Ovulatory Dysfunctional Uterine Bleeding Research Articles

Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

BackgroundYuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.MethodsThe active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein–protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.ResultsThe study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.ConclusionThis novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

Comparison on serum biomarkers for anovulatory and ovulatory dysfunctional uterine bleeding in Lizu females

ObjectiveTo screen, identify, and compare the serum biomarkers between anovulatory dysfunctional uterine bleeding (ADUB) and ovulatory dysfunctional uterine bleeding (ODUB) in Lizu females. MethodsThe subjects included 128 ADUB patients, 63 ODUB patients, and 93 controls. The serum and supernate of the subjects' mense were collected and stored at −80 °C until use. Differential proteins in the sera of three groups were screened using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The screened proteins were then identified by tricine-SDS-PAGE gel and spectrometry. Protein expression levels in the menses of ADUB, ODUB, and control subjects were determined using ELISA, RT-PCR, and Western blotting. SPSS 14.1 was used for statistical analysis and chart drawing (α = 0.05). ResultsThree differential protein peaks with peak values of 11.80, 13.59, and 14.68 km/z were screened and identified as serum amyploid protein A (SAA), vascular endothelial growth factor, and vitamin K epoxide reductase, respectively. The SAA was highly expressed in the menses of ADUB and ODUB patients but poorly expressed in the controls. The vascular endothelial growth factor was highly expressed in the menses of ODUB and controls but poorly expressed in ADUB patients. Meanwhile, the vitamin K epoxide reductase was highly expressed in the menses of ADUB and control subjects but poorly expressed in ODUB patients. ConclusionsThe SAA is the common serum biomarker of ADUB and ODUB. ADUB may be related to angiogenesis impairment, whereas ODUB may be associated with blood coagulation disruption.

Treatment of ovulatory dysfunctional uterine bleeding with oral misoprostol: a comparative study

Objectives: Evaluation of the effects of oral misoprostol in the control of excessive menstrual blood loss in cases of ovulatory dysfunctional uterine bleeding in comparison to antifibrinolytic and antiprostaglandin therapy. Methods: Eighty-six patients with objective menorrhagia secondary to ovulatory dysfunctional uterine bleeding completed this prospective randomized comparative clinical trial of treatment with tranexamic acid(31 patients-group I), misoprostol(29 patients-group II), and mefenamic acid(26 patients-group III). Treatment was given during menstruation for three cycles. Treatment started on day one of menstruation for five days. Menstrual blood loss was assessed before and after treatment using subjective and objective assessment. Pulsatility index (PI) and resistance index (RI) were measured from the uterine arteries before starting treatment and during the third cycle of treatment in all patients. Results: A highly statistical significant reduction in menstrual blood loss occurred by treatment in the three groups (P=0.001). Tranexamic acid produced the highest reduction in menstrual blood loss (reduced menstrual blood loss by a mean of 125.87ml which represents a reduction of 48%). Oral misoprostol was less effective than tranexamic acid (a mean reduction of 91.58ml which represents a reduction of 35.85%)but more effective than mefenamic acid (a mean reduction of 83.66ml which represents a reduction of 30.75), however the only significant statistical difference was between tranexamic and mefenamic acid (P=0.03). Patient satisfaction as shown by the desire to continue treatment after the end of the study was high in groups I (71%) and II (62%). On the other hand, only 15 (57.7%) of patients taking mefenamic acid wished to continue the treatment. There was no significant statistical difference between the three group concerning the PI and RI before and after treatment. Conclusions: Oral misoprostol can be added to the lines of treatment of ovulatory menorrhagia.

Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical impact

The prevalence and impact of most underlying disorders of hemostasis are reviewed in women with excessive menstrual bleeding. The most common underlying bleeding disorder is von Willebrand disease, which occurs in only 1% to 2% of the general population but in approximately 13% of women with excessive menstrual bleeding.

Pathophysiology of endometrial bleeding

Objectives: To review the morphological and molecular events responsible for uterine bleeding in health and disease. Methods: Review of pertinent literature focusing on the histology and pathophysiology of normal and abnormal uterine bleeding (AUB). Results: The seat of normal menstrual bleeding is located in the upper two-thirds of the endometrial mucosa and is recognized by tissue necrosis, disruption of microvasculature, migratory leukocytes and platelet/fibrin thrombi in microvessels. The molecular events responsible for tissue and vascular breakdown are related to the release of proteolytic lysosomal enzymes of endometrial cell and inflammatory cell origin. In cases of AUB, tissue breakdown is located in the superficial layer (subsurface) of the endometrium. It is either focal (breakthrough bleeding) or diffuse (withdrawal bleeding). It is initiated by either chronic endometritis and/or microerosions or vascular fragility due to structural abnormalities of microvessels. Endometritis and microerosions occur in otherwise normal endometrium, polyps, submucosal leiomyomata, atrophy and cancer (organic causes). Primary vascular alterations are found in hyperestrogenic-type endometria, i.e. anovulatory dysfunctional uterine bleeding (DUB) and progestational-type endometrium, i.e. progestational contraceptives and combined, continuous hormonal replacement therapy (HRT) (non-organic causes). Ovulatory DUB and coagulation disorders are not appreciated histologically. These are related to impaired vasoconstriction and fibrinolysis and impaired coagulation factors, respectively. Conclusions: Histology may contribute to better understanding of the mechanisms of action that initiate, regulate and lead to AUB. Better insight may trigger in the development of therapeutic procedures that could either prevent or control vascular breakdown which results in unexpected uterine bleeding.

Mechanisms of abnormal uterine bleeding.

Over the past 10 years there has been an upsurge of interest in the mechanisms underlying normal and disturbed menstrual bleeding. These studies have particularly focused on the mechanisms underlying the common problems of menorrhagia associated with ovulatory and anovulatory dysfunctional uterine bleeding (DUB) and of unpredictable breakthrough bleeding during hormonal contraceptive use. A wide range of abnormalities of endometrial morphology and function have been demonstrated, but it is still not clear how all the pieces of this complex jigsaw puzzle fit together. Ovulatory DUB is predominantly associated with decreased endometrial vasoconstriction and vascular haemostatic plug formation, leading to defective control of the volume of blood which is lost during menstruation. By contrast, breakthrough bleeding is associated with a wide range of molecular disturbances which appear to result in unpredictable vessel breakdown through disturbed endometrial angiogenesis, increased vascular fragility and loss of the integrity of the endothelial, epithelial and stromal supporting structures. Anovulatory DUB is very poorly understood, but may be associated with disturbed angiogenesis, fragile vessels and defective haemostatic processes. Little is known about the actual mechanisms of the common problem of abnormal bleeding associated with specific genital tract pathologies such as uterine myomata.

Dysfunctional uterine bleeding: advances in diagnosis and treatment.

Dysfunctional uterine bleeding occurs during the reproductive years unrelated to structural uterine abnormalities. Ovulatory dysfunctional uterine bleeding occurs secondary to defects in local endometrial hemostasis; while anovulatory dysfunctional uterine bleeding is a systemic disorder, occurring secondary to endocrinologic, neurochemical, or pharmacologic mechanisms. Evaluation of patients with abnormal uterine bleeding and identifying those with dysfunctional uterine bleeding is achieved with a combination of the following: history; physical examination; and judicious use of laboratory evaluation, endometrial sampling and uterine imaging, with sonographic techniques and/or hysteroscopy. Coagulopathies should be considered as should the notion that intramural and subserosal myomas are unlikely to contribute to AUB. High-quality evidence suggests that medical therapy is frequently successful, and newer approaches, such as local delivery of progestins via intrauterine devices, appear to be particularly promising and devoid of systemic side effects. For those intolerant of medical therapy, and/or for whom fertility is no longer desired, a number of minimally invasive surgical options for hysterectomy now exist and are collectively termed endometrial ablation. Endometrial ablation may be performed with or without hysteroscopic guidance. There is an increasing body of evidence that suggests that nonhysteroscopic endometrial ablation may be at least as effective as hysteroscopic endometrial ablation, even when the hysteroscopic procedure is performed by experts.

Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding.

The aim of this study was to develop an objective test for superficial endometrial vascular fragility at hysteroscopy, and to apply this test to women using Norplant((R)) for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial vascular fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity. Superficial endometrial blood vessels were more fragile in Norplant users compared to women with DUB (chi(2) = 11.60, P = 0.02). Superficial endometrial petechiae (chi(2) = 37.9, P < 0.0001) and ecchymoses (chi(2) = 42.2, P = 0.0001) were more frequently observed in the Norplant users than in the menorrhagia group. In Norplant users, superficial endometrial vascular fragility was increased in those with frequent bleeding or spotting during the past 30 days (chi(2) = 6.15, P = 0.01), and in those who were examined during a bleeding episode (chi(2) = 5.3, P = 0.02). Fragility was increased in the menorrhagia group during the perimenstrual period (days 24 to 05; chi(2) = 12.83, P = 0.01). There was no obvious relationship between subepithelial bleeding and circulating concentrations of oestradiol and progesterone.

Endometrial lysosomal enzyme activity in ovulatory dysfunctional uterine bleeding, IUCD users and post-partum women.

The aim of this study was to evaluate the role of lysosomal enzymes in excessively heavy menstruation by comparing women with menorrhagia due to dysfunctional bleeding or intrauterine contraceptive device (IUCD) use with those with normal menstrual periods or with amenorrhoea associated with breastfeeding. This was a prospective cohort investigation of the activity of four endometrial lysosomal enzymes in three contrasting groups: (i) women with ovulatory dysfunctional uterine bleeding and users of intrauterine contraceptive devices; (ii) breastfeeding post-partum women in whom there are long periods of amenorrhoea, particularly in the early months post-partum; and (iii) normal cycling women. It was found that the total activity of lysosomal enzymes, particularly acid phosphatase and N-acetyl-beta-D-glucosaminidase, was markedly elevated (P < 0.001) in IUCD-exposed endometrium, and endometrium from women with dysfunctional uterine bleeding when compared with endometrium from women with a history of entirely normal menstrual periods or that in post-partum breastfeeding women. The activity of alpha-L-fucosidase was moderately elevated in IUCD users (P < 0.05) and ovulatory dysfunctional uterine bleeding (P < 0.05), whereas alphaD-mannosidase activity was elevated in ovulatory dysfunctional uterine bleeding (P < 0.05), but decreased in IUCD users (P < 0.01). No significant differences were observed in the lysosomal enzyme activities of breastfeeding post-partum women and normal cycling women. These results show that total endometrial tissue activity of four lysosomal enzymes was substantially increased throughout the cycle in most circumstances in women with two different causes for increased menstrual bleeding. This suggests a contributory role to the increased bleeding.

Menstrual Blood Loss Measured 5–6 Years After Endometrial Ablation

In Brief Objective To examine objectively the long-term efficacy of endometrial ablation for menorrhagia. Methods Thirty-nine women with menorrhagia due to ovulatory dysfunctional bleeding treated previously by rollerball ablation were followed up 5–6 years later. Menstrual blood in sanitary towels was measured with the alkaline hematin technique in 26 women who were still premenopausal and in whom menstrual blood loss had been measured before and immediately after the original ablation. Results Mean (± standard deviation [SD]) menstrual blood loss (per menstrual period) was reduced from 90 mL ± 14.4 before ablation to 3.8 mL ± 2.1 at 3 months, 1.8 mL ± 1.0 at 6 months, and 3.3 mL ± 1.3 at 5–6 years after ablation. In women who were still menstruating, the mean hemoglobin concentration rose significantly from 126 to 135 g/L (P = .022). Conclusion Rollerball endometrial ablation is a highly effective long-term therapy for carefully selected women with menorrhagia due to ovulatory dysfunctional uterine bleeding. The efficacy of rollerball endometrial ablation in women with menorrhagia due to ovulatory dysfunctional bleeding persists for many years.

Menstrual blood loss measured 5–6 years after endometrial ablation

Objective: To examine objectively the long-term efficacy of endometrial ablation for menorrhagia. Methods: Thirty-nine women with menorrhagia due to ovulatory dysfunctional bleeding treated previously by rollerball ablation were followed up 5–6 years later. Menstrual blood in sanitary towels was measured with the alkaline hematin technique in 26 women who were still premenopausal and in whom menstrual blood loss had been measured before and immediately after the original ablation. Results: Mean (± standard deviation [SD]) menstrual blood loss (per menstrual period) was reduced from 90 mL ± 14.4 before ablation to 3.8 mL ± 2.1 at 3 months, 1.8 mL ± 1.0 at 6 months, and 3.3 mL ± 1.3 at 5–6 years after ablation. In women who were still menstruating, the mean hemoglobin concentration rose significantly from 126 to 135 g/L ( P = .022). Conclusion: Rollerball endometrial ablation is a highly effective long-term therapy for carefully selected women with menorrhagia due to ovulatory dysfunctional uterine bleeding.

Management of abnormal uterine bleeding

Patients treated for dysfunctional uterine bleeding are separated into two groups: those with acute bleeding episodes and those with chronic repetitive bleeding problems. An acute bleeding episode is best controlled with the use of high-dose estrogen. A curettage is indicated for patients with acute bleeding resulting in hypovolemia, and a curettage or hysteroscopically directed biopsies is indicated for women with risk factors for endometrial cancer who have persistent bleeding problems. The management of anovulatory dysfunctional uterine bleeding is determined by the needs of the patient. In the adolescent medroxyprogesterone acetate is administered orally once a day for 10 days each month for ≥3 months, and the patient is monitored closely thereafter. Oral contraceptives are used for women of reproductive age with anovulatory bleeding episodes who also require contraception. Clomiphene citrate is used for women of reproductive age with anovulatory bleeding who want to conceive. Oral medroxyprogesterone acetate is administered 10 days each month for 6 months for the treatment of anovulatory dysfunctional uterine bleeding alone in this age group. For the perimenopausal patient dysfunctional uterine bleeding may be treated by the administration of cyclic progestin or cyclic conjugated equine estrogens for 25 days with the concomitant administration of medroxyprogesterone acetate for days 16 to 25. The perimenopausal patient with dysfunctional uterine bleeding who is a nonsmoker and does not have evidence of vascular disease may also be treated with low-dose combination oral contraceptives. The long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage. The long-term therapy is directed at the reduction in menstrual blood loss. For these patients prolonged progestin use, oral contraceptives, nonsteroidal antiinflammatory drugs, antifibrinolytic agents, danazol, and as a last resort gonadotropin-releasing hormone agonists are part of the therapeutic armamentarium. A combination of two or more of these agents is often required to successfully control the abnormal bleeding. For patients who no longer desire future fertility and have associated pelvic pathologic disorders or for those who fail all medical regimens, surgical therapy may be considered. Either hysterectomy or endometrial ablation has been used. Patients with von Willebrand's disease and excessive menstrual blood loss may be misdiagnosed as having dysfunctional uterine bleeding. von Willebrand's disease is the most common bleeding disorder and is present in approximately 1% of the population. It is much more common than previously recognized. There are improved diagnostic tests to identify this disorder and, most important, there is a high-concentration desmopressin acetate nasal spray available as treatment that does not involve the risk of transmission of hepatitis and human immunodeficiency virus. (Am J Obstet Gynecol 1996;175:787-92.)

Differential diagnosis of abnormal uterine bleeding

The causes of abnormal uterine bleeding include a wide spectrum of diseases of the reproductive system and nongynecologic causes as well. The differential diagnosis of abnormal excessive uterine bleeding includes organic causes that may be subdivided into reproductive tract disease, iatrogenic causes, and systemic disease. Reproductive tract disease that may result in abnormal uterine bleeding comprises the complications of pregnancy (threatened, incomplete, or missed abortion, ectopic pregnancy, trophoblastic disease, placental polyp, and subinvolution of the placental site), malignant tumors (endometrial, cervical, vaginal, vulvar, and oviduct malignancies and granulosa theca cell ovarian tumors), infection (endometritis, salpingitis), and other benign pelvic disorders (traumatic lesions of the vagina, severe vaginal infections, foreign bodies, cervical polyps, cervical erosion, cervicitis, submucous uterine leiomyomas, adenomyosis, endometriosis, and endometrial polyps). Iatrogenic causes of abnormal uterine bleeding include sex steroids, hypothalamic depressants, digitalis, phenytoin, anticoagulants, and intrauterine contraceptive devices. Systemic diseases that may cause abnormal uterine bleeding include hypothyroidism, cirrhosis, and coagulation disorders. Abnormal uterine bleeding that occurs in a woman of reproductive age should be considered the result of a complication of pregnancy until proved otherwise. Abnormal uterine bleeding occurring in a woman of perimenopausal or postmenopausal age should be considered the result of a malignancy until proved otherwise. Menorrhagia occurring in an adolescent should be attributed to a coagulopathy until proved otherwise. When an organic cause of abnormal uterine bleeding cannot be found, then by exclusion the diagnosis of dysfunctional uterine bleeding is assumed. Coagulation disorders, particularly von Willebrand disease, are more common than many physicians realize. Women with a history of high-risk factors, all adolescents with menorrhagia, women with anovulatory dysfunctional uterine bleeding who fail medical or surgical therapy, and women with ovulatory dysfunctional uterine bleeding without an anatomic uterine lesion should be screened for a coagulopathy. (Am J Obstet Gynecol 1996;175:766-9.)

Medium-term follow-up of women with menorrhagia treated by rollerball endometrial ablation

To assess the medium-term efficacy of rollerball endometrial ablation. From January 1990 to December 1993, 142 women underwent rollerball endometrial ablation for menorrhagia, most with ovulatory dysfunctional uterine bleeding. Each was sent a detailed questionnaire 12-52 months later and then followed-up, with an overall 93% response rate. Thirty-two had uterine myomas (13 with hysteroscopic myoma resection) and 11 had a large endometrial polyp (four with both). Most of the women were pretreated with danazol. Thirty-two of 128 (25%) achieved long-term, complete amenorrhea and only three eventually resumed their periods after prolonged amenorrhea. Four women experienced late amenorrhea, which was probably due to menopause. The percentage of satisfactory outcomes decreased gradually with time (95.5, 85.5, and 75% for 13-24, 25-36 and more than 36 months respectively; P = .051); this was not statistically significant. One hundred twenty-one patients (85.2%) did not need further surgical treatment. The incidence of repeat ablation (8.5%) and hysterectomy (8.5%) increased gradually with time over the first 3 years but not thereafter, although total numbers are still small. Cyclic pelvic pain and premenstrual symptoms were much improved in both short and long term. Most women remained satisfied with the operation (84%) and would recommend it to others (89%). Rollerball endometrial ablation is a simple, effective, and acceptable procedure for the management of intractable menorrhagia due to ovulatory dysfunctional uterine bleeding. However, with the findings of slightly less satisfactory results with time, longer-term follow-up is still needed to establish the ultimate effectiveness of the procedure using different techniques.

Depot goserelin and danazol pre-treatment before rollerball endometrial ablation for menorrhagia

To compare the safety and efficacy of a GnRH agonist, depot goserelin, and danazol as preoperative treatments before rollerball endometrial ablation. We performed an open, randomized study of women with clinically convincing histories of menorrhagia. Two treatment groups of equal size (goserelin acetate, 3.6 mg subcutaneous implant given monthly, n = 30; and danazol, 200 mg two times per day, n = 30) were treated for 2 months before undergoing endometrial ablation, which entailed using the rollerball with 80-100 watts of coagulating current. Measured menstrual blood loss decreased dramatically after ablation, with 74% of goserelin users and 62% of danazol users achieving complete amenorrhea by the end of the 6-month follow-up period. Among women who did not achieve complete amenorrhea, those in the danazol group were more likely to experience occasional episodes of moderate or heavy bleeding. Mean measured blood loss decreased from 94.8 to 1.1 mL at 3 months and 1.0 mL at 6 months after goserelin, and 97.9 to 15.0 mL and 7.4 mL after danazol. Menstrual pain also improved markedly. The median duration of surgery was 20 minutes (range 5-55) in both groups, median irrigation fluid deficit was 100 mL (range 0-800), and median operative blood loss was 20 mL (range 1-50). Endometrium was less than 2 mm thick in all goserelin and most danazol users. Side effects of goserelin and danazol therapy were all within the expected pattern for these drugs. Depot goserelin and danazol both provide adequate endometrial preparation before rollerball endometrial ablation for treatment of menorrhagia due to ovulatory dysfunctional uterine bleeding.

Endometrial morphometry in users of intrauterine contraceptive devices and women with ovulatory dysfunctional uterine bleeding: A comparison with normal endometrium

Copper-bearing intrauterine contraceptive divices (IUCD) are commonly associated with menorrhagia. They cause certain morphological changes in the endometrium. These have been extensively reported and the mechanisms of menorrhagia have been investigated in a number of studies. By contrast, ovulatory dysfunctional uterine bleeding has not been as widely studied and mechanisms of menorrhagia in these patients are still not well understood. In this study, we examined endometrial morphometry in a group of women using IUCD, a group of women with ovulatory dysfunctional bleeding, and a control group of women with entirely normal cycles. There was increased leukocytic infiltration of the endometrium in both groups of women with menorrhagia compared to control cases. In addition, IUCD use was associated with greater luteal phase glandular epithelial height, supporting the concept of a secretory function defect in glandular epithelium. Possible links are postulated between static morphometric observations and dynamic biochemical changes.

Use of Transvaginal Ultrasound in Diagnosing the Etiology of Menometrorrhagia

Forty-five women with a chief complaint of abnormal vaginal bleeding from a few days' duration (spotting) to three to six months of bleeding (average, 4.5 months) were evaluated using a standard clinical approach followed by transvaginal ultrasound (US). Serum estradiol (E2), progesterone and/or endometrial biopsy was used to further clarify the etiology of the bleeding and confirm the clinical or ultrasound diagnosis. Anatomic findings were present in 31% of patients by US examination as compared to only 9% by clinical evaluation. An additional 9% of patients had polycystic ovary disease. Of the 16% of study patients on oral contraceptives with a clinical diagnosis of breakthrough bleeding, 33% had anatomic findings associated with the bleeding on US. The ultrasound image of the endometrium predicted the endometrial biopsy findings in all three patients with postmenopausal bleeding. In the remaining patients with a diagnosis of dysfunctional uterine bleeding (DUB) (a diagnosis usually made clinically by excluding other etiologies), US was helpful in excluding many patients with anatomic findings not detected by physical examination and in evaluating the endometrium, helping differentiate anovulatory from ovulatory DUB. US was helpful in predicting the hormonal and histologic endometrial status of the patients. Patients with more severe and prolonged DUB had low serum E2 with US findings of a single-line endometrium (consistent with low serum E2 and anovulation). US can be a valuable aid in evaluating women presenting with a complaint of abnormal vaginal bleeding by demonstrating anatomic findings frequently not discernible on pelvic examination, such as small cysts and leiomyomas and even endometrial carcinoma, and in evaluating the endometrium in terms of its thickness and, indirectly, the endometrial histology and the ovulatory and hormonal status of the patient. US can also be of value in confirming some diagnoses that are generally made clinically by exclusion, such as breakthrough bleeding from oral contraceptive use and DUB.

Treatment of Ovulatory and Anovulatory Dysfunctional Uterine Bleeding with Oral Progestogens

Six anovulatory and 10 ovulatory women with dysfunctional uterine bleeding (DUB) were treated with cyclical oral progestogens (norethisterone or medroxyprogesterone acetate). Anovulatory women were treated from day 12-25 and ovulatory from day 5-25, in doses of 5-10mg 3 times daily. Measured menstrual blood loss was effectively reduced from control to treatment cycles in both anovulatory (control cycle 131ml; treatment 80 and 64ml) and ovulatory women (control cycles 110 and 113ml; treatment 76 and 71 ml). Three women with ovulatory DUB did not show a useful response. Duration of bleeding was reduced in both groups and the pattern of loss changed. These regimens are effective forms of management for most women with ovulatory or anovulatory DUB.

Dysfunctional Uterine Bleeding

Dysfunctional uterine bleeding is classified by the character of the menstrual cycle: ovulatory or anovulatory.23 Anovulation can occur at any age and is physiologic in the first year or two after menarche and for several years before menopause. Anovulatory cycles are characteristically irregular and marked by prolonged episodes of bleeding unassociated with signs or symptoms of ovulation. Specific causes of anovulation such as hyperprolactinemia, thyroid disease, androgen excess, anorexia, obesity, and excess exercise can be treated specifically; otherwise, therapy depends upon patient goals. Cycle regulation can be affected by monthly courses of progestin, such as medroxyprogesterone acetate (Provera), 10 mg daily for 10 days each month. Contraception and cycle regulation can both be accomplished with oral contraceptives. Fertility, on the other hand, will require ovulation induction. Ovulatory dysfunctional uterine bleeding most prevalent in parous women between the ages of 20 and 40 is associated with regular cycle intervals and premenstrual molimina. Midcycle and perimenstrual spotting can often be treated with observation only, but depending upon patient and/or physician concerns, periodic hormonal suppression is effective. The management of menorrhagia should include the following: (1) exclusion of pathology in the genital tract; (2) reduction in activity during days of heavy flow; (3) the avoidance of aspirin in the week before and on days of flow; (4) nonsteroidal anti-inflammatory drugs; (5) cycle suppression—oral contraceptives, danazol (Danocrine), depo-progestin; (6) luteal phase progestin; and (7) surgical intervention.

Dysfunctional uterine bleeding in ovulatory women.

Ovulatory dysfunctional uterine bleeding (DUB), a disease prevalent in the latter half of the reproductive years, is diagnosed when organic causes for bleeding have been excluded by clinical, laboratory, and surgical diagnostic means. Disordered prostaglandin metabolism within the endometrium explains most cases of DUB. Nonsteroidal antiinflammatory drugs, oral contraceptives, and oral progestin are effective medical alternatives for women who wish to retain their uterus or to avoid surgery. Hysterectomy is a rapid cure for DUB and is a therapy that is acceptable to many, if not most, women.