Dysfunctional uterine bleeding overview

# 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 hCG), 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.