Determination of menstrual prostaglandin levels in non-dysmenorrheic and dysmenorrheic subjects

We have developed a method which can measure the menstrual prostaglandin (PG) activity in a single tampon specimen by bioassays. This method makes it possible to monitor the menstrual PG activity continuously during menstruation. Using this technique, we determined the menstrual PG patterns of two normal non-dysmenorrheic subjects, one subject on oral contraceptives (OC) and one subject with moderate to severe dysmenorrhea. Two to four cycles were studied per subject. We observed three mentrual patterns among the four subjects studied. Compared to the two normal controls, the subject on OC had a significantly lower menstrual fluid total and menstrual PG activity. The mean values +/- S.E. per menstrual period were 33.4 g +/- 1.5 vs 21.5 g +/- 2.0 and 28.6 microgram (PGF2alpha equivalent) +/- 1.5 vs 11.3 microgram +/- 4.2 respectively (control vs OC). The dysmenorrheic subject had a menstrual fluid total of 37.0 g +/- 1.9 similar to the two normal controls. Her menstrual PG activity (49.8 microgram +/- 7.7), however, was nearly two times higher than the normal controls. In one cycle studied, the dysmenorrheic subject was treated with a PG synthetase inhibitor, ibuprofen (Motrin). Remarkable relief was achieved. The alleviation of symptoms was accompanied by a concomitant marked reduction in the menstrual PG activity.     

Menstrual-PGF2 alpha, PGE2 and TXA2 in normal and dysmenorrheic women and their temporal relationship to dysmenorrhea

Although it has been demonstrated that primary dysmenorrhea is associated with elevated levels of PGF2 alpha in the menstrual fluid, little is actually known of the menstrual-PG profiles of either dysmenorrheic or normal women. In this study, menstrual fluid from normal and dysmenorrheic women was collected from tampons and extracted for PG-like substances. The PGF2 alpha, PGE2 and TXA2 content was analyzed by RIA. This study demonstrates that dysmenorrheics have significantly higher levels/concentrations of menstrual-PGF2 alpha and PGE2 than do normal women, and that there is no difference in the menstrual-PGF2 alpha : PGE2 ratio between the two groups. Also, there is no significant difference in the amount/concentration of menstrual-thromboxane between dysmenorrheic and normal women. Of the parameters considered, the levels/-concentrations of menstrual-PGF2 alpha, PGE2 and TXA2, dysmenorrheic pain correlates best with the rate of menstrual-PGF2 alpha release.     

Determination of menstrual prostaglandin levels in non-dysmenorrheic and dysmenorrheic subjects

We have developed a method which can measure the menstrual prostaglandin (PG) activity in a single tampon specimen by bioassays. This method makes it possible to monitor the menstrual PG activity continuously during menstruation. Using this technique, we determined the menstrual PG patterns of two normal non-dysmenorrheic subjects, one subject on oral contraceptives (OC) and one subject with moderate to severe dysmenorrhea. Two to four cycles were studied per subject. We observed three menstrual patterns among the four subjects studied. Compared to the two normal controls, the subject on OC had a significantly lower menstrual fluid total and menstrual PG activity. The mean values ± S.E. per menstrual period were 33.4 g ± 1.5 vs 21.5 g ± 2.0 and 28.6 μg (PGF_2α equivalent) ± 1.5 vs 11.3 μg ± 4.2 respectively (control vs OC). The dysmenorrheic subject had a menstrual fluid total of 37.0 g ± 1.9 similar to the two normal controls. Her menstrual PG activity (49.8 μg ± 7.7), however, was nearly two times higher than the normal controls. In one cycle studied, the dysmenorrheic subject was treated with a PG synthetase inhibitor, ibuprofen (Motrin). Remarkable relief was achieved. The alleviation of symptoms was accompanied by a concomitant marked reduction in the menstrual PG activity.     

Anthropological and clinical characteristics in adolescent women with dysmenorrhea

The aim of this study was to examine the prevalence of dysmenorrhea in female adolescents and the influence of anthropological characteristics and lifestyle factors on menstrual pain. Two hundred and ninety seven girls from several elementary and secondary schools were interviewed about the presence of the menstrual pain, their age, height and weight, menarcheal age, menstrual cycles quality, smoking and sexual activity. There were 164 (55%) subjects with and one hundred and thirty three (45%) without dysmenorrhea. The adolescents with dysmenorrhea answered the questions about missing activities and taking pills for pain. No difference was observed between the girls with and the girls without dysmenorrhea in their chronological age, height, weight, menarcheal age, menstrual cycles quality, cigarette smoking and sexual activity. In the group of dysmenorrheic adolescents there was infrequent missing activities and bedrest, but missing school was observed in 22 percent and taking pills for pain was observed in 96 percent of the subjects. Young girls who experienced menstrual pain are good candidates for a prophylactic therapy, such as hormonal contraception. A replication of this study is needed for public health services in the future to improve the quality of life of the dysmenorrheic young women.     

Altered Cytokine Gene Expression in Peripheral Blood Monocytes across the Menstrual Cycle in Primary Dysmenorrhea: A Case-Control Study

Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea.     

Menstrual-PGF2α, PGE2 and TXA2 in normal and dysmenorrheic women and their temporal relationship to dysmenorrhea

Although it has been demonstrated that primary dysmenorrhea is associated with elevated levels of PGF_2α in the menstrual fluid, little is actually known of the menstrual-PG profiles of either dysmenorrheic or normal women. In this study, menstrual fluid from normal and dysmenorrheic women was collected from tampons and extracted for PG-like substances. The PGF_2α, PGE₂ and TXA₂ content was analyzed by RIA.This study demonstrates that dysmenorrheics have significantly higher levels/concentrations of menstrual-PGF_2α and PGe₂ than do normal women, and that there is no difference in the menstrual-PGF_2α: PGE₂ ratio between the two groups. Also, there is no significant difference in the amount/concentration of menstrual-thromboxane between dysmenorrheic and normal women. Of the parameters considered, the levels/-concentrations of menstrual-PGF_2α, PGE₂ and TXA₂, dysmenorrheic pain correlates best with the rate of menstrual-PGF_2α release.     

Prostaglandins,indomethacin and dysmenorrhea

Uterine contractility was recorded during the period of menstruation in six dysmenorrheic women. A variable high tonus was observed in each case. Uterine recordings were repeated during the subsequent menstruation following pre-treatment with indomethacin at an oral dose of 75 mg or 200 mg per day beginning one day before the expected onset of menstruation. A lower uterine tonus was found in all indomethacin-treated cycles. Complete alleviation of spasmodic pain was obtained in the six subjects. The endogenous concentration of 15-keto-13,14-dihydro PGF_2α was determined by the gas chromatography-mass spectrometry method and observed to be relatively high in women with dysmenorrhea.     

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.     

Evaluation of brain-derived neurotrophic factor in menstrual blood and its identification in human endometrium

The presence of high-affinity brain-derived neurotrophic factor receptor Trk B in mouse and in human fetal oocytes, together with the presence of neurotrophins in human follicular fluid suggests a paracrine role for brain-derived neurotrophic factor (BDNF) in female biology. This study aims to evaluate if BDNF is present and quantitatively determined in human menstrual blood and endometrium. Twenty-one women were studied and subdivided in two groups: A, 11 fertile women (27 ± 2 days cycle length) and B, 10 anovulatory women and/or women with inadequate luteal phase (36 ± 2 days cycle length). In fertile women menstrual BDNF levels was higher than plasma (679.3 ± 92.2 vs 301.9 ± 46.7 pg/ml p <0.001). Similarly, in Group B, BDNF in menstrual blood was higher than plasma (386.1 ± 85.2 vs 166.8 ± 24.1 pg/ml p < 0.001). Moreover, both menstrual and plasma BDNF concentrations in Group A were significantly higher respect to Group B (679.3 ± 92.2 vs 386.1 ± 85.2 pg/ml p < 0.001; 301.9 ± 46.7 vs 166.8 ± 24.1 pg/ml p < 0.001). Immunohistochemistry evidence of BDNF in endometrium, during follicular and luteal phase, was also shown. The detection of BDNF in the human menstrual blood and endometrium further supports the role of this neurotrophin in female reproductive function.     

The effect of naproxen-sodium on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

The Prostaglandin-synthesis inhibitor: Naproxen-Sodium (NS) (an analgesic agent) very significantly (P less than 0.001) reduced the "resting" and "active" pressures and the frequency of cyclic uterine activity of 10 dysmenorrheic patients. It also highly significantly reduced (P less than 0.001) menstrual pain. Since these effects were observed after a single oral dose of 1100 mg NS, without side effects or complications, extensive field trials are recommended for assessing therapeutic benefits of this treatment.     

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual periods, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay.The patients receiving placebo had high PGF levels 135 ± 27 ng/ml (Mean ± S.E.) which were significantly reduced by Ibuprofen to 24 ± 5 ng/ml (P<0.001). The PGE concentrations decreased from 5 ± 1 ng/ml to 2 ± 1 ng/ml (P<0.05). Ibuprofen also reduced the menstrual pain significantly (P<0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.     

Biofeedback treatment of dysmenorrhea

Nine dysmenorrheic women were run in EMG and thermal biofeedback procedures with concurrent autogenic relaxation practice. Significant reductions in subjective estimates of symptomology associated with dysmenorrhea were noted in all subjects. EMG levels correlated positively with the reductions in symptoms. Thermal levels did not correlate with EMG. In fact no consistent patterns in thermal measures were noted. However, thermal biofeedback cannot be ruled out as an effective treatment for dysmenorrhea since reductions in symptoms occurred during thermal biofeedback training. Another significant aspect of the present study is the effectiveness of long treatment procedures. A six month period was employed and significant reductions in symptoms were noted following two months of biofeedback treatment. Finally, the importance of beginning biofeedback treatment prior to onset of menstrual symptoms is indicated.     

The effect of ibuprofen on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

In 12 dysmenorrheic patients we examined the therapeutic action of the Prostaglandin-synthesis inhibitor: Ibuprofen, a non-steroidal analgesic agent. Ibuprofen highly significantly reduced the resting pressure (P less than 0.001), active pressure (P less than 0.001) and frequency (P less than 0.05) of cyclic activity of the uterus, as well as menstrual pain (P less than 0.001). Since these effects occurred after a single oral dose of 800 mg Ibuprofen, without side effects or complications, extensive field trials are recommended with this and other PG-synthesis inhibitors, to assess their therapeutic benefits.     

Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression

To investigate whether depression is accompanied by changes in diurnal rhythms of free estradiol and cortisol in different phases of the menstrual cycle, we measured these two hormone levels in saliva samples collected every 2 h for 24 h from 15 healthy normally cycling women and 12 age-matched normally cycling women suffering from major depression taking antidepressants. The assessments were repeated four times over one menstrual cycle: during menstruation and in the late follicular/peri-ovulating, early to mid-luteal and late luteal phases, respectively. Quantification with a nonlinear periodic regression model revealed distinct diurnal rhythms in free estradiol and free cortisol in all subjects. For the diurnal cortisol rhythm, significant differences were found in the peak-width and ultradian amplitude among different menstrual phases, both in controls and depressed patients, while no significant differences were found between the two groups. The diurnal estradiol rhythm, on the other hand, was quite consistent among different menstrual phases within both groups, while the depressed patients had overall larger amplitudes than controls, which is negatively correlated with disease duration. Significant positive correlations between the two hormone rhythms were found for 24-h mean level (mesor), peak, and trough in late luteal phase, and for ultradian harmonics in early to mid-luteal phase in controls, but only for ultradian harmonics in late follicular/peri-ovulating phase and for acrophase in the menstruation phase in depressed patients. A sub-analysis was also performed in patients who received Fluoxetine (n = 7). The findings implicate a close correlation between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, both of which may be involved in depression.     

Effects of daily activities on ambulatory blood pressure during menstrual cycle in normotensive women

The purpose of this study was to determine whether (1) there is a menstrual phase effect on blood pressure (BP) and heart rate (HR), and (2) the effects of physical effort, posture, or moods on BP and HR is mediated by the menstrual phase. Twelve normotensive women, aged between 28 and 50, with normal menstrual cycles were studied. BP was measured at 30- to 60-min intervals during a 24-hr period using an ambulatory BP monitor on Days 1, 8, 15, and 22 of the menstrual cycle. Participants were asked to report their posture, physical effort, and mood (annoyed, tense, and happy) on 5-point Likert-type scales each time the ambulatory BP monitor took measurements. Systolic BP (SBP) was lower on Day 8 of the cycle. Diastolic BP (DBP) and HR were lower on Days 1 and 8. Daytime SBP was affected by the time of the day and posture, but not by moods, whereas daytime DBP was affected by posture and levels of tenseness. The level of physical effort only affected HR, not BP. The average daytime physical and emotional variables had little influence over the average daytime BP. In 1 normotensive women with a normal menstrual cycle, SBP was lower during the follicular phase and DBP and HR were lower during the follicular phase and menstruation even after controlling the effects of other factors. Physical activity or moods had only momentary effects on BP or HR. A cross-validation statistical method used is suggested to study how individuals are affected by various factors. With the use of this method, the inclusion of menstrual phase in the model improved the prediction of SBP for 5 out of the 12 women studied.     

Isotope tracer measures of meal fatty acid metabolism: reproducibility and effects of the menstrual cycle

Oxidation and adipose tissue uptake of dietary fat can be measured by adding fatty acid tracers to meals. These studies were conducted to measure between-study variability of these types of experiments and assess whether dietary fatty acids are handled differently in the follicular vs. luteal phase of the menstrual cycle. Healthy normal-weight men (n = 12) and women (n = 12) participated in these studies, which were block randomized to control for study order, isotope ([3H]triolein vs. [14C]triolein), and menstrual cycle. Energy expenditure (indirect calorimetry), meal fatty acid oxidation, and meal fatty acid uptake into upper body and lower body subcutaneous fat (biopsies) 24 h after the experimental meal were measured. A greater portion of meal fatty acids was stored in upper body subcutaneous adipose tissue (24 +/- 2 vs. 16 +/- 2%, P < 0.005) and lower body fat (12 +/- 1 vs. 7 +/- 1%, P < 0.005) in women than in men. Meal fatty acid oxidation (3H2O generation) was greater in men than in women (52 +/- 3 vs. 45 +/- 2%, P = 0.04). Leg adipose tissue uptake of meal fatty acids was 15 +/- 2% in the follicular phase of the menstrual cycle and 10 +/- 1% in the luteal phase (P = NS). Variance in meal fatty acid uptake was somewhat (P = NS) greater in women than in men, although menstrual cycle factors did not contribute significantly. We conclude that leg uptake of dietary fat is slightly more variable in women than in men, but that there are no major effects of menstrual cycle on meal fatty acid disposal.     

定坤丹联合益母草冲剂治疗孕妇流产后月经失调的临床效果分析

目的:探讨定坤丹联合益母草冲剂治疗孕妇流产后月经失调的临床效果。方法:选取2016年1月-2016年12月我院接受药物流产终止妊娠的妇女120例为研究对象,根据数字随机表法将其随机分为研究组和对照组,每组60例。研究组在妊娠囊排出宫腔后开始服益母草冲剂,1包/次,3次/日,服用2周后加服定坤丹,1丸/次,2次/日,持续服用到月经恢复正常。对照组在同一时间段期间服用益母草冲剂。对比两组患者腹痛消失时间和月经恢复正常时间、恢复正常月经后月经周期、月经量以及治疗有效率。结果:对照组和研究组腹痛消失时间分别为7.62±1.33 d、3.17±0.76 d,月经恢复正常时间分别为69.62±8.45 d、43.21±6.65 d,研究组均显著短于对照组(P0.05)。患者月经恢复后,对照组中有42例正常,研究组有54例正常,研究组月经周期时间正常率显著高于对照组(P0.05)。对照组中月经量有45例正常,研究组中月经量有54例正常,两组月经量比较,研究组月经量正常率显著高于对照组(P0.05)。对照组中痊愈39例,研究组中痊愈51例,研究组治疗有效率显著高于对照组(P0.05)。结论:定坤丹联合益母草冲剂治疗孕妇流产后月经失调临床疗效明显优于单用益母草冲剂治疗。     

Food cravings, mood, and the menstrual cycle

The primary objective of the present investigation was to document positive changes in food cravings, food consumption, and mood changes over the menstrual cycle and to explore the relation between these factors and dieting habits. A total of 32 female undergraduates completed daily self-reports of food cravings, foods eaten, and mood, for 5 or more weeks. Comparisons of these measures in the 10 days preceding (luteal phase) and 10 days following menstruation onset (follicular phase) revealed that both food cravings and amount eaten were greater in the luteal phase than in the follicular phase. Although women also experienced less positive affect in the luteal phase, there was no correlation between mood and either cravings or amount eaten. Women rated as chronic dieters craved less than those rated an nondieters. The findings on mood and eating confirm previous research, whereas those on cravings extend such research by suggesting that carbohydrate cravings may be augmented by the luteal phase in healthy women.     

Efficacy of ketoprofen in treating primary dysmenorrhea.

A 6-month double-blind crossover trial compared ketoprofen with placebo in the treatment of primary dysmenorrhea in 27 women who satisfied explicit inclusion and exclusion criteria. The response to treatment was assessed with a pain scale and a disability scale and by noting amelioration of associated symptoms, such as nausea, vomiting, diarrhea, fatigue, dizziness and headache. Ketoprofen was significantly superior to placebo in relieving the pain (p less than 0.001), disability (p less than 0.001) and headache (p less than 0.01) associated with menstruation. No order effect of treatment was observed. Adverse effects were few and minimal.     

Effects of isoflavone supplement on healthy women

Effects of the isoflavone supplement on hormonal states in young premenopausal women were studied by cross-over study design. Administration of 20 mg or 40 mg isoflavones (IF) by tablets, of which 1 g contained 43.5 mg daidzein, 6.0 mg genistein, 24.0 mg glycitein, to 40 young female students for one month caused a prolonged menstruation in 60% of young women, shortened menstruation in 20% of young women, 17% remained unchanged and 3% became irregular. Larger dose tended to elongate more, but 17beta-estradiol levels in both follicular and luteal phages were not different between 20 mg and 40 mg isoflavone intake. Equor excreters tended to show low plasma progesteron level in the luteal phase. Detailed hormonal analysis on 3 of students by a cross over study design showed decreased level of 17beta-estradiol throughout the menstruation cycle. SHBG significantly increased about 10% in all three. DEAS, androstendione, and testosterone showed different responses according to the follicular or luteal phase. T3 and T4 increased as a result of isoflavone tablet administration in the follicular phase, but it decreased in the luteal phase. These changes suggest that isoflavones influence not only estrogen receptor-related functions but the hypothalamo-hypophysis-gonadal axis.