Pathophysiology of Heavy Menstrual Bleeding

Abstract

Heavy menstrual bleeding (HMB) is a common gynecological complaint with multiple etiologies and diverse pathophysiological origins. This review discusses HMB with reference to the recently proposed PALM-COEIN classification system for abnormal uterine bleeding, initially describing the endometrial events in normal menstruation followed by discussion of the perturbations of normal endometrial shedding that can result in HMB. Our present understanding of the mechanisms of menstrual bleeding as well as many of the pathological aberrations of HMB is incomplete. Further research into the pathophysiology of HMB is urgently needed, as clear knowledge of the mechanisms of this disorder will provide new therapeutic targets to formulate more effective treatments. Keywords: endometrial cancer • endometrial hyperplasia • heavy menstrual bleeding • leiomyoma/fibroid • polycystic ovarian syndromeIn the developed world an average woman undergoes ∼400 repetitive cycles of monthly menstrual bleeding with shedding of her superficial endometrial functional layer. In as many as 20-30% of women, this bleeding is excessive and is termed heavy menstrual bleeding (HMB) [1]. Apart from the physical symptoms of anemia (fatigue, lethargy and exertional dyspnea), HMB can interfere with normal daily life and may affect the social and emotional well being of women, reducing their productivity in society. HMB commonly presents to primary and secondary healthcare providers, with over 1.5 million women suffering from this problem in England and Wales alone [1]. It is the fourth most common reason for secondary gynecological referrals and each year over 30,000 women in England and Wales undergo surgical treatment for HMB [1]. The annual cost to the National Health Service in 2000 was estimated to be over GB£65 million [2] and with the spiraling cost of healthcare provision, it is clear that the current cost of HMB to women, society and the National Health Service is huge.In this review HMB will be discussed with reference to the recently proposed polyps; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic and not yet classified (PALM-COEIN) classification system for abnormal uterine bleeding (AUB), approved by the International Federation of Gynecology and Obstetrics [3]. HMB can present as a chronic disorder of over 12 months duration or as an acute increase in bleeding over a short time period. The age at presentation can range from adolescence to the perimenopausal phase and HMB may occur in the context of either ovulatory or anovulatory cycles. This review will briefly describe the endometrial events in normal menstruation followed by discussion of the perturbations of normal endometrial shedding that can result in HMB. Normal menstruationThe purpose of menstruation is unknown but it is a phenomenon confined mainly to the upper order primates and humans [4], suggesting an associated evolutionary advan- tage. The morphology of human endometrium, relatively greater quantity of menstr...

Endometrial breakdown with sustained progesterone release involves NF-κB-mediated functional progesterone withdrawal in a mouse implant model

“…Irregular bleeding arises from endometrial hemostasis and structural impairments due to inflammation and oxygen stress. The aberrant activities of proteins that regulate angiogenesis appear to contribute to breakthrough bleeding (Lockwood, ; Kayisli et al, ; Hapangama and Bulmer, ), although the exact molecular mechanism is not yet fully elucidated. The use of progesterone subcutaneous implants in mice and guinea pigs represent a convenient model for the investigation of the mechanisms underlying irregular endometrial tissue breakdown or abnormal bleeding in women using LTPOCs (Morison et al, ; Alvarez Gonzalez et al, ; Krikun et al, ).…”

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“…There all cause of menorrhagia is unknown although recent studies have reported fibrinolysis and imbalance of prostaglandins as the cause of excessive uterine bleeding 3,4 . Routine treatment so of menorrhagia include oral contraceptives with estrogen or progesterone alone, gonadotropinreleasing hormone agonists, anti-fibrinolytics, nonsteroidalanti-inflammatory drugs such as mefenamic acid and desmopressin 5 .…”

High prevalence of reduced thrombin generation and/or decreased platelet response in women with unexplained heavy menstrual bleeding

“…HMB is a common medical reason for referral to hospitals. Clinically it is defined as more than 80 mL blood loss per cycle and/or a menstrual bleeding period of longer than 7 days . HMB is a complaint with multiple aetiologies and diverse pathophysiology that is incompletely understood .…”

“…Clinically it is defined as more than 80 mL blood loss per cycle and/or a menstrual bleeding period of longer than 7 days. 5 HMB is a complaint with multiple aetiologies and diverse pathophysiology that is incompletely understood. 6 In 40% of the women, a clear pathophysiological cause can be diagnosed, including hormonal imbalances, dysfunctions in the ovaries and polyps, fibroids, or adenomyosis in the uterus.…”

“…7,10,11 Approximately 83% of women with VWD reported HMB. 12 The current diagnostic infrastructure for HMB does not facilitate testing for haemostasis deficiencies, despite consistent evidence that there is a higher prevalence of VWD, 5,12 impaired platelet function in patients with HMB [12][13][14] and the fact that Von Willebrand factor (VWF) and platelet function testing is recommended by American Academy of Pediatrics Committee on Adolescence and the American College of Obstetricians and Gynecologists Committee on Adolescent Health Care. 15,16 Platelet function testing with light transmission aggregometry (LTA) is routinely used to measure platelet function in patients with bleeding complications.…”