Dysfunctional uterine bleeding pathophysiology

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

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. Either 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 tutors 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.
Iatrogenic Iatrogenic causes refer to inadvertent injuries induced my physicians. Such causes include unopposed and continuous exposure to estrogen and progesterone therapy, as is seen with contraceptive medications, GnRH agonists, and SERMs.[4]
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 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[5] that play a role in shedding and subsequent scarring.[6]

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. 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.
  5. 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.
  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.

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