(Functional uterine bleeding disorders)

As dysfunctional uterine bleeding abnormal uterine bleeding without clinical or sonographic evidence of common causes (structural gynecological abnormalities, tumors, inflammation, systemic diseases, pregnancy, complications of pregnancy, use of oral contraceptives or certain drugs) are designated. Treatment usually consists of hormone therapy such. As oral contraceptives, or NSAIDs.

Dysfunctional uterine bleeding (DUB) are the most common cause of abnormal uterine bleeding; most often they come in women> 45 years (> 50% of cases) and in adolescents (20% of cases) before.

As dysfunctional uterine bleeding abnormal uterine bleeding without clinical or sonographic evidence of common causes (structural gynecological abnormalities, tumors, inflammation, systemic diseases, pregnancy, complications of pregnancy, use of oral contraceptives or certain drugs) are designated. Treatment usually consists of hormone therapy such. As oral contraceptives, or NSAIDs. Dysfunctional uterine bleeding (DUB) are the most common cause of abnormal uterine bleeding; most often they come in women> 45 years (> 50% of cases) and in adolescents (20% of cases) before. About 90% of cases are anovulatory, 10% are ovulatory. Pathophysiology During an anovulatory cycle of the corpus luteum is not formed. So it does not come to normal cyclical progesterone production, and the endometrium is stimulated without misconduct by estrogen. Without progesterone, there is a continuous growth of the endometrium, after all it is growing faster than its blood supply; it is then exfoliated incomplete and irregular bleeding, occasionally abundant or over a long period from. If this pathological process repeatedly, it may lead to endometrial hyperplasia, sometimes with atypical or cancerous cells. In the ovulatory DUB progesterone secretion is extended; Cause of the irregular rejection of the endometrium is thought to be a constant low levels of estrogen, which for bleeding in the vicinity of the threshold value (as it exists at the menses) is located. A ovulatory DUB may occur with high estrogen levels in overweight women, resulting in a change from amenorrhea and irregular or prolonged bleeding. Complications Chronic bleeding lead to iron deficiency anemia. Also, infertility can be the result of dysfunctional uterine bleeding with chronic anovulation. Etiology Any disease or disorder anovulatory DUB is anovulatory dysfunctional to cause uterine bleeding (see table: causes of anovulatory amenorrhea). Anovulation is mostly to the syndrome of PCOS subordinated Idiopathic (sometimes occurs when gonadotropin levels are normal) Sometimes Anovulatios results of hypothyroidism. During perimenopause a DUB may be an early sign of ovarian failure; the follicles develop still, but despite rising FSH levels do not make enough [/ estrogen to trigger ovulation. Around 20% of women with endometriosis have anovulatory DUB unknown origin. ovulatory DUB can occur with polycystic ovary syndrome (due to the extended progesterone) endometriosis, which does not affect ovulation Other causes include a short follicular phase and a luteal phase dysfunction (due to insufficient stimulation of the endometrium by progesterone); a rapid decrease estrogen before ovulation can cause bleeding. Symptoms and complaints Compared to a normal menses can bleeding Frequent occur (distances <21 days = polymenorrhea) with greater blood loss (> 7 days or> 80 ml = menorrhagia or hypermenorrhea) accompanied frequently and irregularly occurring between menses (metrorrhagia) Excessively strong during the menstrual period and often and irregularly occur between menstrual periods (menometrorrhagia) In ovulatory DUB often leads to excessive bleeding during the regular menstrual cycle. Other signs of ovulation may be present, such as premenstrual symptoms, breast tenderness, cramping pain in the middle of the cycle (mean pain), changes in basal body temperature after ovulation (Ovarian dysfunction) and occasionally dysmenorrhea. Anovulatory DUB can occur suddenly and irregularly; there is not a cyclical change in basal body temperature. Diagnosis for other potential causes blood count, pregnancy test and determination of hormone concentrations (eg. As thyroid-stimulating hormone [TSH], prolactin) Usually transvaginal sonography and endometrial biopsy often Sonohysterographie and / or hysteroscopy Suspicion of DUB should come in when the vaginal bleeding differ in their amount and timing of a normal menses. DUB is a diagnosis of exclusion; Other disorders that can cause similar bleeding must be excluded (vaginal bleeding). Pregnancy should be excluded, even in adolescents and in women during perimenopause. Particularly among young people who have anemia or who were in a hospital due to bleeding, coagulation disorders should be considered. Regular cycles with extended or excessively heavy bleeding (possibly ovulatory DUB) point to structural problems. Laboratory tests usually are performed multiple tests: urine or blood pregnancy test blood count determination of TSH, prolactin, and progesterone levels in all women of childbearing age, a pregnancy test should be performed. Routinely, a blood count is performed. However, the hematocrit in females may be normal with heavy bleeding; severe anemia can occur in women with regular heavy menstrual bleeding. For chronic, severe bleeding the serum ferritin level is determined which is a measure of the iron store of the body. TSH levels is usually determined; even in the absence of Galactorrhea prolactin level is measured because thyroid disease and hyperprolactinemia common causes of abnormal menstrual bleeding are. To determine if the bleeding is anovulatory or ovulatory, serum progesterone levels is occasionally in the luteal phase (after 14 days of a normal menstrual cycle or after increase in basal body temperature, as occurs in this phase) was determined. Concentrations of ? 3 ng / ml (? 9.75 nmol / l) for a talk ovulation. Further tests are made and include, depending on the history and physical examination: coagulation in women at increased risk of clotting disorders, bruising or bleeding liver function tests in suspected liver disease testosterone and dehydroepiandrosterone sulfate (DHEAS) levels in suspected polycystic ovary FSH and estradiol levels in suspected primary ovarian failure cervical cancer screening test (eg. as Papanicolaou [Pap] test) HPV test at outdated results test for Neisseria gonorrhea and Chlamydia sp for suspected pelvic inflammatory disease or cervicitis Are all clinically indicated tests normal, the diagnosis dysfunctional uterine bleeding gestellt.Weitere testing is a transvaginal ultrasound is performed at the following criteria: age ? 35 Risk factors for endometrial cancer (eg. As obesity, diabetes, hypertension, polycystic ovary syndrome, chronic eugonadal anovulation, hirsutism, other disorders with prolonged, not against regulated estrogen exposure) Despite empirical hormonal persistent bleeding Pelvic organs that can not be adequately assessed during physical examination Clinical evidence for abnormalities of the ovaries or uterine almost all women with dysfunctional uterine bleeding these criteria are met. By transvaginal sonography structural changes reveal, including most polyps, fibroids, other lesions, endometrial cancer and focal thickening of the endometrium. Is a focal thickening observed, additional studies may be required to identify small intrauterine lesions (eg. As small endometrial polyps, submucosal fibroids). The Sonohysterographie (sonography after instillation of a NaCl solution into the uterine cavity) is used for evaluation of such anomalies. With it, can be found on the one hand whether a hysteroscopy, a more invasive investigation is indicated, on the other hand, the resection of intrauterine lesions is planned. Or Hysteroscopie can be done without Sonohysteroscopie. only about 25% of the endometrium are detected by endometrial biopsy, but the sensitivity for the detection of abnormal cells is about 97%. In most cases the biopsy to rule out hyperplasia or cancer in women is carried out with one of the following characteristics: age> 35 years, with one or more risk factors for endometrial cancer (see above) age <35 years with multiple risk factors for endometrial cancer (see above) Persistent, irregular or excessive bleeding irregular cycles that indicate chronic anovulatory bleeding endometrial> 4 mm with focal or irregular findings in transvaginal sonography Unclear sonographic findings A guided biopsy (with hysteroscopy) is carried out for the direct visualization of the uterine cavity and is directed against abnormal tissue. Anovulation is confirmed that most of the endometrium proliferative or dyssynchrones endometrium included, and no secretory endometrium is found. Treatment control bleeding, usually by NSAIDs, tranexamic acid or hormone therapy in women with endometrial hyperplasia prevention of endometrial bleeding Non Hormonal treatments have lower risks and adverse effects than hormone therapy and can be applied intermittently when bleeding occurs. They are usually indicated for strong regular bleeding (menorrhagia). A choice of NSAID that reduce bleeding by 25-35%, and improve dysmenorrhea by lowering the prostaglandin tranexamic acid, which inhibits plasminogen activator, whereby the blood loss during menstruation is reduced by 40-60% Hormone therapy (eg. As oral contraceptives , progestogens) is often tried first in women during perimenopause. This therapy does the following: suppression of endometrial growth Restore predictable bleeding patterns reduce menstrual bleeding Hormone therapy is carried out usually until the bleeding for several months under control. Often, oral contraceptives are administered. Cyclically or continuously given oral contraceptives can control dysfunctional bleeding. Preliminary data indicate that the following effects through: reduction of blood loss during menstruation by 40-50% Reduced sensitivity of the breasts and dysmenorrhea Reduced risk for uterine and ovarian cancer, it may be a combination preparation of an estrogen and a progestin or progestin only be given. Depending on the oral contraceptive and depending on the patient, there are various risks of OC. Progesterone or another progestin can be used alone in the following cases: estrogen is contraindicated (e.g., in patients with cardiovascular risk factors or previous DVT.). Estrogen is taken from the patient. Combined OCs are ineffective after about three months of use. A withdrawal bleeding with a cyclical progestin therapy (medroxyprogesterone acetate 10 mg / day p.o. or norethindrone acetate p.o. 2.5-5 mg / day) for 21 days / month predictable than with a combined oral contraceptive. Cyclical natural (micronized) progesterone 200 mg / day for 21 days / month can be especially used when a pregnancy may be accepted; but it may have dizziness result and does not reduce the blood loss as strong as a progestin. If a pregnancy in patients taking cyclic progestins or progesterone, to prevent is to pay attention to contraception. Options for contraception levonorgestrel-releasing intrauterine device (IUD): It is effective in up to 97% over 6 months, ensures contraception and improves dysmenorrhea. Depot medroxyprogesterone acetate injections: They cause amenorrhea and ensure contraception, but can lead to irregular bleeding and reversible bone loss. Other treatments that are sometimes used for the treatment of DUB, danazol are: It reduces blood loss during menstruation (by endometrial atrophy), but has many androgenic side effects, which can be improved possibly by lower doses or a vaginal preparation. Danazol is effective only if it is continuous, usually taken for about 3 months. It is usually used when other therapies are contraindicated. Gonadotropin-releasing hormone (GnRH) analogs: These medicines suppress the hormone production in the ovary and cause amenorrhea; They are used for preoperative reduction of fibroids or of the endometrium. However, their hypo-estrogenic side effects (eg. as bone loss) restrict its application. Desmopressin: It is used as a last resort in the treatment of DUB in patients with coagulopathy; it rapidly increases the Von Willebrand factor and factor VIII levels for about 6 hours. Ergot derivatives is not recommended for the treatment of DUB, since they are rarely effective. For fertility and not excessive menses an attempt to ovulation induction with clomiphene (50 mg orally on days 5-9 of the menstrual cycle) indicated. Hysteroscopy with curettage can be used both therapeutically, as well as diagnosis; it may be the treatment of choice for anovulatory bleeding that lasts under hormone therapy. Structural causes such as polyps or fibroids can be detected or removed during hysteroscopy. This method can reduce the bleeding, but in some women it causes amenorrhea by endometrial scarring (Asherman’s syndrome). Endometrial ablation (for. Example, laser, roller ball, resektoskopisch, thermally or freezing) the bleeding can control in 60-80% of cases. Ablation is less invasive than a hysterectomy, and the recovery period is shorter. If significant bleeding after an initially effective ablation again, ablation can be repeated. It has thus unable to control the bleeding or recur, the bleeding continues, adenomyosis can be responsible and then it is no DUB. An endometrial ablation does not prevent pregnancy. The pregnancy rate after the ablation at 5%. Ablation causes scarring that can make the sampling of the endometrium later. An abdominal or vaginal hysterectomy may be recommended patients who decline hormonal therapy or despite other treatments have symptomatic anemia or a low quality of life by persistent irregular bleeding. Immediate measures are rarely, with very heavy bleeding required. The patients are hemodynamically stabilized with intravenous crystalline hydration, blood products and if necessary further action. Persists bleeding, a urinary catheter is placed into the uterus and inflated with water 30 to 60 ml to tamponing the bleeding. If the patient stable, the control of bleeding on hormone therapy takes place. The rare cases of very strong bleeding by anovulatory DUB require the administration of conjugated estrogens 25 mg iv every 4-6 hours with a total of 4 doses. This stops the bleeding in about 70% of the patients, but also increases the risk of thrombosis. Immediately afterwards, a combined contraceptive given continuously until the bleeding for several months under control ist.Endometriumhyperplasie In women after menopause is usually treated atypical adenomatous endometrial hyperplasia by a hysterectomy. In contrast, the disease in premenopausal women with medroxyprogesterone acetate (MPA, 20-40 mg orally 1 times / day for 3-6 months) or with a levonorgestrel-releasing IUD treated (1). When a follow-up biopsy of the endometrium is a regression of the hyperplasia, are employed MPA cyclic (5-10 mg orally 1 times / day for 10-14 days every month) a; when trying to conceive can be given clomiphene. Shows the biopsy persistent or progressive atypical hyperplasia, a hysterectomy is required. A more benign cystic or adenomatous hyperplasia can be treated usually with high-dose progestins (for example, cyclic MPA.) Or a progestin or levonorgestrel-releasing IUDs; a control biopsy after 3 months wiederholt.Behandlungshinweise first Mentrikoski MJ, Shah AA, Hanley KZ, et alAssessing endometrial hyperplasia and carcinoma Treated with progestin therapy. Am J Clin Pathol 38 (4): 524-534, 2012. Summary Anovulatory DUB is the most common cause of bleeding disorders. It should be carried out tests for treatable causes of bleeding; including pregnancy testing, blood count, determination of hormone concentration (TSH, prolactin, progesterone) and often sonography and endometrial biopsy. Women at increased risk should be examined for endometrial hyperplasia and then treated. For the drug treatment of bleeding have NSAIDs, tranexamic acid, have proven oral contraceptives or other hormones to be effective.


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