MyEClinic
MyEClinic
Health Dictionary Find a Doctor

Abnormal uterine bleeding

Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Arooj Naz, M.B.B.S, Vishnu Vardhan Serla M.B.B.S. [2]

For patient information, click here

Synonyms and Keywords: Anovulatory bleeding; DUB; Abnormal uterine bleeding

Overview

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Overview

Dysfunctional uterine bleeding (DUB), often referred to as abnormal uterine bleeding, is an umbrella term used to define any abnormalities in uterine bleeding. Such abnormalities include menorrhagia, dysmenorrhea, menometrorrhagia and inter-menstrual vaginal bleeding. Common causes of DUB include anatomical causes such  Polyp, adenomyosis, Leiomyoma and Malignancy or hyperplasia. Bleeding may also be due to non-structural causes such as Coagulopathy, ovulatory dysfunction, such as PCOS, endometrial disorders, such as endometriosis, as well as Iatrogenic causes.

Historical Perspective

Dysfunctional or abnormal uterine bleeding is a condition experienced by women of varying ages and from various geographical locations. Although there isn’t much information available on dysfunctional uterine bleeding as it encompasses a multitude of possible underlying causes, there is some historical information available regarding some common causes. conditions that have significant historical information include Adenomyosis, Leiomyoma, uterine malignancy, PCOS, as well as endometriosis.

Classification

Dysfunctional uterine bleeding has multiple underlying causes but, at its root, the disease can be subdivided into ovulatory or anovulatory causes. Ovultaory bleeding occurs when there are underlying issues of ovulation. This may be due to ovarian dysfunction as well as hypothalamic axis disorders. Anovulatory causes are those that occur independent of ovulatory dysfunctions such as pregnancy, weight gain, endocrinopathies, and drugs. Idiopathic causes may also contribute to anovulatory dysfunctional uterine bleeding. Affected patients may affect with a range of uterine bleeding patterns such as menometrorrhagia, metrorrhagia, menorrhagia as well as inter menstrual spotting.

Pathophysiology

Dysfunctional uterine bleeding is a condition that affects many women worldwide, especially because it has a wide range of underlying causes. Bleeding can be acute or chronic. By understanding the pathophysiology of the causative conditions, one can understand the cause of dysfunctional uterine bleeding. These include polyps, adenomyosis, leiomyoma, malignancy or hyperplasia, coagulopathies, ovulatory dysfunction, endometrial disorders and iatrogenic causes. In ovulatory causes, unopposed estrogen and progesterone result in continued thickening and proliferation of the endometrium. Along with the effects of these hormones, hypoxia, inflammation and vasoconstriction result in shedding and subsequent scarring.

Causes

Uterine bleeding can be divided into anatomical or structural and non-structural causes. The anatomical causes include Polyp, adenomyosis, Leiomyoma and Malignancy or hyperplasia. The non-structural causes include Coagulopathy, Ovulatory dysfunction, such as PCOS, Endometrial disorders, such as endometriosis, and Iatrogenic causes. In some women, no underlying cause can be identifiedd. These women are thought to have abnormal bleeding due to causes not otherwise classified.

Differential diagnosis

There are many differential diagnosis’ for dysfunctional uterine bleeding, many of them resulting in abnormal presentation of bleeding. Some prevalent conditions include anatomical or structural defects, coagulation disorders, pregnancy related complications, endometrial cancer and hyperplasia, as well as Polycystic Ovarian Syndrome.

Risk Factors

Diseases presenting with dysfunctional uterine bleeding have a multitude of risk factors. Some that are commonly found in multiple conditions include those where estrogen exposure is uncontrolled and excessive. Some examples include early onset of menarche and late onset of menopause, obesity, anovulatory conditions such as PCOS, estrogen exclusive hormonal contraceptives and tamoxifen therapy for breast cancer. It is to be notes that smoking has actually resulted in a reduced risk of some disease, due to its anti-estrogenic causes. The efficacy of smoking in preventing DUB is questionable considering the multitude of other diseases such a behavioural activity results in. Although some conditions affected women of all ages, adenomyosis and malignancy were found to affect older woman.

Natural history, Complications and Prognosis

Dysfunctional uterine bleeding is an irregularity of the menstrual cycle that may affect the duration, frequency and blood volume. Normal cycles last around 24-38 days and average 5-80 mL of blood loss during this time. Commonly associated complications include infertility, anemia and the possibility of underlying endometrial malignancy. Generally, the prognosis is favourable, but may depend on underlying causes and treatment options. The amount of blood loss varies according to hormonal and non-hormonal medications, as well as with surgical interventions.

History and Symptoms

Assessment of anovulatory DUB should always start with a good medical history and physical examination. Laboratory assessment of hemoglobin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, T4, thyroid stimulating hormone (TSH), pregnancy (by βhCG), and androgen profile should also happen. More extensive testing might include an ultrasound and endometrial sampling. It is important to retrieve a complete history including menstrualhistory, sexual and reproductive history, drug history, family history, as well as social activities and hobbies. Assessment for symptoms of anemia should also be done as women can loose large volumes of blood often leading to iron deficiency anemia.

Physical Examination

Physical findings vary amongst patients but it is common to find pelvic and endocrine as well as skin changes. These include changes associated with underlying anemia such as pallor and a pale conjunctiva. Endocrine findings such as increased hair growth, clitoromegaly and acne may help diagnose underlying endocrine related causes of abnormal bleeding. In those experiencing uterine bleeding due to coagulopathies, signs of platelet deficiencies may be present, such as bruising and petechiae. An extensive physical examination may help in diagnosing the cause of abnormal uterine bleeding.

Laboratory Findings

Women afflicted with dysfunctional uterine bleeding commonly present with CBC changes, particularly changes in red blood cells. Significant laboratory findings may include coagulation profile changes, hormonal levels as well as biomedical markers to detect underlying malignancies.

CT

CT scans are not the primary modality of assessing for underlying causes, but it may show some changes. It may be difficult to differentiate polyps, adenomyosis and leiomyoma’s from each other. CT can help asses for the presence of metastasis secondary to endometrial cancer.

MRI

MRI is not commonly performed but it is considered the modality of choice for adenomyosis. Findings for other conditions may also be seen but may not be as reliable as other imaging studies. MRI can assist in furthering diagnosis metastasis.

Ultrasound

Ultrasonography, although not the most sensitive or specific imaging modality, is commonly the primary type of imaging done for patients with dysfunctional uterine bleeding. Transvaginal ultrasounds are more accurate compared to pelvic ultrasound, but pelvic ultrasound reveals certain pathologies, including uterine and adnexal masses, more clearly. Ultrasonography is a simple and easily available diagnostic method for PCOS.

Other Imaging Findings

Other imaging findings include colour doppler, sonohysterography, hysterosalpingography, and nuclear imaging (PET scan). These imaging modalities have proven useful for diagnosing polyps, endometrioma’s and adenomyosis.

Other Diagnostic Studies

Other imaging findings include colour doppler, sonohysterography, hysterosalpingography, and nuclear imaging (PET scan). These imaging modalities have proven useful for diagnosing polyps, endometrioma’s and adenomyosis.

Medical therapy

The treatment for dysfunctional uterine bleeding has often proven to be successful but it is important to considering underlying etiologies, desire for fertility as well as any other symptoms patients may be experiencing. Treatment should be trailored for patients according to these underlying factors. The primary modality of treatment is hormonal, but there are nonhomronal options as well. It is important to treat acute bleeding as it may be life-threatening. Hormonal medications must be avoided in elderly women due to the risk of endometrial hyperplasia and malignancy. Iatrogeniccauses should focus on treating the underlying causes.

Surgery

Surgical procedures are reserved for patients that are unresponsive to medical treatment or those that do not desire fertility. Procedures can be specific according to underlying causes of dysfunctional bleeding as well as cancer stage. Common surgical interventions include hysterectomy, endometrial ablation and laparoscopic removal.

Primary Prevention

The goal of primary prevention is to prevent the occurrence of an illness or a disease before it occurs. Malignancy can be prevented by controlling estrogen exposure with hormonal medications.

Secondary Prevention

Secondary prevention occurs once the disease has developed and aims to prevent progression and development of further complications. Complications due to abnormal uterine bleeding include infertility, anemia, and malignancy.

Cost-Effectiveness of Therapy

Women are subjected to increased financial burden to treat underlying abnormal uterine bleeding. Annually, they loose USD $2,000.00 on account of work absences. Hormonal medications range from USD $172.00 for contraceptive pills, USD $930.00 for levonorgestrel IUD and upwards of USD $30,000.00 for hysterectomies.

Future or Investigational Therapies

Abnormal uterine bleeding has been found to affect a multitude of women, ranging from menarche to menopause. It can often result in conditions that affect an individual’s daily routine and personal life, such as anemia and infertility. Because of such complications, it is important to continue researching and studying the causes of abnormal bleeding and providing further knowledge. Due to the prevalence and high cost associated with surgical treatment of underlying causes, treatment must be tailored to the individual woman. Biomarkers continue to be studied and may provide crucial information. Future studied regarding  progesterone antagonists and progesterone receptor modulators are also being studied and may proove helpful in future therapy.

References

Template:WH Template:WS

Historical Perspective

Historical Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Overview

Dysfunctional or abnormal uterine bleeding is a condition experienced by women of varying ages and from various geographical locations. Although there isn’t much information available on dysfunctional uterine bleeding as it encompasses a multitude of possible underlying causes, there is some historical information available regarding some common causes. conditions that have significant historical information include Adenomyosis, Leiomyoma, uterine malignancy, PCOS, as well as endometriosis.

Historical perspective

Dysfunctional or abnormal uterine bleeding is a condition experienced by women of varying ages and from various geographical locations. Although there isn’t much information available on dysfunctional uterine bleeding as it encompasses a multitude of possible underlying causes, there is some historical information available regarding some common causes.

References

  1. ↑ Taran FA, Stewart EA, Brucker S (2013). “Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy”. Geburtshilfe Frauenheilkd. 73 (9): 924–931. doi:10.1055/s-0033-1350840. PMC 3859152. PMID 24771944.
  2. ↑ Bozini, Nilo; Baracat, Edmund C (2007). “The history of myomectomy at the Medical School of University of São Paulo”. Clinics. 62 (3). doi:10.1590/S1807-59322007000300002. ISSN 1807-5932.
  3. ↑ Childers JM, Surwit EA (1992). “Combined laparoscopic and vaginal surgery for the management of two cases of stage I endometrial cancer”. Gynecol Oncol. 45 (1): 46–51. PMID 1534780.
  4. ↑ Azziz R, Dumesic DA, Goodarzi MO (2011). “Polycystic ovary syndrome: an ancient disorder?”. Fertil. Steril. 95 (5): 1544–8. doi:10.1016/j.fertnstert.2010.09.032. PMC 3164771. PMID 20979996.
  5. ↑ 5.0 5.1 Benagiano G, Brosens I, Lippi D (2014). “The history of endometriosis”. Gynecol Obstet Invest. 78 (1): 1–9. doi:10.1159/000358919. PMID 24853333.

Template:WH Template:WS

Classification

Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S, Vishnu Vardhan Serla M.B.B.S. [2]

Overview

Dysfunctional uterine bleeding has multiple underlying causes but, at its root, the disease can be subdivided into ovulatory or anovulatory causes. Ovultaory bleeding occurs when there are underlying issues of ovulation. This may be due to ovarian dysfunction as well as hypothalamic axis disorders. Anovulatory causes are those that occur independent of ovulatory dysfunctions such as pregnancy, weight gain, endocrinopathies, and drugs. Idiopathic causes may also contribute to anovulatory dysfunctional uterine bleeding. Affected patients may affect with a range of uterine bleeding patterns such as menometrorrhagia, metrorrhagia, menorrhagia as well as inter menstrual spotting.

Classification

It can be classified as ovulatory or anovulatory, depending on whether ovulation is occurring or not.[1]

  • Uterine bleeding is deemed abnormal when there is an irregular amount or an irregular pattern of bleeding.
  • Menometrorrhagia: Excessive and irregular bleeding between cycles and during menstruation
  • Metrorrhagia: Irregular and more frequent bleeding
  • Menorrhagia: Excessive, but regular bleeding

Ovulatory

Ovulatory DUB happens with the involvement of ovulation, and may represent a possible endocrine dysfunction, resulting in menorrhagia or metrorrhagia. Mid-cycle bleeding may indicate a transient estrogen decline, while late-cycle bleeding may indicate progesterone deficiency. Ovulatory causes are associated with vascular disturbances.[2]

Anovulatory

Anovulatory cycle DUB happens without the involvement of ovulation. The etiology can be psychological stress, weight (obesity, anorexia, or a rapid change), exercise, endocrinopathy, neoplasm, drugs, or it may be otherwise idiopathic. anovulatory causes are associated with structural endometrial defects.[3]

References

  1. ↑ Field CS (1988). “Dysfunctional uterine bleeding”. Prim Care. 15 (3): 561–74. PMID 3054963.
  2. ↑ Fraser IS, Hickey M, Song JY (1996). “A comparison of mechanisms underlying disturbances of bleeding caused by spontaneous dysfunctional uterine bleeding or hormonal contraception”. Hum Reprod. 11 Suppl 2: 165–78. doi:10.1093/humrep/11.suppl_2.165. PMID 8982758.
  3. ↑ Fraser IS, Hickey M, Song JY (1996). “A comparison of mechanisms underlying disturbances of bleeding caused by spontaneous dysfunctional uterine bleeding or hormonal contraception”. Hum Reprod. 11 Suppl 2: 165–78. doi:10.1093/humrep/11.suppl_2.165. PMID 8982758.

Template:WH Template:WS

Pathophysiology

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Overview

Dysfunctional uterine bleeding is a condition that affects many women worldwide, especially because it has a wide range of underlying causes. Bleeding can be acute or chronic. By understanding the pathophysiology of the causative conditions, one can understand the cause of dysfunctional uterine bleeding. These include polyps, adenomyosis, leiomyoma, malignancy or hyperplasia, coagulopathies, ovulatory dysfunction, endometrial disorders and iatrogenic causes. In ovulatory causes, unopposed estrogen and progesterone result in continued thickening and proliferation of the endometrium. Along with the effects of these hormones, hypoxia, inflammation and vasoconstriction result in shedding and subsequent scarring.

Pathophysiology

Dysfunctional uterine bleeding can be classified into acute and chronic causes.[1]

  1. Acute Dysfunctional uterine bleeding: Acute bleeding can develop in one of two ways. Bleeding can develop acutely on which immediate intervention is required to prevent excessive blood loss, or it can be imposed upon chronic uterine bleeding. The latter often refers to menstrual irregularities that developed of 6 months or longer.
  2. Chronic Dysfunctional uterine bleeding


At the end of the menstrual cycle, progesterone levels fall significantly leading to a breakdown of the functional layer of the endometrium. This leads to the phenomenon known as the menstrual cycle. This cycle can become irregular due to several causes, especially any derangements in the architectural structure of the endometrium. Common underlying causes include polyps, adenomyosis, leiomyoma, malignancy or hyperplasia, coagulopathies, ovulatory dysfunction, endometrial disorders and iatrogenic causes. DUB that is due to underlying ovulatory causes occurs due to defects in local endometrial functions whereas anovulatory is often due to systemic disorders, endocrine or neurological imbalances. By understanding the pathophysiology of these conditions, one can understand the cause of dysfunctional uterine bleeding:[2]

Pathophysiology of underlying conditions causing DUB
Condition causing DUB Pathophysiology
Polyps Endometrial polyps are overgrowths of endometrial tissue. They can vary in size and eventually result in obstruction to the endometrial outflow path[3] which may lead to unexpected bleeding
Adenomyosis Adenomyosis is characterized by the presence of ectopic endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). Although the pathophysiology is not well understood, the basic Fibroblast Growth Factor receptor/ligand system has shown to be upregulated. Hormones such as estrogen and progesterone as well as oxytocin, FSH, and prolactin also contribute to the pathogenesis of the disease by causing tissue proliferation
Leiomyoma Also referred to as fibroids, leiomyoma are tumours of benign origin made up primarily of smooth muscle and fibrous connective tissue. They can presents as serosal, submucosal, subserosal or pedunculated masses. Leiomyoma has been linked to underlying genetic mutations including translocations (12;14)(q14-q15;q23–24), deletions (7)(q22q32) and rearrangements involving 6p21, 10q, trisomy 12
Malignancy and hyperplasia Typical proliferation due to underlying hyperplasia or malignancy of the endometrium is an important cause of dysfunctional endometrial bleeding and warrants further investigations, especially in older women
Coagulopathies Conditions that lead to defective blood clotting, such as Von Willebrand disease, may contribute to DUB. In vWF deficiency, there is a defect in the platelet plug formation that results in a defective platelet adhesion and clot formation
Ovulatory Ovulatory causes are due to unopposed effects of estrogen, which result in continued thickening and proliferation of the endometrium. When there is an imbalance between estrogen and progesterone hormone levels, heavy menstrual bleeding, as well as an alteration in bleeding patterns and frequency, are noted. Although drugs are considered an anovulatory cause, those drugs that affect dopamine levels interfere with the hypothalamic axis and also contribute to DUB. Although not entirely understood, endometrial bleeding may be due to hypoxia, inflammation and vasoconstriction [4] that play a role in shedding and subsequent scarring [5]
Endometriosis The Sampson theory of retrograde menstruation, the coelomic metaplasia theory, and the lymphatic and vascular dissemination theory explain the implantation and invasion of the endometrial tissue outside the uterine cavity. Immunologic factors and genetic factors are also thought to play a role in the pathogenesis of endometriosis [6]
Iatrogenic Iatrogenic causes refer to inadvertent injuries induced by my physicians. Such causes include unopposed and continuous exposure to estrogen and progesterone therapy, as is seen with contraceptive medications, GnRH agonists, and SERMs.[7]

Blood supply of Endometrium

The ovarian artery arises from the aorta and descends into the retroperitoneum alongside the gonadal vein and ureter. Eventually, it anastomoses with the ovarian branch of the uterine artery at the uterus. Vasoconstriction affects these vessels may contribute to DUB.

Henry Gray (1918) Anatomy of the Human Body

References

  1. ↑ “StatPearls”. 2022. PMID 30422508.
  2. ↑ Munro MG (2001). “Dysfunctional uterine bleeding: advances in diagnosis and treatment”. Curr Opin Obstet Gynecol. 13 (5): 475–89. doi:10.1097/00001703-200110000-00006. PMID 11547028.
  3. ↑ “StatPearls”. 2022. PMID 32491756 Check |pmid= value (help).
  4. ↑ Livingstone M, Fraser IS (2002). “Mechanisms of abnormal uterine bleeding”. Hum Reprod Update. 8 (1): 60–7. doi:10.1093/humupd/8.1.60. PMID 11866241.
  5. ↑ Whitaker L, Critchley HO (2016). “Abnormal uterine bleeding”. Best Pract Res Clin Obstet Gynaecol. 34: 54–65. doi:10.1016/j.bpobgyn.2015.11.012. PMC 4970656. PMID 26803558.
  6. ↑ Bulun, Serdar E. (2009). “Endometriosis”. New England Journal of Medicine. 360 (3): 268–279. doi:10.1056/NEJMra0804690. ISSN 0028-4793.
  7. ↑ Whitaker L, Critchley HO (2016). “Abnormal uterine bleeding”. Best Pract Res Clin Obstet Gynaecol. 34: 54–65. doi:10.1016/j.bpobgyn.2015.11.012. PMC 4970656. PMID 26803558.

Template:WH Template:WS

Causes

Causes


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rinky Agnes Botleroo, M.B.B.S., Arooj Naz, M.B.B.S

Overview

Uterine bleeding can be divided into anatomical or structural and non-structural causes. The anatomical causes include Polyp, adenomyosis, Leiomyoma and Malignancy or hyperplasia. The non-structural causes include Coagulopathy, Ovulatory dysfunction, such as PCOS, Endometrial disorders, such as endometriosis, and Iatrogenic causes. In some women, no underlying cause can be identifiedd. These women are thought to have abnormal bleeding due to causes not otherwise classified.

Causes

Dysfunctional uterine bleeding (DUB) is a historical term for a diagnosis of exclusion, referring to abnormal uterine bleeding unrelated to structural uterine abnormalities.

Other conditions such as uterine fibroids, endometrial polyps and systemic diseases should be excluded by appropriate investigations. In the adolescent, investigations for a coagulopathy should be performed. The pathophysiology of DUB is largely unknown but occurs in both ovulatory and anovulatory menstrual cycles.

Causes of Abnormal Uterine Bleeding

PALM-COEIN is a useful acronym provided by the International Federation of Obstetrics and Gynecology (FIGO) to classify the casuses of abnormal uterine bleeding. The first portion, PALM, describes anatomical issues. The second portion, COEI, describes non-structural causes. The N stands for “not otherwise classified.”[1]

P: Polyp

Endometrial polyps refer to overgrown glands and storm within the uterine cavity. The vary in size, number and location and are most common amongst the ages of 40-49.[2]


A: Adenomyosis

Adenomyosis is characterized by the presence of ectopic endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). It is most commonly seen affects most women in their 30’s and 40’s.[3]


L: Leiomyoma

Leiomyoma are tumours of benign origin made up primarily of smooth muscle and fibrous connective tissue that can presents as serosal, submucosal, subserosalor pedunculated masses. They most often affect women over the age of 50, and especially those of African descent.[4]


M: Malignancy and hyperplasia

Endometrial malignancy is a common cause of post-menopausal bleeding and often has a higher mortality rate. Women between the ages of 65-74 are most often affected.[5]


C: Coagulopathy

Coaguloptahies refer to any conditions, inherited or acquired that result in abnormal uterine bleeding.


O: Ovulatory dysfunction

A very common ovulatory dysfunction resulting in abnormal uterine bleeding is polycystic ovarian syndrome. This most often presents in young women due to a hormonal imbalance.


E: Endometrial disorders

Endometrial disorders, such as endometriosis can result in abnormal bleeding. Endometriosis is the presence of functional endometrial tissue outside the uterine cavity. When proliferating and shedding, endometrial tissue in all various locations will act similarly.


I: Iatrogenic

Iatrogenic causes of abnormal bleeding include unopposed and continuous exposure to estrogen and progesterone therapy, as is seen with contraceptive medications, GnRH agonists, and SERMs.[6] Anticoagulant medications are also included in this category now.


N: Not otherwise classified

This category is reserved for those in whom no other underlying cause can be diagnosed despite examinations and imaging.

Common Causes


Causes by Organ System

Cardiovascular No underlying causes
Chemical / poisoning No underlying causes
Dermatologic No underlying causes
Drug Side Effect Blood thinners, breakthrough bleeding in women using hormonal birth control, copper intrauterine device , depo-Provera

hormone replacement therapy, tamoxifen, corticosteroids, chemotherapy, clomiphene, dilantin, antipsychotic drugs , antibiotics ( due to toxic epidermal necrolysis or Stevens-Johnson syndrome )

Ear Nose Throat No underlying causes
Endocrine Diabetes, hyperthyroidism, hypothyroidism, Cushing’s syndrome, Hormone secreting adrenal and ovarian tumors
Environmental No underlying causes
Gastroenterologic Liver disease
Genetic No underlying causes
Hematologic Clotting disorders, Von Willebrand disease, thrombocytopenia or platelet dysfunction,

acute leukemia ,Some factor deficiencies, Advanced liver disease

Iatrogenic Radiation therapy
Infectious Disease Chlamydia, gonorrhea, uterine infection, genitourinary tract infection, bacterial vaginosis

sexually transmitted diseases, atrophic vaginitis

Musculoskeletal / Ortho No underlying causes
Neurologic No underlying causes
Nutritional / Metabolic No underlying causes
Obstetric/Gynecologic Adenomyosis, atrophy of the tissue lining the vagina and uterus, cervicitis, ectopic pregnancy, endometrial hyperplasia, endometritis, uterine sarcoma, first few months after the first menstrual period, first few weeks after abortion, first few weeks after delivery, intrauterine device, miscarriage, ovarian cysts, placenta previa, polycystic ovarian syndrome, retained products of conception, uterine fibroids, uterine polyps, diseases involving the vulva for example Crohn’s disease, Behcet’s syndrome , pemphigoid , pemphigus , erosive lichen planus , lymphoma, skin tags, sebaceous cysts, condylomata, angiokerataoma
Oncologic Cancer or precancer of the cervix , cancer or precancer of the endometrium, ovarian cancer, uterine cancer, uterine sarcoma
Opthalmologic No underlying causes
Overdose / Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal / Electrolyte Chronic renal disease
Rheum / Immune / Allergy No underlying causes
Sexual Sexual abuse
Trauma Sexual intercourse , sexual abuse , foreign bodies (including IUD) , pelvic trauma, Straddle injuries
Urologic Genitourinary tract infection
Dental No underlying causes
Miscellaneous Foreign body, irritation of the genital area due to bubble baths, soaps, lotions or infection, smoking,

Excessive exercise

Causes in Alphabetical Order


References

  1. ↑ “StatPearls”. 2022. PMID 30422508.
  2. ↑ “StatPearls”.   ( ). 2022:  . PMID 32491756 Check |pmid= value (help).
  3. ↑ “StatPearls”.   ( ). 2022:  . PMID 30969690.
  4. ↑ “StatPearls”.   ( ). 2022:  . PMID 30855861.
  5. ↑ “StatPearls”.   ( ). 2022:  . PMID 32965984 Check |pmid= value (help).
  6. ↑ Whitaker L, Critchley HO (2016). “Abnormal uterine bleeding”. Best Pract Res Clin Obstet Gynaecol. 34: 54–65. doi:10.1016/j.bpobgyn.2015.11.012. PMC 4970656. PMID 26803558.

Template:WH Template:WS

Differentiating Dysfunctional uterine bleeding from other Diseases

Differentiating Dysfunctional uterine bleeding from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S ,Vishnu Vardhan Serla M.B.B.S. [2]

Overview

There are many differential diagnosis’ for dysfunctional uterine bleeding, many of them resulting in abnormal presentation of bleeding. Some prevalent conditions include anatomical or structural defects, coagulation disorders, pregnancy related complications, endometrial cancer and hyperplasia, as well as Polycystic Ovarian Syndrome.

Differential Diagnosis

Differential diagnosis’ for dysfunctional uterine bleeding include anatomical defects, coagulation disorders, pregnancy complications, and endometrial conditions such as malignancy and PCOS.

Differential Diagnosis
Condition Common Underlying Causes Workup
Anatomic or structural lesions Pelvic or transvaginal Ultrasonography
Coagulation disorders Coagulation studies; PT, aPTT, Bleeding Time, and clotting factor studies
Pregnancy complications B-hCG should be the first test to detect the presence of pregnancy. Visualization of the defect requires pelvic or transvaginal ultrasonography
Endometrial cancer[1] Risk factors include: Upon transvaginal ultrasonography, endometrial cancer will present as a thicked endometrial strip. Confirmation requires an endometrial biopsy.
Endometrial hyperplasia
  • Exogenous estrogen
  • Excess of endogenous estrogen
  • DUB (dysfunctional uterine bleeding) is a diagnosis of exclusion
 Endometrial hyperplasia related changes may be seen on ultrasonography. Obtaining a detailed history of medication use may be of assistance in coming to a diagnosis.
Polycystic Ovarian Syndrome (Stein Leventhal Syndrome)[2] Risk factors include: PCOS may initially be suspected upon physical examination, commonly presenting with hirsutism and weight gain. Confirmation requires FSH/LH level abnormalities as well as multiple ovarian cysts seen on ultrasonography.

Other Causes

Apart from common diseases, there are some other causes that may be potential differential diagnosis’. These include:

Abnormal uterine bleeding differential diagnosis

  • Abnormal uterine bleeding differential diagnosis include:[4][5]
  • Endometrial hyperplasia
  • Cervical polyp
  • Cervical leiomyoma
  • Cervical lymphoma
  • Cervical sarcoma
  • Metastases to the cervix
  • Cervical ectopic pregnancy
  • Cervicitis
  • Cervical erosion ( Ectropion )
  • IUD use
  • Pelvic inflammatory disease
  • Endometriosis
  • Adenomyosis
  • Postcoital bleeding
  • Clear cell adenocarcinoma
  • Hematologic causes:
    • Von willebrand disease
    • Thrombocytopenia
    • Clotting disorder
    • Platelet dysfunction
    • Factors deficiency
Abnormal Uterine bleeidng differential diagnosis
Ob-Gyn neoplasm and diseases Clinical manifestations Para-clinical findings Gold standard
Symptoms Physical exam Lab Findings Imaging Histopathology
Abnormal

vaginal bleeding

Other GU/GI symptoms Abdominal pain Pelvic

pain

Constitutional symptoms Gynecological examinations Abdominal

mass

HPV

Pap smear

STI panel

Other labs Ultrasound Other

imagings

Cervical cancer[6][7][8][9][10][11][12][13]

+

+ +
  • Cervical mass on exam
 + ± HPV T2-weighted MRI :
  • Ovoid, heterogeneous tumor distending the cervical canal with stromal involvement. PET/CT scan:
Cervical intraepithelial neoplasia:
Cervical polyp[14] − − −
  • Mass on exam
 − −
  • ↓ RBC count
  • ↓ Hb, ↓ Hct
  • ↓ Serum Iron
  • Hyper/hypoechogenic masses with or without cysts
  • Filling the endocervical or vaginal canal
Cervical leiomyoma[15][16][17][18][19][20][21][22][23]
  • Heavy/prolonged menstrual bleeding
  • Intermenstrual bleeding
 + + − ±
    		−
    • Well circumscribed hyperechoic mass
    		 T2-weighted MRI:
    • Hypointense masses
    • Homogeneous

    enhancement

    • Red degeneration
    • Clinical diagnosis/ and
    Cervical lymphoma[24][25][26]
    • Difficulty urinating
    • Post-coital pain
    		 + + +
    • Irregularity
    		 + Pap smear:
    • Small round blue cells
    • High nuclear/cytoplasm ratio,
    • Scant cytoplasm
    		 Immunohistochemistry markers:
    • Well-defined, solid, concentric, hypoechoic mass
    		 MRI:
    • Intramyometrial infiltrative nodules
    Cervical sarcoma[27][28][29][30] + + ± + − Leiomyosarcoma markers: MRI:
    • Endometrial polypoid mass
    • Hypointense hypervascular solid components
    Cervical erosion(Ectropion)[31][32][33][34][35]
    • Light bleeding after pelvic exam
    • Spotting
    • Post-coital pain
    • Painful cramps
    		 + + − − − N/A N/A N/A
    Cervicitis[36][37][38][39][40]
    • Intermenstrual bleeding
    • Postcoital
    • Bleeding after pelvic exam
    • Pain during urination
    		 + +
    • May have fever only
    • Red,inflammed swollen cervix
    • Inflammation/irritation of vulva/vagina
    		 − STI panel:
      		MRI:

      May be detected as retention cysts in cervix.

      Endometrial carcinoma[41][42][43][44][45]

      bleeding

      • Pain during sex
      • Fulness in pelvic
      • Difficulty emptying bladder
      		 + + ±
      • Often normal
      		 + −
      • Myometrial invasion

      T1-weighted MRI:

      • Hypo-to-isointense

      T2-weighted MRI:

      • Intermediate signal intensity lower than the normal endometrium
      		 Type I endometrioid endometrial carcinomas (EECs):
      • Moderately differentiated
      • Superficial invasion into the myometrium

      Type II non-endometrioid endometrial carcinomas (NEECs):

      Endometrial hyperplasia[46][47][48]
      • +
      		 + −
      • Normal or thickened endometrium
      		 ± − N/A

      T1-weighted MRI:

      • Hypo-to-isointense
      • Complex hyperplasia
      • Simple hyperplasia with atypia
      Endometriosis[49][50][51][52][53][54][55]
      • Heavy mentrual bleeding
      		 + − + −

      (limited value)

      • Ground glass echogenicity of the cyst fluid (Endometrioma)
      • Cysts are unilocular
        Pelvic inflammatory diseases[56][57][58][59]
        • Bleeding after sex
        • Intermenstrual bleeding
        • Pelvic pain
        		 +
        • Oral temperature >101F
        • Vaginal/vulvar tender lesion depending on microbial causes
        		 − STI panel:
        • ↑ WBC
        • Oral temperature >101F
        		 Ultrasound:
        • Thickened, fluid-filled tubes with or without free pelvic or tubo-ovarian complex
        		 MRI findings:
        • Inflammation in pelvic soft tissue
          • Clinical diagnosis is gold standard for diagnosing PID
          Adenemyosis[60][61][62][63][64][65]
          • Abnormal uterine bleeding
          • Painful menstruation
          		 + + −
          • Polypoid mass protruding into the endocervical canal.
          		 −
          • Subendometrial striations
          • Myometrial cysts
          • Asymetrical thickness in myometrium walls
          • Heterogenous echotexture of myometrum
          		 MRI:
          • Thickened junctional zone
          • Presence of ectopic endometrial glands into the myometrium.
          Cervical ectopic pregnancy[66][67] + − −
          • Soft and disporportionally enlarged uterus.
          		 ± − T2-weighted MRI:
          • Hypointense large mass

          T1-weighted MRI:

          • Partially hyperintense mass
          Vaginal cancer[68][69][70][71]
          • Postcoital bleeding
          		 + + ±
          • Ill-defined vaginal ulcer
          		 Ultrasound: MRI:
          • Isointense on T1-weighted images
          • Soft-tissue mass with intermediate-to-high signal intensity on T2-weighted images
          		 Biopsy findings:
          Paget’s disease of vulva to cervix[72][73][74][75][76]
          • Bleeding/oozing from lesion
          • Pain in vulva
          • Itching or burning sensation in vulva
          		 − − −
            		− −
            • Negative for S-100 and Melan-A
            		 N/A MRI:
            • Hyperintense on diffusion weighted imaging
            Nabothian cyst[77][78][79][80]
            • Postcoital bleeding
            		 − −
            • Majority of them are asymptomatic due to their small size (few milimeters)
            		 − − N/A
            • Anechoic well defined cystic lesions
            		 T1-weighted
            • Intermediate or slightly high signal intensity T2-weighted
            • High signal intensity on T2-weighted images
            • Benign cystic lesion
            • Multiple benign cystic masses, usually few milimieters in diameter.
            IUD use[81][82][83]
            • Heavy bleeidng
            		 + + −
            • Normal
            		 − −
            • May have decreased RBC count
            • Linear echogenic intrauterine structures
            		 N/A N/A


            Pregnancy and pregnancy related conditions Clinical manifestations Para-clinical findings Gold standard Additional findings
            Symptoms Physical examination
            Lab Findings Imaging Histopathology
            Abnormal uterine bleeding Other symptoms
            Miscarriage[84][85] +
            • Enlarged uterus
            • Blood clot in cervical os.
            		 Ultrasound:
            Abruptio placenta[86][87] +
            • Uterine tenderness
            • ↓ Fetal heart rate
            • ↓ Fetal movement

            Ultrasound:

            • Uterine hypertonicity
            • Non-reassuring fetal heart
            Placenta previa[88][89][90] +
            • Usually painless vaginal bleeding
            • ↑ Uterine contraction
            • Blood clot or spotting
            		 Ultrasound:
            • Low lying placenta, less than 1cm from cervical os.
            Ectopic pregnancy[91][92] + Ultrasound:
            • Absence of “Sliding sign” on gentle pressure of cervix
            • Tubal rupture
            		 Associated conditions:
            Molar pregnancy[93][94][95] +
            • Heavy vaginal bleeding
            		 Ultrasound:
            • Complex and echogenic intrauterine mass
            • Containing many small cystic spaces
            • Classical “snow storm” appearance
            • Hydropic villi
            • Histological confirmation post-curettage
            		 Associated conditions:
            Hematologic conditions Clinical manifestations Para-clinical findings Gold standard Additional findings
            Symptoms Physical examination
            Lab findings Imaging Histopathology
            Abnormal uterine

            bleeding

            		Other symptoms
            Von willebrand disease[96][97][98] +
            • Easy bruising
            • Gum/dental bleeding
            • Heavy menses
            		 N/A N/A
            • Most common inherited bleeding disorder
            • History of bleeding disorder in family members.
            Factors deficiencies[99][100] +
            • Easy bruising
            • Gum/dental bleeding
            • Heavy menses
            • Fatigue
            • Blood in stool
            • Blood in urine
            		 N/A N/A
            • History of bleeding disorder in family members.
            Platelet dysfunction[101][102][103][104][105] ± N/A N/A Gold standard diagnostic test:
            • Light transmission aggregometry (LTA)

            Other useful diagnostic tests:

            		Associated conditions:
            Metabolic conditions Clinical manifestations Para-clinical findings Gold standard Additional findings
            Symptoms Physical examination
            Lab findings Imaging Histopathology
            Abnormal uterine bleeding Other symptoms
            Hyperthyroidism[106][107] +
            • Wet skin/hair thinning
            • Low TSH
            • TSH receptor antibodies (TRAb)
            		 Ultrasound:
            • Homogenous hypo-echogenicity
            		 Microscopic histology:
            • Lymphocytic infiltration in follicles
            • Enlarged colloids

            For Grave’s disease:

            • TSH receptor antibody
            		 Associated conditions:
            Hypothyroidism[108][109][110][111][112] +
            • Dry skin
            • Hair loss
            		 Ultrasound:
            • Homogenous hypo-echogenicity
            		 Microscopic histology: Associated conditions with Hashimoto thyroiditis:
            Adrenal hyperplasia[113][114][115][116][117] +
            • Irregular menses
            		 Depending upon deficient enzyme:

            Depending upon enzyme deficiencies may include the following:

            		CT-Scan:
            • Enlargement of glands
            • Cosyntropin stimulation test (250 μg cosyntropin intravenously):
            Cushing’s disease[118][119] +
            • Facial plethora
            • Abnormal fat distribution
            • Violacious striae
            • Emotional lability
            		 T1-weighted MRI: Associated conditions:
            Polycystic ovarian syndrome[120][121][122][123][124] + Ultrasound:
            • ↑ Number of follicles
            • ↑ Ovarian volume
            • Fluid filled ovaries
            • Multiple cysts in ovaries bilaterally.
            		 Associated conditions:
            • Insulin resistance
            Medication side effects/ Iatrogenic Clinical manifestations Para-clinical findings Gold standard Additional findings
            Symptoms Physical examination
            Lab Findings Imaging Histopathology
            Abnormal uterine bleeding Other symptoms
            Anticoagulants[125][126][127]
            • +
            • Heavy menstrual bleeding
            • Pallor
            • Heavy menstrual bleeding
            		 N/A N/A
            • Complete medication history
            Antipsychotics[128] +
            • Sexual dysfunction
            		 N/A N/A
            • Complete medication history
            • Serum prolactin test
            • History of mood disorders
            Oral contraceptive pills[129]
            • Break through bleeding
            • Heavy bleeding
            		 N/A N/A
            • Ruling out organic cause, complete history of medication use
            Herbal supplements[130][131][132] +
            • Heavy menstrual bleeding
            • Menstrual irregularity
            		 Ultrasound:
            • Complete medication history

            References

            1. ↑ “StatPearls”. 2022. PMID 30252237.
            2. ↑ Sirmans SM, Pate KA (2013). “Epidemiology, diagnosis, and management of polycystic ovary syndrome”. Clin Epidemiol. 6: 1–13. doi:10.2147/CLEP.S37559. PMC 3872139. PMID 24379699.
            3. ↑ Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016
            4. ↑ Munro, Malcolm G.; Critchley, Hilary O.D.; Broder, Michael S.; Fraser, Ian S. (2011). “FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age”. International Journal of Gynecology & Obstetrics. 113 (1): 3–13. doi:10.1016/j.ijgo.2010.11.011. ISSN 0020-7292.
            5. ↑ Matteson, Kristen A.; Boardman, Lori A.; Munro, Malcolm G.; Clark, Melissa A. (2009). “Abnormal uterine bleeding: a review of patient-based outcome measures”. Fertility and Sterility. 92 (1): 205–216. doi:10.1016/j.fertnstert.2008.04.023. ISSN 0015-0282.
            6. ↑ Hippisley-Cox J, Coupland C (January 2013). “Symptoms and risk factors to identify women with suspected cancer in primary care: derivation and validation of an algorithm”. Br J Gen Pract. 63 (606): e11–21. doi:10.3399/bjgp13X660733. PMC 3529288. PMID 23336450.
            7. ↑ Dunyo, Priscilla; Effah, Kofi; Udofia, Emilia Asuquo (2018). “Factors associated with late presentation of cervical cancer cases at a district hospital: a retrospective study”. BMC Public Health. 18 (1). doi:10.1186/s12889-018-6065-6. ISSN 1471-2458.
            8. ↑ Khalife D, El Housheimi A, Khalil A, Saba C S, Seoud M, Rammal R, Abdallah IE, Abdallah R (February 2019). “Treatment of cervical cancer metastatic to the abdominal wall with reconstruction using a composite myocutaneous flap: A case report”. Gynecol Oncol Rep. 27: 38–41. doi:10.1016/j.gore.2018.12.006. PMC 6302027. PMID 30603660. Vancouver style error: name (help)
            9. ↑ . doi:10.1097/PAS.0000000000000498. Check |doi= value (help). Missing or empty |title= (help)
            10. ↑ Brenner PF (September 1996). “Differential diagnosis of abnormal uterine bleeding”. Am. J. Obstet. Gynecol. 175 (3 Pt 2): 766–9. PMID 8828559.
            11. ↑ Alcázar, Juan Luis; Arribas, Sara; Mínguez, José Angel; Jurado, Matías (2014). “The Role of Ultrasound in the Assessment of Uterine Cervical Cancer”. The Journal of Obstetrics and Gynecology of India. 64 (5): 311–316. doi:10.1007/s13224-014-0622-4. ISSN 0971-9202.
            12. ↑ Qing L, Xiang T, Guofu Z, Weiwei F (September 2014). “Leukemoid reaction in cervical cancer: a case report and review of the literature”. BMC Cancer. 14: 670. doi:10.1186/1471-2407-14-670. PMC 4174654. PMID 25223869.
            13. ↑ Qing L, Xiang T, Guofu Z, Weiwei F (September 2014). “Leukemoid reaction in cervical cancer: a case report and review of the literature”. BMC Cancer. 14: 670. doi:10.1186/1471-2407-14-670. PMC 4174654. PMID 25223869.
            14. ↑ Mitchell H (May 2004). “Vaginal discharge–causes, diagnosis, and treatment”. BMJ. 328 (7451): 1306–8. doi:10.1136/bmj.328.7451.1306. PMC 420177. PMID 15166070.
            15. ↑ Al-Habib A, Elgamal EA, Aldhahri S, Alokaili R, AlShamrani R, Abobotain A, AlRaddadi K, Alkhalidi H (November 2016). “Large primary leiomyoma causing progressive cervical deformity”. J Surg Case Rep. 2016 (11). doi:10.1093/jscr/rjw190. PMC 5159177. PMID 27887011.
            16. ↑ Adaikkalam J (April 2016). “Lipoleiomyoma of Cervix”. J Clin Diagn Res. 10 (4): EJ01–2. doi:10.7860/JCDR/2016/16505.7531. PMID 27190823.
            17. ↑ Houser, L. Murray; Carrasco, C. H.; Sheehan, C. R. (1979). “Lipomatous tumour of the uterus: radiographic and ultrasonic appearance”. The British Journal of Radiology. 52 (624): 992–993. doi:10.1259/0007-1285-52-624-992. ISSN 0007-1285.
            18. ↑ Keriakos, Remon; Maher, Mark (2013). “Management of Cervical Fibroid during the Reproductive Period”. Case Reports in Obstetrics and Gynecology. 2013: 1–3. doi:10.1155/2013/984030. ISSN 2090-6684.
            19. ↑ Coronado GD, Marshall LM, Schwartz SM (May 2000). “Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population-based study”. Obstet Gynecol. 95 (5): 764–9. PMID 10775744.
            20. ↑ Kamra, Hemlata T (2013). “Myxoid Leiomyoma of Cervix”. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. doi:10.7860/JCDR/2013/6171.3805. ISSN 2249-782X.
            21. ↑ El-agwany, Ahmed Samy (2015). “Lipoleiomyoma of the uterine cervix: An unusual variant of uterine leiomyoma”. The Egyptian Journal of Radiology and Nuclear Medicine. 46 (1): 211–213. doi:10.1016/j.ejrnm.2014.10.001. ISSN 0378-603X.
            22. ↑ Chaparala RP, Fawole AS, Ambrose NS, Chapman AH (March 2004). “Large bowel obstruction due to a benign uterine leiomyoma”. Gut. 53 (3): 386, 430. PMC 1773948. PMID 14960521.
            23. ↑ Yokoyama Y, Shinohara A, Hirokawa M, Maeda N (2003). “Erythrocytosis due to an erythropoietin-producing large uterine leiomyoma”. Gynecol. Obstet. Invest. 56 (4): 179–83. doi:10.1159/000074104. PMID 14564105.
            24. ↑ Grace A, O’Connell N, Byrne P, Prendiville W, O’Donnell R, Royston D, Walsh CB, Leader M, Kay E (1999). “Malignant lymphoma of the cervix. An unusual presentation and a rare disease”. Eur. J. Gynaecol. Oncol. 20 (1): 26–8. PMID 10422676.
            25. ↑ Kanaan, Daniel; Parente, Daniella Braz; Constantino, Carolina Pesce Lamas; Souza, Rodrigo Canellas de (2012). “Linfoma de colo de útero: achados na ressonância magnética”. Radiologia Brasileira. 45 (3): 167–169. doi:10.1590/S0100-39842012000300009. ISSN 0100-3984.
            26. ↑ Frey NV, Svoboda J, Andreadis C, Tsai DE, Schuster SJ, Elstrom R, Rubin SC, Nasta SD (September 2006). “Primary lymphomas of the cervix and uterus: the University of Pennsylvania’s experience and a review of the literature”. Leuk. Lymphoma. 47 (9): 1894–901. doi:10.1080/10428190600687653. PMID 17065003.
            27. ↑ Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK (November 2005). “Cervical sarcomas: an analysis of incidence and outcome”. Gynecol. Oncol. 99 (2): 348–51. doi:10.1016/j.ygyno.2005.06.021. PMID 16051326.
            28. ↑ Khosla, Divya; Gupta, Ruchi; Srinivasan, Radhika; Patel, Firuza D.; Rajwanshi, Arvind (2012). “Sarcomas of Uterine Cervix”. International Journal of Gynecological Cancer. 22 (6): 1026–1030. doi:10.1097/IGC.0b013e31825a97f6. ISSN 1048-891X.
            29. ↑ Miccò M, Sala E, Lakhman Y, Hricak H, Vargas HA (December 2015). “Imaging Features of Uncommon Gynecologic Cancers”. AJR Am J Roentgenol. 205 (6): 1346–59. doi:10.2214/AJR.14.12695. PMC 5502476. PMID 26587944.
            30. ↑ . doi:10.1097/IGC.0b013e31825a97f6. Check |doi= value (help). Missing or empty |title= (help)
            31. ↑ Mitchell L, King M, Brillhart H, Goldstein A (September 2017). “Cervical Ectropion May Be a Cause of Desquamative Inflammatory Vaginitis”. Sex Med. 5 (3): e212–e214. doi:10.1016/j.esxm.2017.03.001. PMC 5562466. PMID 28460993.
            32. ↑ Mitchell H (May 2004). “Vaginal discharge–causes, diagnosis, and treatment”. BMJ. 328 (7451): 1306–8. doi:10.1136/bmj.328.7451.1306. PMC 420177. PMID 15166070.
            33. ↑ Sharma, Abhishek; Ojha, Ranapratap; Sengupta, Parama; Chattopadhyay, Sarbani; Mondal, Soumit (2013). “Cervical intramural pregnancy: Report of a rare case”. Nigerian Medical Journal. 54 (4): 271. doi:10.4103/0300-1652.119670. ISSN 0300-1652.
            34. ↑ . doi:10.12865/CHSJ.42.02.11. Missing or empty |title= (help)
            35. ↑ Casey PM, Long ME, Marnach ML (February 2011). “Abnormal cervical appearance: what to do, when to worry?”. Mayo Clin. Proc. 86 (2): 147–50, quiz 151. doi:10.4065/mcp.2010.0512. PMC 3031439. PMID 21270291.
            36. ↑ Mattson SK, Polk JP, Nyirjesy P (July 2016). “Chronic Cervicitis: Presenting Features and Response to Therapy”. J Low Genit Tract Dis. 20 (3): e30–3. doi:10.1097/LGT.0000000000000225. PMID 27243142.
            37. ↑ Rosenfeld WD, Clark J (June 1989). “Vulvovaginitis and cervicitis”. Pediatr. Clin. North Am. 36 (3): 489–511. PMID 2660084.
            38. ↑ Meyer T (August 2016). “Diagnostic Procedures to Detect Chlamydia trachomatis Infections”. Microorganisms. 4 (3). doi:10.3390/microorganisms4030025. PMID 27681919.
            39. ↑ Woods, Jennifer L.; Bailey, Sarabeth L.; Hensel, Devon J.; Scurlock, Amy M. (2011). “Cervicitis in Adolescents: Do Clinicians Understand Diagnosis and Treatment?”. Journal of Pediatric and Adolescent Gynecology. 24 (6): 359–364. doi:10.1016/j.jpag.2011.06.006. ISSN 1083-3188.
            40. ↑ Jayakumar, Naveen Kumar Bhagavathula (2015). “Cervicitis: How Often Is It Non-specific!”. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. doi:10.7860/JCDR/2015/11594.5673. ISSN 2249-782X.
            41. ↑ Bakour SH, Dwarakanath LS, Khan KS, Newton JR, Gupta JK (May 1999). “The diagnostic accuracy of ultrasound scan in predicting endometrial hyperplasia and cancer in postmenopausal bleeding”. Acta Obstet Gynecol Scand. 78 (5): 447–51. PMID 10326893.
            42. ↑ Beddy, Peter; O’Neill, Ailbhe C.; Yamamoto, Adam K.; Addley, Helen C.; Reinhold, Caroline; Sala, Evis (2012). “FIGO Staging System for Endometrial Cancer: Added Benefits of MR Imaging”. RadioGraphics. 32 (1): 241–254. doi:10.1148/rg.321115045. ISSN 0271-5333.
            43. ↑ Byun JM, Jeong DH, Kim YN, Cho EB, Cha JE, Sung MS, Lee KB, Kim KT (November 2015). “Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge”. Obstet Gynecol Sci. 58 (6): 468–74. doi:10.5468/ogs.2015.58.6.468. PMID 26623410.
            44. ↑ Wan-Nor-Asyikeen WA, Siti-Azrin AH, Jalil NA, Othman NH, Zain AA (2016). “Endometrial Cancer in Hospital Universiti Sains Malaysia”. Asian Pac. J. Cancer Prev. 17 (6): 2867–70. PMID 27356704.
            45. ↑ Horn LC, Meinel A, Handzel R, Einenkel J (August 2007). “Histopathology of endometrial hyperplasia and endometrial carcinoma: an update”. Ann Diagn Pathol. 11 (4): 297–311. doi:10.1016/j.anndiagpath.2007.05.002. PMID 17630117.
            46. ↑ Palmer, Julia E; Perunovic, Branko; Tidy, John A (2008). “Endometrial hyperplasia”. The Obstetrician & Gynaecologist. 10 (4): 211–216. doi:10.1576/toag.10.4.211.27436. ISSN 1467-2561.
            47. ↑ Reed SD, Newton KM, Clinton WL, Epplein M, Garcia R, Allison K, Voigt LF, Weiss NS (June 2009). “Incidence of endometrial hyperplasia”. Am. J. Obstet. Gynecol. 200 (6): 678.e1–6. doi:10.1016/j.ajog.2009.02.032. PMC 2692753. PMID 19393600.
            48. ↑ Novac L, Grigore T, Cernea N, Niculescu M, Cotarcea S (2005). “Incidence of endometrial carcinoma in patients with endometrial hyperplasia”. Eur. J. Gynaecol. Oncol. 26 (5): 561–3. PMID 16285581.
            49. ↑ Hsu AL, Khachikyan I, Stratton P (June 2010). “Invasive and noninvasive methods for the diagnosis of endometriosis”. Clin Obstet Gynecol. 53 (2): 413–9. doi:10.1097/GRF.0b013e3181db7ce8. PMC 2880548. PMID 20436318.
            50. ↑ Chamié, Luciana Pardini; Blasbalg, Roberto; Pereira, Ricardo Mendes Alves; Warmbrand, Gisele; Serafini, Paulo Cesar (2011). “Findings of Pelvic Endometriosis at Transvaginal US, MR Imaging, and Laparoscopy”. RadioGraphics. 31 (4): E77–E100. doi:10.1148/rg.314105193. ISSN 0271-5333.
            51. ↑ Datta S, Kunde K (July 2008). “From vaginal discharge to endometriosis: an unusual case of endometriosis in pregnancy”. J Obstet Gynaecol. 28 (5): 552–3. doi:10.1080/01443610802247352. PMID 18850447.
            52. ↑ Chamié, Luciana Pardini; Blasbalg, Roberto; Pereira, Ricardo Mendes Alves; Warmbrand, Gisele; Serafini, Paulo Cesar (2011). “Findings of Pelvic Endometriosis at Transvaginal US, MR Imaging, and Laparoscopy”. RadioGraphics. 31 (4): E77–E100. doi:10.1148/rg.314105193. ISSN 0271-5333.
            53. ↑ Bedaiwy MA, Falcone T (February 2004). “Laboratory testing for endometriosis”. Clin. Chim. Acta. 340 (1–2): 41–56. PMID 14734195.
            54. ↑ Van Holsbeke C, Van Calster B, Guerriero S, Savelli L, Paladini D, Lissoni AA, Czekierdowski A, Fischerova D, Zhang J, Mestdagh G, Testa AC, Bourne T, Valentin L, Timmerman D (June 2010). “Endometriomas: their ultrasound characteristics”. Ultrasound Obstet Gynecol. 35 (6): 730–40. doi:10.1002/uog.7668. PMID 20503240.
            55. ↑ . doi:10.1148/rg.314105193. Check |doi= value (help). Missing or empty |title= (help)
            56. ↑ Hoenderboom BM, van Benthem B, van Bergen J, Dukers-Muijrers N, Götz HM, Hoebe C, Hogewoning AA, Land JA, van der Sande M, Morré SA, van den Broek I (January 2019). “Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial”. Sex Transm Infect. doi:10.1136/sextrans-2018-053778. PMID 30606817. Vancouver style error: initials (help)
            57. ↑ Jaiyeoba O, Soper DE (2011). “A practical approach to the diagnosis of pelvic inflammatory disease”. Infect Dis Obstet Gynecol. 2011: 753037. doi:10.1155/2011/753037. PMC 3148590. PMID 21822367.
            58. ↑ Czeyda-Pommersheim, Ferenc; Kalb, Bobby; Costello, James; Liau, Joy; Meshksar, Arash; Arif Tiwari, Hina; Martin, Diego (2016). “MRI in pelvic inflammatory disease: a pictorial review”. Abdominal Radiology. 42 (3): 935–950. doi:10.1007/s00261-016-1004-4. ISSN 2366-004X.
            59. ↑ Mitchell, Caroline; Prabhu, Malavika (2013). “Pelvic Inflammatory Disease”. Infectious Disease Clinics of North America. 27 (4): 793–809. doi:10.1016/j.idc.2013.08.004. ISSN 0891-5520.
            60. ↑ Filip G, Balzano A, Cagnacci A (November 2018). “Histological evaluation of the prevalence of adenomyosis, myomas and of their concomitance”. Minerva Ginecol. doi:10.23736/S0026-4784.18.04291-0. PMID 30486633.
            61. ↑ Fujino T, Watanabe T, Shinmura R, Hahn L, Nagata Y, Hasui K (December 1992). “Acute abdomen due to adenomyosis of the uterus: a case report”. Asia Oceania J Obstet Gynaecol. 18 (4): 333–7. PMID 1492806.
            62. ↑ Fujino T, Watanabe T, Shinmura R, Hahn L, Nagata Y, Hasui K (December 1992). “Acute abdomen due to adenomyosis of the uterus: a case report”. Asia Oceania J Obstet Gynaecol. 18 (4): 333–7. PMID 1492806.
            63. ↑ Zhou Y, Wu B, Li H (October 1996). “[The value of serum CA125 assays in the diagnosis of uterine adenomyosis]”. Zhonghua Fu Chan Ke Za Zhi (in Chinese). 31 (10): 590–3. PMID 9275451.
            64. ↑ Tamai, Ken; Togashi, Kaori; Ito, Tsuyoshi; Morisawa, Nobuko; Fujiwara, Toshitaka; Koyama, Takashi (2005). “MR Imaging Findings of Adenomyosis: Correlation with Histopathologic Features and Diagnostic Pitfalls”. RadioGraphics. 25 (1): 21–40. doi:10.1148/rg.251045060. ISSN 0271-5333.
            65. ↑ Dartmouth, Katherine (2014). “A systematic review with meta-analysis: the common sonographic characteristics of adenomyosis”. Ultrasound. 22 (3): 148–157. doi:10.1177/1742271X14528837. ISSN 1742-271X.
            66. ↑ Mouhajer M, Obed S, Okpala AM (June 2017). “Cervical Ectopic Pregnancy in Resource Deprived Areas: A Rare and Difficult Diagnosis”. Ghana Med J. 51 (2): 94–97. PMC 5611908. PMID 28955106.
            67. ↑ Rathod, Setu; Samal, SunilKumar (2015). “Cervical ectopic pregnancy”. Journal of Natural Science, Biology and Medicine. 6 (1): 257. doi:10.4103/0976-9668.149221. ISSN 0976-9668.
            68. ↑ Tarney CM, Han J (2014). “Postcoital bleeding: a review on etiology, diagnosis, and management”. Obstet Gynecol Int. 2014: 192087. doi:10.1155/2014/192087. PMC 4086375. PMID 25045355.
            69. ↑ Miccò, Maura; Sala, Evis; Lakhman, Yulia; Hricak, Hedvig; Vargas, Hebert Alberto (2015). “Imaging Features of Uncommon Gynecologic Cancers”. American Journal of Roentgenology. 205 (6): 1346–1359. doi:10.2214/AJR.14.12695. ISSN 0361-803X.
            70. ↑ Kim, Hwi-Gon; Song, Yong Jung; Na, Yong Jin; Choi, Ook-Hwan (2013). “A Case of Vaginal Cancer with Uterine Prolapse”. Journal of Menopausal Medicine. 19 (3): 139. doi:10.6118/jmm.2013.19.3.139. ISSN 2288-6478.
            71. ↑ Karateke A, Tugrul S, Yakut Y, Gürbüz A, Cam C (2006). “Management of a case of primary vaginal cancer with irreducible massive uterine prolapse–a case report”. Eur. J. Gynaecol. Oncol. 27 (5): 528–30. PMID 17139994.
            72. ↑ van der Linden, M.; Meeuwis, K.A.P.; Bulten, J.; Bosse, T.; van Poelgeest, M.I.E.; de Hullu, J.A. (2016). “Paget disease of the vulva”. Critical Reviews in Oncology/Hematology. 101: 60–74. doi:10.1016/j.critrevonc.2016.03.008. ISSN 1040-8428.
            73. ↑ Lloyd J, Evans DJ, Flanagan AM (July 1999). “Extension of extramammary Paget disease of the vulva to the cervix”. J. Clin. Pathol. 52 (7): 538–40. PMC 501500. PMID 10605411.
            74. ↑ Shaco-Levy R, Bean SM, Vollmer RT, Papalas JA, Bentley RC, Selim MA, Robboy SJ (January 2010). “Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course”. Int. J. Gynecol. Pathol. 29 (1): 69–78. doi:10.1097/PGP.0b013e3181b1cc5e. PMID 19952933.
            75. ↑ Asmouki, Hamid; Oumouloud, Rachid; Aboulfalah, Abderrahim; Soummani, Abderraouf; Marrat, Abdelouahed (2012). “Paget’s Disease of the Vulva in Premenopausal Woman Treated with Only Surgery: A Case Report”. Case Reports in Oncological Medicine. 2012: 1–4. doi:10.1155/2012/854827. ISSN 2090-6706.
            76. ↑ Gonçalves Amorim, Andressa; Batista Fraga Mendes, Brunelle; Neves Ferreira, Rodrigo; Chambô Filho, Antônio (2015). “Paget Disease of the Vulva: Diagnosis by Immunohistochemistry”. Case Reports in Dermatological Medicine. 2015: 1–5. doi:10.1155/2015/162483. ISSN 2090-6463.
            77. ↑ Casey PM, Long ME, Marnach ML (February 2011). “Abnormal cervical appearance: what to do, when to worry?”. Mayo Clin. Proc. 86 (2): 147–50, quiz 151. doi:10.4065/mcp.2010.0512. PMC 3031439. PMID 21270291.
            78. ↑ Bin Park, Sung; Lee, Jong Hwa; Lee, Young Ho; Song, Mi Jin; Choi, Hye Jeong (2010). “Multilocular Cystic Lesions in the Uterine Cervix: Broad Spectrum of Imaging Features and Pathologic Correlation”. American Journal of Roentgenology. 195 (2): 517–523. doi:10.2214/AJR.09.3619. ISSN 0361-803X.
            79. ↑ Torky, Haitham A. (2016). “Huge Nabothian cyst causing Hematometra (case report)”. European Journal of Obstetrics & Gynecology and Reproductive Biology. 207: 238–240. doi:10.1016/j.ejogrb.2016.10.042. ISSN 0301-2115.
            80. ↑ Okamoto, Yoshikazu; Tanaka, Yumiko O.; Nishida, Masato; Tsunoda, Hajime; Yoshikawa, Hiroyuki; Itai, Yuji (2003). “MR Imaging of the Uterine Cervix: Imaging-Pathologic Correlation”. RadioGraphics. 23 (2): 425–445. doi:10.1148/rg.232025065. ISSN 0271-5333.
            81. ↑ Trobough GE (March 1978). “Pelvic pain and the IUD”. J Reprod Med. 20 (3): 167–74. PMID 347074.
            82. ↑ Nowitzki, Kristina M.; Hoimes, Matthew L.; Chen, Byron; Zheng, Larry Z.; Kim, Young H. (2015). “Ultrasonography of intrauterine devices”. Ultrasonography. 34 (3): 183–194. doi:10.14366/usg.15010. ISSN 2288-5919.
            83. ↑ . doi:10.5489/cuaj.11100. Check |doi= value (help). Missing or empty |title= (help)
            84. ↑ Sánchez Cortés E (July 1965). “[Renal vascular hypertension. Urological diagnosis]”. Medicina (Madr) (in Spanish; Castilian). 33 (7): 505–15. PMID 5861413.
            85. ↑ . doi:10.1136/bmj.h4579. Check |doi= value (help). Missing or empty |title= (help)
            86. ↑ Elsasser DA, Ananth CV, Prasad V, Vintzileos AM (February 2010). “Diagnosis of placental abruption: relationship between clinical and histopathological findings”. Eur. J. Obstet. Gynecol. Reprod. Biol. 148 (2): 125–30. doi:10.1016/j.ejogrb.2009.10.005. PMC 2814948. PMID 19897298.
            87. ↑ . doi:10.1016/j.ejogrb.2009.10.005. Epub 2009 Nov 7. Check |doi= value (help). Missing or empty |title= (help)
            88. ↑ Alouini S, Megier P, Fauconnier A, Huchon C, Fievet A, Ramos A, Megier C, Valéry A (January 2019). “Diagnosis and management of placenta previa and low placental implantation”. J. Matern. Fetal. Neonatal. Med.: 1–6. doi:10.1080/14767058.2019.1570118. PMID 30688129.
            89. ↑ Kawabe A, Wang L, Kikugawa A, Shibata Y, Kuromaki K, Takagi A (October 2016). “Severe abdominal pain exacerbated by fetal movement is an early sign of the onset of uterine rupture”. Taiwan J Obstet Gynecol. 55 (5): 721–723. doi:10.1016/j.tjog.2015.12.021. PMID 27751423.
            90. ↑ Biswas R, Sawhney H, Dass R, Saran RK, Vasishta K (March 1999). “Histopathological study of placental bed biopsy in placenta previa”. Acta Obstet Gynecol Scand. 78 (3): 173–9. PMID 10078576.
            91. ↑ Taran FA, Kagan KO, Hübner M, Hoopmann M, Wallwiener D, Brucker S (October 2015). “The Diagnosis and Treatment of Ectopic Pregnancy”. Dtsch Arztebl Int. 112 (41): 693–703, quiz 704–5. doi:10.3238/arztebl.2015.0693. PMC 4643163. PMID 26554319.
            92. ↑ Winder S, Reid S, Condous G (May 2011). “Ultrasound diagnosis of ectopic pregnancy”. Australas J Ultrasound Med. 14 (2): 29–33. doi:10.1002/j.2205-0140.2011.tb00192.x. PMC 5024893. PMID 28191110.
            93. ↑ Virmani S, Srinivas SB, Bhat R, Rao R, Kudva R (July 2017). “Transient Thyrotoxicosis in Molar Pregnancy”. J Clin Diagn Res. 11 (7): QD01–QD02. doi:10.7860/JCDR/2017/28561.10133. PMID 28892983.
            94. ↑ Jeffers MD, O’Dwyer P, Curran B, Leader M, Gillan JE (October 1993). “Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis”. Int. J. Gynecol. Pathol. 12 (4): 315–23. PMID 8253548.
            95. ↑ Alhamdan D, Bignardi T, Condous G (August 2009). “Recognising gestational trophoblastic disease”. Best Pract Res Clin Obstet Gynaecol. 23 (4): 565–73. doi:10.1016/j.bpobgyn.2009.03.001. PMID 19375983.
            96. ↑ Cardoso, Mariana Ferreira; Lourenço, Luís Carvalho; Antunes, Margarida; Carvalho e Branco, Joana; Santos, Liliana; Martins, Alexandra; Reis, Jorge A. (2018). “Recurrent Gastrointestinal Bleeding from Dieulafoy’s Lesions in a Patient with Type 1 von Willebrand Disease: A Rare Association”. GE – Portuguese Journal of Gastroenterology: 1–5. doi:10.1159/000490921. ISSN 2341-4545.
            97. ↑ Castaman, Giancarlo; Linari, Silvia (2017). “Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders”. Journal of Clinical Medicine. 6 (4): 45. doi:10.3390/jcm6040045. ISSN 2077-0383.
            98. ↑ Budde U (November 2008). “Diagnosis of von Willebrand disease subtypes: implications for treatment”. Haemophilia. 14 Suppl 5: 27–38. doi:10.1111/j.1365-2516.2008.01849.x. PMID 18786008.
            99. ↑ Al-Shbool G, Vakiti A (2018). “Acquired Hemophilia A Presenting as Intramuscular Hematoma”. J Investig Med High Impact Case Rep. 6: 2324709618817572. doi:10.1177/2324709618817572. PMC 6299309. PMID 30574513.
            100. ↑ Mansouritorghabeh H (May 2015). “Clinical and laboratory approaches to hemophilia a”. Iran J Med Sci. 40 (3): 194–205. PMC 4430880. PMID 25999618.
            101. ↑ Kirchmaier CM, Pillitteri D (2010). “Diagnosis and Management of Inherited Platelet Disorders”. Transfus Med Hemother. 37 (5): 237–246. doi:10.1159/000320257. PMC 2980508. PMID 21113246.
            102. ↑ Hayward CP, Rao AK, Cattaneo M (July 2006). “Congenital platelet disorders: overview of their mechanisms, diagnostic evaluation and treatment”. Haemophilia. 12 Suppl 3: 128–36. doi:10.1111/j.1365-2516.2006.01270.x. PMID 16684008.
            103. ↑ . doi:10.1111/jth.12555. Check |doi= value (help). Missing or empty |title= (help)
            104. ↑ Kanda, Kenji; Kunishima, Shinji; Sato, Aya; Abe, Daisuke; Nishijima, Setsuko; Ishigami, Tsuyoshi (2017). “A Brazilian case of Bernard–Soulier syndrome with two distinct founder mutations”. Human Genome Variation. 4: 17030. doi:10.1038/hgv.2017.30. ISSN 2054-345X.
            105. ↑ Nurden, Alan T (2006). “Glanzmann thrombasthenia”. Orphanet Journal of Rare Diseases. 1 (1). doi:10.1186/1750-1172-1-10. ISSN 1750-1172.
            106. ↑ Deshmukh, Prasad; Boricha, B.; Pandey, Ankita (2015). “The association of thyroid disorders with abnormal uterine bleeding”. International Journal of Reproduction, Contraception, Obstetrics and Gynecology: 701–708. doi:10.18203/2320-1770.ijrcog20150077. ISSN 2320-1770.
            107. ↑ Pishdad P, Pishdad GR, Tavanaa S, Pishdad R, Jalli R (March 2017). “Thyroid Ultrasonography in Differentiation between Graves’ Disease and Hashimoto’s Thyroiditis”. J Biomed Phys Eng. 7 (1): 21–26. PMC 5401130. PMID 28451576.
            108. ↑ Deshmukh, Prasad; Boricha, B.; Pandey, Ankita (2015). “The association of thyroid disorders with abnormal uterine bleeding”. International Journal of Reproduction, Contraception, Obstetrics and Gynecology: 701–708. doi:10.18203/2320-1770.ijrcog20150077. ISSN 2320-1770.
            109. ↑ Pishdad P, Pishdad GR, Tavanaa S, Pishdad R, Jalli R (March 2017). “Thyroid Ultrasonography in Differentiation between Graves’ Disease and Hashimoto’s Thyroiditis”. J Biomed Phys Eng. 7 (1): 21–26. PMC 5401130. PMID 28451576.
            110. ↑ Mizukami Y, Michigishi T, Nonomura A, Hashimoto T, Tonami N, Matsubara F, Takazakura E (February 1993). “Iodine-induced hypothyroidism: a clinical and histological study of 28 patients”. J. Clin. Endocrinol. Metab. 76 (2): 466–71. doi:10.1210/jcem.76.2.8432791. PMID 8432791.
            111. ↑ Lee, Ju-Han; Kim, Younghye; Choi, Jung-Woo; Kim, Young-Sik (2013). “The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis”. European Journal of Endocrinology. 168 (3): 343–349. doi:10.1530/EJE-12-0903. ISSN 0804-4643.
            112. ↑ Lapcević M (October 2005). “[Autoimmune thyroid disease and associated diseases]”. Srp Arh Celok Lek. 133 Suppl 1: 84–7. PMID 16405263.
            113. ↑ Vigliani MB, Buster JE (April 2012). “Nonclassic 21-hydroxylase deficiency presenting as endometrial hyperplasia with uterine bleeding in a 67-year-old woman”. Fertil. Steril. 97 (4): 950–2. doi:10.1016/j.fertnstert.2012.01.089. PMID 22270556.
            114. ↑ Gioco F, Seccia TM, Gomez-Sanchez EP, Rossi GP, Gomez-Sanchez CE (October 2015). “Adrenal histopathology in primary aldosteronism: is it time for a change?”. Hypertension. 66 (4): 724–30. doi:10.1161/HYPERTENSIONAHA.115.05873. PMID 26238443.
            115. ↑ . doi:10.1515/jpem-2017-0235. Check |doi= value (help). Missing or empty |title= (help)
            116. ↑ Choudhary A, Spigland N, Poppas D, Kovanlikaya A, Nimkarn S (February 2013). “Vaginal bleeding leading to incidental diagnosis of ovarian torsion in an infant with 21 hydroxylase deficiency congenital adrenal hyperplasia”. J. Pediatr. 162 (2): 432–432.e1. doi:10.1016/j.jpeds.2012.08.026. PMID 23040792.
            117. ↑ Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP, Yau M, New M. PMID 25905311. Missing or empty |title= (help)
            118. ↑ Zada, Gabriel (2013). “Diagnosis and Multimodality Management of Cushing’s Disease: A Practical Review”. International Journal of Endocrinology. 2013: 1–7. doi:10.1155/2013/893781. ISSN 1687-8337.
            119. ↑ Olivier L, Vila-Porcile E (September 1988). “Pituitary pathology in Cushing’s disease. Histology and morphometry of pituitary tissues removed through microsurgery”. Pathol. Res. Pract. 183 (5): 587–91. doi:10.1016/S0344-0338(88)80017-7. PMID 3237548.
            120. ↑ Lie Fong, S.; Laven, J.S.E.; Duhamel, A.; Dewailly, D. (2017). “Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis”. Human Reproduction. 32 (8): 1723–1731. doi:10.1093/humrep/dex226. ISSN 0268-1161.
            121. ↑ Lie Fong S, Laven J, Duhamel A, Dewailly D (August 2017). “Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis”. Hum. Reprod. 32 (8): 1723–1731. doi:10.1093/humrep/dex226. PMID 28854584. Vancouver style error: initials (help)
            122. ↑ Pembe AB, Abeid MS (October 2009). “Polycystic ovaries and associated clinical and biochemical features among women with infertility in a tertiary hospital in Tanzania”. Tanzan J Health Res. 11 (4): 175–80. PMID 20734696.
            123. ↑ Fleischman A, Mansfield J (September 2005). “Diagnosis and treatment of polycystic ovarian syndrome and insulin resistance”. Pediatr Ann. 34 (9): 733–8, 741–2. PMID 16222950.
            124. ↑ McManus, Shilpa; Levitsky, Lynne; Misra, Madhusmita (2013). “Polycystic Ovary Syndrome: Clinical Presentation in Normal-Weight Compared with Overweight Adolescents”. Endocrine Practice. 19 (3): 471–478. doi:10.4158/EP12235.OR. ISSN 1530-891X.
            125. ↑ Munro, Malcolm G.; Critchley, Hilary O.D.; Broder, Michael S.; Fraser, Ian S. (2011). “FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age”. International Journal of Gynecology & Obstetrics. 113 (1): 3–13. doi:10.1016/j.ijgo.2010.11.011. ISSN 0020-7292.
            126. ↑ James, A. H. (2016). “Heavy menstrual bleeding: work-up and management”. Hematology. 2016 (1): 236–242. doi:10.1182/asheducation-2016.1.236. ISSN 1520-4391.
            127. ↑ Bryk AH, Piróg M, Plens K, Undas A (December 2016). “Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K antagonists and the risk of recurrent venous thromboembolism”. Vascul. Pharmacol. 87: 242–247. doi:10.1016/j.vph.2016.11.003. PMID 27865826.
            128. ↑ Adra, Abdallah; El Zibdeh, Mazen Yousef; Abdul Malek, Abdul Malek Mohammed; Hamrahian, Amir H.; Abdelhamid, Amr Mohamed Salaheldin; Colao, Annamaria; Anastasiades, Elie; Ahmed, Essam Moustafa Aboul Fetooh; Ezzeddine, Jihad Ibrahim; El Sattar, Mahmoud Ibrahim Abd; Dabit, Suleiman Tawfiq; Ghanameh, Wadih; Nedjatian, Navid; El-Kak, Faysal (2016). “Differential diagnosis and management of abnormal uterine bleeding due to hyperprolactinemia”. Middle East Fertility Society Journal. 21 (3): 137–147. doi:10.1016/j.mefs.2016.02.001. ISSN 1110-5690.
            129. ↑ Shakerinejad, Ghodratollah; Hidarnia, Alireza; Motlagh, Mohammad Esmaeil; Karami, Khodabakhsh; Niknami, Shamsoddin; Montazeri, Ali (2013). “Factors predicting mood changes in oral contraceptive pill users”. Reproductive Health. 10 (1). doi:10.1186/1742-4755-10-45. ISSN 1742-4755.
            130. ↑ van Hunsel FP, Kampschöer P (2012). “[Postmenopausal bleeding and dietary supplements: a possible causal relationship with hop- and soy-containing preparations]”. Ned Tijdschr Geneeskd (in Dutch; Flemish). 156 (41): A5095. PMID 23062258.
            131. ↑ Tu, Xiang; Huang, Gaomin; Tan, Shengkui (2009). “Chinese Herbal Medicine for Dysfunctional Uterine Bleeding: A Meta-Analysis”. Evidence-Based Complementary and Alternative Medicine. 6 (1): 99–105. doi:10.1093/ecam/nem063. ISSN 1741-427X.
            132. ↑ Kabalak AA, Soyal OB, Urfalioglu A, Saracoglu F, Gogus N (September 2004). “Menometrorrhagia and tachyarrhythmia after using oral and topical ginseng”. J Womens Health (Larchmt). 13 (7): 830–3. PMID 15385077.

            Template:WH Template:WS

            Epidemiology and Demographics

            Epidemiology and Demographics

            Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

            Overview

            Around 3%-30% of women worldwide are affected by dysfunctional uterine bleed. A majority of cases occur either at menarche or near menopause. during this time, the imbalance between estrogen and progesterone is treated, leading to abnormal bleeding patterns. In younger girls, an immature hypothalamic axis contributes to the conditions well.

            Epidemiology and Demographics

            Worldwide, the incidence of women affected by dysfunctional uterine bleeding is estimated to be around 3%-30%. It is more common for cases to occur around menarche when the menstrual cycle initially begins or around menopause when the natural menstrual cycle is nearing its end.[1] Of the women affected, 25% are in their reproductive ages.[2] Over 80% of patients experiencing with menorrhagia presenting with some sort of underlying cause of dysfunctional endometrial bleeding.[3]

            • In the UK, uptown 800,000 women present with abnormal uterine bleeding every year.[2]
            • A study done in Turkey showed that the average age of affected patients was 15 years and almost 63% had at least one episode of irregular bleeding.[4]

            The epidemiology of DUB can also be divided up based upon the underlying causes.

            • Polyps occur in all ages but are most common amongst the ages of 40-49. The prevalence is 20%-40%. As many women go undiagnosed, 10% of cases are found upon autopsy while confirming death from another cause.[5] Polyps are less likely to be makignant in premenopausal women but have an increased incidence of malignancy in those that are postmenopausal.
            • Adenomyosis has a prevalence of 20%-35% and most often affect women in their 30’s and 40’s. Women younger than 30 can experience a rare form of adenomysosis referred to as “juvenile cystic adenomyosis”. This presents with extensive loss of blood inside endometrial cysts.[6] 70% of women affected are premenopausal. The disease varies widely amongst racial and ethnic groups as well as amongst different geographical regions[7]
            • Leiomyoma is seemingly more common than would be expected. By the age of 50, approximately 70% of Caucasian women and 80% of African women will have experienced uterine bleeding due to leiomyoma. Black women experience symptoms twice compared to Caucasians.[8]
            • In the United States, approximately 65,000 women are diagnosed with uterine cancer annually of which more than 90% are of endometrial origin. Death due to uterine malignancy is most common between the ages of 65-74 leading to a high mortality rate. The mortality rate is furthered in the elderly due to aggressiveness of the tumour, advancement of the disease upon initial presentation, and decreased compliance for surgical treatment owing to older age and other co-morbidities.[9]
            • Worldwide, the prevalence of endometriosis is approximately 11,000 per 100,000 females in reproductive age group.[10] Endometriosis accounts for 33,000 per 100,000 cases with chronic pelvic pain and 17,000 per 100,000 cases with infertility.[11]
            • Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women, with a prevalence of 4-12% in the United States. Up to 10% of women are diagnosed with PCOS. The prevalence among first-degree relatives of patients with PCOS is 25% to 50%, suggesting a strong inheritance of the syndrome.

            References

            1. ↑ “StatPearls”. 2022. PMID 30422508.
            2. ↑ 2.0 2.1 Whitaker L, Critchley HO (2016). “Abnormal uterine bleeding”. Best Pract Res Clin Obstet Gynaecol. 34: 54–65. doi:10.1016/j.bpobgyn.2015.11.012. PMC 4970656. PMID 26803558.
            3. ↑ Cameron IT (1989). “Dysfunctional uterine bleeding”. Baillieres Clin Obstet Gynaecol. 3 (2): 315–27. doi:10.1016/s0950-3552(89)80024-0. PMID 2692922.
            4. ↑ Demir SC, Kadayýfçý TO, Vardar MA, Atay Y (2000). “Dysfunctional uterine bleeding and other menstrual problems of secondary school students in Adana, Turkey”. J Pediatr Adolesc Gynecol. 13 (4): 171–5. doi:10.1016/s1083-3188(00)00061-9. PMID 11173019.
            5. ↑ “StatPearls”.   ( ). 2022:  . PMID 32491756 Check |pmid= value (help).
            6. ↑ “StatPearls”.   ( ). 2022:  . PMID 30969690.
            7. ↑ Taran FA, Stewart EA, Brucker S (2013). “Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy”. Geburtshilfe Frauenheilkd. 73 (9): 924–931. doi:10.1055/s-0033-1350840. PMC 3859152. PMID 24771944.
            8. ↑ “StatPearls”.   ( ). 2022:  . PMID 30855861.
            9. ↑ “StatPearls”.   ( ). 2022:  . PMID 32965984 Check |pmid= value (help).
            10. ↑ Buck Louis, Germaine M.; Hediger, Mary L.; Peterson, C. Matthew; Croughan, Mary; Sundaram, Rajeshwari; Stanford, Joseph; Chen, Zhen; Fujimoto, Victor Y.; Varner, Michael W.; Trumble, Ann; Giudice, Linda C. (2011). “Incidence of endometriosis by study population and diagnostic method: the ENDO study”. Fertility and Sterility. 96 (2): 360–365. doi:10.1016/j.fertnstert.2011.05.087. ISSN 0015-0282.
            11. ↑ McDonald JS (2001). “Diagnosis and treatment issues of chronic pelvic pain”. World J Urol. 19 (3): 200–7. PMID 11469608.

            Template:WH Template:WS

            Risk Factors

            Risk Factors

            Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

            Overview

            Diseases presenting with dysfunctional uterine bleeding have a multitude of risk factors. Some that are commonly found in multiple conditions include those where estrogen exposure is uncontrolled and excessive. Some examples include early onset of menarche and late onset of menopause, obesity, anovulatory conditions such as PCOS, estrogen exclusive hormonal contraceptives and tamoxifen therapy for breast cancer. It is to be notes that smoking has actually resulted in a reduced risk of some disease, due to its anti-estrogenic causes. The efficacy of smoking in preventing DUB is questionable considering the multitude of other diseases such a behavioural activity results in. Although some conditions affected women of all ages, adenomyosis and malignancy were found to affect older woman.

            Risk Factors

            Dysfunctional uterine bleeding may be due to many various diseases and although many have similar risk factors, it may be helpful to understand them individually based on the underlying cause.

            Risk factors of underlying conditions causing DUB
            Condition causing DUB Risk Factors
            Polyps
            Adenomyosis[1][2]
            Leiomyoma[3]
            • Race (more prevalent in those of African descent)
            • Early menarche
            • Obesity
            • Use of oral contraceptives; the use of progestin-only contraceptives were shown to reduce the risk of leiomyoma
            • Multiparity has also been shown to reduce the risk
            Malignancy and hyperplasia[4][5]
            Coagulopathies
            Polycystic Ovarian Syndrome
            Endometrial disorders (Endometriosis)


            References

            1. ↑ “StatPearls”.   ( ). 2022:  . PMID 30969690.
            2. ↑ Taran FA, Stewart EA, Brucker S (2013). “Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy”. Geburtshilfe Frauenheilkd. 73 (9): 924–931. doi:10.1055/s-0033-1350840. PMC 3859152. PMID 24771944.
            3. ↑ “StatPearls”.   ( ). 2022:  . PMID 30855861.
            4. ↑ “StatPearls”.   ( ). 2022:  . PMID 32965984 Check |pmid= value (help).
            5. ↑ Ali AT (2013). “Risk factors for endometrial cancer”. Ceska Gynekol. 78 (5): 448–59. PMID 24313431.

            Template:WH Template:WS

            Natural History, Complications and Prognosis

            Natural History, Complications and Prognosis

            Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

            Overview

            Dysfunctional uterine bleeding is an irregularity of the menstrual cycle that may affect the duration, frequency and blood volume. Normal cycles last around 24-38 days and average 5-80 mL of blood loss during this time. Commonly associated complications include infertility, anemia and the possibility of underlying endometrial malignancy. Generally, the prognosis is favourable, but may depend on underlying causes and treatment options. The amount of blood loss varies according to hormonal and non-hormonal medications, as well as with surgical interventions.

            Natural History

            Dysfunctional uterine bleeding is a commonly presenting symptom and is defined as any irregularity of the menstrual cycle. This can include the duration, frequency and blood volume. It most commonly presents in women that have undergone menarche but are still perimenopausal. This is usually between the ages of 15-49. Each cycle often lasts around 24-38 days, with an average of 5-80 mL of blood loss.[1]

            Complications

            The effect on a woman’s lifestyle is one of the most important complications that patients face. Generally, the associated abdominal pain and unexpected bleeding can greatly affect one’s lifestyle.

            Other complications include:

            • Infertility: this complication may be the time when many women actually get diagnosed with endometriosis
            • Anemia: severe anemia may lead to death and is important to manage early on
            • Endometrial malignancy: it is important to rule out endometrial malignancy, as this can be one of the underlying causes of DUB. An endometrial biopsy is helpful in diagnosing the condition

            Prognosis

            The prognosis is generally favourable, but it may be altered depending on the underlying cause as well as the treatment modality.[1]

            References

            1. ↑ 1.0 1.1 “StatPearls”. 2022. PMID 30422508.
            2. ↑ “StatPearls”.   ( ). 2022:  . PMID 32491756 Check |pmid= value (help).
            3. ↑ “StatPearls”.   ( ). 2022:  . PMID 30855861.
            4. ↑ “StatPearls”.   ( ). 2022:  . PMID 32965984 Check |pmid= value (help).

            Template:WH Template:WS

            Diagnosis

            Diagnosis

            History and Symptoms | Physical Examination | Laboratory Findings | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies

            Treatment

            Treatment

            Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

            Case Studies

            Case Studies

            Case #1

            Looking for the patient version?

            Back to the patient-friendly article

            Imprint

            Privacy Policy

            Terms and Conditions

            © 2026 MyEClinic – IFTM Institut für Telematik in der Medizin GmbH