What is Dysfunctional Uterine Bleeding?
Dysfunctional uterine bleeding (DMK) is caused by impaired cyclic ovarian hormone production. With DMK, there are no anatomical changes in the reproductive system that could cause bleeding. Functional changes as a cause of uterine bleeding are possible at any level of regulation of menstrual function: in the cerebral cortex, hypothalamus, pituitary, adrenal glands, thyroid, ovaries. DMK recur and often lead to impaired reproductive function, the development of hyperplastic processes up to precancer and endometrial cancer.
There are DMK juvenile period – in 12-18 years; MQD reproductive period – in 18-45 years; climacteric bleeding – in 45-55 years.
Dysfunctional uterine bleeding of the reproductive period
MQD is about 4-5% of gynecological diseases of the reproductive period and remain the most common hormonal pathology of the reproductive system of a woman.
Causes of Dysfunctional Uterine Bleeding
The etiological factors of the cortex-hypothalamus-pituitary-ovary-uterus system damage can be: stressful situations, climate change, mental and physical fatigue, occupational hazards, unfavorable living conditions, hypovitaminosis, intoxication and infection, disorders of hormonal homeostasis after abortion, some drugs.
In addition to the primary disorders in the cortex-hypothalamus-pituitary system, primary disorders at the ovarian level are possible. The cause of ovulation disorders can be inflammatory and infectious diseases: in 75% of cases with inflammatory diseases of the uterus, various disorders of the menstrual function develop. Inflammation may cause thickening of the ovarian tunica, impaired blood supply and a decrease in reactive sensitivity to gonadotropic hormones.
Violations of the hypothalamic-pituitary system lead to functional and morphological changes in the ovaries and uterus. Depending on the pathogenetic mechanisms and clinical and morphological features of the DMC is divided into anovulatory and ovulatory.
- against the background of the persistence of the follicle (absolute hyperestrogenia);
- against the background of atresia of the follicle (relative hyperestrogenism).
- due to persistence of the corpus luteum.
In the reproductive period, the end result of the hypothalamic-pituitary disorders are anovulation and anovulatory hemorrhages, which are based on the absence of ovulation and the luteal phase. When DMK in the reproductive age in the ovaries is longer than normal, there is a mature follicle – the persistence of the follicle occurs and a progesterone deficient condition develops. The persistence of the follicle is like stopping the normal menstrual cycle in a period close to ovulation: the follicle, reaching maturity, does not undergo further physiological transformations and continues to secrete estrogens (absolute hyperestrogenism). With the persistence of the follicle, as in the middle of the menstrual cycle, the follicle in the ovary is well developed. The level of estrogen hormones is sufficient. Prolonged exposure to elevated levels of estrogen causes excessive growth of the endometrium with the proliferation of stroma glands and blood vessels. Prolongation and enhancement of proliferative processes in the endometrium leads to the development of hyperplastic processes and the risk of atypical hyperplasia and endometrial adenocarcinoma. Due to the lack of ovulation and the corpus luteum, progesterone secretion for the secretory transformation of the proliferative endometrium and its normal rejection does not occur. The bleeding mechanism is associated with vascular changes in response to a decline in hormone levels: congestive plethora with a sharp expansion of capillaries in the endometrium, impaired blood circulation, tissue hypoxia are accompanied by dystrophic changes and the appearance of necrotic processes against the background of blood stasis and thrombosis, which leads to prolonged and uneven rejection of the endometrium. The morphological structure of the mucous membrane is variegated: along with the areas of disintegration and rejection, foci of regeneration appear. The rejection of the functional layer is also difficult due to the formation of a dense net-fibrous structure, which penetrates the mucous membrane of the uterus in the form of a kind of skeleton on the border of the basal and functional layers.
Anovulatory bleeding can result from relative hyperestrogenism. In the ovary, one or several follicles stop at any stage of development, not being subjected to further cyclic transformations, but also not ceasing to function until a certain time, and subsequently the atrescing follicles disintegrate or turn into small cysts. The level of estrogen in atresia of the follicles may be low, but they act on the endometrium for a long time and cause hyperplasia (relative hyperestrogenism). Bleeding in such cases is associated with a drop in hormone levels as a result of follicle atresia. According to the morphology of the functional layer of the endometrium, it is possible to determine the phase in which atresia of the follicle occurred.
Ovulatory DMK make up about 20% of all MQD of the reproductive period. There are intermenstrual DMK and DMK, due to the persistence of the corpus luteum. Ovarian dysfunctions associated with pathology of the corpus luteum are possible in a mature woman of any age, are somewhat more likely to be over the age of 30 and constitute 5-10% of all DMC.
In the middle of the menstrual cycle, after ovulation, there is normally some decrease in the level of estrogen, but it does not lead to bleeding, since the general hormonal level is maintained by the corpus luteum starting to function. With a significant and sharp drop in the level of hormones after the ovulatory peak, intermenstrual DMK is observed for 2-3 days. There is a temporary inhibition of the cycle at the stage of the bursting follicle.
MQD due to impaired function of the corpus luteum is much less common than bleeding as a result of impaired follicle development. Dysfunction of the corpus luteum is in its long-term functional activity – the persistence of the corpus luteum. As a result, the level of gestagens does not fall fast enough or persists for a long time. Uneven rejection of the functional layer causes prolonged menstrual bleeding. Reducing the tone of the uterus under the influence of elevated levels of progesterone in the blood also contributes to bleeding. At the same time, the corpus luteum either has no signs of reverse development at all, or along with luteal cells that are in a state of reverse development, there are areas with pronounced signs of functional activity. The persistence of the corpus luteum is indicated by a high level of pregnandiol in bleeding, whereas normally the release of pregnandiol is stopped on the eve of menstruation or simultaneously with its onset.
Blood loss during menstruation limits prostaglan-dines with different properties: prostaglandin E2 and prostacyclin are vasodilators and antiplatelet agents, prostaglandin F2 and thromboxane are vasoconstrictors and aggregation stimulants.
Prostaglandin production is regulated by estrogen and progesterone: progesterone acts as an inhibitor of prostaglandin synthesis in the endometrium, a decrease in its level contributes to an increase in prostaglandin production.
In addition to prostaglandins, many other cellular regulators, growth factors, cytokines that affect the vascular and stromal components of the endometrium, regeneration and proliferation of the endometrium are involved in the mechanisms of menstrual bleeding.
Symptoms of Dysfunctional Uterine Bleeding
Clinical manifestations are usually determined by changes in the ovaries. The main complaint of patients with DMK is a violation of the rhythm of menstruation.
The persistence of the follicle may be short-term, within the normal menstrual cycle. With the reverse development of a persistent follicle and the associated drop in hormone levels, uterine bleeding does not differ from normal menstruation in intensity and duration. Anovulatory menstrual cycles occur throughout life, but more often the persistence of the follicle is much longer and bleeding occurs after some delay of menstruation (the delay can be 6-8 weeks). Bleeding often begins as moderate, periodically decreases and increases again and lasts a very long time. The functional layer of the endometrium can gradually collapse to the basal layer. Estrogen saturation is also gradually reduced. Prolonged bleeding can lead to anemia and weakening of the body.
MQD due to persistence of the corpus luteum – menstruation, occurring on time or after some delay. With each new cycle, it becomes longer and more abundant, turning into bleeding that lasts up to 1-1.5 months.
Ovarian dysfunction in patients with DMK can lead to infertility, but due to the alternation of ovulatory and anovulatory cycles, this infertility is relative.
Diagnosis of Dysfunctional Uterine Bleeding
At the reproductive age, uterine bleeding can be caused by various organic diseases of the reproductive system: benign and malignant diseases of the genitals, endometriosis, uterine myoma, injuries of the genital organs, inflammation of the uterus and appendages, interrupted uterine and ectopic pregnancies, remnants of the ovarian arteries, abnormal uterus and ectopic pregnancies, remnants of the ovarian arteries, or uterine abnormal pregnancies, remnants of a fetal egg after an arthritic abortion, or a template. , placental polyp after childbirth or abortion. Uterine bleeding occurs when extragenital diseases: diseases of the blood, liver, cardiovascular system, endocrine pathology. In patients with DMK of the reproductive period, organic lesions of the cerebral cortex, hypothalamus, pituitary, ovaries, uterus, thyroid, adrenal glands, as well as extragenital pathology must be identified or eliminated. Examination should include the study of functional disorders in the hypothalamus-pituitary-ovary-uterus system using publicly available and, if necessary, additional methods of examination. Methods of examination for DMK:
- clinical (history study; objective examination – general and gynecological examination);
- examination according to tests of functional diagnostics (measurement of basal temperature, a symptom of “pupil”, a symptom of tension of the cervical mucus, calculation of the karyopicnotic index);
- X-ray of the skull (Turkish saddle), EEG and echo-EG, REG;
- determination of hormone levels in blood plasma and urine (hormones of the pituitary, ovaries, thyroid and adrenal glands);
- ultrasound, hydrosonography, hysterosalpingography;
- hysteroscopy with separate diagnostic curettage and morphological examination of scrapings;
- examination by a therapist, an ophthalmologist, an endocrinologist, a neuropathologist, a hematologist, a psychiatrist.
Careful analysis of anamnestic data helps to clarify the causes of bleeding and allows differential diagnosis with diseases that have similar clinical manifestations. As a rule, D M K appear on an unfavorable background: after infectious diseases, inflammatory processes of uterine appendages, in patients with late menarche. The irregularity of menstruation from the period of menarche, juvenile MQD indicate the instability of the reproductive system. If the reproductive function is violated in the reproductive period (recurrent miscarriage, infertility), indirectly, anovulatory bleeding and hypofunction of the ovaries with a luteal phase deficiency can be assumed. Indications of cyclical bleeding – menorrhagia indicate organic pathology (uterine fibroids with submucous node, endometrial pathology). Painful bleeding is characteristic of adenomyosis.
During the general examination, attention is paid to the condition and color of the skin, the distribution of subcutaneous fatty tissue with increased body weight, the severity and prevalence of body hair, stretch bands, the state of the thyroid gland and mammary glands.
With a special gynecological examination, signs of hyper- or hypoestrogenism can be detected. When hyperestrogenic DMK mucous membranes of the vagina and cervix juicy, the uterus is somewhat enlarged, sharply positive symptoms of “pupil” and tension of the cervical mucus. When hypoestrogenic bleeding mucous membranes of the vagina and cervix dry, pale, symptoms of “pupil” and tension of the cervical mucus weakly positive. In a two-handed study, determine the state of the cervix, the size and consistency of the body and uterus.
The next stage of the survey is the assessment of the functional state of various parts of the reproductive system. Hormonal status is studied with the help of functional diagnostics tests during 3-4 menstrual cycles outside the bleeding period, i.e. after cessation of bleeding or after diagnostic curettage. The basal temperature in DMC is almost always monophasic. The pronounced phenomenon of “pupil” remains positive during the whole period of delayed menstruation with the persistence of the follicle. With atresia of the follicle, the phenomenon of the “pupil” is quite pronounced, but persists for a long time. With the persistence of the follicle there is a significant predominance of keratinizing cells (KPI 70-80%), the tension of the cervical mucus is more than 10 cm, with atresia – small fluctuations of the KPI from 20 to 30%, the tension of the cervical mucus not more than 4 cm.
In clinical practice, hormonal studies are conducted to assess the patient’s hormonal status: the study of the secretion of pituitary gonadotropic hormones (FSH, LH, Prl); excretion of estrogen, progesterone in the blood plasma; T3, T4, TSH, testosterone and cortisol in plasma and 17-KS in urine are determined.
The definition of estrogen indicates a prolonged, monotonous excretion and the predominance of their most active fraction (the predominance of estradiol over estrone and estriol). Levels of pregnandiol in the urine and progesterone in the blood indicate a deficiency of the luteal phase in patients with anovulatory DMK.
Diagnosis of thyroid pathology is based on the results of a comprehensive clinical and laboratory examination. An increase in thyroid function, hyperthyroidism, usually leads to the appearance of uterine bleeding. Increased secretion of T3 or T4 and a decrease in TSH allow you to verify the diagnosis.
To identify organic diseases of the hypothalamic-pituitary region, as well as their X-ray features, use radiography of the skull and the Turkish saddle, magnetic resonance imaging.
Ultrasound as a non-invasive and practically safe method of research can be used in dynamics, it allows to diagnose myomatous nodes, endometrial pathology, endometriosis, pregnancy and, most importantly, ovarian tumors. To identify intrauterine pathology in recent years using hydrosonography (ultrasound with a contrast agent).
The most important stage of diagnosis is the histological examination of the material of separate curettage of the uterus and cervical canal. The scrapings are the most informative a few days before the expected menstruation, but they are not always possible to get them, because in some patients, curettage with diagnostic and simultaneously with the hemostatic goal has to be carried out at the height of bleeding. Separate diagnostic curettage is performed under the control of hysteroscopy.
Treatment of Dysfunctional Uterine Bleeding
Treatment of patients with DMK of the reproductive period depends on the clinical manifestations. It is necessary to take into account the nature of menstrual dysfunction, the state of the endometrium, the duration of the disease, the severity of anemia.
When a patient is treated with DMK, hysteroscopy and separate diagnostic curettage are performed. This stops bleeding, and according to the results of histological examination of scrapings, therapy is determined.
With recurrent bleeding, hormonal hemostasis is possible, but if information on the state of the endometrium was received no later than 2-3 months ago. There are several methods of hormonal hemostasis with the use of estrogens, progestins, synthetic progestins. To quickly stop bleeding, estrogens are widely used, which in large doses have an inhibitory effect on the hypothalamus and pituitary, suppressing the release of follitropin, and increase the secretion of lyutropin. More often, shock doses of estrogens are used at regular intervals until the bleeding stops: folliculin 10 thousand. Units or synestrol 0.1% solution 1 ml 3-4 times every 1.5-2 hours. Then reduce the daily dose of estrogens and continue treatment with minimal doses. until 12-14th day, then gestagens are added (progesterone 10 ml 6-8 days or prolonged progestogen oxyprogesterone capronate – 17-OPC 12.5% -125 mg). After the abolition of gestagens appear menstrual discharge.
Hemostasis with gestagens is based on their ability to cause desquamation and complete rejection of the endometrium. However, progestin hemostasis does not give a quick effect.
The next stage of treatment is hormone therapy, taking into account the characteristics of the structure of the endometrium, the nature of the impaired ovarian function and the level of blood estrogen. Goals of hormone therapy:
- normalization of menstrual function;
- rehabilitation of impaired reproductive function with a decrease in fertility or infertility;
- prevention of bleeding.
With hyperestrogenism (follicle persistence), treatment is carried out with gestagens in the second phase of the menstrual cycle (progesterone, norcolute, duphaston, uterogestan) for 3-4 cycles, with estrogen-gestagens with a high content of gestagens (Rigevonon, microginin, selest) for 4-6 cycles .
During hypoestrogenism (follicle atresia), cyclic estrogen and progestogen therapy is indicated for 3-4 cycles in combination with vitamin therapy (in the first phase – folic acid, in the second – ascorbic acid) against the background of anti-inflammatory therapy.
Preventive therapy is carried out in intermittent courses (3 months of treatment – 3 months break). Repeated courses of hormone therapy prescribed according to indications, depending on the effectiveness of the previous course. The absence of an adequate response to hormone therapy at any stage should be considered as an indication for a detailed examination of the patient.
In order to rehabilitate the impaired reproductive function, ovulation is stimulated with clomiphene from the 5th to the 9th day of the menstrual reaction to progestins after scraping the endometrium. The control of the ovulatory cycle are the basal temperature, the presence of a dominant follicle and the thickness of the endometrium with ultrasound.
General non-specific therapy is aimed at removing negative emotions, physical and mental overwork, eliminating infections and intoxications and consists of effects on the central nervous system (psychotherapy, autogenic training, hypnosis, sedatives, hypnotics and tranquilizers, vitamins) and antianemic therapy.
MIC in the reproductive period with inadequate therapy are prone to relapse. Recurrence of bleeding is possible due to the ineffectiveness of hormone therapy or incorrectly established causes of bleeding. In addition, impaired hormonal homeostasis in DMS become the background for the development of hormone-dependent diseases and menopausal complications. All this increases the risk of developing breast cancer and endometrial adenocarcinoma.