Ciężkie krwawienia miesiączkowe – Patofizjologia i mechanizm

Ciężkie krwawienia miesiączkowe
Patofizjologia i mechanizm

Ciężkie krwawienia miesiączkowe (HMB), definiowane jako utrata krwi przekraczająca 80 ml na cykl, mają złożoną patofizjologię obejmującą zaburzenia hormonalne, hemostazy, wazokonstrykcji oraz zmiany strukturalne w macicy. W cyklach owulacyjnych HMB wiąże się z lokalną dysregulacją cytokin naczynioskurczowych, zwiększoną fibrynolizą oraz zmienioną ekspresją czynników sygnalizacyjnych, takich jak SMAD3 i TGF-β. W cyklach bezowulacyjnych, często obserwowanych u nastolatek i kobiet okołomenopauzalnych, brak progesteronu prowadzi do niekontrolowanej proliferacji endometrium, jego niestabilności i nieregularnego, obfitego krwawienia. Istotną rolę odgrywają także zaburzenia krzepnięcia, w tym choroba von Willebranda (występująca u 13-33% pacjentek z HMB), oraz czynniki strukturalne, takie jak mięśniaki, adenomioza, polipy endometrialne i hiperplazja endometrium, które wpływają na kurczliwość miometrium, lokalną angiogenezę i stabilność naczyń.

Patogeneza ciężkich krwawień miesiączkowych

Ciężkie krwawienia miesiączkowe (Heavy Menstrual Bleeding, HMB), znane również jako menorrhagia, to nadmierne lub przedłużone krwawienie miesiączkowe, które negatywnie wpływa na jakość życia kobiety. Klinicznie definiuje się je jako utratę krwi przekraczającą 80 ml na cykl miesiączkowy. Patofizjologia HMB jest złożona i obejmuje wiele mechanizmów, które zaburzają prawidłowe funkcjonowanie endometrium oraz procesy hemostazy podczas miesiączki.¹²³

Mechanizmy fizjologiczne prawidłowego krwawienia miesiączkowego

Prawidłowe krwawienie miesiączkowe zależy od sekwencyjnej ekspozycji endometrium na estrogen i progesteron, a następnie od wycofania progesteronu pod koniec cyklu miesiączkowego. Jakiekolwiek zaburzenia endokrynologiczne, które zakłócają te sekwencyjne zdarzenia, mogą potencjalnie prowadzić do HMB.⁴

Hemostaza podczas miesiączki opiera się na wystarczającej wazokonstrykcji i prawidłowo funkcjonującym systemie krzepnięcia. Zaburzenie któregokolwiek z tych elementów może wpływać na przebieg miesiączki i prowadzić do ciężkich krwawień.⁵

Przyczyny ciężkich krwawień miesiączkowych podczas cykli owulacyjnych

W cyklach owulacyjnych ciężkie krwawienia miesiączkowe mogą być związane z miejscowymi zaburzeniami hemostazy i wazokonstrykcji w endometrium. Badania wykazały, że tkanka endometrium u kobiet z HMB ma zmienione cytokiny o działaniu naczynioskurczowym, takie jak endoteliny i prostaglandyny.⁶⁷

Endometrium kobiet cierpiących na menorrhagię ma wyższe poziomy aktywatorów plazminogenu niż endometrium kobiet z prawidłowym krwawieniem, co prowadzi do zwiększonej fibrynolizy i przedłużonego krwawienia.⁸

Ponadto, badania wykazały związek pomiędzy ciężkimi krwawieniami miesiączkowymi a:

Zmniejszoną ekspresją SMAD3 podczas miesiączki u kobiet z HMB, co wskazuje na rolę sygnalizacji TGF-β w patogenezie tego zaburzenia⁹
Zwiększonym poziomem omega-6 AA w tkankach macicy, co prowadzi do wyższego poziomu prostaglandyn (E2, F2alfa i innych)¹⁰
Deficytem glikolizy, który może być związany z ciężkimi krwawieniami miesiączkowymi, szczególnie w przypadkach adenomiozy¹¹¹²

Przyczyny ciężkich krwawień miesiączkowych podczas cykli bezowulacyjnych

Krwawienia bezowulacyjne stanowią najczęstszą przyczynę HMB. Patogeneza tego procesu jest dobrze udokumentowana i obejmuje:¹³¹⁴¹⁵

Brak owulacji, co prowadzi do niewykształcenia się ciałka żółtego
Brak wydzielania progesteronu, co skutkuje niezrównoważonym działaniem estrogenu
Ciągłą proliferację endometrium pod wpływem niezrównoważonego estrogenu
Rozrost endometrium, które przekracza swoje zaopatrzenie w krew
Niestabilność strukturalną rozrośniętego endometrium i brak prawidłowego systemu podtrzymania
Niekompletne złuszczanie się endometrium i krwawienie o nieregularnym charakterze, często obfite i przedłużone

Cykle bezowulacyjne są szczególnie powszechne w okresie dojrzewania oraz w okresie okołomenopauzalnym. W przypadku młodych dziewcząt, niedojrzałość osi podwzgórze-przysadka-jajniki prowadzi do nieregularnych owulacji.¹⁶¹⁷

W okresie okołomenopauzalnym, ciężkie krwawienia miesiączkowe mogą być wczesnym objawem niewydolności jajników. Pęcherzyki jajnikowe wciąż się rozwijają, ale pomimo zwiększonego poziomu hormonu folikulotropowego (FSH), nie produkują wystarczającej ilości estrogenu, aby wywołać owulację.¹⁸

Zaburzenia krzepnięcia jako przyczyna HMB

Zaburzenia krzepnięcia stanowią ważną przyczynę ciężkich krwawień miesiączkowych, szczególnie u młodych kobiet. Ogólna częstość występowania laboratoryjnego rozpoznania choroby von Willebranda u kobiet z HMB została określona na poziomie nawet 13%. Nieprawidłowa agregacja płytek krwi również jest często zgłaszana.¹⁹

Około 20% kobiet z HMB ma podstawowe zaburzenia krzepnięcia, a u adolescentek hospitalizowanych z powodu ciężkich krwawień miesiączkowych odsetek ten wzrasta do 33%.²⁰

Zmniejszenie siły i integralności skrzepu z powodu rozkładu fibryny prowadzi do zwiększonej utraty krwi podczas miesiączki. Kwas traneksamowy, który otrzymał zatwierdzenie do leczenia HMB w 2009 roku, działa jako antyfibrynolityk, który odwracalnie wiąże się z plazminogenem, zapobiegając degradacji fibryny.²¹²²

Strukturalne przyczyny ciężkich krwawień miesiączkowych

Mięśniaki macicy

Mięśniaki macicy (leiomyoma) to niezłośliwe guzy, które rozwijają się w ścianach macicy i są częstą przyczyną ciężkich krwawień miesiączkowych. Mechanizm, w jakim mięśniaki powodują HMB, nie jest w pełni zrozumiały, ale obecne hipotezy obejmują:²³²⁴

Ucisk mięśniaków na wyściółkę macicy, powodujący większe krwawienie niż zwykle
Zaburzenie prawidłowej kurczliwości mięśniówki macicy, co oznacza, że nie może ona prawidłowo zatrzymać krwawienia
Stymulowanie wzrostu naczyń krwionośnych, co przyczynia się do cięższych lub nieregularnych miesiączek oraz plamienia między miesiączkami
Podwyższone poziomy prostaglandyn, które również mogą przyczyniać się do ciężkich krwawień

Klasyczna teoria, zaproponowana po raz pierwszy przez Sampsona w 1912 roku, stwierdza, że miejscowa dysregulacja struktur naczyniowych w macicy jest odpowiedzialna za nieprawidłowe krwawienie. Nowsze badania wykazują dysregulację różnych czynników wzrostu w macicy z mięśniakami.²⁵

Hipoteza, która najlepiej wyjaśnia krwawienia związane z mięśniakami, stwierdza, że podstawowym zdarzeniem jest zmiana w strukturach żylnych w endometrium i miometrium, prowadząca do ektazji żylnej. Obecne dowody sugerują, że to nie kompresja fizyczna, ale lokalne działanie wazoaktywnych czynników wzrostu, których synteza, ekspresja lub sekwestracja w mięśniakach ulega zmianie, odpowiada za te nieprawidłowości naczyniowe.²⁶

Czynniki wzrostu lub ich receptory, które są różnicowo regulowane w mięśniakach lub endometrium macicy z mięśniakami, to potencjalne mediatory powikłań związanych z mięśniakami. Czynniki te obejmują bFGF, naczyniowy czynnik wzrostu śródbłonka (VEGF), heparynowy czynnik wzrostu naskórka (HBEGF), płytkopochodny czynnik wzrostu (PDGF), TGF-β, PTHrP oraz prolaktynę.²⁷

Adenomioza

Adenomioza to stan, w którym gruczoły z wyściółki macicy wrastają w ścianę mięśniową macicy, co może powodować ciężkie krwawienia i bolesne miesiączki. Przyczyna HMB w adenomiozie nie jest znana.²⁸²⁹

Podobnie jak w przypadku mięśniaków, adenomioza może wpływać na prawidłową kurczliwość miometrium, co może przyczyniać się do HMB. Patogeneza adenomiozy jest niepewna i zaproponowano różne wyjaśnienia. Najpopularniejsza hipoteza zakłada, że endometrium zagłębia się w miometrium z warstwy podstawnej podczas okresów regeneracji i gojenia.³⁰

U kobiet z adenomiozą chroniczny stan zapalny może prowadzić do zaburzenia równowagi hormonów i innych substancji regulacyjnych ważnych dla cyklu miesiączkowego, co skutkuje nieprawidłowym krwawieniem, takim jak ciężkie, przedłużone miesiączki.³¹

Polipy endometrialne

Polipy endometrialne to małe, łagodne wyrośla na wyściółce macicy, które mogą powodować ciężkie lub przedłużone krwawienie miesiączkowe. Mogą one również powodować krwawienie między miesiączkami oraz plamienie po menopauzie.³²³³

Mechanizm, w jakim polipy endometrialne przyczyniają się do HMB, nie jest w pełni zrozumiały, ale obejmuje prawdopodobnie zwiększoną powierzchnię endometrium oraz lokalną dysregulację czynników wzrostu i hormonów.

Hiperplazja endometrium

Hiperplazja endometrium to stan przedrakowy, który może prowadzić do ciężkich krwawień miesiączkowych. Jest ona wynikiem nadmiernej stymulacji estrogenu bez przeciwdziałania progesteronu, co prowadzi do nadmiernego pogrubienia wyściółki macicy.³⁴

Mechanizmy, za pomocą których hiperplazja endometrium (EH) wywołuje HMB, nie są w pełni zrozumiałe. Prawdopodobne wyjaśnienia obejmują brak zwykłego obniżenia progesteronu, aby zainicjować złuszczanie grubych i nadmiernych tkanek endometrium, ciągłą aktywność proliferacyjną w endometrium nawet w czasie złuszczania oraz możliwie obfity przepływ krwi, który jest ustanowiony, aby wspierać zwiększony wzrost endometrium. Wszystko to może powodować przedłużone, obfite krwawienie, a także niepełne ustanie krwawienia.³⁵

Niestrukturalne przyczyny ciężkich krwawień miesiączkowych

Zaburzenia hormonalne

Hormony takie jak estrogen i progesteron regulują cykl miesiączkowy, w tym nasilenie krwawień miesiączkowych. Posiadanie stanu, który powoduje zaburzenie równowagi hormonalnej, może prowadzić do ciężkich krwawień miesiączkowych.³⁶

W typowym cyklu miesiączkowym istnieje równowaga między hormonami estrogenem i progesteronem. Kontroluje to rozbudowę wyściółki macicy, znanej również jako endometrium. Ta wyściółka jest zrzucana podczas miesiączki. Gdy hormony są niezrównoważone, wyściółka staje się zbyt gruba i zrzuca się poprzez ciężkie krwawienie miesiączkowe lub nieoczekiwane krwawienie między miesiączkami.³⁷

Szczególne zaburzenia hormonalne związane z HMB obejmują:

Zaburzenia owulacji

Dysfunkcja owulacyjna (brak owulacji lub oligo-owulacja) jest najczęstszą przyczyną HMB u kobiet w wieku rozrodczym i występuje najczęściej u kobiet w wieku powyżej 45 lat (50% przypadków) oraz u nastolatek (20% przypadków).³⁸

Podczas cyklu bezowulacyjnego wytwarzany jest estrogen, ale ciałko żółte nie tworzy się. W związku z tym nie występuje normalne cykliczne wydzielanie progesteronu, a estrogen stymuluje endometrium bez przeciwdziałania. Bez przeciwdziałania progesteronu, endometrium nadal proliferuje, ostatecznie przerastając swoje zaopatrzenie w krew; następnie złuszcza się niekompletnie i krwawi nieregularnie, a czasem obficie lub przez wiele dni.³⁹

Zespół policystycznych jajników

Zespół policystycznych jajników (PCOS) to zaburzenie hormonalne powodujące powiększenie jajników z małymi torbielami. Prowadzi to do zaburzeń hormonalnych, powodując nieregularne cykle miesiączkowe i nieprzewidywalne ciężkie krwawienia.⁴⁰⁴¹

PCOS często prowadzi do pogrubienia wyściółki macicy bez regularnego złuszczania, co prowadzi do nieregularnego krwawienia. Kiedy rozpoczyna się leczenie, poprzednia wyściółka macicy zaczyna się złuszczać, co prawdopodobnie powoduje ciężkie krwawienie.⁴²

Niedoczynność tarczycy

Niedoczynność tarczycy może powodować ciężkie krwawienia miesiączkowe. Mechanizm niedoczynności tarczycy prowadzący do nadmiernego krwawienia macicy jest wieloczynnikowy, w tym zaburzenie hemostazy i dysfunkcja neuro-endokrynna.⁴³

Uznaje się, że jawna, a nawet subkliniczna niedoczynność tarczycy może powodować nie tylko anemię, ale także dysfunkcję płytek krwi, szczególnie nabyty zespół von Willebranda. Pojawiają się dowody potwierdzające ścisłe fizjologiczne i patologiczne interakcje między osią podwzgórze-przysadka-tarczyca (HPT) a osią podwzgórze-przysadka-jajniki (HPO).⁴⁴

U pacjentki z ciężką niedoczynnością tarczycy, TSH jest znacznie podwyższony z powodu osłabionego lub braku negatywnego sprzężenia zwrotnego z tyroksyn (T4 i T3). Hipersekrecja TSH może prowadzić do hiperplazji tyreotropów w przysadce mózgowej. Efekt masy hiperplazji przysadki może hamować wydzielanie LH. Z powodu tego samego mechanizmu braku hamowania sprzężenia zwrotnego, oczekuje się również podwyższenia TRH przysadki, co zwiększa wydzielanie zarówno TSH, jak i prolaktyny (PRL); hiperprolaktynemia z kolei tłumi LH. TSH ma niewielki efekt podobny do FSH i LH. W zależności od stopnia zaburzenia tych hormonów wyższego poziomu, poziom estrogenu może pozostać nieprawidłowo podwyższony i niezrównoważony, co skutkuje anovulacyjnym dysfunkcyjnym krwawieniem macicy (DUB).⁴⁵

Wpływ leków na ciężkie krwawienia miesiączkowe

Niektóre leki mogą powodować ciężkie krwawienia miesiączkowe. Ważnym czynnikiem do rozważenia i znaczącą przyczyną HMB są leki przyjmowane przez pacjentkę. Nienaruszony szlak krzepnięcia jest niezbędny do regulacji miesiączki, a leki, które wchodzą w interakcje z płytkami krwi i czynnikami krzepnięcia, mogą prowadzić do ostrego HMB.⁴⁶

Lista leków, które mogą prowadzić do HMB, obejmuje:⁴⁷⁴⁸

Warfaryna, aspiryna, klopidogrel i inne leki przeciwzakrzepowe
Leki koncepcyjne i urządzenia
Tamoksyfen
Trójcykliczne leki przeciwdepresyjne
Leki przeciwpsychotyczne
Kortykosteroidy

Następstwa kliniczne ciężkich krwawień miesiączkowych

Niedokrwistość jako powikłanie HMB

Ciężkie krwawienia miesiączkowe mogą prowadzić do anemii z niedoboru żelaza. Anemia to stan, w którym organizmowi brakuje wystarczającej ilości czerwonych krwinek do przenoszenia tlenu do tkanek. Liczba czerwonych krwinek jest mierzona przez hemoglobinę. Hemoglobina to białko w czerwonych krwinkach, które przenosi tlen do tkanek w całym organizmie.⁴⁹

Utrata krwi podczas ciężkich miesiączek może obniżyć poziom żelaza. Może to prowadzić do niedokrwistości z niedoboru żelaza, która może powodować zmęczenie, osłabienie i inne objawy.⁵⁰⁵¹

Co interesujące, istnieje dwukierunkowa zależność między anemią a HMB: chociaż dobrze wiadomo, że ciężkie krwawienia miesiączkowe mogą prowadzić do anemii z niedoboru żelaza, nie jest tak dobrze rozpoznane, że anemia z niedoboru żelaza może faktycznie powodować lub pogarszać menorrhagię. Niedobór żelaza może powodować osłabienie mięśni macicy, zmniejszając tym samym zdolność tych mięśni do zaciskania się na naczyniach krwionośnych, co jest konieczne do zmniejszenia lub zatrzymania krwawienia.⁵²

Badania wskazują również na związek między deficytem witamin a HMB:

Badania wykazały, że niedobór witaminy A zaburza produkcję hormonów i aktywność enzymów w jajnikach zwierząt⁵³
Badania wykazały, że niedobór witamin z grupy B powoduje utratę zdolności wątroby do dezaktywacji estrogenu, co teoretycznie może prowadzić do nadmiaru estrogenu⁵⁴

Wpływ na jakość życia

Ciężkie krwawienia miesiączkowe mogą znacząco wpływać na jakość życia kobiet. Przepływ krwi i skurcze utrudniają wykonywanie zwykłych czynności. Jeśli obawiasz się swojego okresu z powodu ciężkich krwawień miesiączkowych, porozmawiaj ze swoim lekarzem. Istnieje wiele metod leczenia, które mogą pomóc.⁵⁵

Cierpienie pacjentki może być bardziej związane z zakłóceniami w pracy, aktywności seksualnej lub jakości życia niż samym objętością miesiączki. Postrzeganie przez kobietę utraty krwi i zakłóceń, które powoduje, są kluczowymi determinantami późniejszego leczenia.⁵⁶

Nieleczone ciężkie miesiączki mogą zakłócać twoje życie i prowadzić do poważnych problemów zdrowotnych jak anemia, która może być poważna.⁵⁷

Podsumowanie patogenezy HMB

Patogeneza ciężkich krwawień miesiączkowych jest złożona i wieloczynnikowa. Nie ma pojedynczej ścieżki, która jest związana z HMB, co doprowadziło do kilku interwencji terapeutycznych specyficznie zmieniających różne ścieżki, skutkujących zmniejszeniem utraty krwi podczas miesiączki.⁵⁸

Ciężkie krwawienia miesiączkowe są objawem związanym z różnymi stanami, w tym zaburzeniami krzepnięcia i zaburzeniami niekrwotocznymi. Nasza obecna wiedza na temat mechanizmów krwawienia miesiączkowego, a także wielu patologicznych aberracji HMB jest niepełna. Dalsze badania nad patofizjologią HMB są pilnie potrzebne, ponieważ jasna wiedza o mechanizmach tego zaburzenia zapewni nowe cele terapeutyczne do opracowania bardziej skutecznych metod leczenia.⁵⁹⁶⁰

Każdy proces, który zakłóca normalne funkcje endokrynne, parakrynne lub hemostatyczne endometrium, a także możliwe zakłócenia kurczliwości miometrium, może powodować HMB. Patofizjologię HMB można omówić w kontekście zarówno cykli owulacyjnych, jak i bezowulacyjnych.⁶¹

Badania wykazały kluczową rolę licznych procesów w patogenezie HMB, w tym:

Zaburzenia równowagi hormonalnej, zwłaszcza między estrogenem a progesteronem
Dysregulacja czynników wzrostu i ich receptorów
Zaburzenia hemostazy i wazokonstrykcji
Zmiany strukturalne w macicy, takie jak mięśniaki, adenomioza i polipy
Zaburzenia krzepnięcia
Wpływ leków, szczególnie tych wpływających na krzepnięcie krwi

Lepsze zrozumienie tych mechanizmów patogenetycznych może prowadzić do opracowania bardziej ukierunkowanych i spersonalizowanych metod leczenia ciężkich krwawień miesiączkowych, co potencjalnie zmniejszy potrzebę inwazyjnych interwencji, takich jak histerektomia.⁶²

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Materiały źródłowe

#1 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
Heavy menstrual bleeding (HMB) is a common gynecological complaint with multiple etiologies and diverse pathophysiological origins. […] 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. […] Any process that interferes with the normal endocrine, paracrine or hemostatic functions of the endometrium as well as possibly any interference with myometrial contractility may cause HMB. […] The pathophysiology of HMB may be discussed in the context of both ovulatory and anovulatory cycles. […] The mechanisms by which EH induces HMB are not fully understood.
#2 Systematic review and meta-analysis of the etiology of heavy menstrual bleeding in 2,770 adolescent females | BMC Women’s Health | Full Text
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-024-02921-7
Adolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. […] The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. […] The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 2225.5%), Coagulation Disorders (19.4%; 95% CredI 17.821.1%), and Platelet Disorders (6.23%; 95% CredI 5.277.27%) with 45.9% (95% CredI 43.847.%9) of the cases of indeterminate origin. […] The leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. […] Heavy menstrual bleeding (HMB), defined as excessive menstrual blood loss that interferes with a womans physical, social, emotional, or material quality of life, is currently classified according to the FIGO abnormal uterine bleeding system 2 PALM-COEIN classification system.
#3 Accelerating Innovations to Address Heavy Menstrual Bleeding
https://gcgh.grandchallenges.org/challenge/accelerating-innovations-address-heavy-menstrual-bleeding-women-low-resource-settings
Heavy menstrual bleeding (HMB) affects millions of women globally. Clinically, HMB is defined as excessive menstrual blood loss that negatively affects a woman’s physical, emotional, and social well-being. In research settings, HMB is defined as directly measured blood loss exceeding 80 milliliters per menstrual cycle. […] The underlying biological mechanisms, particularly related to endometrial dysfunction-related HMB also remain poorly understood. […] Research priorities in HMB include understanding the underlying biological mechanisms, particularly related to endometrial dysfunction-related HMB, developing and introducing cost-effective and easy to scale-up diagnostics to identify causes of HMB and guide treatment, and identifying ways to increase acceptability and access to treatments such as the hormonal intrauterine device for women in low-resource settings. […] Biological Mechanisms Advancing understanding of the fundamental biology of HMB to identify targets for innovative diagnostics and treatments.
#4 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
Normal menstrual bleeding depends on the sequential exposure of the estrogen-primed endometrium to estrogen and progesterone, followed by withdrawal of progesterone at the end of the menstrual cycle. […] Any endocrine irregularity that prevents these sequential events may potentially result in HMB.
#5 Menorrhagia: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/255540-overview
Knowledge of normal menstrual function is imperative in understanding the etiologies of menorrhagia. […] Hemostasis relies on sufficient vasoconstriction and a functioning coagulation system, and a disruption in either element can affect menstruation. […] Many cases of AUB are secondary to anovulation. […] Anatomic defects or growths (most typically polyps or fibroids but also malignancy) within the uterus can alter either of the aforementioned pathways (endocrinologic/hemostatic), causing significant uterine bleeding. […] Organic diseases also contribute to menorrhagia in the female patient. […] Due to the overwhelming factors that can contribute to the dysfunction of either the endocrine or hematologic pathways, in-depth knowledge of an existing organic disease is just as imperative as understanding the menstrual cycle itself.
#6 Abnormal (Dysfunctional) Uterine Bleeding: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/257007-overview
The hallmark of PCOS is prolonged unopposed estrogen with continuous endometrial proliferation combined with unpredictable structural breakdown. […] Endometrial AUB, referred to as ovulatory dysfunctional uterine bleeding in the past, is classically a condition in women of heavy regular cycles. […] Research studies point to a local disturbance in hemostasis and vasoconstriction. Endometrial tissue has altered vasoconstrictive cytokines such as endothelins and prostaglandins. […] Causes of iatrogenic AUB include IUD use (discussed previously) and chronic progestin exposure. AUB associated with depot-medroxyprogesterone acetate (DMPA) is very common and tends to decrease with time.
#7 Ibuprofen might make your periods lighter, but itâs not a long-term solution
https://theconversation.com/ibuprofen-might-make-your-periods-lighter-but-its-not-a-long-term-solution-130885
Theres some evidence non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, can reduce menstrual flow. But they shouldnt be seen as a long-term solution. Women who experience heavy or painful periods regularly should speak to a doctor. […] Women who have heavy bleeding, and who experience painful periods, have elevated levels of hormones called prostaglandins. Prostaglandins act to dilate blood vessels, slow the clotting process and also help the body shed the uterine lining by inducing muscle contractions. So having higher levels of these hormones can lead to heavier bleeding and more severe cramping. […] Ibuprofen has been shown to reduce prostaglandin levels in the lining of the uterus, which may be one way it reduces menstrual flow, though the exact mechanism remains uncertain.
#8 Managing Menorrhagia
https://www.uspharmacist.com/article/managing-menorrhagia
Anything that causes thickening of the endometrium, and hence increases its vascularization, can cause menorrhagia. […] The endometrium of women who experience menorrhagia has been shown to have higher levels of plasminogen activators than that of women with normal flow. […] Tranexamic acid is a synthetic lysine derivative that exerts its effect by blocking lysine binding sites on plasminogen, thus preventing fibrin degradation. […] Danazol works by suppressing the pituitary-ovarian axis and inhibiting the pituitary output of gonadotropins, hormones that increase in the endometrium. […] GnRH analogues are competitive agonists at GnRH receptors in the pituitary. GnRH-releasing cells are eventually desensitized, resulting in a hypogonadotropic state, which causes hypoestrogenism, endometrial atrophy, and amenorrhea.
#9 Transforming growth factor-β superfamily signalling and its role in the pathogenesis of heavy menstrual bleeding | SFEBES2014 | Society for Endocrinology BES 2014 | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0034/ea0034p330
Transforming growth factor- superfamily signalling and its role in the pathogenesis of heavy menstrual bleeding […] Aberrations in endometrial repair may lead to pathology such as heavy menstrual bleeding (HMB). […] The prolonged bleeding identified in women with HMB is consistent with defective endometrial repair. The presence of active SMAD2/3 protein at menstruation and decreased SMAD3 expression at this time in women with HMB implicates TGF- signalling in the pathogenesis of this common disorder.
#10 Heavy menstrual bleeding – Wikipedia
https://en.wikipedia.org/wiki/Heavy_menstrual_bleeding
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hematomunia, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB). […] Abnormal uterine bleeding can be caused by structural abnormalities in the reproductive tract, skipping ovulation (anovulation), bleeding disorders, hormonal issues (such as hypothyroidism) or cancer of the reproductive tract. […] HMB is associated with increased omega-6 AA in uterine tissues. The endometrium of people with HMB have higher levels of prostaglandin (E2, F2alpha and others) when compared with women with normal menses. It is thought that prostaglandins are a by product of omega 6 build up. Furthermore, prostaglandins have been found to trigger abnormal, painful uterine contractions, making it a source for targeted therapy.
#11
https://link.springer.com/article/10.1007/s43032-022-01150-3
Menstrual cycle is a major determinant in female reproductive health. […] In a recent report, Mao et al. (2022) associated deficient glycolysis with heavy menstrual bleeding. […] Recently, a study by Chenyu Mao, Xishi Liu, and Sun-Wei Guo reports that decreased glycolysis is associated with heavy menstrual bleeding. […] The authors discovered reduced immunostaining of HK2 indicating reduced glycolysis in women with excessive menstrual bleeding suggesting that defective glycolysis causes heavy menstrual bleeding also in humans. […] On a more fundamental level, it still remains unresolved whether endometrial disorders that lead to heavy menstrual bleeding are primary endometrial disorders or secondary endometrial disorders. […] The proximity of the samples to adenomyosis lesions suggests that the described defect in glycolysis could be specific to adenomyosis-induced heavy menstrual bleeding.
#12
https://link.springer.com/article/10.1007/s43032-022-01150-3
Thus, in both cases, the downregulation of glycolytic enzymes can be conceived as evidence of decidualization defect, which would also include the view of endometrial glycolysis defect as primary endometrial disorder originating from the endometrial cell functions, and not as a secondary effect from physically measured conditions such as adenomyosis. […] In any case, collectively, the evidence points out that a well-balanced glycolytic drive is essential for healthy endometrial function.
#13 Menorrhagia: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/255540-overview
Knowledge of normal menstrual function is imperative in understanding the etiologies of menorrhagia. […] Hemostasis relies on sufficient vasoconstriction and a functioning coagulation system, and a disruption in either element can affect menstruation. […] Many cases of AUB are secondary to anovulation. […] Anatomic defects or growths (most typically polyps or fibroids but also malignancy) within the uterus can alter either of the aforementioned pathways (endocrinologic/hemostatic), causing significant uterine bleeding. […] Organic diseases also contribute to menorrhagia in the female patient. […] Due to the overwhelming factors that can contribute to the dysfunction of either the endocrine or hematologic pathways, in-depth knowledge of an existing organic disease is just as imperative as understanding the menstrual cycle itself.
#14 Abnormal Uterine Bleeding – Gynecology and Obstetrics – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/abnormal-uterine-bleeding
Abnormal uterine bleeding (AUB) in patients of reproductive age is a bleeding pattern that is not consistent with normal menstrual cycle parameters (frequency, regularity, duration, and volume). […] Ovulatory dysfunction (anovulation or oligo-ovulation) is the most common cause of AUB in women of reproductive age and occurs most often in women 45 years old (50% of cases) and in adolescents (20% of cases). […] During an anovulatory cycle, estrogen is produced, but the corpus luteum does not form. Thus, the normal cyclical secretion of progesterone does not occur, and estrogen stimulates the endometrium unopposed. Without opposition by progesterone, the endometrium continues to proliferate, eventually outgrowing its blood supply; it then sloughs incompletely and bleeds irregularly and sometimes profusely or for many days.
#15
https://step2.medbullets.com/gynecology/121755/abnormal-uterine-bleeding-aub
Pathogenesis mechanism of AUB due to anovulation: corpus luteum does not form, absence of progesterone, unopposed estrogen continues to proliferate the endometrium, the endometrium becomes unstable and outgrows its blood supply, endometrial sloughing and breakthrough bleeding results. […] May be at increased risk for endometrial cancer or hyperplasia in AUB secondary to anovulation.
#16 Hormonal Causes of HMB – Your Period
https://www.yourperiod.ca/abnormal-pain-and-menstrual-bleeding/heavy-menstrual-bleeding/hormonal-causes-of-heavy-menstrual-bleeding/
The normal menstrual cycle relies on a properly balanced, complex system of hormones. Disorders that alter your hormones can result in HMB. […] In the 2-3 years that follow the first period, many adolescent girls experience irregular periods. Sometimes this comes in the form of missed or very light periods, while others may experience heavy menstrual bleeding (HMB). The menstrual cycle is controlled by complex interactions between the hypothalamus, the pituitary gland, and the ovaries (called the hypothalamic-pituitary-ovarian axis). This system takes time to mature, and when it is not functioning properly, ovulation may not occur. When ovulation does not happen, there is no progesterone present in the uterus, and the lining of the uterus becomes very thick and contain more blood vessels than usual. This can result in a heavy and prolonged period. This is one of the most common cause of HMB in adolescents.
#17 Adolescent gynaecology – Heavy menstrual bleeding
https://www.rch.org.au/clinicalguide/guideline_index/adolescent_gynaecology_menorrhagia/
The most common cause of Heavy Menstrual Bleeding (HMB) in adolescents is anovulatory cycles […] Anovulatory uterine bleeding is excessive noncyclic uterine bleeding related to immaturity of the hypothalamic-pituitary-ovarian axis (in the absence of structural uterine lesions or systemic disease) […] Treatment is targeted to the underlying cause; for anovulatory bleeding, the objective is to stabilise the endometrium (oestrogen for initial haemostasis and progestins for extended endometrial stability) […] Progestins (eg norethisterone 5 mg, medroxy-progesterone acetate 10 mg) generates a secretory endometrium and are good for anovulation (infrequent periods) due to the lack of progesterone.
#18 Abnormal Uterine Bleeding – Gynecology and Obstetrics – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/abnormal-uterine-bleeding
When abnormal uterine bleeding occurs in patients with ovulatory cycles, progesterone secretion is prolonged; irregular shedding of the endometrium results, probably because estrogen levels remain low, near the threshold for bleeding (as occurs during menses). […] Chronic heavy or prolonged uterine bleeding may cause iron deficiency anemia. […] If AUB is due to ovulatory dysfunction, infertility may also be present. […] AUB due to ovulatory dysfunction (AUB-O) is the most common type of nonstructural AUB and the most common cause overall. […] During perimenopause, AUB-O may be an early sign of ovarian insufficiency; follicles are still developing but, despite increasing levels of follicle-stimulating hormone (FSH), do not produce enough estrogen to trigger ovulation. […] Approximately 20% of women with endometriosis have AUB-O due to unknown mechanisms.
#19 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
In common with leiomyoma, adenomyosis can affect normal myometrial contractility and this may contribute to the HMB. […] The pathogenesis of adenomyosis is uncertain and various explanations have been suggested. […] The most popular hypothesis is that endometrium invaginates into myometrium from the stratum basalis during periods of regeneration and healing. […] The overall prevalence of a laboratory diagnosis of von Willebrand disease in women presenting with HMB has been reported to be as high as 13%. […] Abnormal platelet aggregation has also been reported to be common and these two conditions should be ruled out before embarking on investigations for other haemostatic disorders in women presenting with primary HMB. […] A decrease in clot strength and integrity due to the breakdown of fibrin results in an increased blood loss during menstruation.
#20 Heavy Menstrual Bleeding in Adolescents: ACOG Management Recommendations | AAFP
https://www.aafp.org/pubs/afp/issues/2020/0515/p633.html
One in five adolescents with heavy menstrual bleeding has an underlying bleeding disorder. […] Anovulation is the most common cause of heavy menstrual bleeding in adolescents; an underlying bleeding disorder is the second most common cause. Approximately 20% of all adolescent girls with heavy menstrual bleeding and 33% of adolescent girls hospitalized for heavy menstrual bleeding have an underlying bleeding disorder. The most common bleeding disorders are von Willebrand disease, platelet function defects, thrombocytopenia, and clotting factor deficiencies. […] A combination of hormonal and nonhormonal therapies may be necessary to control heavy menstrual bleeding in adolescent girls with bleeding disorders. Effective options include combined oral contraceptives with higher estrogen levels, the transdermal contraceptive patch, the vaginal contraceptive ring, and the levonorgestrel-releasing intrauterine device (Mirena), all of which can be used continuously with minimal or no withdrawal periods.
#21 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
In common with leiomyoma, adenomyosis can affect normal myometrial contractility and this may contribute to the HMB. […] The pathogenesis of adenomyosis is uncertain and various explanations have been suggested. […] The most popular hypothesis is that endometrium invaginates into myometrium from the stratum basalis during periods of regeneration and healing. […] The overall prevalence of a laboratory diagnosis of von Willebrand disease in women presenting with HMB has been reported to be as high as 13%. […] Abnormal platelet aggregation has also been reported to be common and these two conditions should be ruled out before embarking on investigations for other haemostatic disorders in women presenting with primary HMB. […] A decrease in clot strength and integrity due to the breakdown of fibrin results in an increased blood loss during menstruation.
#22 Menorrhagia(Archived) – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK536910/
Another important consideration and a significant cause of AUB are the patients medications. An intact coagulation pathway is essential for menstrual regulation and medications that interact with platelets and coagulation factors can lead to Acute AUB. The following is a list of some medications that can lead to AUB: Warfarin, aspirin, clopidogrel, and other anticoagulants; Conceptive medications and devices; Tamoxifen; Tricyclic antidepressants; Antipsychotics; Corticosteroids. […] The mechanism of action of estrogen therapy is the rapid regrowth of the endometrium over the exposed epithelial surface. […] Tranexamic acid received approval for the treatment of AUB in 2009. This drug is an antifibrinolytic that reversibly binds to plasminogen preventing fibrin degradation.
#23 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
The plausible explanations include lack of the usual reduction in progesterone to initiate shedding of the thick and excessive endometrial tissues; ongoing proliferative activity in the endometrium even at the time of shedding and possibly generous blood flow that is established to support the enhanced endometrial growth; all of which may cause prolonged, heavy bleeding as well as incomplete cessation of bleeding. […] Despite advances in understanding of the molecular changes in leiomyomas and associated myometrium and endometrium, it remains unclear why clinical symptoms are so varied. […] HMB is seen in some women with leiomyomas but it does not correlate clearly with the size or location of fibroids or with the expression of angiogenic growth factors or blood flow. […] The cause of HMB in adenomyosis is unknown.
#24 The Link Between Uterine Fibroids and Heavy Menstrual Bleeding
https://www.everydayhealth.com/womens-health/uterine-fibroids-heavy-menstrual-bleeding/
Heavy menstrual bleeding is typically defined as a period that lasts more than seven days and requires frequent changing of sanitary products. […] While there’s no one reason uterine fibroids cause heavy, prolonged periods, there are a few theories. […] Uterine fibroids may press against the uterine lining, causing more bleeding than usual. […] The uterus may not contract properly, which means it can’t stop the bleeding. […] Fibroids may stimulate the growth of blood vessels, which contributes to heavier or irregular periods and spotting between periods. […] Elevated levels of hormones called prostaglandins may also contribute to heavy bleeding. […] Heavy menstrual bleeding related to uterine fibroids is typically based on the location of the fibroids, contractility of the uterus, the presence of ancillary prostaglandins, and any distortion to the lining of the uterus, explains Bradley.
#25
https://www.fibroids.net/pubfart4.html
Leiomyomas are an important cause of menorrhagia and other forms of abnormal uterine bleeding. The pathogenesis of this process is largely unknown, however. A classic theory, first suggested by Sampson’s work in 1912, states that local dysregulation of the vascular structures in the uterus is responsible for this abnormal bleeding. Recent work demonstrates dysregulation of a number of growth factors in the myomatous uterus. […] We hypothesize that this dysregulation of growth factors or their receptors provides the molecular mechanism underlying these vascular abnormalities. In turn, these abnormal vessels lead women with leiomyomas to experience menorrhagia. […] Current treatment regimens for women with leiomyoma-related bleeding depend on the manipulation of the steroid hormone environment. By better understanding the pathogenesis of this disease process, therapies directed against growth factor abnormalities may result in better treatment with less harmful side-effects.
#26
https://www.fibroids.net/pubfart4.html
Effective treatment strategies are limited by a narrow understanding of the pathogenesis of this disease. Classic studies suggest that there is a fundamental alteration in the vascular structures of the myomatous uterus. Recent progress in defining the molecular mechanisms of angiogenesis in the uterus lends support to this theory by demonstrating local dysregulation of vasoactive growth factors or growth factor receptors in leiomyomas or leiomyomatous myometrium. Thus, the molecular mechanisms underlying the process of leiomyoma-related menorrhagia are delineated. […] The theory that best explains leiomyoma-related abnormal bleeding states that the primary event is a change in venous structures in the endometrium and myometrium resulting in venule ectasia. […] Current evidence suggests that it is not physical compression but the local action of vasoactive growth factors which have altered synthesis, expression or sequestration in leiomyomas, that account for these vascular abnormalities. With ectatic venules, the hemostatic actions of the platelet and fibrin plug may be overwhelmed by the increased diameter of the vessels which causes the „flooding” clinically seen in women with menorrhagia.
#27
https://www.fibroids.net/pubfart4.html
Thus, multiple somatic mutations can result in the same phenotypic changes. This paradigm of dysregulation of growth factor function that results in disruption of normal vascular function appears relevant for non-uterine bleeding disorders. […] Growth factors or their receptors that are differentially regulated in the leiomyomas or the endometrium of leiomyomatous uteri are potential mediators of leiomyoma-related complications. These differentially regulated factors, which are known to act on vascular tissue by increasing proliferation or changing vessel caliber, are potential causes of leiomyoma-related menorrhagia. […] The factors that meet these criteria include bFGF, vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor (HBEGF), platelet derived growth factor (PDGF), TGF-b, PTHrP and prolactin. […] Thus, these factors represent a wide array of potential actions that regulate vascular function in the uterus.
#28 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
In common with leiomyoma, adenomyosis can affect normal myometrial contractility and this may contribute to the HMB. […] The pathogenesis of adenomyosis is uncertain and various explanations have been suggested. […] The most popular hypothesis is that endometrium invaginates into myometrium from the stratum basalis during periods of regeneration and healing. […] The overall prevalence of a laboratory diagnosis of von Willebrand disease in women presenting with HMB has been reported to be as high as 13%. […] Abnormal platelet aggregation has also been reported to be common and these two conditions should be ruled out before embarking on investigations for other haemostatic disorders in women presenting with primary HMB. […] A decrease in clot strength and integrity due to the breakdown of fibrin results in an increased blood loss during menstruation.
#29 Heavy menstrual bleeding – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829
Adenomyosis. In this condition, glands from the lining of the uterus grow into the wall of the uterus itself. This can cause heavy bleeding and painful periods. […] Heavy menstrual bleeding can cause anemia related to blood loss. Anemia is a condition in which the body lacks enough red blood cells to carry oxygen to tissues. The number of red blood cells is measured by hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen to tissues throughout the body. […] Heavy menstrual bleeding may make iron levels too low. This may result in iron deficiency anemia.
#30 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
In common with leiomyoma, adenomyosis can affect normal myometrial contractility and this may contribute to the HMB. […] The pathogenesis of adenomyosis is uncertain and various explanations have been suggested. […] The most popular hypothesis is that endometrium invaginates into myometrium from the stratum basalis during periods of regeneration and healing. […] The overall prevalence of a laboratory diagnosis of von Willebrand disease in women presenting with HMB has been reported to be as high as 13%. […] Abnormal platelet aggregation has also been reported to be common and these two conditions should be ruled out before embarking on investigations for other haemostatic disorders in women presenting with primary HMB. […] A decrease in clot strength and integrity due to the breakdown of fibrin results in an increased blood loss during menstruation.
#31 Is Heavy Menstrual Bleeding a Sign of Endometriosis?
https://www.healthline.com/health/endometriosis/menorrhagia-and-endometriosis
Menorrhagia (or heavy menstrual bleeding) and endometriosis may often show up together, but how endometriosis affects your period flow is a more indirect process. […] Menorrhagia, also known as heavy menstrual bleeding (HMB) or heavy uterine bleeding, is a common experience for people living with endometriosis. Menorrhagia features unusually heavy period flow or a prolonged period lasting longer than 7 days. […] Menorrhagia in endometriosis doesn’t result from blood in endometriosis lesions. Structural changes from endometriosis and chemical imbalances underlie the link between these conditions. […] Endometriosis inflammation and scarring may impair the natural structures and functions of your uterus, ovaries, and fallopian tubes. […] Chronic inflammation from endometriosis can also lead to an imbalance in hormones and other regulatory substances important to the menstrual cycle, resulting in abnormal bleeding like heavy, prolonged menstrual periods.
#32 Heavy menstrual bleeding – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829
Problems with the ovaries. Sometimes ovaries don’t release an egg during a menstrual cycle. This also is known as anovulation. When this happens, the body doesn’t make the hormone progesterone the way it usually does during a menstrual cycle. This leads to hormone imbalance and may result in heavy menstrual bleeding or unexpected bleeding between periods. […] Uterine fibroids. These tumors develop during childbearing years. They are benign, which means they are not cancerous. Uterine fibroids may cause heavier than normal menstrual bleeding or bleeding that goes on for a long time. […] Polyps. These small growths on the lining of the uterus may cause menstrual bleeding that is heavy or lasts for a long time. They may cause bleeding between periods. Polyps also can cause spotting or bleeding after menopause. The growths are not cancerous.
#33 Heavy periods (menorrhagia)
https://www.nj.gov/health/womenshealth/reproductive-health/periods-menstruation/heavy-periods/
Polyps are small, benign growths on the lining of the uterus and can cause heavy or prolonged bleeding. […] This condition occurs when the glands from the uterus become embedded in the uterine muscle. It often leads to heavy bleeding and painful periods. […] Heavy bleeding can be a side effect of using a nonhormonal IUD for birth control. […] Uterine cancer and cervical cancer can result in excessive bleeding, particularly if you are postmenopausal or have had an abnormal Pap test in the past. […] Certain bleeding disorders like von Willebrand’s disease, which affects blood-clotting, can lead to abnormal bleeding. […] Some medications, such as anti-inflammatory drugs, hormonal medications like estrogen and progestins, and anticoagulants like warfarin or enoxaparin, can contribute to heavy or prolonged bleeding.
#34 Menorrhagia (Heavy Menstrual Bleeding): Causes & Treatment
https://my.clevelandclinic.org/health/diseases/17734-menorrhagia-heavy-menstrual-bleeding
A precancerous condition called endometrial hyperplasia can lead to menorrhagia. Other cancers that affect your reproductive system can also cause heavy menstrual bleeding. […] Certain medicines can cause heavy menstrual bleeding, too. […] Anyone can get menorrhagia, but it tends to be more common in people who are approaching menopause. […] Heavy menstrual bleeding can be serious if you lose so much blood that you show signs of anemia. […] Your healthcare provider will ask a series of questions about your medical history and menstrual cycle to diagnose menorrhagia. […] Treatment depends on what’s causing your bleeding, how severe your bleeding is, your health, age and medical history. […] If medication doesn’t improve your symptoms, your provider may recommend a surgical procedure. […] Heavy bleeding can lead to anemia, which can be serious. […] Yes, it’s possible that menorrhagia can go away without treatment. […] You can’t prevent all causes of heavy period bleeding. […] Left untreated, heavy periods can interfere with your life.
#35 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
The plausible explanations include lack of the usual reduction in progesterone to initiate shedding of the thick and excessive endometrial tissues; ongoing proliferative activity in the endometrium even at the time of shedding and possibly generous blood flow that is established to support the enhanced endometrial growth; all of which may cause prolonged, heavy bleeding as well as incomplete cessation of bleeding. […] Despite advances in understanding of the molecular changes in leiomyomas and associated myometrium and endometrium, it remains unclear why clinical symptoms are so varied. […] HMB is seen in some women with leiomyomas but it does not correlate clearly with the size or location of fibroids or with the expression of angiogenic growth factors or blood flow. […] The cause of HMB in adenomyosis is unknown.
#36 Menorrhagia (Heavy Menstrual Bleeding): Causes & Treatment
https://my.clevelandclinic.org/health/diseases/17734-menorrhagia-heavy-menstrual-bleeding
Menorrhagia is heavy menstrual bleeding or losing more blood than is typical during menstruation. […] Menorrhagia can have many causes, ranging from hormone-related issues to medical conditions or medications. […] The hormones that your body produces, like estrogen and progesterone, help regulate your menstrual cycle, including how heavy your periods are. Having a condition that causes your hormones to become imbalanced can lead to heavy period bleeding. […] Benign growths in your uterus and conditions that cause cells in your uterus to grow improperly can cause heavy menstrual bleeding, too. […] Infections, including sexually transmitted infections (STIs) can cause heavy bleeding. […] Heavy bleeding can be a warning sign of pregnancy complications. […] Menorrhagia is a symptom associated with various conditions, including bleeding disorders and non-bleeding disorders.
#37 Heavy menstrual bleeding – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829
Some women have menstrual bleeding that is heavy or lasts for more than a few days. This condition used to be called menorrhagia. Heavy menstrual bleeding is a common concern. But most women don’t have enough blood loss for it to be called heavy menstrual bleeding. […] With heavy menstrual bleeding, blood flow and cramping make it harder to do your usual activities. If you dread your period because you have heavy menstrual bleeding, talk with your doctor. There are many treatments that can help. […] In some cases, the reason for heavy menstrual bleeding is unknown. But a number of conditions may cause heavy menstrual bleeding. They include: […] Hormones being out of balance. In a typical menstrual cycle, there’s a balance between the hormones estrogen and progesterone. This controls the buildup of the lining of the uterus. The lining of the uterus also is known as the endometrium. This lining is shed during a menstrual period. When hormones are out of balance, the lining becomes too thick and sheds by way of heavy menstrual bleeding or unexpected bleeding between periods.
#38 Abnormal Uterine Bleeding – Gynecology and Obstetrics – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/abnormal-uterine-bleeding
Abnormal uterine bleeding (AUB) in patients of reproductive age is a bleeding pattern that is not consistent with normal menstrual cycle parameters (frequency, regularity, duration, and volume). […] Ovulatory dysfunction (anovulation or oligo-ovulation) is the most common cause of AUB in women of reproductive age and occurs most often in women 45 years old (50% of cases) and in adolescents (20% of cases). […] During an anovulatory cycle, estrogen is produced, but the corpus luteum does not form. Thus, the normal cyclical secretion of progesterone does not occur, and estrogen stimulates the endometrium unopposed. Without opposition by progesterone, the endometrium continues to proliferate, eventually outgrowing its blood supply; it then sloughs incompletely and bleeds irregularly and sometimes profusely or for many days.
#39 Abnormal Uterine Bleeding – Gynecology and Obstetrics – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/abnormal-uterine-bleeding
Abnormal uterine bleeding (AUB) in patients of reproductive age is a bleeding pattern that is not consistent with normal menstrual cycle parameters (frequency, regularity, duration, and volume). […] Ovulatory dysfunction (anovulation or oligo-ovulation) is the most common cause of AUB in women of reproductive age and occurs most often in women 45 years old (50% of cases) and in adolescents (20% of cases). […] During an anovulatory cycle, estrogen is produced, but the corpus luteum does not form. Thus, the normal cyclical secretion of progesterone does not occur, and estrogen stimulates the endometrium unopposed. Without opposition by progesterone, the endometrium continues to proliferate, eventually outgrowing its blood supply; it then sloughs incompletely and bleeds irregularly and sometimes profusely or for many days.
#40 Heavy Menstrual Bleeding (Menorrhagia) > Fact Sheets > Yale Medicine
https://www.yalemedicine.org/conditions/heavy-menstrual-bleeding-menorrhagia
Ovulation issues: If you don’t ovulate regularly, parts of the uterine lining may become too thick. This can occur in women with polycystic ovary syndrome, which is a hormonal disorder causing enlarged ovaries with small cysts. It can also occur in women with hypothyroidism, which is when the thyroid gland doesn’t produce enough of the thyroid hormone. […] Cancer: Heavy menstrual bleeding can be an early sign of uterine cancer. […] Bleeding disorders: Conditions such as von Willebrand disease (a genetic disorder caused by low levels of clotting protein in the blood) and others can cause menorrhagia. […] Endometriosis: This condition, in which the uterine lining grows outside the uterus, can cause menorrhagia. […] Pregnancy problems: Ectopic pregnancy (when the fertilized egg implants outside the uterus) and miscarriage can cause heavy menstrual bleeding.
#41 I have heavy bleeding with clots. Is it serious?
https://www.icliniq.com/qa/heavy-bleeding/what-causes-heavy-menstrual-bleeding-with-clots
PCOS often leads to hormonal imbalances, causing irregular menstrual cycles and unpredictable heavy bleeding. […] The presence of tissue-like material during menstruation may indicate the shedding of the uterine lining, which can happen during heavy bleeding episodes. […] While small clots can be normal, passing large clots or tissue may be concerning. […] PCOS often causes the uterine lining to build up without regular shedding, leading to irregular bleeding. […] Since you have started medication, your previous uterine lining is now shedding, which is likely causing heavy bleeding.
#42 I have heavy bleeding with clots. Is it serious?
https://www.icliniq.com/qa/heavy-bleeding/what-causes-heavy-menstrual-bleeding-with-clots
PCOS often leads to hormonal imbalances, causing irregular menstrual cycles and unpredictable heavy bleeding. […] The presence of tissue-like material during menstruation may indicate the shedding of the uterine lining, which can happen during heavy bleeding episodes. […] While small clots can be normal, passing large clots or tissue may be concerning. […] PCOS often causes the uterine lining to build up without regular shedding, leading to irregular bleeding. […] Since you have started medication, your previous uterine lining is now shedding, which is likely causing heavy bleeding.
#43 Excessive Uterine Bleeding in a Non-Compliant Patient With Profound Hypothyroidism: A Case Report and Review of the Literatures | Ma | Journal of Medical Cases
https://www.journalmc.org/index.php/JMC/article/view/2502/1870
Studies suggest that dysthyroidism is associated with disturbances in female menstruation with hypothyroidism being associated with abnormal uterine bleeding. […] The mechanism of hypothyroidism to cause dysfunctional uterine bleeding (DUB) is multifactorial, including impairment of hemostasis and neuro-endocrine dysfunction. […] It was well documented that hypothyroidism is associated with polymenorrhea or menorrhagia; profound hypothyroidism has been reported to cause life-threatening menorrhagic anemia. […] The mechanism of hypothyroidism to cause excessive uterine bleeding is multifactorial. […] It is recognized that overt or even subclinical hypothyroidism can not only cause anemia, but also the platelet dysfunction, particularly the acquired von Willebrand syndrome. […] Emerging evidence supports close physiologic and pathologic interactions between hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-ovarian (HPO) axis.
#44 Excessive Uterine Bleeding in a Non-Compliant Patient With Profound Hypothyroidism: A Case Report and Review of the Literatures | Ma | Journal of Medical Cases
https://www.journalmc.org/index.php/JMC/article/view/2502/1870
Studies suggest that dysthyroidism is associated with disturbances in female menstruation with hypothyroidism being associated with abnormal uterine bleeding. […] The mechanism of hypothyroidism to cause dysfunctional uterine bleeding (DUB) is multifactorial, including impairment of hemostasis and neuro-endocrine dysfunction. […] It was well documented that hypothyroidism is associated with polymenorrhea or menorrhagia; profound hypothyroidism has been reported to cause life-threatening menorrhagic anemia. […] The mechanism of hypothyroidism to cause excessive uterine bleeding is multifactorial. […] It is recognized that overt or even subclinical hypothyroidism can not only cause anemia, but also the platelet dysfunction, particularly the acquired von Willebrand syndrome. […] Emerging evidence supports close physiologic and pathologic interactions between hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-ovarian (HPO) axis.
#45 Excessive Uterine Bleeding in a Non-Compliant Patient With Profound Hypothyroidism: A Case Report and Review of the Literatures | Ma | Journal of Medical Cases
https://www.journalmc.org/index.php/JMC/article/view/2502/1870
In severe hypothyroid patient, the TSH is markedly increased due to the weakened or absence of negative feedback from thyroxines (T4 and T3). […] The hypersecretion of TSH may result in hyperplasia of thyrotropes in the pituitary gland. […] The mass effect of pituitary hyperplasia can suppress the secretion of LH. […] Due to the same mechanism of lack of feedback suppression, the hypophyseal TRH is also expected to be elevated, which increases the secretion of both TSH and prolactine (PRL) levels; the hyperprolactinemia will in turn suppress the LH. […] TSH has a small FSH- and LH-like effect. […] Depending on the degree of disturbance of these upper level hormones, the estrogen level may remain elevated inappropriately and unopposed, which results in anovulatory DUB. […] All these abnormalities could contribute to DUB or menorrhagia.
#46 Menorrhagia(Archived) – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK536910/
Another important consideration and a significant cause of AUB are the patients medications. An intact coagulation pathway is essential for menstrual regulation and medications that interact with platelets and coagulation factors can lead to Acute AUB. The following is a list of some medications that can lead to AUB: Warfarin, aspirin, clopidogrel, and other anticoagulants; Conceptive medications and devices; Tamoxifen; Tricyclic antidepressants; Antipsychotics; Corticosteroids. […] The mechanism of action of estrogen therapy is the rapid regrowth of the endometrium over the exposed epithelial surface. […] Tranexamic acid received approval for the treatment of AUB in 2009. This drug is an antifibrinolytic that reversibly binds to plasminogen preventing fibrin degradation.
#47 Menorrhagia(Archived) – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK536910/
Another important consideration and a significant cause of AUB are the patients medications. An intact coagulation pathway is essential for menstrual regulation and medications that interact with platelets and coagulation factors can lead to Acute AUB. The following is a list of some medications that can lead to AUB: Warfarin, aspirin, clopidogrel, and other anticoagulants; Conceptive medications and devices; Tamoxifen; Tricyclic antidepressants; Antipsychotics; Corticosteroids. […] The mechanism of action of estrogen therapy is the rapid regrowth of the endometrium over the exposed epithelial surface. […] Tranexamic acid received approval for the treatment of AUB in 2009. This drug is an antifibrinolytic that reversibly binds to plasminogen preventing fibrin degradation.
#48 Menorrhagia: Why Is My Period So Heavy?
https://www.webmd.com/women/heavy-period-causes-treatments
Certain medications. Blood thinners like apixaban and warfarin; drugs that fight inflammation like NSAIDs; and some hormonal medications, like birth control pills, can cause heavy periods. […] If your menstrual flow is still painful or the heavy bleeding is interrupting your lifestyle after trying medication, your doctor may recommend one of several kinds of medical procedures. […] Other procedures such as endometrial ablation and endometrial resection permanently remove or destroy the lining of the uterus. Women have much lighter periods or no periods afterward. […] Menorrhagia isn’t typically a dangerous condition. Some conditions that cause heavy menstrual bleeding — like endometriosis, uterine fibroids, and PCOS — can make it harder to get pregnant.
#49 Heavy menstrual bleeding – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829
Adenomyosis. In this condition, glands from the lining of the uterus grow into the wall of the uterus itself. This can cause heavy bleeding and painful periods. […] Heavy menstrual bleeding can cause anemia related to blood loss. Anemia is a condition in which the body lacks enough red blood cells to carry oxygen to tissues. The number of red blood cells is measured by hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen to tissues throughout the body. […] Heavy menstrual bleeding may make iron levels too low. This may result in iron deficiency anemia.
#50 Heavy menstrual bleeding – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829
Adenomyosis. In this condition, glands from the lining of the uterus grow into the wall of the uterus itself. This can cause heavy bleeding and painful periods. […] Heavy menstrual bleeding can cause anemia related to blood loss. Anemia is a condition in which the body lacks enough red blood cells to carry oxygen to tissues. The number of red blood cells is measured by hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen to tissues throughout the body. […] Heavy menstrual bleeding may make iron levels too low. This may result in iron deficiency anemia.
#51 Treatment of Anemia Owing to Increased Menstrual Blood Loss: Activity of Physiological Modulators | Cornelli | Journal of Hematology
https://thejh.org/index.php/jh/article/view/215/161
Heavy menstrual bleeding can lead to iron-deficiency anemia. […] Heavy menstrual bleeding is a common problem among women of reproductive age, which has been reported in some national surveys as affecting between 13% and 19% of women. […] Excessive bleeding causes a decrease in iron stores in the body, and a negative iron balance is slowly induced, followed by insufficient iron supply to erythrocyte precursors. The final result is a decrease in Hb concentration. […] The treatment of anemia owing to menstrual bleeding is based on iron supplementation at variable dosages, ranging from 14 mg/day to 60 mg/week or 60 mg/day only during menstruation. […] The aim of this trial was to treat anemia in women with heavy menstrual bleeding using the physiological modulator concepts. […] The Hb synthesis seen in this trial seems to have no explanation.
#52 Natural Treatment of Heavy Periods — Walnut Creek Naturopathic
https://www.walnutcreeknaturopathic.com/blog/natural-treatment-of-heavy-periods
DUB can occur at any age, but is most common in adolescents and perimenopausal women. Approximately 20% of DUB cases are adolescents after their first menstrual cycle. […] A common finding with menorrhagia is the passing of blood clots. There are varying medical perspectives as to the cause of menstrual clots. One view is that the clots form if blood accumulates faster than the body’s ability to transfer it out of the uterus through the cervix. […] Although it is well known that heavy menstrual bleeding can lead to iron-deficiency anemia, it is not as well recognized that iron-deficiency anemia can actually cause or worsen menorrhagia. Iron deficiency may cause the muscles of the uterus to weaken, thereby reducing the ability of these muscles to clamp down on blood vessels, which is necessary to decrease or stop bleeding.
#53 Natural Treatment of Heavy Periods — Walnut Creek Naturopathic
https://www.walnutcreeknaturopathic.com/blog/natural-treatment-of-heavy-periods
Research has shown that a deficiency in vitamin A impairs hormone production and enzyme activity in the ovaries of animals. […] Studies have shown that a deficiency in B vitamins causes the liver to lose its ability to inactivate estrogen, which could theoretically result in an estrogen excess. […] Hypothyroidism is a common cause of menorrhagia. This is included under treatment for DUB because studies have shown reduction in menstrual blood loss in women treated for hypothyroid who had normal thyroid results but showed clinical evidence of the condition.
#54 Natural Treatment of Heavy Periods — Walnut Creek Naturopathic
https://www.walnutcreeknaturopathic.com/blog/natural-treatment-of-heavy-periods
Research has shown that a deficiency in vitamin A impairs hormone production and enzyme activity in the ovaries of animals. […] Studies have shown that a deficiency in B vitamins causes the liver to lose its ability to inactivate estrogen, which could theoretically result in an estrogen excess. […] Hypothyroidism is a common cause of menorrhagia. This is included under treatment for DUB because studies have shown reduction in menstrual blood loss in women treated for hypothyroid who had normal thyroid results but showed clinical evidence of the condition.
#55 Heavy menstrual bleeding – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829
Some women have menstrual bleeding that is heavy or lasts for more than a few days. This condition used to be called menorrhagia. Heavy menstrual bleeding is a common concern. But most women don’t have enough blood loss for it to be called heavy menstrual bleeding. […] With heavy menstrual bleeding, blood flow and cramping make it harder to do your usual activities. If you dread your period because you have heavy menstrual bleeding, talk with your doctor. There are many treatments that can help. […] In some cases, the reason for heavy menstrual bleeding is unknown. But a number of conditions may cause heavy menstrual bleeding. They include: […] Hormones being out of balance. In a typical menstrual cycle, there’s a balance between the hormones estrogen and progesterone. This controls the buildup of the lining of the uterus. The lining of the uterus also is known as the endometrium. This lining is shed during a menstrual period. When hormones are out of balance, the lining becomes too thick and sheds by way of heavy menstrual bleeding or unexpected bleeding between periods.
#56 Treatment of Menorrhagia | AAFP
https://www.aafp.org/pubs/afp/issues/2007/0615/p1813.html
Patient distress may be related more to disruptions in work, sexual activity, or quality of life than menstrual volume alone. […] A woman’s perception of blood loss and the disruption that it causes are the key determinants of subsequent treatment. […] Established risk factors for menorrhagia include increased age, premenopausal leiomyomata, and endometrial polyps. […] Abnormalities of platelet function, such as von Wille-brand’s disease, appear to be more prevalent in women with menorrhagia than in the general population. […] The American College of Obstetricians and Gynecologists (ACOG) recommends testing for von Willebrand’s disease in adolescents with severe menorrhagia, in adult women with menorrhagia, and in women undergoing hysterectomy for the sole indication of menorrhagia.
#57 Menorrhagia (Heavy Menstrual Bleeding): Causes & Treatment
https://my.clevelandclinic.org/health/diseases/17734-menorrhagia-heavy-menstrual-bleeding
A precancerous condition called endometrial hyperplasia can lead to menorrhagia. Other cancers that affect your reproductive system can also cause heavy menstrual bleeding. […] Certain medicines can cause heavy menstrual bleeding, too. […] Anyone can get menorrhagia, but it tends to be more common in people who are approaching menopause. […] Heavy menstrual bleeding can be serious if you lose so much blood that you show signs of anemia. […] Your healthcare provider will ask a series of questions about your medical history and menstrual cycle to diagnose menorrhagia. […] Treatment depends on what’s causing your bleeding, how severe your bleeding is, your health, age and medical history. […] If medication doesn’t improve your symptoms, your provider may recommend a surgical procedure. […] Heavy bleeding can lead to anemia, which can be serious. […] Yes, it’s possible that menorrhagia can go away without treatment. […] You can’t prevent all causes of heavy period bleeding. […] Left untreated, heavy periods can interfere with your life.
#58 Heavy menstrual bleeding diagnosis and medical management | Contraception and Reproductive Medicine | Full Text
https://contraceptionmedicine.biomedcentral.com/articles/10.1186/s40834-017-0047-4
Heavy menstrual bleeding (HMB) is a common gynecological problem that has a significant impact on a womans quality of life and the activities of daily living. […] As there is no single pathway that is associated with HMB, there are several therapeutic interventions involving different molecular pathways to reduce HMB. […] The mechanism(s) whereby myomas increase menstrual blood loss is unclear, but abnormal bleeding due to leiomyomas may be related to uterine vasculature abnormalities or impaired or dysregulated endometrial hemostasis. […] Several different pathways that result or cause hemostatic dysfunctions have been implicated in increased menstrual blood loss. […] No single pathway explains the cause of HMB. This has resulted in several therapeutic interventions specifically altering different pathways resulting in reduced blood loss with menstruation.
#59 Menorrhagia (Heavy Menstrual Bleeding): Causes & Treatment
https://my.clevelandclinic.org/health/diseases/17734-menorrhagia-heavy-menstrual-bleeding
Menorrhagia is heavy menstrual bleeding or losing more blood than is typical during menstruation. […] Menorrhagia can have many causes, ranging from hormone-related issues to medical conditions or medications. […] The hormones that your body produces, like estrogen and progesterone, help regulate your menstrual cycle, including how heavy your periods are. Having a condition that causes your hormones to become imbalanced can lead to heavy period bleeding. […] Benign growths in your uterus and conditions that cause cells in your uterus to grow improperly can cause heavy menstrual bleeding, too. […] Infections, including sexually transmitted infections (STIs) can cause heavy bleeding. […] Heavy bleeding can be a warning sign of pregnancy complications. […] Menorrhagia is a symptom associated with various conditions, including bleeding disorders and non-bleeding disorders.
#60 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
Heavy menstrual bleeding (HMB) is a common gynecological complaint with multiple etiologies and diverse pathophysiological origins. […] 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. […] Any process that interferes with the normal endocrine, paracrine or hemostatic functions of the endometrium as well as possibly any interference with myometrial contractility may cause HMB. […] The pathophysiology of HMB may be discussed in the context of both ovulatory and anovulatory cycles. […] The mechanisms by which EH induces HMB are not fully understood.
#61 Pathophysiology of Heavy Menstrual Bleeding
https://pmc.ncbi.nlm.nih.gov/articles/PMC5779569/
Heavy menstrual bleeding (HMB) is a common gynecological complaint with multiple etiologies and diverse pathophysiological origins. […] 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. […] Any process that interferes with the normal endocrine, paracrine or hemostatic functions of the endometrium as well as possibly any interference with myometrial contractility may cause HMB. […] The pathophysiology of HMB may be discussed in the context of both ovulatory and anovulatory cycles. […] The mechanisms by which EH induces HMB are not fully understood.
#62 Uterine bleeding: how understanding endometrial physiology underpins menstrual health | Nature Reviews Endocrinology
https://www.nature.com/articles/s41574-021-00629-4
Menstruation is a physiological process that is typically uncomplicated. However, up to one third of women globally will be affected by abnormal uterine bleeding (AUB) at some point in their reproductive years. Menstruation (that is, endometrial shedding) is a fine balance between proliferation, decidualization, inflammation, hypoxia, apoptosis, haemostasis, vasoconstriction and, finally, repair and regeneration. An imbalance in any one of these processes can lead to the abnormal endometrial phenotype of AUB. […] AUB is a debilitating symptom that affects up to one third of reproductive-aged women; comprehensive knowledge of menstrual cycle physiology is crucial for understanding and progressing endometrial physiology research. […] The terminology and definitions for diagnosing causes of AUB are now standardized in the International Federation of Gynecology and Obstetrics Systems 1 and 2, and should be followed for ease of clinical and research synchrony. […] Treatments for AUB are not specific and a third of patients resort to a hysterectomy for resolution of symptoms, highlighting a clinically unmet need for more targeted and personalized treatments.