Dysfunctional uterine bleeding - Causes and pathogenesis

The causes of menstrual cycle disorders (correct cyclic functioning of the reproductive system) can be quite diverse, sometimes combined with each other. The site of application of the damaging effect can be located at any level of regulation of the menstrual cycle, but usually, due to the close interconnection of all links of the reproductive system, the entire chain is involved in the pathological process. Often, one and the same causal factor leads to dysfunction of several levels of the neuroendocrine system.

Among the etiological factors causing menstrual cycle disorders such as dysfunctional uterine bleeding, a large place is occupied by acute and chronic infections, intoxications, occupational hazards, vitamin deficiencies, stressful situations, physical and mental fatigue, severe somatic diseases, disorders of the peripheral endocrine glands (thyroid, adrenal glands), inflammatory lesions of the reproductive system, etc. Menstrual cycle disorders in young women are often associated with the inferiority of the sex glands and instability of the central links of the reproductive system due to unfavorable effects in the antenatal period of their existence.

The pathogenesis of dysfunctional uterine bleeding is complex and multifaceted. The most vulnerable moment in the complex mechanism of the neuroendocrine system that regulates the menstrual cycle is ovulation. Therefore, in most cases, uterine bleeding occurs against the background of anovulation. In some patients, the dominant follicle reaches a sufficient degree of maturity, but without ovulating, continues to exist (persists) and produces estrogens in large quantities. Hyperestrogenism leads to endometrial hyperplasia. In another category of patients, several follicles develop, but without reaching maturity, they undergo atresia; new follicles grow to replace them, again undergoing atresia. Long-term wave-like action of moderate amounts of estrogens also leads to proliferation or hyperplasia of the endometrium. Dysfunctional uterine bleeding in both cases of anovulation can be explained by two mechanisms: estrogen withdrawal or estrogen breakthrough.

In some patients, dysfunctional uterine bleeding is observed against the background of preserved ovulation. Bleeding may occur in the middle of the menstrual cycle due to the rejection of the endometrium due to a short-term decrease in estrogen production. Small blood discharge before menstruation may indicate an insufficiently functioning corpus luteum, and prolonged menstrual bleeding may indicate a defective follicle. The long-term existence (persistence) of the corpus luteum, which produces progesterone and estrogen in sufficient quantities, temporarily delays the rejection of the endometrium, and then leads to breakthrough bleeding.

Based on the characteristics of pathogenesis, dysfunctional uterine bleeding is classified as follows (table)

Classification of dysfunctional uterine bleeding

Nature of bleeding	Ovulatory bleeding	Anovulatory bleeding
Cyclic Acyclic	Follicle failure Corpus luteum insufficiency Intermenstrual Persistence of the corpus luteum	Short-term rhythmic persistence of the follicle Follicle persistence Follicular atresia

Anovulatory dysfunctional uterine bleeding. Anovulatory menstrual cycles are characterized by continued production of 17beta-estradiol without formation of the corpus luteum and formation of progesterone. Excessive proliferation of the endometrium as a result of continued estrogen exposure eventually outpaces blood vessel growth, leading to unpredictable and non-cyclic shedding of the endometrium.

The cycle is single-phase, without the formation of a functionally active corpus luteum, or there is no cyclicity.

During puberty, lactation and premenopause, frequently occurring anovulatory cycles may not be accompanied by pathological bleeding and do not require pathogenetic therapy.

Depending on the level of estrogens produced by the ovaries, anovulatory cycles are distinguished:

1. With insufficient maturation of the follicle, which subsequently undergoes reverse development (atresia). It is characterized by an extended cycle followed by scanty, prolonged bleeding; often occurs in juveniles.
2. Long-term persistence of the follicle (hemorrhagic metropathy of Schroeder). The mature follicle does not ovulate, continuing to produce estrogens in increased quantities, the corpus luteum does not form.

The disease is often characterized by heavy, prolonged bleeding for up to three months, which may be preceded by delays in menstruation for up to 2-3 months. It occurs more often in women over 30 years of age with concomitant hyperplastic processes of the target organs of the reproductive system or in early premenopause. It is accompanied by anemia, hypotension, and dysfunction of the nervous and cardiovascular systems.

Ovulatory dysfunctional uterine bleeding. Spotting bloody discharge from the genital tract in the middle of the menstrual cycle, which occurs after the increase in the concentration of luteinizing hormone, is usually physiological. Polymenorrhea most often occurs due to shortening of the follicular phase of the menstrual cycle. On the other hand, polymenorrhea can be caused by lengthening of the luteal phase with persistence of the corpus luteum.

Ovulatory bleeding is characterized by the preservation of the two-phase cycle, but with a disruption of the rhythmic production of ovarian hormones of the type:

• Shortening of the follicular phase. Occurs more often during puberty and menopause. During the reproductive period, they can be caused by inflammatory diseases, secondary endocrine disorders, and vegetative neurosis. In this case, the interval between periods is reduced to 2-3 weeks, and periods occur as hyperpolymenorrhea.

When studying the TFD of the ovaries, the rise in rectal temperature above 37° C begins on the 8th-10th day of the cycle, cytological smears indicate a shortening of the 1st phase, histological examination of the endometrium gives a picture of secretory transformations of its type of insufficiency of the 2nd phase.

Treatment is primarily aimed at eliminating the underlying disease. Symptomatic treatment - hemostatic (Vikasol, Dicynone, Syntocinon, calcium preparations, rutin, ascorbic acid). In case of heavy bleeding - oral contraceptives (Non-Ovlon, Ovidon) according to the contraceptive (or initially hemostatic - up to 3-5 tablets per day) scheme - 2-3 cycles.

• Shortening of the luteal phase is often characterized by the appearance of usually small bloody discharge before and after menstruation.

According to the TFD of the ovaries, an increase in rectal temperature after ovulation is noted only for 2-7 days; cytologically and histologically, insufficiency of secretory transformations of the endometrium is revealed.

Treatment consists of prescribing corpus luteum drugs - gestagens (progesterone, 17-OPK, duphaston, uterozhestan, norethisterone, norcolut).

• Prolongation of the luteal phase (persistence of the corpus luteum). Occurs when the pituitary gland is dysfunctional, often associated with hyperprolactinemia. Clinically, it can be expressed as a slight delay in menstruation followed by hyperpolymenorrhea (meno-, menometrorrhagia).

TFD: prolongation of the rise in rectal temperature after ovulation to 14 days or more; histological examination of uterine scraping - insufficient secretory transformation of the endometrium, scraping is often moderate.

Dysfunctional uterine bleeding in systemic diseases. Menstrual cycle pathology may be the first manifestation of diseases such as hyperthyroidism and hypothyroidism. Blood diseases (von Willebrand disease) often manifest themselves with profuse uterine bleeding in adolescence. Severe damage to various organs (renal or liver failure) may sometimes be accompanied by severe irregular bleeding.

Iatrogenic dysfunctional uterine bleeding. Oral contraceptives (OCPs) often cause irregular bleeding during the first 3 months of use if the dose is inadequate or if the woman smokes. Irregular bleeding is also often caused by long-acting contraceptives containing only progestins (Depo-Provera), levonorgestrel (Nornlant). In some cases, dysfunctional uterine bleeding may be caused by taking herbal remedies that affect the endometrium.

Each period of a woman's life leaves its mark on the course of dysfunctional uterine bleeding, requiring a special approach to diagnostic measures and therapy. Therefore, in clinical practice it is customary to distinguish:

1. dysfunctional uterine bleeding during puberty (juvenile bleeding) in girls under 18 years of age;
2. dysfunctional uterine bleeding during the reproductive period;
3. dysfunctional uterine bleeding during the premenopausal period (climacteric bleeding) in women over 40 years of age.

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