Ge-gen decoction alleviates primary dysmenorrhoea symptoms in a rat model.

BACKGROUND: Existing treatments for primary dysmenorrhoea (PD), such as NSAIDs, impart side effects. Ge-Gen decoction (GGD), a traditional Chinese medicine, has shown promise in treating PD, but its exact mechanisms remain unclear. Here, we aimed to investigate the efficiency of GGD in alleviating PD using a rat model to understand its precise mechanism of action. METHODS: We established a rat model of dysmenorrhoea induced by oestradiol and oxytocin. The PD rats were administered GGD or Ibuprofen (positive control) intragastrically once daily for seven consecutive days. Serum levels of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), ß-endorphin (ß-EP), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression levels of oestrogen receptor alpha (ERα) and cyclooxygenase-2 (COX-2) in uterine tissue were measured using immunohistochemical assays, and those of phosphorylated and total extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were assessed using western blot analysis. RESULTS: Treatment with GGD significantly reduced writhing behaviour, histopathological scores, and levels of COX-2, PGE2, and PGF2α in the serum of PD rats. Additionally, GGD increased ß-EP content and inhibited ERK1/2 activation and ERα expression in uterine tissues. CONCLUSIONS: The results of this study suggest that GGD alleviates PD in rats by suppressing the COX-2-mediated release of PGE2 and PGF2α, modulating the ERα/ERK1/2/COX-2 pathway, and increasing ß-EP content. These results provide insights into the potential mechanisms of GGD in treating PD and support its further investigation as an alternative therapy for this condition.

Ge-Gen decoction is commonly used to alleviate primary dysmenorrhoea. However, its anti-dysmenorrhoea mechanism remains elusive. In this study, using a rat model of primary dysmenorrhoea, we demonstrate that Ge-Gen decoction reduced the levels of cyclooxygenase-2, prostaglandin E2, and prostaglandin F2 alpha in serum and phosphorylated extracellular signal-regulated protein kinases 1 and 2 in the uterus. These results suggest that Ge-Gen decoction alleviates primary dysmenorrhoea via inactivation of the oestrogen receptor alpha/extracellular signal-regulated protein kinases 1 and 2/cyclooxygenase-2 pathway. This study enhances our understanding of the pathogenesis of primary dysmenorrhoea and may potentially inform the development of novel treatment approaches.

The role of probiotics in improving menstrual health in women with primary dysmenorrhoea: A randomized, double-blind, placebo-controlled trial (the PERIOD study).

BACKGROUND: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea. OBJECTIVE: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea. DESIGN: Randomized placebo-controlled trial. METHODS: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment. RESULTS: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26-1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines. CONCLUSION: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings. REGISTRATION: This study is registered under ClinicalTrials.gov (NCT04119011).

Use of Probiotic in Primary DysmenorrhoeaThis study looked at whether taking probiotics (good bacteria) for 3 months could improve the quality of life and reduce pain in women with painful periods. The study found that probiotics did not significantly improve quality of life scores, but did reduce the use of painkillers and improve mental health scores. However, the probiotics did not have a significant effect on inflammatory markers in the body. More research is needed to confirm the findings.

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Uncommon Location for a Common Disease, Simulating Cervical Cancer: A Rare Case Report.

BACKGROUND: Genital tuberculosis (GTB) is a common form of extra-pulmonary TB with cervical TB being a rare entity accounting for 0.1-0.65% of all TB cases globally. It is usually asymptomatic but may present with infertility, menstrual irregularities, dyspareunia, dysmenorrhoea, or vaginal discharge. CASE PRESENTATION: The present case report briefs about a 39 years old nulliparous infertile woman who presented with complaints of irregular menstrual cycles and amenorrhea with an erosive papillary growth over the cervix simulating invasive cervical carcinoma. Her Pap smear report revealed the presence of granulomas. On cervical punch biopsy also a large number of granulomas were seen and on Ziehl Nielsen staining the diagnosis of TB was further confirmed by the presence of acid-fast rodlike bacilli. The patient responded well to anti-tubercular drugs. DISCUSSION: GTB in most of the cases remains asymptomatic with infertility being the most common presenting complaint. Other symptoms include menstrual irregularities, amenorrhoea, dysmenorrhoea, dyspareunia, chronic pelvic pain, and occasionally abnormal vaginal discharge. Tuberculous cervicitis is difficult to diagnose clinically and many times mimics cervical malignancy. RESULT AND CONCLUSION: Hence, cervical tuberculosis should be kept in the differential diagnosis of cervical cancer especially in an infertile woman from a developing country.

[Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis].

This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.

Dysmenorrhea, intermenstrual bleeding, menstrual flow volume changes, and irregularities following COVID-19 vaccination and the association with vaccine skepticism: A retrospective observational study.

BACKGROUND: COVID-19 vaccines have provided fertile ground for research, especially with the unprecedented spread of misinformation about this disease and its vaccines. Among women, one of the most frequently reported side effects of the vaccine has been menstrual disturbance. OBJECTIVE: To investigate the perceived impact of COVID-19 vaccines on the menstrual cycle. In addition, the research seeks to identify factors that could predispose certain individuals to experience these effects, thereby contributing to a deeper understanding of the interplay between vaccines and menstrual health. DESIGN: We conducted a retrospective observational cross-sectional study. METHODS: Any woman of menstruating age who received at least one dose of the COVID-19 vaccine and currently resides in Saudi Arabia was invited to complete an online questionnaire. The questionnaire compared menstruation characteristics-regularity, volume, intermenstrual bleeding, and dysmenorrhea-before and after receiving the COVID-19 vaccine, taking into consideration possible predisposing factors such as polycystic ovarian syndrome, contraceptives, or period-blocking pills. RESULTS: Women without polycystic ovarian syndrome experienced less change in dysmenorrhea post-vaccine compared to those with polycystic ovarian syndrome (23.88% versus 37.78%, p = 0.045). Women using hormonal contraceptives were about two times more likely to experience changes in volume compared to those not using contraceptives (odds ratio = 2.09, 95% confidence interval = 1.23-3.57, p = 0.006). COVID-19 vaccine skeptics were about three times more likely to perceive changes in regularity post-vaccine compared to non-skeptics (odds ratio = 2.96, 95% confidence interval = 1.79-4.90, p < 0.001). They were also three times more likely to perceive changes in volume post-vaccine (odds ratio = 3.04, 95% confidence interval = 1.95-4.74, p < 0.001). CONCLUSION: Our data suggest significant associations between COVID-19 skepticism, the use of hormonal contraceptives, and the reported post-vaccine menstrual disturbances. This underscores the importance of public education efforts aimed at dispelling misinformation and addressing controversies related to these vaccines.

Effect of curcumin on inflammatory biomarkers and iron profile in patients with premenstrual syndrome and dysmenorrhea: A randomized controlled trial.

Premenstrual syndrome (PMS) and primary dysmenorrhea are common gynecological problems and inflammation may have a role in their etiology. Curcumin is a polyphenolic natural product for which there is increasing evidence of anti-inflammatory and iron chelation effects. This study assessed the effects of curcumin on inflammatory biomarkers and iron profile in young women with PMS and dysmenorrhea. A sample of 76 patients was included in this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 38) and control groups (n = 38). Each participant received one capsule (500 mg of curcuminoid+ piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum iron, ferritin, total iron-binding capacity (TIBC) and high-sensitivity C-reactive protein (hsCRP), as well as white blood cell, lymphocyte, neutrophil, platelet counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were quantified. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. Curcumin significantly decreased the median (interquartile range) serum levels of hsCRP [from 0.30 mg/L (0.0-1.10) to 0.20 mg/L (0.0-1.3); p = 0.041] compared with placebo, but did not show any difference for neutrophil, RDW, MPV, NLR, PLR and RPR values (p > 0.05). The treatment schedule was well-tolerated, and none of markers of iron metabolism statistically changed after the intervention in the curcumin group (p > 0.05). Curcumin supplementation may have positive effects on serum hsCRP, a marker of inflammation, with no any changes on iron homeostasis in healthy women with PMS and dysmenorrhea.

Transvaginal ultrasound- and laparoscopy-guided percutaneous microwave ablation for adenomyosis has short- and long-term benefits: a single-center study.

OBJECTIVES: Transvaginal ultrasound- and laparoscopy-guided percutaneous microwave ablation (TLPMA) is a minimally invasive alternative technique with low risk, fast recovery and few side effects. We aimed to evaluate the safety and long-term efficacy of TLPMA for treating adenomyosis. METHODS: We included 79 patients with symptomatic adenomyosis who underwent TLPMA and 44 patients with adenomyosis who received the levonorgestrel-releasing intrauterine system (LNG-IUS). We evaluated the role of laparoscopy in TLPMA as well as the short- and long-term effects of TLPMA. RESULTS: The mean age of the 79 patients who underwent TLPMA was 41.8 years. There was no difference in the mean age between the TLPMA and LNG-IUS groups. Laparoscopy could help to separate pelvic adhesions, provide a wide antenna path, and observe the uterine surface and bowel movement. No major complications were found in patients who underwent TLPMA. There was a significant post-treatment reduction in both the uterine and lesion volumes (p < 0.001). After a median follow-up duration of 36 months (range: 1-60 months), the uterine and lesion volumes remained stable. Additionally, most patients remained without dysmenorrhea, which confirms the long-term efficacy of TLPMA. CONCLUSIONS: TLPMA is a feasible, minimally invasive technique for the treatment of adenomyosis, which significantly decreases the uterine and lesion volumes and has a good long-term effect.

Investigating the efficacy of ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on pro-inflammatory cytokine levels: A single-arm clinical trial.

BACKGROUND: Endometriosis is a chronic inflammatory disease affecting about 10% of women of reproductive age. Endometrioma is the most common presentation of endometriosis in ovaries. OBJECTIVES: Herein, the authors study the effect of the ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on the plasma levels of pro-inflammatory cytokines. MATERIALS AND METHODS: Each endometrioma was aspirated and washed with 0.9% saline until clearance and then 2/3 of the cyst volume was filled with ethanol 98%. Patients were followed for 3 months. After that, changes in their cyst diameter, dyspareunia, dysmenorrhea, and antral follicular count were assessed. Also, the sera levels of Interleukin 1ß (IL-ß), IL-6, and IL-8 were assayed before and after the treatment. The primary sera levels were also compared with a control group. RESULTS: In the treatment and control groups, 23 and 25 individuals (respectively) with a matched mean age (p-value = 0.680) were enrolled in the study. Among the laboratory variables, IL-1ß (p-value = 0.035), as well as AMH (p-value = 0.002), were lower, and IL-6 (p-value = 0.011) was higher in the endometriosis group compared to the controls. Following the treatment, dysmenorrhea, dyspareunia, and the mean diameter of all cysts were significantly (p-values < 0.001) decreased in the treatment group. Also, right (p-value = 0.022) and left (p-value = 0.002) ovaries' antral follicular counts were increased following the treatment. No significant change was found among any of the investigated laboratory levels (p-value > 0.05). CONCLUSION: Ethanol retention method is proven to be safe and could improve the clinical status of patients with endometrioma. Although further studies are necessary.

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms: A Randomized Clinical Trial.

Importance: Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment. Objective: To determine whether mifepristone is effective and safe for adenomyosis treatment. Design, Setting, and Participants: This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020. Interventions: Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks. Main Outcomes and Measures: The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations. Results: In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported. Conclusions and Relevance: This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT03520439.

El alivio natural: Sauzgatillo (Vitex agnus-castus) para el síndrome premenstrual y la dismenorrea / The natural relief: Chasteberry (Vitex agnus-castus) for premenstrual syndrome and dysmenorrhea

El síndrome premenstrual es un trastorno común en mujeres en edad reproductiva y se caracteriza por al menos un síntoma físico, emocional o conductual, que aparece en la fase lútea del ciclo menstrual y se resuelve poco después del inicio de la menstruación. Los tratamientos convencionales para el dolor perimenstrual cíclico tienen inconvenientes que incluyen efectos secundarios, interferencia con la función reproductiva de las mujeres o escasa efectividad en el alivio de los síntomas. Muchas mujeres recurren a terapias naturales para tratar una gran variedad de síntomas menstruales. Esta revisión se centra en una de esas opciones naturales, el Sauzgatillo (Vitex agnus-castus). Se realizó una búsqueda e identificación de artículos publicados hasta mayo de 2022 recopilados por medio de sistemas de búsqueda electrónicos como Google Scholar, Medline, PubMed y Scopus. Las palabras de búsqueda fueron: “Premenstrual syndrome”, “dysmenorrhea” AND “Vitex agnus-castus”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre el síndrome premenstrual y la dismenorrea.

Premenstrual syndrome is a common disorder in women of reproductive age and is characterized by at least one physical, emotional, or behavioral symptom, which appears in the luteal phase of the menstrual cycle and resolves shortly after the onset of menstruation. Conventional treatments for cyclical perimenstrual pain have drawbacks that include side effects, interference with womens reproductive function, or limited effectiveness in relieving symptoms. Many women turn to natural therapies to treat a wide variety of menstrual symptoms. This review focuses on one of those natural options, Chasteberry (Vitex agnus-castus). The information available until May 2022 was collected via the library and electronic search systems such as Google Scholar, Medline, PubMed, and Scopus. The search words were: “Premenstrual syndrome”, “dysmenorrhea” AND “Vitex agnus-castus”. Preclinical studies point to a mechanism of action in its involvement in the serotoninergic system, as well as its binding to dopamine receptors. Clinical studies prove safety and positive effect on premenstrual syndrome and dysmenorrhea.

Decrease of dysmenorrhoea with hormonal treatment is a marker of endometriosis severity.

RESEARCH QUESTION: Is a decrease in dysmenorrhoea after suppressive hormonal therapy a marker of the endometriosis phenotype and of greater disease severity? DESIGN: Retrospective observational cohort study conducted in a French university hospital, between January 2004 and December 2019. Non-pregnant women aged younger than 42 years, who tested for dysmenorrhoea relief after suppressive hormonal therapy before surgery, and who had histological confirmation of endometriosis, were included. The comparisons were carried out according to the results of the suppressive hormonal test. RESULTS: Of the 578 histologically proven endometriosis patients with preoperative pain symptoms, the rate of dysmenorrhoea decrease after suppressive hormonal therapy was 88.2% (n = 510). These patients had a higher incidence of deep infiltrating endometriosis (DIE) intestinal lesions (45.7% [233/510] versus 30.8% [21/68], P = 0.01) and an increased rate of multiple DIE lesions (two or more) (72.8% [287/394] versus 56.4% [22/39], P = 0.02). After multivariate analysis, decrease of dysmenorrhoea after suppressive hormonal therapy remained significantly associated with the severe DIE phenotype (adjusted OR 3.9, 95% CI 2.0 to 7.6, P < 0.001). CONCLUSION: In women with endometriosis, a decrease of dysmenorrhoea after suppressive hormonal therapy is associated with the DIE phenotype and is a marker of greater severity.

Clinical and sonographic impact of oral contraception in patients with deep endometriosis and adenomyosis at 2 years of follow-up.

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 µg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.

Integrated UPLC-Q-TOF-MS and network pharmacology approach-driven quality marker discovery of Danggui Shaoyao San for primary dysmenorrhea.

Danggui Shaoyao San (DSS), a famous prescription, has been clinically proved to be effective in treating primary dysmenorrhea (PD). Currently there is no valid quality control data available for DSS. The main aim of the current research was to explore quality markers (Q-markers) of DSS. The chemical constituents of DSS were qualitatively identified using ultra-performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) technology. On this basis, the targets of DSS and PD were predicted and screened using the TCMSP, SwissTargetPrediction, GeneCards, OMIM and TTD databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed on the core intersection targets using string and Cytoscape 3.7.1 software. Then molecular docking was conducted to screen the Q-markers of DSS in PD. A total of 126 chemical constituents, including 22 organic acids, 14 phthalides, 24 monoterpenoids, five sesquiterpene lactones, 22 triterpenoids, four phenylpropanoids and 35 other compounds were preliminarily characterized. According to network pharmacology prediction analysis, six compounds containing polyporenic acid C, senkyunolide P, alisol B 23-acetate, naringenin, gallic acid, ferulic acid and albiflorin were regarded as Q-markers of DSS. The present research established an integrative UPLC-Q-TOF-MS and network pharmacology method to discover the latent Q-markers of DSS and provided a theoretical data for the follow-up quality control of DSS.

Clinical evaluation of high-intensity focused ultrasound ablation combined with mifepristone and levonorgestrel-releasing intrauterine system to treat symptomatic adenomyosis.

OBJECTIVE: To evaluate the clinical efficacy of the combination of high-intensity focused ultrasound (HIFU), mifepristone, and levonorgestrel-releasing intrauterine system (LNG-IUS) in adenomyosis treatment. METHODS: HIFU treatment was performed in 123 patients with symptomatic adenomyosis who had refused treatment with gonadotropin-releasing hormone agonist (GnRH-a) at Anyang Maternal and Child Health Care Hospital. In the control group, 34 patients were treated with HIFU alone, 29 patients with HIFU combined with mifepristone, 10 patients with HIFU combined with LNG-IUS. In the study group, 50 patients were treated with HIFU combined with mifepristone and LNG-IUS. RESULTS: Uterine volume, dysmenorrhea pain score, menstruation volume score, and serum CA125 level were significantly lower after treatment with HIFU combined with mifepristone and LNG-IUS than before treatment (p < .05). Moreover, hemoglobin level was significantly higher than that before treatment (p < .05). After 24 months, the efficacy of HIFU combined with mifepristone and LNG-IUS was significantly higher than that of HIFU alone, HIFU combined with mifepristone or HIFU with LNG-IUS (p < .05). CONCLUSIONS: Combination therapy of HIFU, mifepristone, and LNG-IUS is an effective, safe, and inexpensive treatment for patients with symptomatic adenomyosis. This combination therapy demonstrates superior efficacy to treatment with HIFU alone, HIFU combined with mifepristone, and HIFU combined with LNG-IUS.

Clinical efficacy and safety of trimonthly administration of goserelin acetate 10.8 mg in premenopausal Chinese females with symptomatic adenomyosis: a prospective cohort study.

OBJECTIVE: This prospective cohort study aimed to compare the clinical efficacy and safety of goserelin 10.8 mg administered trimonthly with goserelin 3.6 mg administered monthly in premenopausal females with symptomatic adenomyosis. METHODS: We recruited 139 premenopausal females with adenomyosis who complained of dysmenorrhea and/or menorrhagia. The first group (n = 70) received a single subcutaneous injection of goserelin 10.8 mg, and the second group (n = 69) received monthly subcutaneous goserelin 3.6 mg administered for 3 months. Follow-up was performed at the outpatient department after 12 weeks. RESULTS: Ultimately, 130 patients completed the study, including 68 and 62 patients in the goserelin 10.8 mg (n = 70) and 3.6 mg (n = 69) groups, respectively. We observed a significant decrease in the dysmenorrhea (NRS) score, uterine volume, and cancer antigen 125 (CA125) levels, and a significant increase in hemoglobin (HGB) levels in both treatment groups. There was no significant difference between the two groups. The sum of the adverse event scores was slightly higher in the goserelin 3.6 mg than in the 10.8 mg group. CONCLUSIONS: The clinical efficacy of trimonthly administration of goserelin 10.8 mg was equivalent to monthly 3.6 mg dosing and was non-inferior regarding safety and tolerability. Hence, it can be a more cost-effective and convenient alternative treatment option in premenopausal females with symptomatic adenomyosis. TRIAL REGISTRATION: ChiCTR2200059548.

Levonorgestrel-Releasing Intrauterine System Improves Menorrhagia-Related Quality of Life in Patients with Symptomatic Adenomyosis.

Levonorgestrel-releasing intrauterine system (LNG-IUS) relieves dysmenorrhea and heavy menstrual bleeding (HMB) in adenomyosis. However, its efficacy on health-related quality of life (HR-QOL) in patients with symptomatic adenomyosis remains unclear. The menorrhagia multi-attribute scale (MMAS), which measures HR-QOL improvement through the treatment of HMB, has never been used for evaluating menorrhagia-specific HR-QOL in patients with symptomatic adenomyosis. Hence, this study aimed to investigate the efficacy of LNG-IUS in improving menorrhagia-specific HR-QOL in these patients using the MMAS. The participants were diagnosed by magnetic resonance imaging. We also assessed the relationships between menorrhagia-specific HR-QOL, blood hemoglobin levels, and the degree of dysmenorrhea before and during LNG-IUS treatment. The LNG-IUS treatment improved the menorrhagia-specific HR-QOL more effectively in incipient type adenomyosis than in advanced type adenomyosis. The efficacy of LNG-IUS treatment on dysmenorrhea evaluated by the visual analog scale score tended to be better in the incipient type than in the advanced type. By the treatment of LNG-IUS, the blood hemoglobin level was not improved in the advanced type but in the incipient type. Furthermore, dysmenorrhea and HMB-related anemia were associated with HR-QOL impairment, and LNG-IUS treatment may improve the HR-QOL by relieving the symptoms. In conclusion, the effectiveness of LNG-IUS on HR-QOL is decreased by advanced adenomyosis. Thus, magnetic resonance imaging use should be reinforced to predict LNG-IUS efficacy in improving the HR-QOL of patients with adenomyosis.

Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?

Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.

The mechanism of ginger and its processed products in the treatment of estradiol valerate coupled with oxytocin-induced dysmenorrhea in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway.

Ginger (Rhizoma zingiberis, RZ) has been used as a food, spice, supplement, flavoring agent, and as an edible herbal medicine. It is characterized by its pungency and aroma, and is rich in nutrients with remarkable pharmacological effects. It is used in traditional medicine clinics to treat diseases and symptoms, such as colds, headache, and primary dysmenorrhea (PD). In China, a variety of processed products of RZ are used as herbal medicines, such as baked ginger (BG) or ginger charcoal (GC) to treat different diseases and symptoms. However, the molecular mechanism of the therapeutic effect of RZ and its processed products (RZPPs, including BG or GC) against PD has not been well characterized. Moreover, whether the transient receptor potential (TRP) ion channels are involved in this process is not clear. In the present study, UHPLC-Q-TOF MS was adopted to analyse the differential quality markers (DQMs) between RZ and RZPPs. In addition, differential metabolomics (DMs) was acquired between RZ- and RZPPs-treated estradiol valerate coupled with an oxytocin-induced PD mouse uterus using untargeted metabolomics (UM). A correlation analysis between DQMs and DMs was also conducted. Benzenoids, lipids, and lipid-like molecules were the main DQMs between RZ and RZPPs. RZ and RZPPs were found to improve the pathological status of the uterus of a PD mouse, with significantly decreased serum levels of E2, PGF2α, TXB2 and remarkably increased levels of PROG and 6-keto-PGF1α. Moreover, RZ and RZPPs alleviated PD in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway. Our results indicate that the therapeutic effect of RZ and RZPPs against PD may be mediated by regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway, and provide a reference for the development of new dietary supplements or medicines.