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PubMed2001

Vascular repair after menstruation involves regulation of vascular endothelial growth factor-receptor phosphorylation by sFLT-1.

Regeneration of the endometrium after menstruation requires a rapid and highly organized vascular response. Potential regulators of this process include members of the vascular endothelial growth factor (VEGF) family of proteins and their receptors. Although VEGF expression has been detected in the endometrium, the relationship between VEGF production, receptor activation, and endothelial cell proliferation during the endometrial cycle is poorly understood. To better ascertain the relevance of VEGF family members during postmenstrual repair, we have evaluated ligands, receptors, and activity by receptor phosphorylation in human endometrium throughout the menstrual cycle. We found that VEGF is significantly increased at the onset of menstruation, a result of the additive effects of hypoxia, transforming growth factor-alpha, and interleukin-1beta. Both VEGF receptors, FLT-1 and KDR, followed a similar pattern. However, functional activity of KDR, as determined by phosphorylation studies, revealed activation in the late menstrual and early proliferative phases. The degree of KDR phosphorylation was inversely correlated with the presence of sFLT-1. Endothelial cell proliferation analysis in endometrium showed a peak during the late menstrual and early proliferative phases in concert with the presence of VEGF, VEGF receptor phosphorylation, and decrease of sFLT-1. Together, these results suggest that VEGF receptor activation and the subsequent modulation of sFLT-1 in the late menstrual phase likely contributes to the onset of angiogenesis and endothelial repair in the human endometrium.

Adult↗

PubMed1992

Directionality of menstrual flow: cervical os diameter as a determinant of retrograde menstruation.

OBJECTIVE: To develop a mathematical model to examine the factors that control the directionality of menstrual flow. DESIGN: The model consisted of a rigid cavity, filled with a viscous liquid, with three outflow ports: a set of paired outflow ports (fallopian tube ostia) and an additional single outflow port (cervical os). The Darcy-Weisbach equation was used to calculate flow rates through the ports. RESULTS: At cervical os diameters of less than 0.5 mm, more than 50% of flow was through the fallopian tubes over a wide range of values for cervical length and fallopian tube ostia diameter and length. The diameter of the fallopian tube ostia was also an important determinant of the directionality of flow. The lengths of the cervical os and fallopian tube ostia were of secondary importance in determining directionality of menstrual flow. CONCLUSION: If retrograde menstruation is a risk factor for the development of endometriosis, menstruating women with cervical os diameters less than 2.0 mm may be at increased risk for developing endometriosis.

Biomechanical Phenomena↗

PubMed1998

Paracrine regulation of menstruation.

Endometrial proliferation, secretion, vascular neoformation and modification to shedding is under direct and/or indirect control of steroid hormones. The progressive modification of the endometrial architecture is due to its growth and differentiation. The new tissue regenerates monthly from a 2-5 mm to a 12-18 mm of complex tissue until it sheds under a co-ordinated network of bioactive molecules produced and activated during the menstrual cycle. The steroid hormones, the HLA-DR and integrin molecules, the intense production of several proteins, the vascular damage, and the disconnection of cell-cell and cell-matrix interaction are participating in both the endometrial preparation for embryonic implantation and the shedding and bleeding of the tissue itself. Menstruation is a process associated with damage to the epithelium, endothelium and extracellular matrix, ending on controlled bleeding, tissue dissolution and repair. Endometrial proteinases and tissue factor (TF) contribute to systemic factors to control the mechanisms of regulation of tissue dissolution, tissue shedding, and vascular bleeding during menstruation.

Animals↗

PubMed1996

Why do women menstruate? Historical and evolutionary review.

Theories regarding the significance of menstruation from the time of Aristotle to the present are reviewed, followed by a brief description of the evolutionary changes in the uterus. A specific duct for the transport of ova first appears in jawed fishes. Its important role in the evolution of internal fertilisation and the protection and nourishment of the embryo is followed through the vertebrate orders, amphibia, reptiles and mammals. The problems associated with the presence of a gamete or zygote of different genetic make up inside the maternal tract is stressed, and the mechanisms to overcome or modify the maternal inflammation reaction discussed. In egg laying reptiles and birds, the secretion of coverings around the embryo presumably shields the foreignness of the tissue, while in viviparous animals, the secretion of progesterone plays a major role in controlling the inflammatory reaction. In some mammals, for example the mouse, the invasiveness of the trophoblast is such that the blastocyst penetrates inside the wall of the endometrium. The stroma responds under the influence of progesterone, to undergo an implantation/decidual reaction which bears considerable resemblance to an inflammatory/granulation tissue reaction. A similar reaction occurs in women during the luteal phase in anticipation of a very invasive blastocyst. When there is no fertilisation the progesterone drops and the differentiated stromal tissue is shed with bleeding; menstruation.

Animals↗

PubMed2001

Socio-cultural aspects of menstruation in an urban slum in Delhi, India.

This paper attempts to understand the experience of menstruation in the socio-cultural context of an urban Indian slum. Observations were gathered as part of a larger study of reproductive tract infections in women in Delhi, using both qualitative and quantitative methods. The qualitative phase consisted of 52 in-depth interviews, three focus groups discussions and five key informant interviews. In the quantitative phase inferences were drawn from 380 respondents. Mean age at menarche was 13.5. Onset of menarche is associated with physical maturity and the ability to marry and reproduce. However, a culture of silence surrounds menarche, an event which took the women interviewed almost by surprise. Most were previously unaware that it would happen and the information they were given was sparse. Menstruation is associated with taboos and restrictions on work, sex, food and bathing, but the taboos observed by most of the women were avoidance of sex and not participating in religious practices; the taboo on not going into the kitchen, which had been observed in rural joint households, was not being observed after migration from rural areas due to lack of social support mechanisms. There is a clear need to provide information to young women on these subjects in ways that are acceptable to their parents, schools and the larger community, and that allow them to raise their own concerns. Education on these subjects should be envisaged as a long-term, continuous process, beginning well before menarche and continuing long after it.

Adolescent↗

PubMed1999

Disturbances of menstruation in hypothyroidism.

OBJECTIVES: Most thyroid textbooks describe hypothyroidism resulting in changes in the length of the menstrual cycle and in the amount of bleeding. Our experience at a busy thyroid clinic had given a picture which differs from that presented in the literature. The aim of this study was to determine the frequency and type of menstrual irregularities in premenopausal hypothyroid patients. DESIGN AND PATIENTS: We investigated the menstrual history, starting 6 months before the discovery of the disease, in 171 female premenopausal hypothyroid patients and 214 normal controls, with similar age and body mass index (BMI). MEASUREMENTS: TSH, TT4, TT3 and thyroid antibodies were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m2. RESULTS: Of the 171 hypothyroid patients, 131 (76.6%) had regular cycles and 40 (23.4%) irregular periods. Oligomenorrhoea and menorrhagia were the most common features in the latter group. No difference in BMI was found between the patients with or without menstrual abnormalities, or between patients and controls. TSH, TT4 and TT3 levels did not differ between patients with normal and abnormal menstruation. Forty-six (26.9%) out of 171 patients had subclinical hypothyroidism (group A), 42 (24.6%) mild hypothyroidism (group B) and 83 (48.5%) severe hypothyroidism (group C). Thirty-seven from group A (80.4%), 32 from group B (76.2%) and 62 from group C (74.7%) had normal periods. These differences were not statistically significant. Eighty-eight (88.9%) out of 99 patients in whom thyroid antibodies were measured had positive titres. Nineteen (21.6%) of the patients with positive thyroid antibodies had menstrual irregularities. This percentage did not differ from that found in the whole group of patients (23.4%). Out of 214 normal controls, 196 (91.6%) had normal menstruation and 19 (8.4%) irregular cycles. The latter group included mainly women with oligomenorrhoea. CONCLUSIONS: These data demonstrate that hypothyroidism in women is less frequently associated with menstrual disturbance than was previously described. Also, menstrual irregularities tend to be more frequent in sever hypothyroidism in comparison with mild cases, although this finding was not statistically significant. Oligomenorrhoea and menorrhagia are the most common menstrual disturbances.

Adult↗

PubMed2001

The endocrinology of menstruation--a role for the immune system.

The human endometrium displays characteristic features, both structural and functional, across the menstrual cycle. It is the sex steroid hormones, oestrogen and progesterone, that drive the endometrium through the different phases of the cycle. Oestrogen and progesterone act sequentially to regulate cellular concentrations of their respective receptors, this interaction initiates gene transcription. Thereafter a cascade of local events prepares the endometrium for implantation, but in the absence of pregnancy, progesterone withdrawal leads to menstruation and cyclic repair. Withdrawal of progesterone from an oestrogen-progesterone primed endometrium is the initiating event for the cascade of molecular and cellular interactions that result in menstruation. Progesterone withdrawal first affects cells with progesterone receptors. Early events in the menstrual process are vasoconstriction and cytokine up-regulation. The activation of lytic mechanisms is a later event and involves cells that may lack progesterone receptors, for example, uterine leucocytes and epithelial cells. Hence progesterone withdrawal results in a local increase of inflammatory mediators and the enzymes responsible for tissue breakdown. The total complex of local factors implicated in normal menstrual and aberrant menstrual bleeding are yet to be fully defined.

Adult↗

PubMed2002

Coping with menstruation: understanding the needs of women with Parkinson's disease.

AIMS: To understand how women with Parkinson's disease (PD) experience and cope with menstruation and associated gynaecological problems, and adjustments to womanhood. This paper focuses on menstruation. RATIONALE: Unique hormonal fluctuations are known to affect women with idiopathic PD, however, our understanding of the impact of these changes on daily lives and opportunities for nursing support are limited. METHODS: Descriptive multiple case study design was adopted, and data collection involved a variety of approaches. Including semi-structured interviews, conversational interviews, group interview, reflective diaries and creative writing. A flexible approach was encouraged whereby consenting women chose how and when they wanted to participate. FINDINGS: A total of 19 women participated, 17 were experiencing naturally occurring periods. The majority had been diagnosed around the age of 39 years, and at the time of study participants ages ranged from 34 to 56 years. Three of the women reported no change in the experience of their periods following diagnosis, 15 reported worsening problems which in two extreme situations led to hysterectomy. During the monthly cycle PD symptoms were often exaggerated, medication effectiveness reduced and 'off times' increased. The period itself involved high levels of pain, fatigue and sometimes humiliating experiences when self-care was impossible. CONCLUSIONS: This study offers a unique contribution to our understanding of the needs of young women with PD, and suggests that health professionals need to look beyond the mask of a disease associated with old age. The nursing profession has a responsibility to develop models of best practice to enable women of any age to be themselves and to adapt to the rhythm of their hormones as they live and grow older with PD.

Activities of Daily Living↗

PubMed2003

The impact of intensive serial plasmapheresis and iron supplementation on iron metabolism and Hb concentration in menstruating women: a prospective randomized placebo-controlled double-blind study.

BACKGROUND: Iron (Fe) depletion is common among regular whole-blood donors, but can be prevented through regular oral Fe supplementation. Little is known, however, about the Fe metabolism of donors undergoing intensive plasmapheresis. These donors lose considerable amounts of blood drawn for laboratory analyses and remaining in the disposable plastic sets. STUDY DESIGN AND METHODS: Menstruating women were enrolled in a prospective placebo- controlled double-blind study. One hundred women were randomly allocated to receive either 100 mg of elemental Fe per day or placebo over 24 weeks and asked to donate plasma at 1-week intervals. Hb was determined before each plasmapheresis. Ferritin, transferrin, and Fe concentration and reticulocyte count were measured every 4 weeks. RESULTS: Thirty donors in the placebo group and 29 receiving Fe completed the study. The total mean blood loss was 526 mL in the placebo group and 546 mL in the Fe arm (p=0.271). The number of donations with Hb values lower than 12.5 g per dL requiring prolongation of the time interval until the next plasmapheresis was significantly greater in the placebo arm. In the placebo group (n=30), ferritin levels began to decline significantly 4 weeks after entry. When the study was completed, Hb concentration and reticulocyte count also were found to be significantly lower in the placebo group than in the Fe study arm (p=0.028 and p=0.036, respectively). Hb, ferritin, and transferrin levels and reticulocyte counts did not change significantly in the Fe group during the observation period. CONCLUSION: Menstruating women undergoing regular plasmapheresis at short intervals are prone to develop Fe depletion. This can be prevented by regular Fe intake. Laboratory analyses in product plasma instead of serum gained from whole-blood samples could be an alternative to reduce blood loss.

Adult↗

PubMed1990

Human menstruation and eicosanoids.

Menstruation is an event restricted to humans and subhuman primates and in which uterine bleeding and contractions occur. Prostaglandins and leukotrienes are thought to play a major role in the normal process of menstruation as well as in the disorders menorrhagia and dysmenorrhoea.

Dysmenorrhea↗

PubMed2000

Young western women's experiences of menarche and menstruation.

A qualitative approach was used to examine young women's experiences of menarche and menstruation that were included in personal stories of growing up sexually. The personal experiences were examined by cross-case analysis to learn more about the narrators' attitudes toward menarche and their menstrual-related education. This was a secondary analysis using data collected for a study of common themes in the stories gathered in a 1998 study by Beausang. The data came from 332 stories written by students taking a sexuality course in a Midwestern community college. Of 227 stories written by women, 85 stories included menstrual experiences. Eleven narrators described menarche as a positive experience. In 10 of these stories, the mother was the primary teacher. The two most frequently identified sources of information by narrators were mothers and schoolteachers, with most narrators having a primarily negative view of their menstrual education regardless of the source. Problems with menstrual-related education were described as perceptions of unwillingness by teachers to discuss menstruation, time limits for education, unclear instruction leading to misconceptions, and the presence of peers in group learning situations that lead to embarrassment.

Adolescent↗

PubMed2004

Improving pre- and postmenarcheal 12-year-old girls' attitudes toward menstruation.

Adolescence is a time of rapid changes, including risk for unwanted pregnancies and sexually transmitted infections. Education may improve understanding and attitudes toward menstruation among adolescents thus increasing their awareness of risks and enabling them to protect themselves accordingly. To investigate effects of education on attitudes, two interventions were compared in 345 12-year-old girls. The new, active intervention given to premenarcheal girls just before menarche resulted in improvements in attitudes toward menstruation compared with standard intervention. Thus, just before menarche girls should be offered education modeled after the active intervention. The education must be concrete and based on multisensory learning.

Adolescent↗

PubMed2005

Cyclic menstruation-like bleeding during denied pregnancy. Is there a particular hormonal cause?

OBJECTIVE: To investigate whether particular hormonal patterns could explain the persistence of cyclic menstruation-like bleeding during denied pregnancies. METHODS: Hormone measurements were performed immediately after delivery in a total of 28 subjects with denied pregnancies. The results were studied in three patient subgroups: subjects with any cyclic bleeding during pregnancy (n = 22), subjects with cyclic bleeding during pregnancy until the delivery date (n = 7) and subjects with amenorrhea (n = 6). These data were compared with those of a control group (n = 126). In some of the women who reported cyclic bleeding, hormone assessments were also done once the lactation period ended. RESULTS: For estradiol, free estriol and progesterone, no more than two values in each group were outside the 95% confidence interval of the control group. Several results for prolactin were remarkably lower. The findings for human chorionic gonadotropin, free testosterone, dehydroepiandrosterone sulfate, alpha-fetoprotein and thyroid-stimulating hormone were almost all within the 95% confidence interval. In seven subjects, abnormal results were obtained for the gondaotropin-releasing hormone/thyrotropin-releasing hormone test and the metoclopramid test after delivery and lactation. All of these subjects showed signs of corpus luteum insufficiency. In five subjects, evidence of hyperprolactinemia was found. CONCLUSION: Results revealed that hormonal patterns assessed immediately after delivery do not provide any causal explanation for the cyclic menstruation-like bleeding that occurs during denied pregnancies. Hormone assessments performed after the lactation period, i.e. during a normal menstrual cycle, showed a number of abnormalities. However, a causal relationship could not be drawn.

Adolescent↗

PubMed1990

Obesity and iron status in menstruating women.

The relationship between iron stores and obesity in menstruating women was studied in 20 obese and 20 nonobese women matched for age and contraception. Although no difference was observed in serum iron or total-iron-binding capacity, the obese group showed significantly higher hemoglobin (137 +/- 9 vs 10 g/L, mean +/- SD; P less than 0.01), hematocrit (0.41 +/- 0.02 vs 0.39 +/- 0.03, P less than 0.05), and serum ferritin concentrations (48.0 +/- 44.3 vs 25.8 +/- 19.5 micrograms/L, P less than 0.05). There was no difference between obese and nonobese women in either the menstrual-cycle interval or the duration of the menstrual flow. Iron intake was significantly higher in the obese group (15.9 +/- 2.9 vs 14.1 +/- 2.9 mg/d, P less than 0.05). These results suggest that obese menstruating women are at low risk of depleting iron stores, possibly because of high iron intake. Iron-fortification programs might thus be undesirable in such subjects.

Adult↗

PubMed1984

Beliefs of Orthodox Jewish girls about menstruation.

A questionnaire about attitudes and beliefs concerning menstruation was answered by 281 pupils at a boarding school for Orthodox Jewish girls in Israel. Nearly 90% of the girls expected to experience pain with their periods. Half the girls thought they could not go swimming during their periods. In connection with religious beliefs, several girls thought they could not prepare food or wine during their period, 27% thought they could not handle holy books or go to a cemetery, 9% thought that they could not go to the synagogue. Attitudes of the Orthodox Jewish religion to menstruation are discussed, along with the importance of recognizing cultural differences in the school and the surgery.

Adolescent↗

PubMed1996

Matrix metalloproteinases in normal menstruation.

Matrix metalloproteinases (MMP) are strongly implicated in menstruation. Messenger RNA for proMMP-1 and -3 was detectable in normal cycle endometrium only peri-menstrually and menstrually, although mRNA for their tissue inhibitors, TIMP-1 and TIMP-2, was present throughout the cycle. MMP-1, -3 and -9 were demonstrated immunohistochemically to be specifically associated with degraded tissue in menstrual endometrium. Activated mast cells and eosinophils, which release regulators of MMP expression and activators of latent enzymes, were also a marked feature of menstrual endometrium. Cultured endometrial stromal cells released MMP-1, -2, -3 and -9 and TIMP-1 and -2, whereas production by epithelial cells was minimal. Progesterone withdrawal from stromal cell cultures (for the final 4 days of a 10 day culture) increased the release of all four enzymes: all but MMP-2 were also stimulated by interleukin-1 or tumour necrosis factor alpha added to short-term stromal cultures. We postulate that an alteration in the balance of MMP and their inhibitors and the activation of MMP are prerequisites for tissue degradation at menstruation, and that this is regulated by a combination of progesterone withdrawal and paracrine factors from epithelial and stromal cells and from mast cells and eosinophils.

Endometrium↗

PubMed1996

Regulation and restricted expression of interstitial collagenase suggest a pivotal role in the initiation of menstruation.

Collagenases are the only mammalian enzymes able to cleave, at neutral pH, the triple helical domain of fibrillar collagens, major constituents of the extracellular matrix of the endometrium. Interstitial collagenase is expressed, secreted and activated in human endometrium only just before and during menstruation. The expression of interstitial collagenase is restricted to the areas of the functional layer of the endometrium which are breaking down and to fragments which have been shed. In endometrial explants, combined sex steroids tightly control the expression, secretion and activation of interstitial collagenase, as well as the preservation of the extracellular matrix. These observations imply a pivotal role for this proteinase in the initiation of menstruation.

Biopsy↗

PubMed2002

Expression of hypoxia-inducible factors in human endometrium and suppression of matrix metalloproteinases under hypoxic conditions do not support a major role for hypoxia in regulating tissue breakdown at menstruation.

BACKGROUND: Classical studies in monkeys suggested that menstruation results from vasoconstriction, hypoxia and necrosis. The heterodimeric hypoxia-inducible factor (HIF) complex is critical in oxygen homeostasis via increased stability of HIF-1alpha/2alpha monomers, and these act as markers of hypoxia. We hypothesized that focal hypoxia in perimenstrual endometrium results in locally increased matrix metalloproteinases (MMP), leading to tissue destruction. METHODS: HIF-1alpha, HIF-2alpha and HIF-1beta were immunolocalized in cycling endometrium. Endometrial stromal cells were cultured under hypoxic and normoxic conditions and MMP measured by zymography and Western blots. RESULTS: HIF-1alpha and HIF-2alpha were detected in only some endometrial samples, and not confined to the perimenstrual tissue. Where present, they were primarily cytoplasmic, not nuclear. HIF-1beta was localized in epithelium, leukocytes and some decidual cells. Cultured endometrial stromal cells responded to hypoxia with increased cellular HIF-1alpha and secreted vascular endothelial growth factor. ProMMP-1 and proMMP-3 production was reduced in response to hypoxia regardless of the steroidal milieu (no added steroids, estrogen or estrogen plus progesterone). Active MMP-2 and membrane type 1 MMP but not proMMP-2 or proMMP-9 production were also inhibited by hypoxia. CONCLUSIONS: These results do not support a role for hypoxia in the focally increased production and activation of MMP observed prior to and during menstruation.

Aryl Hydrocarbon Receptor Nuclear Translocator↗