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Cyclical abnormalities in the bactericidal function, superoxide production, and lysozyme activity of neutrophils obtained from a healthy woman during menstruation: reversal by pretreatment with aspirin.

Neutrophils obtained from most of 13 healthy young women during menstruation and those obtained from the same women on nonmenstrual days killed comparable numbers of Staphylococcus aureus strain 502A, produced comparable amounts of superoxide anion, and had comparable lysozyme levels. In contrast, neutrophils obtained from a few women during menstruation exhibited decreased function. In particular, neutrophils from one healthy woman developed transient menstrual period-related abnormalities in bactericidal function, superoxide anion production, and lysozyme activity and release; these abnormalities occurred during each of three menstrual periods tested but not during three menstrual periods following the ingestion of aspirin for 14 days. The results suggest that menstrual period-related dysfunction of neutrophils may occur in some healthy women, sometimes rendering them more susceptible to menstrual period-related infections.

Adult↗

In-vitro studies of the potential role of neutrophils in the process of menstruation.

Significant numbers of neutrophils are found extravascularly within the endometrium only during the immediate premenstrual and menstrual phases of the cycle. In this study we investigated the effect of neutrophil products on the synthesis and activation of matrix metalloproteinases (MMP), enzymes considered to play a crucial role in the degradation of endometrial tissue that occurs at menstruation. Latent MMP-2, MMP-3 and MMP-9 released by endometrial stromal fibroblasts and peripheral blood neutrophils were activated when the two cell types were cultured together. Tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were also degraded in this system. Neutralization studies identified a role for the serine protease, elastase, in the observed activation of MMP. Although cultured endometrial neutrophils behaved similarly to peripheral blood neutrophils in their ability to release latent MMP-9 and elastase, no active forms of MMP-2. MMP-3 and MMP-9 were detected in supernatant from co-cultures containing endometrial neutrophils and stromal fibroblasts. This appeared to be due to an alteration in the neutrophil production of elastase and inhibitors. e.g. alpha1-antitrypsin, in these cultures so that active elastase was not available. Our results demonstrate that any involvement of neutrophils in the tissue destruction occurring at menstruation may be tightly regulated by the focal concentration of degradative enzymes and their respective inhibitors.

Adult↗

Progesterone control of interleukin-8 production in endometrium and chorio-decidual cells underlines the role of the neutrophil in menstruation and parturition.

Interleukin-8 (IL-8) attracts neutrophils into tissues and causes them to degranulate. Both menstruation and parturition involve neutrophil migration into uterine tissues and therefore IL-8 is a likely mediator of the tissue re-arrangements that accompany these events. We have examined the ability of endometrium explants and chorion cells in culture to synthesize and release IL-8 and the ability of progesterone, a synthetic progestin [medroxyprogesterone acetate (MPA)] and dexamethasone to inhibit this production. In endometrium, the stage of the menstrual cycle did not affect IL-8 production but a 10(-6) M concentration of progesterone or dexamethasone significantly reduced the concentration of IL-8 in medium after 24 h. After a further 24 h with lipopolysaccharide (LPS) stimulation, only MPA and dexamethasone inhibited production significantly. In chorion cells, IL-8 production was significantly decreased by both MPA and dexamethasone in the LPS stimulated cells but the reduction in the first 24 h was not significant. The IL-8 produced in uterine tissues might act synergistically with prostaglandin E (PGE), a likely site for this interaction being blood vessels where PGE production is also repressed by progesterone. Such a cooperative action would maintain low leukocyte entry into uterine tissues in the presence of progesterone and falling steroid levels would induce leukocyte immigration and activation with consequent tissue destruction. Such steroid-dependent interactions are important in our understanding of the mechanisms of menstruation and parturition and could allow new approaches to the treatment of uterine pathology.

Cells, Cultured↗

A comparison of modality-specific somatosensory changes during menstruation in dysmenorrheic and nondysmenorrheic women.

OBJECTIVE: The objective was to evaluate somatosensory thresholds to a multimodality stimulation regimen applied both within and outside areas of referred menstrual pain in dysmenorrheic women, over four phases of confirmed ovulatory cycles, and to compare them with thresholds in nondysmenorrheic women during menstruation. DESIGN: Twenty dysmenorrheic women with menstrual pain scoring 5.45 +/- 0.39 cm (mean +/- standard error of mean) on a visual analog scale (10 cm) participated. Fifteen nondysmenorrheic women with a menstrual pain score of 0.4 +/- 0.2 cm participated as controls. Ovulation was confirmed by an enzyme-multiplied immunoassay technique. Menstrual pain was described with the McGill Pain Questionnaire. Areas within menstrual pain referral were two abdominal sites and the midline of the low back, and the arm and thigh were the control areas. The pressure pain threshold (PPT) and pinch pain threshold were determined by a hand-held electronic pressure algometer, the heat pain threshold (HPT) by a contact thermode, and the tactile threshold with von Frey hairs. RESULTS: In dysmenorrheic women the McGill Pain Questionnaire showed a larger sensory and affective component of pain than the evaluative and miscellaneous groups. The HPT and PPT were lower in the menstrual phase than in the ovulatory, luteal, and premenstrual phases, both within and outside areas of referred menstrual pain (p <0.01), with a more pronounced decrease at the referral pain areas. The pinch pain threshold was lower in the menstrual phase than in the ovulatory phase (p <0.02), and the tactile threshold did not differ significantly across the menstrual phases or within any site. Dysmenorrheic women had a lower HPT at the control sites and a lower PPT at the abdomen, back, and control sites, than in those of nondysmenorrheic women in the menstrual phase. CONCLUSIONS: The results show reduced somatosensory pain thresholds during menstruation to heat and pressure stimulation, both within and outside areas of referred menstrual pain in dysmenorrheic women. Dysmenorrheic women showed a lower HPT at the control sites and a lower PPT at all the sites than those for nondysmenorrheic women in the menstrual phase. The altered somatosensory thresholds may be dependent on a spinal mechanism of central hyperexcitability, induced by recurrent moderate to severe menstrual pain.

Adult↗

Physiologic uterine uptake of FDG during menstruation demonstrated with serial combined positron emission tomography and computed tomography.

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used extensively to stage, restage, and follow neoplastic disease. However, focal accumulation of FDG may cause false-positive results in certain physiologic conditions. In this report, a unique PET and computed tomography (CT) combination scan helped define physiologic accumulation of FDG in the uterus during menstruation in a 40-year-old woman with a history of rectal melanoma and possible recurrent disease. An initial PET study, performed during menstruation, was followed immediately by a PET-CT scan, which showed marked accumulation of FDG in the posterior pelvis, localized to a retroverted uterus. An FDG PET-CT scan repeated 2 weeks later confirmed resolution of this "lesion." Thus, combined PET-CT correctly differentiated physiologic FDG uptake in a retroverted uterus from recurrent rectal melanoma. This case shows that physiologic FDG accumulation in the uterus should be considered when focal FDG accumulation is observed in the pelvis in women of reproductive age.

Adult↗

Normal menstruation and pregnancy in a patient with Nelson's syndrome.

The patient with Nelson's syndrome in this report represents an unusual case in which regular cyclic menstruation was preserved even though a large ACTH-producing pituitary adenoma was present. Despite normal menses and pregnancy, the radiologic findings of an enlarged sella turcica and an enhanced lesion on CAT scan were identified. This case demonstrates that patients with normal menstruation can have significant pituitary disease, and it exemplifies the need for regular follow-up examination to look for radiologic abnormalities in patients who have had adrenalectomy for treatment of Cushing's disease.

Adenoma↗

Painful crises and menstruation in sickle cell disease.

Fifty-two women with sickle cell disease, having genotypes of hemoglobin SS, SC, and S-thalassemia, participated in a questionnaire study pertaining to the relationship of their menses and the occurrence of painful crises. The data indicated that those patients who had sickle cell crises were significantly older and had been menstruating longer, with heavier periods. The results point to the onset of menstruation as a possible precipitant of painful crises in some women with sickle cell disease.

Adolescent↗

Grave anaphylactic-like reaction in the course of menstruation. A case report.

The case of a woman with a serious anaphylactic pattern during menstruation is described. The patient had a clinical picture of urticaria, angioedema and shock at each menstruation for a period of 2 years until hysterectomy was performed. The studies showed no hormonal or immunological change. The only relevant finding was the extraordinarily strong vasodilating action of the menstrual fluid in the patient, and not in the controls. The results of the study suggest the possibility of two mechanisms: 1) an IgE-mediated mechanism causing hypersensitivity to some metabolic substance in the menstrual fluid and 2) an excessive pharmacological vasodilatory action produced by the prostacyclin in the fluid itself.

Adult↗

Prevalence of toxic shock syndrome toxin 1-producing Staphylococcus aureus and the presence of antibodies to this superantigen in menstruating women.

Menstrual toxic shock syndrome (mTSS) is thought to be associated with colonization with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus in women with insufficient antibody titers. mTSS has been associated with menstruation and tampon use, and although it is rare, the effects can be life threatening. It remains of interest because of the widespread use of tampons, reported to be about 70% of women in the United States, Canada, and much of Western Europe. This comprehensive study was designed to determine S. aureus colonization and TSST-1 serum antibody titers in 3,012 menstruating women in North America between the ages of 13 and 40, particularly among age and racial groups that could not be assessed reliably in previous small studies. One out of every four subjects was found to be colonized with S. aureus in at least one of three body sites (nose, vagina, or anus), with approximately 9% colonized vaginally. Eighty-five percent of subjects had antibody titers (> or =1:32) to TSST-1, and the vast majority (81%) of teenaged subjects (13 to 18 years) had already developed antibody titers. Among carriers of toxigenic S. aureus, a significantly lower percentage of black women than of white or Hispanic women were found to have antibody titers (> or =1:32) to TSST-1 (89% versus 98% and 100%). These findings demonstrate that the majority of teenagers have antibody titers (> or =1:32) to TSST-1 and are presumed to be protected from mTSS. These findings also suggest that black women may be more susceptible to mTSS than previously thought.

Adolescent↗

Cultural variations in attitudes toward menstruation.

Attitudes towards menstruation play an important role in the perception of menstrual distress. The influence of cultural and social factors was studied in a group of 48 Indian women using the Menstrual Attitudes Questionnaire (modified version). Women over 25 years of age were significantly more likely to consider menstruation as being "natural". No other significant relationships were found between menstrual attitudes and demographic variables. The menstrual attitudes of Indian and American college women (from a previous study) were also compared.

Adult↗

Attitudes about menstruation among fifth-, sixth-, and seventh-grade pre- and post-menarcheal girls.

A descriptive study of 106 fifth-, sixth-, and seventh-grade girls was conducted to determine their attitudes toward menarche. Attitudes of affirmation and worry were examined based on grade level, menarcheal status, and various other variables, including whether the participants had talked with their mother or a close friend, or seen a video on menstruation. Worry scores increased independently of menarcheal status from the fifth to sixth grade. From the sixth to seventh grade, there was no change in the level of worry of post-menarcheal girls, but there was a significant decrease in worry for pre-menarcheal girls. Perhaps these girls sought reassurance from a supportive person that their late menses was not abnormal. If so, this reassurance may have accounted for their decrease in worry scores. There was a decrease in worry in those girls who had sisters. Also, girls who had talked with someone about menstruation had higher affirmation scores than those who had not. Nursing implications include the need for school nurses to provide ongoing education for young females from fifth through seventh grades, and to encourage them to communicate with their support systems.

Adolescent↗

Decreased follicular phase gonadotropin secretion is associated with impaired estradiol and progesterone secretion during the follicular and luteal phases in normally menstruating women.

We tested the hypothesis that disturbed follicular development and disturbed luteal progesterone (P4) secretion are associated with reduced gonadotropin secretion in the early follicular phase by measuring pulsatile LH and FSH secretion at that time in 53 normally menstruating women. Three groups of women were identified on the basis of serum sex steroid concentrations (measured daily throughout the cycle) and luteal phase length. Group A (n = 27) had normal ovarian hormone secretion with peak serum estradiol (E2) concentrations of 440 pmol/L or more, peak serum P4 concentrations of 19 nmol/L or more, and luteal phase length of 9 days or more. Group B (n = 16) had normal peak serum E2 values, but peak serum P4 values less than 19 nmol/L and/or luteal phase length less than 9 days. Group C (n = 10) had peak serum E2 values below 440 pmol/L. Risk factors for the disturbances found in groups B and C were exercise and/or intermittent dieting. Compared to group A, both groups B and C had reduced mean serum LH concentrations (3.1 +/- 1.5 vs. 2.3 +/- 1.4 and 2.0 +/- 1.0 IU/L; P less than 0.05) and reduced LH pulse frequencies (5.2 +/- 2.1 vs. 3.5 +/- 1.8 and 3.3 +/- 2.3 pulses/12 h; P less than 0.02). LH amplitude was similar in all 3 groups. Mean serum FSH concentrations were slightly but not significantly lower in group C. We conclude that reduced gonadotropin secretion during the follicular phase may indeed affect E2 and P4 secretion at later stages of the menstrual cycle. The patterns of alteration associated with disturbed E2 and P4 secretion in normally menstruating women are similar to those that occur in women with hypothalamic amenorrhea.

Adult↗

Hypoxia and cAMP stimulate vascular endothelial growth factor (VEGF) in human endometrial stromal cells: potential relevance to menstruation and endometrial regeneration.

The human female reproductive tract shows unique cycle-specific changes in vascularization. Vascular endothelial growth factor (VEGF) is a specific vascular endothelial mitogen which is produced by human endometrium and is known to be regulated by steroid hormones. Vasoconstriction during menstruation leads to endometrial hypoxia, a possible stimulus for angiogenesis. In the current study we tested the hypothesis that hypoxia and cAMP, a known stimulus for endometrial decidualization, can induce VEGF in human endometrial stromal cells. Decidualized as well as non decidualized stromal cells from 6 patients were exposed to normoxia (20% oxygen) and hypoxia (2% oxygen) for up to 72h. VEGF levels were assessed by Northern analysis using a 605 bp BamHI fragment of the human VEGF cDNA, and hybridization signals were normalized to levels of 18S RNA. VEGF protein was determined by ELISA. Hypoxia stimulated VEGF mRNA in decidualized stromal cells by 10.2 fold at 48h compared to normoxic controls. VEGF protein increased 10 fold by 48h and increased further to 13 fold at 72h. In the presence of 2% oxygen VEGF mRNA in nondecidualized endometrial stromal cells was increased 1.2-8 fold between 2 and 72h of treatment. VEGF protein also increased 1.2-9 fold in this time period. cAMP regulated both VEGF mRNA and protein in non decidualized stromal cells. VEGF mRNA increased 2-4 fold in 2-72h and protein production showed a 2-6 fold increase. VEGF was seen to be regulated by both cAMP and hypoxia in an additive manner. These results demonstrate that both non-decidualized and decidualized endometrial stromal cells respond to hypoxia with increasing levels of VEGF. 8Br-cAMP, which is shown to increase VEGF levels in endometrial cells per se, has an additive effect on VEGF production under hypoxic conditions. This effect may have physiologic and pathophysiologic relevance during the process of menstruation and in post menstrual endometrial repair and angiogenesis.

Adult↗

Conceptions and misconceptions of menstruation.

College women were asked a series of open-ended questions about their conceptions of menstruation prior to menarche as part of a retrospective study. Their responses were rated as indicating correct information, misinformation, or lack of information. A conceptual analysis of these descriptive data reveals some of the emotional and cognitive limitations of pre-adolescence that lead ostensibly well-informed girls to harbor misconceptions about menstruation. Based on this conceptual analysis, a revised approach to menstrual education is suggested.

Adult↗

The effect of culture on how women experience menstruation: Jewish women and Mikvah.

Mikvah is a practice in Judaism consisting of ritual bathing that occurs at the end of the menstrual period. This study compared 161 married Jewish women, 82 mikvah users, and 79 non-users in order to learn how this ritual affects attitudes towards menstruation and the perception of menstrual and premenstrual distress. Women participating in mikvah, a ritual that defines them as "unclean," were expected to have more negative conceptions of menstrual cycle symptomatology and more positive menstrual attitudes than women in the same culture not participating in this ritual. These hypotheses were not supported by the findings. What was found was a similarity between the two groups in attitudes towards menstruation, frequency and type of symptoms surrounding the menstrual period, and the degree to which any of these symptoms were experienced.

Adult↗

Attitudes toward and experience with menstruation in the US and India.

Sixty-seven women students who were attending a university in southern India and 61 women students who were attending a liberal arts college in New England volunteered to participate in this study. The women supplied demographic information, information about their knowledge and levels of preparedness prior to menarche, and sources of their information about the menstrual cycle. They also completed the Menstrual Attitude Questionnaire (Indian version), the Menstrual Distress Questionnaire, and a test of knowledge about the menstrual cycle. American women scored significantly higher than Indian women on the knowledge test, and they also reported that they had better preparation for menarche than Indian women did. Indian women scored significantly higher than American women on the attitude subscales: Menstruation as a Natural Event and Denial of the Effects of Menstruation. Implications of these findings are discussed in light of cultural messages women receive.

Adult↗

A case of 17 alpha-hydroxylase deficiency with retained menstruation.

A patient with 17 alpha-hydroxylase deficiency (17OHD) who continued to menstruate is reported. A 24-year-old woman who presented with hypertension, hypokalemia and irregular menses had increased plasma ACTH and mineralocorticoids without any increase in glucocorticoids or sex steroids, and a bilateral adrenal enlargement on abdominal X-ray CT. ACTH stimulation test revealed hyperresponse of the metabolites of the mineralocorticoid pathway and blunted or absent response of those of the glucocorticoid and androgen pathway. Almost all of the abnormalities disappeared after dexamethasone administration. While 17OHD is usually known to accompany hypergonadotropic hypogonadism, the patient continued to menstruate, though irregularly. Although human chorionic gonadotropin administration failed to induce response, basal plasma levels of ovarian steroid (estradiol) and gonadotropins as well as response to LHRH stimulation test were all normal. Thus, the clinical and biochemical features of this case is compatible with the partial deficiency of both adrenals and ovaries, being less severe in the latter. A further analysis especially at molecular level is needed to elucidate the basis for the heterogeneity of this disorder.

Adrenal Hyperplasia, Congenital↗

Dynamic evaluation of prolactin secretion with sulpiride and thyrotrophin releasing hormone in amenorrhoeic and normally menstruating women.

Sulpiride and TRH were used to evaluate the dynamics of prolactin (Prl) release in normoprolactinaemic, amenorrhoeic and normally menstruating women. The two tests were performed in a randomomized order with an interval of 2-3 days. In the normal women the first test was carried out between days 2 and 4 of their cycle. Basal values during the two tests were not statistically different (9.6 +/- 1.2 SE vs. 10.7 +/- 1.4 ng/ml in amenorrhoeic women with sulpiride and 11.3 +/- 1.4 vs. 12.4 +/- 1.7 in amenorrhoeic women during the TRH test). The two tests were performed while the subjects of the two groups had identical serum oestrogen concentrations. The Prl response following TRH administration was similar in both groups (delta max mean 49.5 +/- 12.5 SE and 49.4+/- 8.5 SE in normal and amenorrhoeic women, respectively). In contast, when release by sulpiride administration was studied the normal women had greater Prl release (delta max mean 169.9 +/- 18.2 SE) than amenorrhoeic women (delta max mean 99.8 +/- 9.4). Either the different oestrogen status (lower in amenorrhoeic women than in menstruating women) or the hypothalamic pituitary dysfunction likely to be responsible for the amenorrhoea in our patients, may explain the lower Prl release observed after sulpiride in subjects with amenorrhoea.

Adolescent↗