of the hypothalamus controls the pituitary, yet both the pituitary and the hypothalamus receive feedback from the follicle

Cycle abnormalities Apparently normal menstrual bleeding can occur without ovulation preceding it (anovulatory cycle - "an-" meaning "absence of" +ovulation). In some women, follicular development may start but not be completed; nevertheless, estrogens will form and will stimulate the uterine lining. Anovulatory bleeding resulting from a very thick endometrium caused by prolonged, continued high estrogen levels is called estrogen breakthrough bleeding. Anovulatory bleeding triggered by a sudden drop in estrogen levels is called estrogen withdrawal bleeding. Anovulatory bleeding may occur on a regular basis, but more commonly happens with irregular frequency. Anovulatory bleeding commonly occurs prior to (premenopause) or in women with polycystic ovary syndrome. Infrequent or irregular ovulation is called oligoovulation. Flow Sudden heavy flows or amounts in excess of 80 mL (hypermenorrhea or menorrhagia) are not normal. Bleeding very little (less than 10mL) is called . Prolonged bleeding (metrorrhagia, also meno-metrorrhagia) no longer shows a clear interval pattern. Dysfunctional uterine bleeding refers to hormonally caused bleeding abnormalities, typically anovulation. All bleeding abnormalities need medical attention; they may indicate hormone imbalances, uterine fibroids, or other problems. As pregnant patients may bleed, a pregnancy test forms part of the evaluation of abnormal bleeding.

Cycle length The medical term for cycles with intervals of 21 days or fewer is polymenorrhea and, on the other hand, the term for cycles with intervals exceeding 35 days is (or if intervals exceed 180 days). Amenorrhea refers to a prolonged absence of menses during the reproductive years of a woman. For example, women with very low body fat, such as athletes, may cease to menstruate. Amenorrhea also occurs during pregancy. Early menarche The condition precocious puberty has caused menstruation to occur in girls as young as eight months old.

CONTROL QWESTIONS 1. What is menstrual cycle? 2. What is menarche? 3. What is menstruation? 4. What phase is menstrual cycle divided into? 5. What is during normal menstrual cycle and menstruation? 6. What does the terms “ovulation” mean? 7. What characteristic does normal menstrual cycle have? 8. What hormones are follicular phase controlled? 9. What hormones are luteal phase controlled? 10. What menstrual disorders do you know?

Materials for self-control:

TESTS 1.At which day at 28 day of menstrual cycle ovulation take place? A. at 14-15 B. at 10-12 C. at 12-13 D. at 16-17 E. at 19-20 2.Which hormone is produced by luteal body? A. progesteron B. foliculin C. estriol D. lutropin E. prolactin 3.Under influence of which hormone uterine endometrium transform into decidua membrane? A. progesteron B. foliculin C. estriol D. lutropin E. prolactin 4.Where the prostaglandins are synthesized? A. in all tissues of organism B. in pituitary gland C. in ovaries D. in adrenal glands E. in pancreas 5.Which of the following change in puberty is influenced by the estrogen: A. all of the above B. growth of the acinar buds of the breast C. epiphyseal fusion D. proliferatve phase E. none of the above 6.Glycogen is seen in the lumina of endometrial glands : A. during the luteal phase B. during pregnancy only C. during pre and post ovulatory D. during proliferative phase only E. none of the above 7.Large amount of alkaline phosphatase may be demonstrated in the endometrium of: A. proliferative phase B. decidua C. secretory phase D. all of the above E. none of the above 8.The cyclic production of pituitary hormones is dependant upon: A. an intact pituitary- portal system B. normal menstruation C. an adult anterior pituitary gland D. all of the above E. none of the above 9.Which of the following is suggestive of ovulation: A. regularcycle with B. drop at least 0.5C in the second half of the cycle C. day 21 estrogen level is elevated D. progesterone level on day ten of the cycle is elevated E. oligomenorrhoea 10.The luteal phase of the menstrual cycle is associated with: A. highprogesterone levels high luteinizing hormone level B. high prolactin level C. low basal body temperature D. proliferative changes in the endometrium

SITUATIONAL TASKS 1. A sample of cervical mucus is taken on day 12 of the menstrual cycle. The mucus isthin, clear, & stretchy. It placed on a slide and allowed to air dry. When placedunder microscopic, what would you expect? 2.An involuted corpus luteum becomes a hyalinized mass known as a: 3.On Examination of endometrial tissue obtained from a biopsy reveals simplecolumnar epithelium with no sub nuclear vacuoles. The stroma is edematous, & atortuous gland contains secretions. These findings are consistent which stage of menstrual cycle: 4.A 13 year old girl consulted the school doctor on account of moderate bloody discharge from the genital tracts, which appeared 2 days ago. Secondary sexual characters are developed. What is the most probable cause of bloody discharge? 5.During in vitro fertilization, medical stimulation causes multiple follicles to develop to the stage of ovulation, rather than just one dominant follicle. What hormone is responsible for this multifollicular development?

List of recommended literature Main 1. Williams. Gynecology. Second edition. 2012. 2. Hacker. Essentials of Obstetrics and Gynecology. Fifth edition. 2010.-443 p. 3. Dewhurst’s textbook of obstetrics and . – 7th ed. / edited by D. Keith Edmonds. – 2007. - 717 p. 4. 6.General gynecology: the requisites in obstertics & gynecology / Edited by Andrew I.Sokol, Eric R. Sokol. – 1st ed. - 2007. – 811 p. 5. 7.Smith, Roger P. Netter’s obstetrics and gynecology / Roger P. Smith;– 2nd ed. - 2008. - 635 p.