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The Overview of Menstrual Physiology: A Narrative Literature Review
Abstract
Menstruation is a physiological or normal condition, namely events of the production of blood, mucus, and cell waste periodically originate from the uterine mucosa and occur relatively regularly from menarche until menopause, except during pregnancy and lactation. Menstruation is the result of very neat and standard cooperation from the hypothalamus-pituitary-ovarian endocrine axis. Hypothalamus spurs the pituitary gland by secreting gonadotropin-releasing hormone (GnRH), a deca-peptide secreted pulsatively by the hypothalamus. Menstruation is considered normal if it occurs between 22-35 days. Disturbance menstruation is most common at the beginning and end of the reproductive period, namely in those under 19 years of age and over 39 years of age. These disturbances may be related to the length of the menstrual cycle or the number and duration of menstruation. One person Women can experience both disorders. This literature review aimed to describe the menstrual cycle physiologically and the disorders that accompany it.
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Women’s health concerns are generally underrepresented in basic and translational research, but reproductive health in particular has been hampered by a lack of understanding of basic uterine and menstrual physiology. Menstrual health is an integral part of overall health as between menarche and menopause, most women menstruate. Yet for tens of millions of women around the world, menstruation regularly and often catastrophically disrupts their physical, mental, and social well-being. Enhancing our understanding of the underlying phenomena involved in menstruation, abnormal uterine bleeding (AUB), and other menstruation-related disorders will move us closer to the goal of personalised care. Further, a deeper mechanistic understanding of menstruation – a fast, scarless healing process in healthy individuals – will likely yield insights into myriad other diseases involving regulation of vascular function locally and systemically. We also recognize that many women now delay pregnancy and that there is an increasing desire for fertility and uterine preservation. In September 2018, the Gynecologic Health and Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (GHDB NICHD) convened a two-day meeting, “Menstruation: Science and Society” with an aim to “identify gaps and opportunities in menstruation science and to raise awareness of the need for more research in this field”. Experts in fields ranging from the evolutionary role of menstruation, to basic endometrial biology (including -omic analysis of the endometrium, stem cells and tissue engineering of the endometrium, endometrial microbiome, and AUB and fibroids), translational medicine (imaging and sampling modalities, patient-focused analysis of menstrual disorders including AUB, smart technologies/apps and mHealth platforms) to societal challenges in health literacy and dissemination frameworks across different economic and cultural landscapes shared current state-of-the art and future vision, incorporating the patient voice at the launch of the meeting. Here, we provide an enhanced meeting report with extensive up-to-date (as of submission) context, capturing the spectrum from how the basic processes of menstruation commence in response to progesterone withdrawal, through the role of tissue-resident and circulating stem and progenitor cells in monthly regeneration – and current gaps in knowledge in how dysregulation leads to AUB and other menstrual-related disorders such as adenomysosis, endometriosis, and fibroids – to the clinical challenges in diagnostics, treatment, patient and societal education. We conclude with an overview of how the global agenda concerning menstruation, and specifically menstrual health and hygiene, is gaining momentum, ranging from increasing investment in addressing menstruation-related barriers facing girls in schools in low/middle-income countries, to the more recent “menstrual equity” and “period poverty” movements spreading across high-income countries.
The use of apps that record detailed menstrual cycle data presents a new opportunity to study the menstrual cycle. The aim of this study is to describe menstrual cycle characteristics observed from a large database of cycles collected through an app and investigate associations of menstrual cycle characteristics with cycle length, age and body mass index (BMI). Menstrual cycle parameters, including menstruation, basal body temperature (BBT) and luteinising hormone (LH) tests as well as age and BMI were collected anonymously from real-world users of the Natural Cycles app. We analysed 612,613 ovulatory cycles with a mean length of 29.3 days from 124,648 users. The mean follicular phase length was 16.9 days (95% CI: 10–30) and mean luteal phase length was 12.4 days (95% CI: 7–17). Mean cycle length decreased by 0.18 days (95% CI: 0.17–0.18, R2 = 0.99) and mean follicular phase length decreased by 0.19 days (95% CI: 0.19–0.20, R2 = 0.99) per year of age from 25 to 45 years. Mean variation of cycle length per woman was 0.4 days or 14% higher in women with a BMI of over 35 relative to women with a BMI of 18.5–25. This analysis details variations in menstrual cycle characteristics that are not widely known yet have significant implications for health and well-being. Clinically, women who wish to plan a pregnancy need to have intercourse on their fertile days. In order to identify the fertile period it is important to track physiological parameters such as basal body temperature and not just cycle length.
Background:
Advances in research relating to menstruation and associated disorders (eg, endometriosis and premenstrual syndrome) have been hindered by the lack of an appropriate animal model. Menstruation, the cyclical shedding of the decidualized endometrium in the absence of pregnancy, is believed to be limited to 78 higher-order primates (human beings and Old World monkeys), 4 species of bat, and the elephant shrew. This represents only 1.5% of the known 5502 mammalian species and <0.09% of these are nonprimates. Thus, many aspects of menstruation remain poorly understood, limiting the development of effective treatments for women with menstrual disorders. Menstruation occurs as a consequence of progesterone priming of the endometrial stroma and a spontaneous decidual reaction. At the end of each infertile cycle as progesterone levels decline the uterus is unable to maintain this terminally differentiated stroma and the superficial endometrium is shed. True menstruation has never been reported in rodents.
Objective:
Here we describe the first observation of menstruation in a rodent, the spiny mouse (Acomys cahirinus).
Study design:
Virgin female spiny mice (n = 14) aged 12-16 weeks were sampled through daily vaginal lavage for 2 complete reproductive cycles. Stage-specific collection of reproductive tissue and plasma was used for histology, prolactin immunohistochemistry, and enzyme-linked immunosorbent assay of progesterone (n = 4-5/stage of the menstrual cycle). Normally distributed data are reported as the mean ± SE and significant differences calculated using a 1-way analysis of variance. Nonnormal data are displayed as the median values of replicates (with interquartile range) and significant differences calculated using Kruskal-Wallis test.
Results:
Mean menstrual cycle length was 8.7 ± 0.4 days with red blood cells observed in the lavages over 3.0 ± 0.2 days. Cyclic endometrial shedding and blood in the vaginal canal concluding with each infertile cycle was confirmed in all virgin females. The endometrium was thickest during the luteal phase at 322.6 μm (254.8, 512.2), when plasma progesterone peaked at 102.1 ng/mL (70.1, 198.6) and the optical density for prolactin immunoreactivity was strongest (0.071 ± 0.01 arbitrary units).
Conclusion:
The spiny mouse undergoes spontaneous decidualization, demonstrating for the first time menstruation in a rodent. The spiny mouse provides a readily accessible nonprimate model to study the mechanisms of menstrual shedding and repair, and may therefore be useful in furthering studies of human menstrual and pregnancy-associated disorders.
Background:
Both iron deficiency and iron deficiency anemia are common in the United States with a prevalence amongst women of 12 % and 4 % respectively. These numbers are even higher in African-American women (AAW) and are often a result of heavy menstrual bleeding (HMB). The primary objective of this study was to determine if perceived assessment of menstrual bleeding was associated with objective and subjective measures of anemia in AAW.
Methods:
Quantitative cross-sectional pilot study with surveys and venipuncture.
Results:
44 premenopausal AAW (mean age 37.9 years ± 9. 4) participated in the study. Iron deficiency was present in 68.2 % of the participants and 18.2 % were anemic. Almost half of the participants reported that their menses were heavy or very heavy, and there was a relationship between perceived heaviness of menstrual flow and anemia (P = 0.021). Of the individuals who reported that their menses were heavy or very heavy, 35.0 % were anemic. AAW who reported heavy or very heavy menses had significantly lower hemoglobin (P = 0.015), hematocrit (P = 0.003), and ferritin (P = 0.012) levels, as well as more general (P = 0.006) and menses-associated symptoms of anemia (P = 0.015) than those who reported normal or light menses.
Conclusions:
This pilot study of premenopausal AAW found that a significant percentage of women who report HMB are not only iron deficient, but also anemic. AAW should be educated on the consequences of HMB and counseled to seek care with a women's health provider when they perceive HMB. More importantly, providers should be aware that when AAW report HMB, evaluation for iron deficiency and anemia are essential.
Each month the endometrium becomes inflamed, and the luminal portion is shed during menstruation. The subsequent repair is remarkable, allowing implantation to occur if fertilization takes place. Aberrations in menstrual physiology can lead to common gynaecological conditions, such as heavy or prolonged bleeding. Increased knowledge of the processes involved in menstrual physiology may also have translational benefits at other tissue sites.
Pubmed and Cochrane databases were searched for all original and review articles published in English until April 2015. Search terms included 'endometrium', 'menstruation', 'endometrial repair', 'endometrial regeneration' 'angiogenesis', 'inflammation' and 'heavy menstrual bleeding' or 'menorrhagia'.
Menstruation occurs naturally in very few species. Human menstruation is thought to occur as a consequence of preimplantation decidualization, conferring embryo selectivity and the ability to adapt to optimize function. We highlight how current and future study of endometrial inflammation, vascular changes and repair/regeneration will allow us to identify new therapeutic targets for common gynaecological disorders. In addition, we describe how increased knowledge of this endometrial physiology will have many translational applications at other tissue sites. We highlight the clinical applications of what we know, the key questions that remain and the scientific and medical possibilities for the future.
The study of menstruation, in both normal and abnormal scenarios, is essential for the production of novel, acceptable medical treatments for common gynaecological complaints. Furthermore, collaboration and communication with specialists in other fields could significantly advance the therapeutic potential of this dynamic tissue.
© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005-2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.
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.
Patient-reported outcome measures (PROMs) have the potential to be extremely valuable in clinical care delivery for women who report heavy menstrual bleeding (HMB). Increasingly, studies on HMB have incorporated PROMs to evaluate the impact of bleeding on quality of life. These measures have included semi-quantitative charts and pictograms, questionnaires to assess symptoms and impact on quality of life, and health-related quality of life questionnaires. Recent systematic reviews have highlighted inconsistency of outcome measurement across studies on HMB as a challenge limiting the interpretability of the body of literature and the ability to generate consensus on the relative effectiveness of treatment options. Consequently, research initiatives and international collaborations are working to harmonize outcome measurement. Harmonizing the use of questionnaires in research and clinical care has the potential to improve patient-centered care delivery for women with HMB and improve the generation of patient-focused evidence-based guidelines for evaluation and treatment of HMB.
To qualitatively assess the burden of uterine fibroids on women's emotional health.
Sixty women (n=60) with symptomatic uterine fibroids were recruited from an urban academic medical center and community-based organizations. Women completed qualitative, semi-structured interviews and demographic surveys. Interviews were recorded and transcribed verbatim. Using a grounded theory approach, three coders independently identified major themes and subthemes that emerged from the interviews.
The kappa among coders was 0.94. The mean age of participants was 43.0±6.8. 61.7% of participants self-identified as African-American, 25.0% as Caucasian, 8.3% as Hispanic and 5.0% as Asian. Most participants exhibited a significant emotional response to their fibroids, including fear, anxiety, anger, and depression. Half of the women felt helpless and believed that they had no control over their fibroids. Many women possessed a negative self-image and cited concern over appearing less attractive, which led to difficulties becoming intimate. Several women felt that they lacked substantial support to help them deal with these issues.
In addition to the known high prevalence and severe physical impact of uterine fibroids, there is a significant psychological impact on women. Many women lack support to help them deal with these issues and very few seek help from a mental health professional. There is an opportunity and a need for the mental health community to address the concerns in this population, in order to improve psychological health and quality of life in patients living with this chronic condition.
Copyright © 2014. Published by Elsevier Inc.
Objective
Previous studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population.DesignProspective community-based cohort study.SettingUSA: southeastern Michigan, northern California and Los Angeles, California.PopulationA total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women.Methods
Women completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan–Meier survival analysis and multivariable regression were used to analyse the data.Main outcome measuresMenses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days.ResultsAt least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7–93.2), of 6+ days of spotting by 66.8% (95% CI 55.2–78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2–39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding.Conclusions
These data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.
Objective
To assess self-reported prevalence, knowledge, and health literacy regarding heavy menstrual bleeding (HMB) among African American women.
Methods
A quantitative cross-sectional survey study was conducted. An original survey was developed and distributed to a convenience sample of African American women aged 18–60 years at a community fair in a large city in the Midwestern region of the USA.
Results
Of the 274 surveys distributed, 247 were returned, 193 of which met the inclusion criteria. Overall, 163 (84.5%) participants demonstrated adequate health literacy; however, 168 (87.0%) answered fewer than 8 of 15 knowledge questions correctly. Although 75 (38.9%) women reported seeing a clinician for HMB, 89 (46.1%) believed that there was nothing that they could do to prevent it from occurring.
Conclusion
The present study found that the proportion of HMB among participants was higher than the nationwide prevalence. However, a gap existed in knowledge of HMB among the women surveyed. The study findings indicate an opportunity for community-based education to raise awareness of HMB, its associated clinical presentations, and available treatment modalities.
Background:
Traditionally, research on abnormal uterine bleeding (AUB) focused on measured menstrual blood loss. However, the main burden of this symptom from the patient perspective is its impact on quality of life. Better describing the demographic characteristics, quality of life, and utilization of medical care of women with AUB could assist with health resource planning for this population.
Methods:
We analyzed data from the Medical Expenditures Panel Survey from 2002 to 2010. AUB was identified by International Classification of Diseases, ninth edition (ICD-9) code group 626, disorders of menstruation and other abnormal bleeding from the female genital tract. Health-related quality of life was assessed by the Short-form 12 Health Survey (SF-12, QualityMetric) physical and mental component summary scores (PCS and MCS). Poorer health-related quality of life was defined as PCS or MCS <50. Odds ratios (OR) and 95% confidence intervals (CI) for the association of AUB with poorer SF-12 scores and having a usual source of care were estimated by multivariable logistic regression models.
Results:
Data analyzed represented an annual average of 56.2 million nonpregnant women between ages 18 and 50 years. We estimate that 1.4 million women per year (95% CI: 1.3-1.5 million) reported AUB. Women with AUB were more likely to be younger, Caucasian, and obese than women without AUB. Compared to women without AUB, women with AUB had greater odds of a poorer PCS score (OR=1.30, 95% CI: 1.10-1.55), a poorer MCS score (OR=1.28, 95% CI: 1.10-1.51), and a usual source of care (OR=1.85, 95% CI: 1.44-2.38).
Conclusions:
AUB is associated with diminished physical and mental health status and having a usual source of medical care.
The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia.
A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.).
A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001).
Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.
There has been increasing recent recognition of the worldwide confusion in the terminology and definitions for abnormalities of menstrual and uterine bleeding. The present review was undertaken to objectively explore some of the origins and current uses of terms for symptoms, signs, and causes of abnormal uterine bleeding and to demonstrate the international lack of uniformity.
A detailed, but not systematic, search of the huge current and historical literature across the range of menstrual terminology, definitions, and some causes, with an emphasis on "menorrhagia" and "dysfunctional uterine bleeding."
An international collaboration to study ways of reaching worldwide agreement on descriptive terms and definitions for abnormal bleeding.
A large number of synonyms and overlapping terms for heavy menstrual bleeding have been identified, as well as smaller numbers of terms for other symptoms and causes of abnormal uterine bleeding. The origins and meanings of several of these terms have been explored in detail and wide variations in meaning demonstrated.
There is great confusion in the way these terminologies are used and there is an urgent need for international agreement on consistent use of terms and definitions for symptoms, signs, and causes of abnormal uterine bleeding.