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Physiological Reviews Jul 2020The physiological functions of the uterine endometrium (uterine lining) are preparation for implantation, maintenance of pregnancy if implantation occurs, and... (Review)
Review
The physiological functions of the uterine endometrium (uterine lining) are preparation for implantation, maintenance of pregnancy if implantation occurs, and menstruation in the absence of pregnancy. The endometrium thus plays a pivotal role in reproduction and continuation of our species. Menstruation is a steroid-regulated event, and there are alternatives for a progesterone-primed endometrium, i.e., pregnancy or menstruation. Progesterone withdrawal is the trigger for menstruation. The menstruating endometrium is a physiological example of an injured or "wounded" surface that is required to rapidly repair each month. The physiological events of menstruation and endometrial repair provide an accessible in vivo human model of inflammation and tissue repair. Progress in our understanding of endometrial pathophysiology has been facilitated by modern cellular and molecular discovery tools, along with animal models of simulated menses. Abnormal uterine bleeding (AUB), including heavy menstrual bleeding (HMB), imposes a massive burden on society, affecting one in four women of reproductive age. Understanding structural and nonstructural causes underpinning AUB is essential to optimize and provide precision in patient management. This is facilitated by careful classification of causes of bleeding. We highlight the crucial need for understanding mechanisms underpinning menstruation and its aberrations. The endometrium is a prime target tissue for selective progesterone receptor modulators (SPRMs). This class of compounds has therapeutic potential for the clinical unmet need of HMB. SPRMs reduce menstrual bleeding by mechanisms still largely unknown. Human menstruation remains a taboo topic, and many questions concerning endometrial physiology that pertain to menstrual bleeding are yet to be answered.
Topics: Animals; Endometrium; Female; Glucocorticoids; Humans; Menstruation; Pregnancy; Steroids
PubMed: 32031903
DOI: 10.1152/physrev.00031.2019 -
Best Practice & Research. Clinical... Jul 2018Historically, the evolutionary origins of menstruation have been based on two theories: the ability to eliminate infectious agents carried to the uterus with spermatozoa... (Review)
Review
Historically, the evolutionary origins of menstruation have been based on two theories: the ability to eliminate infectious agents carried to the uterus with spermatozoa and the comparative conservation of energy with menstruation compared to its absence. In the menstruating species, more recent theories have identified spontaneous decidualization as the key adaptive mechanism. Spontaneous decidualization is seen as a mechanism to provide the mother with protection from the invasive characteristics of the embryo. Physiologically, menstruation involves complex interactions of inflammation and vascular mechanisms to stabilize the endometrium and allow a regulated loss of endometrial tissues and blood. A variety of human illnesses can be better understood as vulnerabilities associated with these evolutionary developments, including recurrent pregnancy loss, placenta accreta, ectopic pregnancy, endometriosis, adenomyosis, dysmenorrhea, and chronic pelvic pain. While the evolutionary aspects of these diseases indicate why such illnesses can occur, in some instances, they also provide a basis for treatment, prevention and future research direction.
Topics: Animals; Biological Evolution; Decidua; Female; Humans; Menstruation
PubMed: 29530426
DOI: 10.1016/j.bpobgyn.2018.01.007 -
JAMA Network Open May 2024
Topics: Humans; Menstruation; Female; Vital Signs; Adult
PubMed: 38809558
DOI: 10.1001/jamanetworkopen.2024.12778 -
Contraception Dec 2000For many women in the United States, menstruation is a major health concern because menstrual disorders and other conditions that may be aggravated during menses (e.g.,... (Review)
Review
For many women in the United States, menstruation is a major health concern because menstrual disorders and other conditions that may be aggravated during menses (e.g., migraine headaches, epilepsy) carry substantial morbidity. Women today menstruate nearly 3 times as often as in primitive societies, and evidence suggests that frequent, repetitive menstrual cycles may increase health risks. Because the conventional 21/7 combination oral contraceptive (OC) regimen provides only limited relief for women with menstrual disorders, alternative OC regimens that reduce menstrual frequency have been proposed. A new OC formulation specifically designed to decrease menstrual bleeding to 4 times per year is currently under investigation. Most women welcome less frequent menses or even amenorrhea. Women who may derive particular benefit from reduced menstrual frequency include not only those with medical conditions directly caused or aggravated by menses, but also those serving in the military, female athletes, mentally-retarded women with menstrual hygiene problems, young teens, and perimenopausal women.
Topics: Adolescent; Adult; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans; Menstruation; Menstruation Disturbances; Middle Aged
PubMed: 11239613
DOI: 10.1016/s0010-7824(00)00182-7 -
The Quarterly Review of Biology Sep 1993Sperm are vectors of disease. During mammalian insemination bacteria from the male and female genitalia regularly cling to sperm tails and are transported to the uterus.... (Review)
Review
Sperm are vectors of disease. During mammalian insemination bacteria from the male and female genitalia regularly cling to sperm tails and are transported to the uterus. I propose that menstruation functions to protect the uterus and oviducts from colonization by pathogens. Menstrual blood exerts mechanical pressure on uterine tissue, forcing it to shed, and delivers large numbers of immune cells throughout the uterine cavity, directly combating pathogens. The mechanisms of menstruation show evidence of adaptive design. Spiral arteries that open to the lining of the uterus trigger menstruation by abruptly constricting, which deprives the local tissue of blood, and then abruptly dilating, which causes blood to force loose the necrotic tissue. Menstrual blood flows easily, unlike blood at most wound sites, because it lacks the normal level of clotting factors. Overt (externally visible) or covert (not externally visible) menstruation has been documented in many species of primate, including Old World monkeys and apes, New World monkeys, and prosimians, as well as in various species of bat and insectivore. The antipathogen hypothesis predicts that: (1) menstruation (overt or covert) is either universal or nearly so among mammalian species; (2) if the latter, then the existence of menstruation among species varies inversely with the probability of becoming pregnant per estrous cycle (menstruation would be especially adaptive in species with significantly less than 100% probability of becoming pregnant per estrous cycle); (3) among menstruating species, the average degree of menstrual bleeding for a given species is a function of the factors affecting menstruation's costs and benefits--in particular, the degree of bleeding is positively correlated with the average body size and sexually transmitted pathogen load of that species (profuse bleeding would be especially adaptive in large-bodied species with either promiscuous breeding systems or continuous sexual receptivity); and (4) other forms of normal uterine bleeding--proestrous, periovulatory, implantation, and postpartum--also have an antipathogen function. The hypothesis presented in this article has implications for the diagnosis, treatment and prevention of uterine infection and, therefore, for the prevention of pathogen-induced infertility. The uterus appears to be designed to increase its bleeding if it detects infection: Human uteri that become infected (or otherwise inflamed) bleed more profusely, bleed on more days per cycle, and often bleed intermittently throughout the cycle. Thus artificially curtailing infection-induced uterine bleeding may be contraindicated.
Topics: Animals; Bacterial Infections; Female; Humans; Male; Menstruation; Models, Biological; Primates; Species Specificity; Spermatozoa; Uterine Diseases
PubMed: 8210311
DOI: 10.1086/418170 -
The Quarterly Review of Biology Jun 1998Although adaptive explanations for menstruation go back at least twenty-five hundred years, in the last decade two new hypotheses have been advanced. The first suggests... (Review)
Review
Although adaptive explanations for menstruation go back at least twenty-five hundred years, in the last decade two new hypotheses have been advanced. The first suggests that menstruation evolved to cleanse the uterus of pathogens introduced by sperm, and the second argues that the function of endometrial regression (with the associated menstruation in humans) is to save energy by getting rid of tissue, rather than maintaining it in the absence of an available blastocyst. Both these suggestions may be questioned on the grounds that they do not take into account the physiology of the reproductive processes involved. Menstruation is not an independent physiological process and is unlikely to have been selected for independently of the evolutionary events that led to it. Furthermore, most primitive menstruating animals would have menstruated infrequently, and many may have reproduced or died without ever menstruating. In order to provide a context for understanding how menstruation may have come about, the evolution of the female vertebrate reproductive tract is briefly reviewed. In later stages, the coevolution of the embryo and uterus resulted in an intimate association between the trophoblast and the uterine blood vessels. As the embryo became more invasive, the uterus responded with increased cellular growth and differentiation of the endometrium to accommodate it. This reached its peak in mammals (such as rodents and humans), where the embryo passes through the epithelium into the endometrial stroma, which responds with differentiation of cells and blood vessels. Progesterone, secreted after ovulation, plays a crucial role in preparation for pregnancy. In addition to its well-known effects on the uterus, progesterone may be important in suppressing the inflammatory reaction that would be expected in response to the presence of a foreign body, such as an embryo. It is also suggested that vascular and cellular differentiation of the endometrial stroma has evolved by adaptation of the inflammatory (granulation tissue) reaction. When progesterone levels fall at the end of the cycle, there is tissue breakdown and bleeding. The uterus then reforms for the next ovulatory cycle. It is shown that the female reproductive tract has multiple functions that must occur in sequence. The coevolution of the embryo and maternal tract thus led to the close contact of two genetically different tissues, and problems such as the inflammatory reaction had to be overcome. Menstruation is a necessary consequence of these evolutionary changes, and needed no adaptive value in order to evolve.
Topics: Adaptation, Physiological; Animals; Biological Evolution; Endometrium; Female; Genitalia, Female; Humans; Inflammation; Luteolysis; Male; Maternal-Fetal Exchange; Menstruation; Models, Biological; Pregnancy; Reproduction; Uterus
PubMed: 9618925
DOI: 10.1086/420183 -
Journal of Reproductive Immunology Sep 1999Menstruation occurs at the end of a normal reproductive cycle in the human female, following the fall in progesterone resulting from the demise of the corpus luteum.... (Review)
Review
Menstruation occurs at the end of a normal reproductive cycle in the human female, following the fall in progesterone resulting from the demise of the corpus luteum. Current data support a central role for the matrix metalloproteinases in menstruation but their focal pattern of expression within peri-menstrual and menstrual endometrium suggests local rather than hormonal regulation. This review emphasizes the similarities between menstruation and an inflammatory process and examines the relationship between cells of hemopoietic lineage, particularly mast cells, eosinophils, neutrophils and macrophages, and the local production and activation of matrix metalloproteinases within the endometrium. It proposes a complex of critical regulatory circuits, initially activated by the withdrawal of progesterone, which provide interactions between the migratory cells that produce a myriad of important regulatory molecules and endometrial stromal and epithelial cells which produce both chemokines and matrix metalloproteinases. These mechanisms could account for the focal nature of the tissue degradation at menstruation.
Topics: Animals; Extracellular Matrix; Female; Humans; Inflammation; Leukocytes; Menstruation; Metalloendopeptidases
PubMed: 10530758
DOI: 10.1016/s0165-0378(99)00002-9 -
Zentralblatt Fur Gynakologie Oct 2005The impact of menstruation on women's health manifests itself on different levels. The sociocultural dimension shows the influence of societal and cultural norm, which... (Review)
Review
The impact of menstruation on women's health manifests itself on different levels. The sociocultural dimension shows the influence of societal and cultural norm, which regulate the way of dealing with menstruating women. These rules are at first glance in most cultures characterized by rather expulsion, rejection and submission of women. At a closer look many traditions however reflect the fascination and the power which is associated with the "blood of women", which means that throughout history menstruation is conceived in an ambivalent manner. This ambivalence is still present in the subjective experience of modern women, who experience the biological process of menstruation but finally attribute emotional and cognitive meaning to it. This means that women finally decide when menstruation becomes a "disease" for them. Many empirical studies show that although a majority of women declare menstruation as something negative and disturbing, only a much smaller percentage would want to get rid of it, because menstruation seems to be associated with feelings of connectedness with nature and with other women. The biomedical view on menstruation is historically new and quite different: uterine bleeding can either be a sign of disease (uterus, ovaries) or it can lead to anemia, pain, anxiety, frustration in women consulting. Menstrual disorders are in fact one of the most frequent reasons for consultation. Modern medicine has developed a large range of interventions which modify or abolish menstruation. From a medical standpoint menstruation is not necessary and may be obsolete. The transition from "healthy menstruation" to "menstruation related diminution of quality of life", to "Menstrual Disease" is continuous and has to be elaborated in the physician patient interaction, the patient being expert for her values, aims and health objectives and the physician being the expert for knowledge and information. The patient has to use this to come to a personal and individual solution of her menstruation problem.
Topics: Female; Germany; Humans; Menstruation; Women's Health
PubMed: 16195970
DOI: 10.1055/s-2005-836862 -
Headache Feb 2017A review of treatment options for menstrual migraine. (Review)
Review
OBJECTIVE
A review of treatment options for menstrual migraine.
BACKGROUND
Migraine affects ∼30 million people in the US. A subset of female migraineurs have migraines that are mainly associated with menstruation. Menstrual migraine (MM) is divided into pure MM and menstrually related migraine. Pure MM attacks occur only with menstruation and have a prevalence of 1%. Menstrually related migraine has a prevalence of 6-7%, and occurs both during menstruation as well as during the rest of the cycle. MM is usually without aura and is more severe, longer lasting, and more resistant to treatment due to the effects of ovarian hormones, specifically estrogen. MM treatment is divided into acute, short-term prophylaxis, and daily prevention. The best-studied acute treatments are triptans. For short-term prophylaxis, triptans, non-triptans, or combinations are used. Some preventive medications may be used daily to prevent MM. Many anti-epileptic medications used in migraine prevention can affect the efficacy of oral contraceptives and hormonal treatments, so caution is indicated when these are used.
METHODS
PubMed, Scopus, Cochrane, and Embase were searched for MM and treatments.
RESULTS
Many randomized, placebo-controlled, prospective studies have evaluated the efficacy of sumatriptan, rizatriptan, naratriptan, zolmitriptan, and almotriptan in MM. Reviewing numerous studies with statistically significant results, rizatriptan has the best overall evidence for acute treatment of MM, ranging from pain-free responses of 33-73% at 2 hours. Sumatriptan and rizatriptan have shown similar efficacies of 61-63% in terms of 2 hour pain freedom. Rizatriptan showed sustained pain relief between 2 and 24 hours with an efficacy of 63% and sustained pain freedom for MM between 2 and 24 hours with an efficacy of 32%. For short-term prevention of MM, there were four randomized controlled trials for frovatriptan taken twice daily, one trial for zolmitriptan taken three times daily, and two studies for naratriptan taken twice daily, all of which showed statistically significant results. Among studies on non-triptans for short-term prevention of MM, magnesium, estrogen, naproxen sodium, and dihydroergotamine all had statistically significant results. Many antiepileptic medications taken for prevention of MM can cause enzyme induction affecting oral contraceptives (OCs) and hormonal treatments to different degrees. Topiramate has the least effect on OCs at doses below 200 mg/day. Lamotrigine noticeably decreases oral contraceptive levels; however, the evidence for it as a preventive medication is not strong.
CONCLUSION
MM can be very difficult to treat. For acute treatments, rizatriptan has the best overall evidence. For short-term prevention, frovatriptan, zolmitriptan, or naratriptan, as well as magnesium, estrogen, naproxen sodium, or dihydroergotamine may be useful.
Topics: Female; Humans; Menstruation; Migraine Disorders; Randomized Controlled Trials as Topic
PubMed: 27910087
DOI: 10.1111/head.12978 -
The Lancet. Child & Adolescent Health Jun 2018
Topics: Adolescent; Female; Humans; Menstruation; Poverty; Power, Psychological
PubMed: 30169273
DOI: 10.1016/S2352-4642(18)30143-3