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PubMed2000

Regulation of matrix metalloproteinases in human endometrium.

Considerable evidence supports a role for matrix metalloproteinases (MMP) in menstruation, but their focal pattern of expression within perimenstrual and menstrual endometrium suggests local rather than hormonal regulation. Menstruation shares a number of features with inflammatory responses, with leukocyte infiltration, proliferation and activation, occurring in the endometrium prior to menstruation. We propose that the leukocytes release MMP at this time and also that interactions between leukocytes and the stromal and epithelial cells of the endometrium induce and activate MMP. Co-culture studies using mast cells or neutrophils with endometrial stromal cells support this hypothesis. How leukocytes enter the endometrium is not understood but a role for chemokines has been proposed. The expression patterns of eotaxin and its receptor CCR3 in endometrium support a role in chemoattraction of eosinophils but expression of monocyte chemotactic proteins 1 and 2 does not correlate with macrophage numbers. Nothing is known of how the leukocytes become activated. Nevertheless, the overall result is a tissue in which an inflammatory-type reaction occurs with release of a myriad of potent regulators. These induce production and activation of MMP and alter the ratio between these and their tissue inhibitors, resulting in tissue breakdown.

Cell Communication↗
PubMed2003

Effect of long-term treatment with low-dose mifepristone on the endometrium.

BACKGROUND: Mifepristone in low daily doses has contraceptive potential by inhibiting ovulation and menstruation. Because follicular development is maintained, the endometrium is exposed to estrogen for prolonged periods unopposed by progesterone. METHODS: Endometrial biopsies were collected from 90 women in Edinburgh and Shanghai before (late proliferative) and 60 and 120 days after taking 2 or 5 mg mifepristone per day for 120 days. RESULTS: Ovulation and menstruation were inhibited in >90% of cycles and estrogen production was similar to that observed during the follicular phase of the control cycle. By 120 days, endometrial thickness increased significantly in women in Edinburgh but decreased in Shanghai. Endometrial histology showed inactive proliferative or cystic changes with dense stroma. There was a significant decrease in markers of proliferation, i.e. mitotic index and Ki67 staining. There were no pregnancies in a total of 200 women-months in 50 sexually active women who used no other method of contraception. CONCLUSIONS: We confirm that ovulation and menstruation were suppressed in the majority of cycles and there was asynchrony between ovarian activity and endometrial histology, which showed no signs of hyperplasia or atypia. These preliminary data suggest that daily low-dose mifepristone is potentially a safe estrogen-free contraceptive pill which has the added health benefit of amenorrhoea.

Adult↗
PubMed2003

Fertility and pregnancy outcome following pelvic arterial embolization for severe post-partum haemorrhage. A cohort study.

BACKGROUND: Pelvic arterial embolization is a safe, effective life-saving procedure in post-partum haemorrhage, but little information is yet available about its impact on menstruation and fertility. METHODS: A cohort of 28 women who underwent pelvic embolization for post-partum haemorrhage in our tertiary centre was studied. Patients were contacted by telephone to obtain long-term outcome for menstruation, clinical signs of estrogen insufficiency, desire for fertility and subsequent pregnancies. RESULTS: We found no menstrual abnormalities or signs of early menopause among the 17 patients we were able to reach. Six women expressed a clear desire for subsequent pregnancies. Five patients reported a total of six pregnancies (one biochemical pregnancy, one early miscarriage and four deliveries). The four patients with complete gestations gave birth to healthy babies, but post-partum haemorrhage recurred for all and led to two hysterectomies. No undesired pregnancies occurred. CONCLUSIONS: Embolization in post-partum haemorrhage appears to be a safe procedure that does not impair subsequent menstruation and fertility. Recurrence of severe post-partum haemorrhage may occur at subsequent deliveries.

Adult↗
PubMed1994

Reproductive function and contraception in the postpartum period.

The postpartum period is a time of major cellular and hormonal change enabling the return of pelvic organs and the hypothalamic-pituitary-ovarian axis to the nonpregnant state. Breast-feeding modifies this change and maintains the endocrine profile and uterine endometrium in a "static" state. In nonlactating women, menstruation returns on average by day 55 to 60 postpartum and ovulation returns on average by day 40 to 50 postpartum. Breast-feeding prolongs the return of menstruation to some 8 to 15 months postpartum and the first ovulation on average was between 30 to 40 weeks postpartum. However, in breast-feeding women, the return of menstruation and ovulation can be quite variable and is influenced by the pattern of breast-feeding, in particular, the intensity and pattern of suckling. There is concern that breast-feeding, although an effective contraceptive on a wide population scale, is unpredictable for the individual. An overall pregnancy rate of 2 to 10 per cent during lactational amenorrhea has been reported. Barrier methods, intrauterine contraceptive devices, and progestogen-only contraceptives are some of the highly effective and most commonly used additional methods of contraception by lactating women. Other methods of contraception during this period include the use of periodic abstinence and combined oral contraceptives. This paper provides an overview of postpartum reproductive function in relation to breast-feeding and the use of contraception in this unique period.

Breast Feeding↗
PubMed1975

The investigation of ovarian function by measurement of urinary oestrogen and pregnanediol excretion.

Urinary oestrogen and pregnanediol excretion was measued daily ("daily monitoring") for a complete cycle in 20 normally menstruating women, in one patient with an anovulatory cycle and for 28 days in a patient with secondary amenorrhoea. The measurements were also performed on urine specimens collected at weekly intervals for 4 to 6 weeks ("weekly tracking") from 506 patients with evidence of abnormal ovarian function. These included 9 patients with primary amenorrhoea, 132 patients with secondary amenorrheoa, 138 patients with oligomenorrhoea and 227 patients with evidence of ovarian dysfunction and cycle lengths of 25 to 42 days. The results were subjected to statistical analysis. In the normal cycles, ovulation could be identified on the criteria of a rising pregnanediol value reaching or exceeding 2-0 mg. per 24 hours for a period of 7 days or more. Valid conclusions on the overall mean oestrogen and pregnanediol values for a complete cycle could be made from the results of weekly tracking, irrespective of which day the tracking commenced. Correlations were obtained by comparing the mean and maximum urinary oestrogen values and the variability of the values with the evidence of ovarian function indicated by the clinical classifications of the patients, the duration of the disorders and the subsequent occurrence of uterine bleeding. Mean oestrogen values of 10 mug. per 24 hours or less were associated with lack of ovarian function. For values higher than this a discriminant function based on both the mean oestrogen value and the variability of the oestrogen values was useful in predicting onset of spontaneous menstruation. A single urine specimen collected 4 to 8 days before onset of menstruation showing a raised pregnanediol value of 2-0 mg. per 24 hours or more provided a valid test for ovulation in women with regular cycles, and a single urine specimen giving an oestrogen value of 10 mug per 24 hours or less gave a valid indication of absent ovarian function in women with amenorrhoea for two years or more. In all other circumstances serial sampling at weekly intervals provided a valid assessment of ovarian activity. Application of these principles allows the greatest amount of information on ovarian function to be obtained with the greatest economy of effort.

Amenorrhea↗
PubMed1985

Hormonal studies in women with premenstrual tension.

Serum hormone concentrations were determined at intervals during the last 17 days of the menstrual cycle in 35 patients with premenstrual tension (PMT) and 11 control subjects without symptoms. The maximum mean concentration of oestradiol occurred 17 days before menstruation in the patients and 14 days before in the controls. The maximum concentrations of progesterone were similar in the two groups but the mean concentrations rose earlier in the cycle in the patients with PMT. These results suggested that the patients tended to ovulate earlier in the cycle than the controls and on the basis of the ovulatory surge in gonadotrophins two groups could be identified, group A who showed signs of ovulation 14 days or less before menstruation (17 patients, 9 controls) and group B who ovulated more than 14 days before menstruation (18 patients, 2 controls). There were no significant differences between the groups in prolactin, thyroid stimulating hormone or testosterone levels, but cortisol concentrations were uniformly higher in both groups of patients compared with those in the controls. Follicular growth was assessed with ultrasound in 18 patients and 16 control subjects. Mean follicular diameters were significantly lower in the patients than in the control group at the time of ovulation. Oestradiol determinations done at the same time correlated with the diameters and were also significantly lower in the patient group. The results suggest that ovulation tends to occur prematurely in women with PMT.

Adult↗
PubMed2004

The need to bleed: women's attitudes and beliefs about menstrual suppression.

PURPOSE: To describe how women feel about monthly menstruation in general and menstrual suppression in particular. DATA SOURCES: This descriptive, exploratory study used a convenience sample of 221 women who completed a self-administered questionnaire on attitudes toward monthly menstruation and menstrual suppression. Descriptive statistics and correlations were used to analyze the data. CONCLUSIONS: Women not using oral contraceptives (OCs) had more menstrual symptoms than women using OCs. Negative feelings about menstruation were correlated with interest in menstrual suppression. Over two thirds expressed interest in reducing menstrual pain and the amount of menstrual discharge, particularly if not taking OCs. Women who were not interested in changing their menstrual pattern said they would be anxious about not having a menstrual flow and said it would not be normal. IMPLICATIONS FOR PRACTICE: Advanced practice nurses play an important role in educating women about menstrual health. Clinicians can use this information to assess women's attitudes and beliefs about menstrual symptoms and to educate them about misconceptions. The FDA approved Seasonale in September 2003, the first dedicated OC created to reduce the number of menstrual cycles yearly. Women need to be educated about the pros and cons of suppression; some women will benefit from suppression, and others will consider it unnatural.

Adolescent↗
PubMed2002

Macrophages, oxidation, and endometriosis.

Retrograde menstruation has been suggested to be the cause for the presence of endometrial cells in the peritoneal cavity. However, little is known about the events that lead to the adhesion and growth of these cells that ultimately result in endometriosis, considering the fact that the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. We postulate that, in normal women, the endometrial cells and tissue that arrive in the peritoneal cavity during menstruation are effectively removed by macrophages that are chemoattracted and become resident tissue macrophages in the peritoneal cavity. In contrast, the peritoneal macrophages in women with endometriosis are nonadherent and ineffectively scavenged, resulting in the sustained presence and growth of the endometrial cells. We also postulate that the peritoneal fluid is not a passive reservoir of the factors secreted by cells of the peritoneum, but actively promotes endometriosis. The peritoneal fluid is rich in lipoproteins, particularly low-density lipoprotein, which generates oxidized lipid components in a macrophage-rich inflammatory milieu. The oxidants exacerbate the growth of endometriosis by inducing chemoattractants such as MCP-1 and endometrial cell growth-promoting activity. We provide evidence for the presence of oxidative milieu in the peritoneal cavity of women with endometriosis, the nonscavenging properties of macrophages that are nonadherent, and the synergistic interaction between macrophages, oxidative stress, and the endometrial cells. For example, the peritoneal fluid lipoproteins of subjects with endometriosis have increased the propensity to undergo oxidation as compared with plasma lipoproteins, and the subjects also have increased titer of autoantibodies to oxidatively modified proteins. If the oxidative proinflammatory nature of the peritoneal fluid is an important mediator of endometriosis growth, anti-inflammatory agents and antioxidants might afford protection against endometriosis.

Ascitic Fluid↗
PubMed2005

In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses.

Previous in vitro and in vivo animal studies showed that O(2) and CO(2) concentrations can affect virulence of pathogenic bacteria such as Staphylococcus aureus. The objective of this work was to measure O(2) and CO(2) levels in the vaginal environment during tampon wear using newly available sensor technology. Measurements by two vaginal sensors showed a decrease in vaginal O(2) levels after tampon insertion. These decreases were independent of the type of tampons used and the time of measurement (mid-cycle or during menstruation). These results are not in agreement with a previous study that concluded that oxygenation of the vaginal environment during tampon use occurred via delivery of a bolus of O(2) during the insertion process. Our measurements of gas levels in menses showed the presence of both O(2) and CO(2) in menses. The tampons inserted into the vagina contained O(2) and CO(2) levels consistent with atmospheric conditions. Over time during tampon use, levels of O(2) in the tampon decreased and levels of CO(2) increased. Tampon absorbent capacity, menses loading, and wear time influenced the kinetics of these changes. Colonization with S. aureus had no effect on the gas profiles during menstruation. Taken collectively, these findings have important implications on the current understanding of gaseous changes in the vaginal environment during menstruation and the potential role(s) they may play in affecting bacterial virulence factor production.

Adult↗
PubMed2000

Menstrual knowledge and practices amongst secondary school girls in Ile Ife, Nigeria.

The menstrual knowledge and practices of 352 randomly selected healthy Nigerian schoolgirls were studied. 187 (53.1%) had attained menarche. 40% of subjects were deficient in knowledge about menstruation. Although menstrual knowledge was higher in post-menarcheal girls, 10% of these were totally ignorant about menses and 84% were not psychologically prepared for the first menses. Girls' menstrual knowledge was positively associated with parental education. The major source of menstrual information was the family. Although more than half of the girls menstruated regularly, 66.3%, used insanitary materials as menstrual absorbent. The mean duration of menstrual flow was 4.32 +/- 1.15 days (mean +/- SD) with a range of 3-7 days in 95.2% of the study population. There is an acute need for education and psychological preparation of girls for menstruation well ahead of menarche.

Adolescent↗
PubMed1988

Epidermal growth factor in urine of nonpregnant women and pregnant women throughout pregnancy and at delivery.

Human epidermal growth factor (EGF) concentrations were measured by a specific solid phase RIA in random urine samples collected throughout the menstrual cycle of normal menstruating women (n = 8), women with tubal sterilization (n = 6), women taking a low dose oral contraceptive (n = 5), and women throughout pregnancy (n = 52) and delivery (n = 35). There were no differences in EGF concentrations between the proliferative and secretory phases of the menstrual cycle (P greater than 0.05). Normal menstruating women had higher urinary EGF concentrations [mean +/- SE, 37.2 +/- 6.0 micrograms/g creatinine (4.23 +/- 0.68 ng/mumol)] than women with tubal sterilization [32.7 +/- 4.0 (3.71 +/- 0.45)] or women taking a low dose oral contraceptive [19.5 +/- 6.0 (2.21 +/- 0.68)], but the differences were not significant (P greater than 0.05). During pregnancy, urinary EGF concentrations increased linearly from 6-20 weeks gestation (r = 0.76; P less than 0.001), then declined toward term (r = -0.71; P less than 0.001). EGF concentrations in early pregnancy (less than 12 weeks) or at term did not differ significantly from those in normal menstruating women (P greater than 0.05). For women delivering normal, appropriate for gestational age (AGA) infants, there was no correlation between urinary EGF concentrations and fetal weight or sex (P greater than 0.05). Urinary EGF concentrations in women delivering normal AGA infants [52.7 +/- 2.5 (5.98 +/- 0.28); n = 16] did not differ significantly (P greater than 0.05) from those in women with class A/B diabetes [41.9 +/- 2.8 (4.76 +/- 0.31); n = 6] or women delivering twins [45.6 +/- 2.6 (5.18 +/- 0.29); n = 8] with a greater fetoplacental mass. However, women delivering an intrauterine growth-retarded fetus with decreased fetoplacental mass had lower urinary EGF concentrations (24.9 +/- 2.2 (2.83 +/- 0.25); n = 5] than women with normal AGA infants (P less than 0.01). The significance of the rise in the urinary EGF concentration late in the second trimester and lower urinary EGF concentrations in women delivering intrauterine growth-retarded infants is not known, but may reflect an important physiological role for EGF in fetal-maternal hormonal interaction and development.

Adolescent↗
PubMed1990

Religious influence on menstrual attitudes and symptoms.

Menstrual attitudes and symptoms of 18 Orthodox Jewish Mikvah attenders, 23 Orthodox Jewish Mikvah non-attenders, 35 Protestant women, and 45 Catholic women were compared. When age, education, number of pregnancies, and religiosity were controlled, Mikvah non-attenders and Protestants most strongly endorsed a view of menstruation as a bothersome event. No significant differences were found, however, in expected or retrospectively reported menstrual symptoms. Correlational analyses indicated that attitudes, expectancies, and symptoms were significantly correlated only for the Catholic women. Differences between groups in religiosity and socialization were found. The Jewish women endorsed doctrines such as "menstruation makes women unclean" more than Catholic or Protestant women. Results support the hypothesized differential religious training regarding menstruation, but only offer weak support for the effects of this training on menstrual attitudes, expectancies, and symptoms.

Adult↗
PubMed1975

Serum tsh and serum t3 levels during normal menstrual cycles and during cycles on oral contraceptives.

Serum TSH and serum T3 levels were studied in 35 normally menstruating women and in 35 women on oral contraceptives in order to find out whether the levels of TSH and T3 were related to the menstrual cycle or changed by oral contraceptives. Serum TSH AND T3 were found to be unchanged throughout the normal menstrual cycles and during the cycles of oral contraceptives. The TSH level was higher in the women on oral contraceptives than in the normally menstruating women. This might be due to a direct thyroid inhibitory effect of oestrogen. As could be expected the levels of T3 and T4 were higher in women on oral contraceptives than in normally menstruating women.

Contraceptives, Oral↗
PubMed1975

Effect of methylergobasine maleate on serum gonadotrophin and prolactin in humans.

Intramuscular injection of 0.2 mg methylergobasine maleate3) (Methergin, Sandoz) in women on day 3 post-partum, in regularly menstruating women and in adult men, is followed within 30 to 75 min by a 50% decrease in serum prolactin concentration: the levels remain low until 180 min and increase between 180 and 240 min. The amplitude of the decrease is the same when prolactin is measured in terms of the same serum prolactin standard by a homologous ovine assay and by a homologous human assay. However, in the case of regularly menstruating women and of men serum prolactin concentration is some three times higher when estimated by the ovine assay than when estimated by the human assay. This difference between assay results obtained by the two radioimmunoassay methods could be due to heterogeneity of serum prolactin. However, non-specific effects of serum are not excluded. In regularly menstruating women and in men, intramuscular injection of 0.2 mg methylergobasine maleate is followed within 45 to 75 min by a 50% decrease in immunoreactive serum LH concentration without concomtant change in immunoreactive FSH. The depression of LH secretion lasts for 1 to 2 h. The circulating levels of HCG in post-partum women are not modified after intramuscular injection of Methergin. In humans as in animals and in in vitro studies, inhibition of prolactin and LH release induced by ergot drugs are likely due to both an indirect effect via the hypothalamus and to a direct effect on the pituitary cells.

Adult↗
PubMed1984

Metergoline as an alternative to bromocriptine in amenorrhoea.

The results of this study offer further evidence that metergoline is a valuable alternative to bromocriptine in the suppression of excessive prolactin secretion. Forty-nine hyperprolactinaemic and 44 normoprolactinaemic women with amenorrhoea took part in a double-blind trial to compare the efficacy of metergoline 12 mg/day and bromocriptine 7.5 mg/day in restoring menstruation and ovulation. All the women had normal results on conventional tomography of the sella turcica, normal gonadotrophin levels and normal androgen levels. In the hyperprolactinaemic group, metergoline and bromocriptine were equally effective, with 84 and 75% respectively achieving menstruation, and 76 and 67% respectively achieving ovulation, within 4 months. In the normoprolactinaemic group, 47% menstruated and 40% ovulated on metergoline, against comparative figures of 36 and 21% for bromocriptine and 20 and 13% for placebo, but the differences were not statistically significant. Side effects were not a major problem.

Adult↗
PubMed1999

Apoptosis of human endometrium mediated by perforin and granzyme B of NK cells and cytotoxic T lymphocytes.

Endometrial stromal granulocytes (EGs) were found to be a major component of human endometrial stroma in the late secretory phase. However, the role of EGs in the mechanism of human endometrial menstruation has not been clarified. Immunohistochemistry of CD56, perforin, granzyme B, and vimentin, in situ detection of apoptosis by TUNEL (TdT-mediated dUTP-biotin nick and labeling) and electron microscopy were performed in endometrial tissue samples with normal menstrual cycles. We analyzed the number of immunostained cells in the functional layer of stroma and the number of apoptotic cells detected by TUNEL in the endometrial glandular cells. Double-staining revealed that CD56-positive endometrial stromal cells were simultaneously positive for both perforin and granzyme B, and negative for vimentin, which recognized stromal tissue. Vimentin was positive for the predecidual cells and negative for EGs. CD56-positive EGs involving perforin and granzyme B were progressively recruited during the secretory phases before menstruation. Apoptosis in endometrial glandular cells increased from the late secretory phase, which maximized at the menstrual period. This finding suggests that the cytotoxic granules released from EGs, which are derived from cytotoxic T lymphocytes and natural killer cells, are initiators of the apoptotic pathway that induces endometrial menstruation.

Adult↗
PubMed1987

Plasma concentrations of vasopressin and a prostaglandin F2 alpha metabolite in women with primary dysmenorrhoea before and during treatment with a combined oral contraceptive.

Oral contraceptives reduce menstrual pain but the interaction with vasopressin and prostaglandin F2 alpha, two uterine stimulants related to the condition, is unknown. Ten women with a history of moderate to severe dysmenorrhoea were studied. Repeated blood samples were taken during a first menstrual cycle without treatment, during the first 21 days of a second cycle when they received an oral contraceptive (150 micrograms levonorgestrel and 30 micrograms ethynyloestradiol) and on the first or second day of the bleeding following hormonal withdrawal. Measurements were made of plasma concentrations of arginine vasopressin, 15-keto-13,14-dihydroprostaglandin F2 alpha, oestradiol-17 beta, progesterone, ethynyloestradiol, levonorgestrel, FSH, LH and prolactin, and serum osmolality was measured. Seven of the women rated their discomfort as moderate to severe on the first two menstruations, but as none or light at the withdrawal bleeding; with the rating scale for degree of pain that was used, this decrease in pain was significant (P less than 0.001). The plasma concentration of vasopressin in these seven women showed significant variation, with the highest concentrations being obtained at the beginning of the two painful menstruations (3.76 +/- 0.76 and 1.75 +/- 0.30 (S.E.M.) pmol/l) and at ovulation in the control cycle (1.91 +/- 0.58 pmol/l). During treatment the concentrations were consistently low, except on the first day of withdrawal bleeding (2.33 +/- 0.35 pmol/l). The concentrations of the prostaglandin F2 alpha metabolite showed less variation, but again the values at withdrawal bleeding (271 +/- 39 pmol/l) were not different from those obtained over the painful menstruations (255 +/- 24 and 217 +/- 25 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Risk factors for breast cancer in women undergoing mammography.

To determine risk factors for carcinoma of the breast, we compared women with cancer on screening and diagnostic mammography with those in whom cancer was not detected. For 39 months, medical histories were collected by mammography technologists on 3492 women having routine screenings or diagnostic mammograms at our institution. Potential risk factors of women with biopsy-proved breast cancer were compared with those in women who had normal findings on mammograms or negative biopsy results (control subjects). Of the 3492 women, 49 had biopsy-proved breast cancer. There were 3361 patients in the control group, including those women with normal findings on mammograms (3294) and those with negative biopsy results (67). Eighty-two women had incomplete questionnaires or were lost to follow up. Nearly all of the patients with breast cancer were postmenopausal compared with 68% of the control subjects. The mean length of lactation for breast cancer patients was significantly less than for control subjects: 5.6 vs 7.5 weeks (p = .015). This was true also for the postmenopausal patients: 8.1 vs 6.1 weeks (p = .041). Postmenopausal breast cancer patients had menstruated significantly more years (p = .016) than the postmenopausal control subjects: 34 vs 31 years, although the mean age at menarche was not different. When corrected for age, there was no significant difference in the total duration of menstruation in the postmenopausal cancer patients compared with the postmenopausal control subjects. Postmenopausal breast cancer patients had a significantly greater (p = .021) average body weight than postmenopausal control subjects: 71.7 vs 66.7 kg, although body weight was the same when all patients were considered. Similar results were found when Quetelet's index for obesity (weight in kg/height in cm2) (p = .004) was calculated for postmenopausal patients: 28 for cancer patients and 26 for control subjects. There was no significant difference in height between the cancer patients and control subjects when all patients or just the postmenopausal patients were considered. History of oral contraceptive use was significantly less common among postmenopausal breast cancer patients than among postmenopausal control subjects: 9% vs 20%. Patients with breast cancer had lower parity than the control subjects. In our series of patients, women in whom breast cancer was detected on mammography lactated less, showed no significant difference in years of menstruation when corrected for age, had a greater average body weight, used oral contraceptives less often, and had fewer children than women in whom no cancer was detected on mammography.

Body Height↗