The influence of physical activity, body mass index and urinary levels of prostaglandin (PGF2α) with the incidence of primary dysmenorrhea in adolescents.

OBJECTIVE: This study aims to investigate the effect of physical activity, body mass index (BMI), and levels of prostaglandins (PGF2α) urine on the occurrence of dysmenorrhea in adolescents. METHODS: A total of 128 female students included in the study. The study was conducted from January to March 2023 using a cross-sectional design. This study utilized the Menstrual Symptom Questionnaire (MSQ) and gynecological examination with ultrasonography. The urinary prostaglandin (PGF2α) was measured using the enzyme linked immuno sorbent assay (ELISA). Data were analyzed using the chi-square test and logistic regression test. RESULTS: The age range of the participants included in the study was 14-17, with a mean age of 15.85 ± 0.65. There was an correlation between physical activity, BMI, and urinary prostaglandin (PGF2α) levels with the incidence of dysmenorrhea in adolescents (p < 0.001). In multivariate analysis, it revealed that underweight, and had a high urinary prostaglandin significant correlated to primary dysmenorrhea with odds ratio 4.78 (95% confidence interval [CI] 1.98-11.54) and 4.88 (95% CI 1.98-12.08), respectively. High physical activity and overweight was not associated with incidence of dysmenorrhea in adolescents. CONCLUSION: This study provides valuable insights into the correlation between physical activity, BMI, and levels of prostaglandins (PGF2α) in urine. A high level of urinary prostaglandin was found to be the most influential factor in the incidence of primary dysmenorrhea in adolescents. By addressing factors associated with dysmenorrhea in adolescents, healthcare professionals can potentially enhance well-being by reducing menstrual pain and encouraging a healthy lifestyle to prevent dysmenorrhea.

Metabolomic study of biochemical changes in the plasma and urine of primary dysmenorrhea patients using UPLC-MS coupled with a pattern recognition approach.

Primary dysmenorrhea (PD) is characterized by painful menstrual cramps without any organic pathology and has a prevalence of up to 90% in adolescents. Recent advances in its etiology and pathogenesis are providing more speculative hypotheses focused on integral systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we explored the changes of metabolic profiling in plasma/urine simultaneously between PD patients and healthy controls before and after a 3-month herbal medicine (namely Shaofu Zhuyu formula concentrated-granule, SFZYFG) therapy. To detect and identify potential biomarkers associated with PD and SFZYFG treatment, we also performed a combined UPLC-QTOF-MS/MS-based metabolomic profiling of the plasma/urine samples, indicating a further deviation of the patients' global metabolic profile from that of controls. The total thirty-five metabolites (nineteen in plasma and sixteen in urine), up-regulated or down-regulated (p < 0.05 or 0.01), were identified and contributed to PD progress. These promising identified biomarkers underpinning the metabolic pathway including sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism are disturbed in PD patients, which were identified by using pathway analysis with MetPA. Twenty-four altered metabolites and fourteen biochemical indicators were restored back to the control-like level after the treatment of SFZYFG and could be potential biomarkers for monitoring therapeutic efficacy. These findings may be promising to yield a valuable insight into the pathophysiology of PD and to advance the approaches of treatment, diagnosis, and prevention of PD and related syndromes.

An integrated study of metabolomics and transcriptomics to reveal the anti-primary dysmenorrhea mechanism of Akebiae Fructus.

ETHNOPHARMACOLOGICAL RELEVANCE: Akebiae Fructus, a Tujia minority folk medicine and a well-known traditional Chinese medicine for soothing the liver, regulating Qi, promoting blood circulation and relieving pain, is widely used in the treatment of primary dysmenorrhea. However, little is known about its underlying mechanism. AIM OF THE STUDY: To explore the effect of Akebiae Fructus on primary dysmenorrhea model induced by estradiol benzoate and oxytocin, and to provide better understanding of the mechanism of Akebiae Fructus for primary dysmenorrhea treatment. MATERIALS AND METHODS: The primary dysmenorrhea mouse model was used in this study. Except for the control group and the normal administration group, the mice of other groups were subcutaneously injected with estradiol benzoate (10 mg/kg/d) for 10 consecutive days. From the 5th day of the ten-day model period, the positive control groups were given 0.075 g/kg ibuprofen and 7.5 g/kg Leonurus granule, the drug groups were given 0.2 g/kg, 0.4 g/kg, 0.8 g/kg Akebiae Fructus extract, the normal administration group was given 0.8 g/kg Akebiae Fructus extract, and the same volume saline was given in the control group. On the tenth day, oxytocin (10 U/kg) was peritoneally injected after estradiol benzoate injected 1 h. After the oxytocin injection, writhing behavior was observed for 30 min. Then the uterine tissue was collected to measure the level of PGF2α and PGE2, and for histological analysis and transcriptomics analysis. Meanwhile, plasma and urine samples were collected for metabolomic analysis. RESULTS: Akebiae Fructus inhibited the writhing, decreased the PGF2α level and ameliorated the morphological changes. 32 potential metabolic biomarkers in plasma and 17 in urine were found for primary dysmenorrhea, and after Akebiae Fructus treatment, 25 metabolites in plasma and 14 in urine were restored. These altered metabolites were mainly involved in lipid, amino acid and organic acid metabolism. For the transcriptomic study, a total of 2244 differentially expressed genes (1346 up-regulated and 898 down-regulated) were obtained between the control and model group, and 148 differentially expressed genes (DEGs) were found related with Akebiae Fructus treatment of primary dysmenorrhea. Correlation analysis was carried out based on the transcriptomic and metabolomic data. 5 differentially expressed genes (Plpp3, Sgpp2, Arg1, Adcy8, Ak5) were found related with the enrichment metabolic pathways. The mechanism by which Akebiae Fructus ameliorates primary dysmenorrhea may account for the regulation of the gene expression to control the key enzymes in the sphingolipid metabolism, arginine and proline metabolism, glycerophospholipid metabolism and purine metabolism, inhibiting the abnormal secretion of PGF2α, alleviating the uterine contraction and reducing inflammation and pain. CONCLUSIONS: Akebiae Fructus could effectively alleviate the symptoms of primary dysmenorrhea, regulate metabolic disorders, and control the related gene expression in primary dysmenorrhea. The study may provide clues for further study of Akebiae Fructus treatment on primary dysmenorrhea.

An integrative urinary metabolomic study of the therapeutic effect of Guizhi Fuling capsule on primary dysmenorrheal rats based 1H NMR and UPLC-MS.

Guizhi Fuling capsule (GFC) was an important traditional Chinese herbal medicine used for the treatment of primary dysmenorrheal (PD). The aim of this study was to evaluate the anti-dysmenorrheal effect of GFC on dysmenorrheal rats induced by oxytocin and to investigate its mechanism of action. An integrative urinary metabolomic study based on 1H NMR and UPLC-MS was used to investigate the therapeutic effect of GFC on PD rats. In addition, in order to obtain more potential biomarkers and to investigate the global urine metabolic profile associated with PD, we combined the characteristics of RP-UPLC-MS with HILIC-UPLC-MS on metabolomic platform to find non-polar and polar metabolites. Finally, a total of 36 potential biomarkers were identified as being primarily involved in the TCA cycle, gluconeogenesis, glycolysis, pentose phosphate pathway, lipid metabolism, energy metabolism, amino acid metabolism and intestinal flora metabolism, and PD could influence the balance of many of these metabolic pathways in vivo. Furthermore, these results also suggested that the GFC had therapeutic effects on PD rats via the regulation of multiple metabolic pathways. In conclusion, the variations in potential biomarkers revealed the therapeutic mechanism of GFC, and these potential biomarkers were both significant for early diagnosis and predicting PD.

Role of leukotrienes in the pathogenesis of dysmenorrhea in adolescent girls.

Although dysmenorrhea is a leading cause of gynecologic complaints among adolescents, its pathogenesis is incompletely understood. The purpose of this study was to determine the role of prostaglandins and leukotrienes in the pathogenesis of dysmenorrhea. Twenty patients with dysmenorrhea aged 16.2+/-1.2 years and 20 healthy age-matched controls with eumenorrhea (absence of pain during menstruation) were included in the study. Serial measurements of serum PGF2alpha and urinary LTE4 levels during the menstrual cycle were obtained; serum progesterone was measured and ultrasonographic evaluations were made. LTE4 and PGF2alpha levels decreased on the third day and recovered on the 10th day of the menstrual cycle in both groups. Urinary LTE4 levels were higher in the control group than in the patient group on the 1st, 3rd and 10th days of the cycle (p<0.05 for each). This study suggests that there is a distinct pattern of leukotriene production during the menstrual cycle, but the changes in the systemic level are not responsible for their role in the pathogenesis of dysmenorrhea. Further studies at the local level in the target organ are necessary to elucidate the role of the lipid mediators in the pathogenesis of dysmenorrhea.

Metabolomics study on primary dysmenorrhea patients during the luteal regression stage based on ultra performance liquid chromatography coupled with quadrupole­time­of­flight mass spectrometry.

Primary dysmenorrhea (PD) is a common gynecological disorder which, while not life­threatening, severely affects the quality of life of women. Most patients with PD suffer ovarian hormone imbalances caused by uterine contraction, which results in dysmenorrhea. PD patients may also suffer from increases in estrogen levels caused by increased levels of prostaglandin synthesis and release during luteal regression and early menstruation. Although PD pathogenesis has been previously reported on, these studies only examined the menstrual period and neglected the importance of the luteal regression stage. Therefore, the present study used urine metabolomics to examine changes in endogenous substances and detect urine biomarkers for PD during luteal regression. Ultra performance liquid chromatography coupled with quadrupole­time­of­flight mass spectrometry was used to create metabolomic profiles for 36 patients with PD and 27 healthy controls. Principal component analysis and partial least squares discriminate analysis were used to investigate the metabolic alterations associated with PD. Ten biomarkers for PD were identified, including ornithine, dihydrocortisol, histidine, citrulline, sphinganine, phytosphingosine, progesterone, 17­hydroxyprogesterone, androstenedione, and 15­keto­prostaglandin F2α. The specificity and sensitivity of these biomarkers was assessed based on the area under the curve of receiver operator characteristic curves, which can be used to distinguish patients with PD from healthy controls. These results provide novel targets for the treatment of PD.

Urinary leukotriene (LT) E(4) in adolescents with dysmenorrhea: a pilot study.

In the present study we measured levels of urinary leukotriene (LT) E(4) as an index of LT production during the menstrual cycle in adolescents. Mean urinary LTE(4) levels in girls with dysmenorrhea was approximately threefold higher than normal laboratory values on Day 1 of the menstrual period and approximately twofold higher than normal laboratory values on Day 5 of the menstrual period. Compared with urinary LTE(4) levels in girls with eumenorrhea, urinary LTE(4) levels in girls with dysmenorrhea were higher on Day 1 [361 +/- 123 pg/mg creatinine vs. 122 +/- 37 pg/mg creatinine, p =.1; not significant (NS)] and on Day 5 (202 +/- 26 pg/mg creatinine vs. 117 +/- 26 pg/mg creatinine, p <.05) of the menstrual period, as well as on Day 10 (159 +/- 33 pg/mg creatinine vs. 88 +/- 21 pg/mg creatinine, p =.1; NS) of the menstrual cycle. Increased urinary excretion of leukotrienes, inflammatory mediators known to cause potent vasoconstriction and uterine contractions, in girls with dysmenorrhea in this pilot study, suggests that these mediators may be involved in generating dysmenorrhea symptoms in adolescents.

Urine peptide patterns for non-invasive diagnosis of endometriosis: a preliminary prospective study.

OBJECTIVE: To detect endometriosis by urine peptide biomarkers using magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and to identify interesting peptides using liquid chromatography tandem mass spectrometry. STUDY DESIGN: Prospective case-control study in a university-based gynecological department and central laboratory. A total of 122 patients suffering from dysmenorrhea, pelvic pain and infertility were enrolled in the study. Urine samples were collected before laparoscopy. Urine samples were analyzed by the MALDI-TOF technique to generate peptide profiling and ClinProTools software was used to set up a diagnostic model for endometriosis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to identify interesting peptides. RESULTS: At laparoscopy 60 patients were diagnosed with endometriosis and 62 patients were disease-free. There were 36 different peptides expressed in endometriosis patients detected by MALDI-TOF compared with controls. We established a genetic algorithm as a diagnostic model with the combination of five peptides (m/z=1433.9, 1599.4, 2085.6, 6798.0 and 3217.2). The model showed a sensitivity of 90.9% and specificity of 92.9%. Urine from another 26 symptomatic patients before laparoscopy were randomly selected and analyzed accordingly. A genetic algorithm showed a sensitivity of 90.9% and specificity of 92.9% in predicting endometriosis before laparoscopy. We also identified two peptides not belonging to the diagnostic model as collagen precursors. CONCLUSIONS: Patients with endometriosis have a unique cluster of peptides in urine. Peptide proteomic profiling provides a novel method for non-invasive diagnosis of endometriosis.

Biomarkers of primary dysmenorrhea and herbal formula intervention: an exploratory metabonomics study of blood plasma and urine.

Primary dysmenorrhea (PDM), a common clinical endocrine disorder affecting young women, is associated with endocrinopathy and metabolic abnormalities. Although some physiological and pathological function parameters have been investigated, little information about the changes of small metabolites in biofluids has been reported, which may cause poor diagnosis and treatment for PDM. The Xiang-Fu-Si-Wu Formula (XFSWF) is a Chinese herbal formula used to treat PDM for hundreds of years. The aim of this study was to establish the metabolic profile of PDM and investigate the action mechanism of XFSWF effect. In this cross-sectional study of 25 patients with PDM and 12 healthy controls, contents of small molecular endogenous metabolites in blood plasma and urine samples were measured by ultra performance liquid chromatography (UPLC) coupled with quadrupole-time-of-flight mass spectrometry (QTOF/MS) and triple quadrupole mass spectrometry (QqQ/MS) based techniques and analyzed by multivariate statistical methods. The levels of LPCs including lypso (16 : 1), lysoPC(20 : 4), lysoPC(18 : 2), lysoPC(16 : 0), lysoPC(18 : 1), lysoPC(10 : 1), estrone, 17-hydroxyprogesterone, myristoylglycine and palmitoylglycine increased significantly (p < 0.05) in PDM, while the levels of phytosphingosine, dihydrocortisol and sphingosine decreased significantly (p < 0.05) compared with the healthy controls. These significant perturbations are involved in glycerophospholipid metabolism and sphingolipid metabolism, as well as steroid hormone biosynthesis. The metabolic deviations recovered to the normal level after XFSWF intervention. The results demonstrated that biofluids metabonomics was a powerful tool in clinical diagnosis and treatment of PDM for providing information on changes in metabolites and neural, endocrinal and immune pathways. XFSWF can be used for the treatment of PDM cases, especially for those adolescents who do not desire a contraceptive method, to reduce the risk of secondary dysmenorrhea.