**5. Insufficient follicular maturation**

Increased FSH levels are associated with abnormal menstrual in duration and time. Impact on adolescents is including 20–55% of the cycles in the first year and one-third of the cycles in the third year after menstruation which are still anovulatory. Anabolism is the most common cause of dysfunctional hemorrhages in adolescence and indeed it can even lead to hospital care [35]. This is due to functional immaturity of the hypothalamic-pituitary-ovarian axis.

Adolescents whose menstruation appears before the 12th year of age have in 50% anovulatory cycles during the first year, while those who are menopausal at the age of 12–13 years it is needed to pass a period of up to 3 years to make ovulation cycles. Hemorrhage due to hyperestrogenic cycles are usually characterized by histologically persistent productive endometrium and hyperplasia caused by progesterone prolonged and progesterone deficient estrogen mitotic activity [9]. The morphological changes in the endometrium are similar to those observed in women receiving estrogen replacement therapy. The origin of bleeding can be sought in the apoptosis of the layer accompanied by red blood cell extravasation, the formation of platelet thrombi and fibrin clots in the capillaries, and the existence of processes related to the reconstitution, including layer formation and hypertrophy of the regenerated epithelium. Morphological lesions are typically focal and located near or on the surface of the endometrium. In contrast, in cases of interruption of the E2/P relationship, they are diffuse. The exact mechanism of tissue apoptosis in hyperestrogenic endometrium is unclear. The abnormal development of the endometrium includes additional qualitative and quantitative changes in microvascularization such as spiral arterial compression and venous growth, which are often stretched, thus forming abnormal venous networks. Of particular interest is the fact that the process of neovascularization is inadequate in or near the hemorrhage focal area while adjacent intact endometrium does not show an increase in microvascularization. The abnormal morphology of microvascularization accompanies or is the cause of endometrial hemostasis disorders. Because of the lack of the arachidonic acid precursor, prostaglandin production is inadequate. Prostaglandins cause more dilation than contraction, and angiotensin-2 production is reduced. All of the above leads to the conclusion that bleeding, in these cases, is caused by vascular density disorders accompanied by structural abnormalities leading to rupture or degradation of the microvascular system. This process is followed by the release of lysosomal proteolytic enzymes from the epithelial and stromal cells and from endometrial migrating leukocytes and macrophages, while granulocytes and activated NK cells secrete perforins. In addition, the ability of contraction of basal and myometrial vessels is inadequate or absent. All of the above changes contribute to the inadequate structure and layout and ultimately to the degradation of the capillary network and constitute the major agents of extensive hemorrhage. Based on the above, the best therapeutic results are obtained when the bleeding hypertrophic-hyperplastic endometrium is excluded by performing suction biopsy or scraping. In these cases, an extensive stripping of the base layer is created followed by vasoconstriction of the arteries and arterioles as well as by tissue reconstruction. Functional hemorrhage due to progesteronism manifests as escape bleeding in women taking progestogens or using contraceptive tablets. The intensity, duration, and other features of these cases' bleeding depend on: type, dose and duration of progestogen administration, the estrogen-progestogen relationship, endogenous estradiol levels and the particular endometrial response to hormonal administration [7, 9]. Endometrial histology in these cases is predominantly influenced by progesterone and ranges between atrophy with or without cortical conversion of the layer and mixed appearance of productive and secretory elements. The greater the dose and the duration of administration, the more pronounced is the secretory type atrophy with a pronounced pro-stratum gland-layer relationship. In this case there is a corrugated endometrial layer especially in the initial periods of use containing migratory lymphocytes and macrophages as well as granular endometrial cells. All of the above lesions are associated with abnormalities of endometrial angiogenesis. These changes are accompanied by structural lesions and vasodilation leading to bleeding during the first months of use. The increased concentration of migratory leukocytes and other cells associated with immunity and the imbalance between metalloproteinases (proteolytic MMP enzymes that cause an intrauterine extracellular matrix) and their inhibitors against them, cause even greater vasodilation [7, 9]. In conclusion, the development of an abnormal and fragile network of microvascular surfaces in combination with the release of proteolytic enzymes and poor vasoconstriction due to reduced production of vasoconstrictors as a result of increased degradation by endopeptidase is the key factor in the manifestation of the above functional bleeding. Fortunately, the continuation of contraceptives decreases the frequency with the end result being usually observed only during the first 6–12 months of use.

and fibrinogen deficiency (2nd phase of hemostasis), mutation of the M.T.H.F.R. (C677T) gene (LAME). In these cases, there is a lack of primary platelet clot and fibrin production. Finally, fibrinolysis (3rd phase of hemostasis) in endometrium can be also observed, especially in

Female genital hormone equilibrium disorders observed either in cases of hyperestrogenism (estrogen escape bleeding) or in cases of sudden subestrogenism (interruption of exogenous administration – bilateral ovariectomy), or, finally, in cases of progesteronism (progesterone bleeding bleeding-progesterone withdrawal contraceptive). Diagnosis is often raised by exclusions (malignant diseases, genital tract, PCO, and hypothyroidism liver cirrhosis). The mechanisms involved in the pathophysiology of the above-mentioned bleeding cases are systemic in their nature, although it is possible to observe inadequacy of local hemostatic mechanisms resulting from the absence of cyclic production of progesterone and related endothelin-1, prostaglandins and other substances that contribute positively to local hemostasis of the endometrium [9]. Additionally, lack of ovulation causes unexpected bleeding, which adversely affects the quality of life of the patient. Functional hypothalamic or pituitary disorders that cause suppression of gonadotropin production, anovulation, and the approach

Progressively shorter cycles due to a gradual decrease in follicles and a corresponding fall in

Increased FSH levels are associated with abnormal menstrual in duration and time. Impact on adolescents is including 20–55% of the cycles in the first year and one-third of the cycles in the third year after menstruation which are still anovulatory. Anabolism is the most common cause of dysfunctional hemorrhages in adolescence and indeed it can even lead to hospital care [35]. This is due to functional immaturity of the hypothalamic-pituitary-ovarian axis.

Adolescents whose menstruation appears before the 12th year of age have in 50% anovulatory cycles during the first year, while those who are menopausal at the age of 12–13 years it is needed to pass a period of up to 3 years to make ovulation cycles. Hemorrhage due to hyperestrogenic cycles are usually characterized by histologically persistent productive endometrium and hyperplasia caused by progesterone prolonged and progesterone deficient estrogen mitotic activity [9]. The morphological changes in the endometrium are similar to those observed in women receiving estrogen replacement therapy. The origin of bleeding can be sought in the apoptosis of the layer accompanied by red blood cell extravasation, the formation of platelet thrombi and fibrin clots in the capillaries, and the existence of processes related to the reconstitution, including layer formation and hypertrophy of the regenerated epithelium. Morphological lesions are typically focal and located near or on the

cases of unexplained or intense menorrhagia [9].

to perimenopausal age cause typical changes in the genital cycle.

ovarian function lead to metrorrhagia [9].

**5. Insufficient follicular maturation**

**4. Anovulatory cycles**

192 Family Planning
