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Implicit messages concerning menstruation in commercial educational materials prepared for young adolescent girls.

Interviews with young girls aged 9 to 18 revealed that commercial educational materials are an important source of information about menstruation. Although these materials are valuable educational supplements, they do not provide a complete, accurate, and realistic description of menarcheal changes and emphasize good hygiene rather than dealing with the young girl's emotional needs and anxieties. The authors stress the need for more research into the physiological, cognitive, and psychological changes during puberty and the obligation of parents, schools, and other social institutions to provide more comprehensive information to the maturing girl about the essential issues of pubertal development.

Adolescent↗

Front-loaded infusion therapy of rT-PA during active menstruation. A case report.

The authors report use of intravenous (IV) tissue plasminogen activator (TPA) to treat acute anterior wall myocardial infarction in a forty-two-year-old woman during the active menstrual period. The patient received the TPA with the front-loading system with excellent result. Hemoglobin remained unchanged. This case demonstrates that TPA infusion can be used in a menstruating woman without causing a dangerous hemorrhage.

Adult↗

A critical period of progesterone withdrawal precedes menstruation in macaques.

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12-24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked.

Animals↗

Matrix metalloproteinase and matrix metalloproteinase inhibitor expression in endometrial stromal cells during progestin-initiated decidualization and menstruation-related progestin withdrawal.

Estradiol (E) primes human endometrial stromal cells (HESCs) for the decidualizing effects of progesterone in vivo and in vitro. Matrix metalloproteinase (MMP) expression was evaluated in confluent HESCs incubated in control medium, and in medium supplemented with either E, or the synthetic progestin medroxyprogesterone acetate (P), or E + P. Measurements with a specific ELISA indicated that basal pro-MMP-1 output was unaffected by E, whereas E + P, which induces the expression of several decidualization-related markers, produced a time-dependent inhibition in HESC-secreted levels of pro-MMP-1. Consistent with progestin inhibition of MMP-1 protein expression in the HESCs, P but not E, reduced steady state levels of MMP-1 messenger RNA (mRNA) as determined by Northern analysis. By contrast, mRNA levels for MMP-2 and the MMP inhibitor TIMP-1 were not altered by either P or E. Steroid withdrawal studies indicated that after MMP-1 expression was suppressed by incubation of the HESCs with E + P, 4 days of exposure to the antiprogestin RU 486 (mifepristone) significantly up-regulated MMP-1 levels in the conditioned medium by severalfold compared with cultures maintained in E + P. The change to steroid-free control medium required a more prolonged period of withdrawal to attain up regulatory effects that were comparable with those evoked by RU 486. The ELISA measurements were validated by immunoblot analysis with a specific MMP-1 antibody, which showed corresponding changes in a band at the expected mobility of about 50 kDa. Moreover, Northern analysis revealed parallel changes in MMP-1 mRNA levels, whereas neither MMP-2 nor TIMP-1 mRNA levels were modulated by adding or withdrawing steroids. The contrast between regulated MMP-1 expression and constitutive MMP-2 expression observed in the cultured HESCs is consistent with the demonstrated presence on the MMP-1 promoter of regulatory elements such as AP-1 and PEA-3 that are absent from the MMP-2 promoter. Extrapolation of these in vitro changes in HESCs to in vivo endometrial events suggests that: 1) inhibition of MMP-1 expression by E and progesterone would stabilize the perivascular endometrial ECM to prevent local hemorrhage during endovascular invasion by the implanting trophoblast; 2) enhanced expression of MMP-1 evoked by steroid withdrawal would mediate endometrial ECM degradation leading to sloughing of the functional layer during menstruation.

Blotting, Northern↗

Identification of chemokines important for leukocyte recruitment to the human endometrium at the times of embryo implantation and menstruation.

Human endometrium possesses a unique immunological environment enabling implantation of the semiallogeneic embryo. Large populations of macrophages and uterine-specific natural killer cells infiltrate the implantation site, believed to be important modulators of trophoblast invasion and decidualization. In the absence of pregnancy, there is a dramatic influx of neutrophils, eosinophils, and macrophages, likely to be critical for focal inflammatory endometrial destruction. However, little is known regarding selective recruitment of leukocyte subtypes. We employed a gene array approach to analyze the expression of 21 chemokines in endometrium. Real-time RT-PCR and immunohistochemistry was conducted to verify expression patterns and determine cellular source. Nine chemokines were highly abundant in human endometrium: monocyte chemotactic protein-3, eotaxin, fractalkine, macrophage inflammatory protein-1beta, 6Ckine, IL-8, hemofiltrate CC chemokine-1 and -4, and macrophage-derived chemokine. Chemokine mRNA was generally up-regulated during endometrial receptivity and early pregnancy, particularly of macrophage and natural killer chemoattractants. Chemokine protein was predominantly localized to epithelial glands, whereas differentiated stromal cells were a major source of chemokines after decidualization. This is the first study to use an unbiased approach to screen for endometrial chemokines, and we report the selective regulation of chemokines, corresponding to the recruitment of distinct leukocyte subpopulations required for pregnancy and menstruation.

Cell Movement↗

Differences in insulin receptors between men and menstruating women and influence of sex hormones on insulin binding during the menstrual cycle.

Specific binding of [125I]insulin to circulating monocytes and erythrocytes from nine normal menstruating women and nine normal men was determined during a 28-day period (one sample every 7 days). In women, insulin binding was higher to both monocytes (P less than 0.001) and erythrocytes (P less than 0.02) in the follicular phase than in the luteal phase. In men, insulin binding to monocytes was similar to the follicular phase values for women; however, insulin binding to erythrocytes from men showed higher values than insulin binding to erythrocytes from women in both the follicular (P less than 0.001) and luteal (P less than 0.001) phases. These differences were due primarily to changes in receptor concentration rather than receptor affinity. An inverse relationship was found between insulin binding to monocytes and levels of 17 beta-estradiol, progesterone, and 17 alpha-hydroxyprogesterone; this relationship was not observed in insulin binding to erythrocytes. The present data, therefore, suggest that sex hormones may play a role in the control of insulin receptors. Furthermore, it appears that other factors exist during the follicular phase that lower insulin binding to erythrocyte insulin receptors. If insulin receptors on circulating cells reflect the behavior of the main insulin target tissues, the present data might in part explain the reduction in glucose tolerance reported by various authors in the second half of the menstrual cycle.

Adult↗

Progesterone withdrawal up-regulates vascular endothelial growth factor receptor type 2 in the superficial zone stroma of the human and macaque endometrium: potential relevance to menstruation.

Several reports indicate that vascular endothelial growth factor (VEGF) expression is increased in endometrial glands and stroma during the menstrual phase in the human endometrium. Here we report that VEGF receptor type 2 (KDR), normally expressed only in the vascular endothelium, was dramatically up-regulated in the stromal cells of the superficial endometrial zones during the premenstrual phase in both human and macaque endometrium. This increase was detectable by Northern analysis, in situ hybridization, and immunocytochemistry and was cell specific, zone specific, cycle phase specific, and VEGF receptor type specific. That is, it only occurred during the premenstrual/menstrual phase, did not occur in glandular epithelium, endothelium, or stromal cells of the deepest endometrial zones, and was not observed for VEGF receptor type 1. The upregulation of stromal KDR was induced by progesterone (P) withdrawal in both women and macaques, and adding back P 24 h after P withdrawal in macaques blocked stromal, but not vascular, endothelial KDR expression. Promatrix metalloproteinase-1 (MMP-1) was coordinately up-regulated in the same stromal cell population by P withdrawal. Because of reports that VEGF can enhance MMP expression, we hypothesize that VEGF-KDR interactions may influence MMP expression in the superficial zones of the primate endometrium during the premenstrual phase, and that these interactions play a role in the induction of menstruation.

Adult↗

A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity?

A 13-year-old girl showed periodic episodes of somnolence without megaphagia recurring in association with each menstruation. During somnolent episodes total sleep time averaged 14 hours and 19 minutes per 24 hours. The level of performance evaluated by means of the Wilkinson Addition Test was significantly impaired. There was an abnormal increase of 5-hydroxyindolacetic acid in the cerebrospinal fluid after probenecid test, suggesting an increase of the turnover of 5-hydroxytryptamine during periodic hypersomnia. Investigation of the menstrual cycle failed to document any striking hormonal abnormality. Nevertheless, the close relationship between the episodes of hypersomnia and the end of the menstrual cycle led us to hypothesize a role of progesterone and to try a hormonal type of treatment that is thus far successful.

Adolescent↗

A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine.

Headaches associated with menstruation are often resistant to abortive and preventative medications. We performed an open-label study in 20 female migraineurs, employing oral sumatriptan perimenstrually as short-term prophylaxis of menstrual migraine. In 126 sumatriptan-treated cycles, headache was absent in 52.4% and reduced in severity by 50% or greater in 42%. Breakthrough headaches were rare and significantly reduced in severity compared with baseline headaches.

Adult↗

Withdrawal of ovarian steroids stimulates prostaglandin F2alpha production through nuclear factor-kappaB activation via oxygen radicals in human endometrial stromal cells: potential relevance to menstruation.

The present study was undertaken to investigate whether withdrawal of estrogen and progesterone (EP-withdrawal) stimulates prostaglandin F2alpha (PGF2alpha) production through oxygen radical (ROS)-induced NF-kappaB activation in human endometrial stromal cells (ESC). To study the EP-withdrawal, ESC that had been treated with estradiol (E, 10(-8) M) and medroxyprogesterone acetate (MPA, 10(-6) M) for 12 days were then incubated with or without E+MPA for a further 11 days. PGF2alpha concentrations in the medium and cyclooxygenase-2 (COX-2) mRNA levels were significantly increased after EP-withdrawal, while they were unchanged by the continuous treatment with E+MPA. When ESC were incubated with N-acetyl-L-cysteine (Nac, 50 mM), an antioxidant, during EP-withdrawal, Nac blocked the increases in PGF2alpha production and COX-2 mRNA expression caused by EP-withdrawal. Next, we examined whether ROS generated in response to EP-withdrawal acted through NF-kappaB activation. Electrophoretic mobility shift assay revealed that EP-withdrawal caused marked increases in NF-kappaB DNA binding activity, which was completely suppressed by Nac. Furthermore, when ESC were incubated with MG132 (3 microM), which inhibits NF-kappaB activation, during EP-withdrawal, MG132 blocked the increases in PGF2alpha production and COX-2 mRNA expression caused by EP-withdrawal. In conclusion, EP-withdrawal stimulates COX-2 expression and PGF2alpha production through ROS-induced NF-kappaB activation, suggesting a possible mechanism for menstruation.

Acetylcysteine↗

Lifting the curse of menstruation: toward a feminist perspective on the menstrual cycle.

Lifting the curse of menstruation is examined as a process of freeing the imagination rather than rejecting the importance of biology. The defining features of the feminist and biomedical perspectives are discussed and an overview is offered of unexamined assumptions about women, the cycle, and the conduct of research which operate within modern scientific medicine. The real alternative to these unexamined assumptions is seen as the development of a revolutionary system of classification in which even the smallest unit of analysis is a multidimensional process. Suggestions are offered about the proper role of the feminist perspective in helping to free our imaginations and move us toward such an alternative paradigm.

Adolescent↗

Poor metabolic control during menstruation and sexual abuse issues in an adolescent with diabetes.

A case study is presented that describes the deterioration of a patient's diabetes control during her menstrual cycle in terms of her psychological functioning and family context. Therapeutic interventions pertinent toward improving diabetes control, resolving issues of abuse, and increasing family communication are addressed. The outcome of this case study supports the contention that psychological factors can impact diabetes control significantly during menstruation in young women.

Adolescent↗

A case of menstruation-associated asthma: treatment with oral contraceptives.

A menstrual rhythm has been documented for exacerbations of asthma, which may have important clinical relevance to the patient with severe asthma. We report the case of a 26-year-old patient with menstruation-associated asthma who showed a dramatic response to oral contraceptives. It was noted that falls in peak respiratory flow rate coincided with ovulation. We concluded that oral contraceptive therapy is useful in this particular group of asthmatic patients.

Adult↗

Effect of HCG on human corpus luteum of menstruation and early gestation.

In order to evaluate the luteotropic effect of human chorionic gonadotropin (HCG) on the human corpus luteum, HCG was administered at the menstrual luteal phase and early gestation. Serum progesterone (P) and estradiol (E2) levels were compared after determination by radioimmunoassay. At the mid-luteal phase, although E2 secretion did not increase significantly, P secretion showed a significant increase and peaked 6-8 hr after intravenous injection of 20,000 IU HCG. Three intramuscular injections of 5,000 IU HCG were administered every other day. An increase in sex steroid production and prolongation of luteal span occurred when HCG was administered in the +7 to +11 day period (following LH peak), rather than the +3 to +7 day period. During early pregnancy (from 5 to 10 weeks' gestation) in threatened abortion cases followed by either normal continuation of pregnancy or abortion, neither a single high dosage of HCG (20,000 to 100,000 IU) nor 20,000 IU per day for 7 days produced any significant change in sex steroid secretion. From these observations, it is likely that exogenous HCG shows a luteotropic effect on the human corpus luteum during menstruation, but not during gestation.

Adult↗

Urinary unconjugated cortisol in normally menstruating women and during estrogen-gestagen treatment.

Changes in 24-hour excretion of unconjugated urinary cortisol and creatinine clearance were determined in 9 normally menstruating women and in 9 women undergoing estrogen-gestagen treatment on 3 consecutive days. A correlation between the cortisol excretion and the creatinine clearance was found only in the luteal phase of the menstrual cycle. The cortisol excretion increased neither during the menstrual cycle nor during the estrogen-gestagen treatment. A marked intra-individual variation in the excretion of unconjugated urinary cortisol was demonstrated in both groups.

Adult↗

Spinal cord vascular malformations with symptoms during menstruation. Report of two cases.

Two patients had the initial complaint of fluctuating paraparesis, which was most evident at menstruation. One patient had a semimonthly fluctuating deficit. Spinal cord compression and ischemia, secondary to the vascular mass, were considered the most likely mechanisms. Blood levels of estrogen and progesterone during the menstrual cycle may have had a contributory effect. Fluctuating spinal cord deficits associated with a consistent portion of the menstrual cycle should alert the physician to the possibility of an arteriovenous malformation of the spinal cord.

Adult↗

A sacral dural arteriovenous fistula presenting with an intermittent myelopathy aggravated by menstruation. Case report.

The case is reported of a woman with a spinal dural arteriovenous fistula whose intermittent myelopathy became aggravated with menstruation. Her symptoms recurred in spite of successful acrylic embolization of the lateral sacral arteriovenous fistula. Repeat angiography showed venous drainage from the uterus toward the medullary vein. Total abdominal hysterectomy cured her symptoms. The pathophysiological basis for this peculiar clinical manifestation and its management are discussed.

Arteries↗

Increase of leptin levels following exogenous administration of estrogen in women with normal menstruation.

To investigate the acute effect of exogenous estrogen on the changes of leptin production, the time sequence of changes in plasma leptin concentration were determined following i.v. administration of premarin, a conjugated estrogen, during the follicular phase (days 5-9) in women (n = 12) with normal menstruation. The mean circulating estradiol level abruptly (P < 0.0001) increased from 4 h to a level of 72-fold from baseline and was still significantly (P < 0.05) elevated at 72 h after injection of conjugated estrogen. The mean leptin level showed a significant (P < 0.05) gradual increase from 24 h (10.8 +/- 1.0 ng/mL) continuing on up to a peak at 32 h (11.6 +/- 0.9 ng/mL); significantly (P < 0.05) sustained to 48 h (10.7 +/- 0.7 ng/mL) and then slowly decreased at 56 h after injection of premarin, as compared with the preinjection level (7.8 +/- 0.7 ng/mL). However, there were no changes of leptin levels in women (n = 10) who received normal saline injection. These data clearly suggest that a higher level of estrogen could stimulate the increase of plasma leptin concentration during the follicular phase of normal cyclic women. This result provides evidence that supraphysiological level of estrogen may act on the adipocyte to modulate leptin production through the endocrine mechanism.

Adult↗