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Fertility and Sterility Dec 2022To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of endometriosis-associated pain.
DESIGN
Systematic review and network meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Premenopausal women with endometriosis who had experienced moderate or severe pain.
INTERVENTION(S)
The Web of Science, Embase, Scopus, and MEDLINE were searched until April 10, 2022. Only randomized controlled trials were included. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool 2. A Bayesian random-effects network meta-analysis was used to perform indirect comparisons. I was used to assess the global heterogeneity. Relative treatment estimates were performed. Treatment ranking was performed through the surface under the cumulative ranking curve. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework.
MAIN OUTCOME MEASURE(S)
Endometriosis-associated pain, dysmenorrhea, dyspareunia, and noncyclic pelvic pain reduction.
RESULT
(s): Five studies and 6 randomized controlled trials, including a total of 2,796 women and 10 different doses of oral GnRH antagonist treatments, were eligible for inclusion. All studies were considered to have a low risk of bias. Almost all efficacy- and safety-related outcomes showed a dose-response relationship. Regarding endometriosis-associated pain, the top 3 treatments were elagolix 400 mg, linzagolix 75 mg, and linzagolix 200 mg, with mean differences of -1.26 (95% credible interval [CrI], -1.70 to -0.79), -0.98 (95% CrI, -1.84 to -0.15), and -0.98 (95% CrI, -1.90 to -0.064), respectively. The top 3 treatments to decrease dysmenorrhea were relugolix 40 mg, elagolix 400 mg, and relugolix 20 mg, with mean differences of -1.60 (95% CrI, -2.07 to -1.14), -1.25 (95% CrI, -1.56 to -0.95), and -1.10 (95% CrI, -1.59 to -0.62), respectively. However, only high-dose treatments were significantly associated with most quality of life- and adverse effect-related outcomes. Relugolix 40 and 20 mg and elagolix 400 mg, with odds ratios of 6.88 (95% CrI, 2.18-24.58), 1.60 (95% CrI, 0.62-4.13), and 1.85 (95% CrI, 1.05-3.30), had a significantly increased incidence of adverse events.
CONCLUSION
(s): Oral GnRH antagonists are effective for endometriosis-associated pain and dysmenorrhea and the patient global impression. The incidence of ovarian hypoestrogenic effects in a short-term duration was significant in a dose-effect response, particularly the highest dose.
CLINICAL TRIAL REGISTRATION NUMBER
International Prospective Register of Systematic Reviews registration number CRD42022332904.
Topics: Female; Humans; Bayes Theorem; Dysmenorrhea; Endometriosis; Gonadotropin-Releasing Hormone; Hormone Antagonists; Network Meta-Analysis; Pelvic Pain; Quality of Life
PubMed: 36283862
DOI: 10.1016/j.fertnstert.2022.08.856 -
Frontiers in Pharmacology 2023Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result...
Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result from inflammatory processes and increased contractile activity in the myometrium. The reported use of preparations against inflammation and pain in ethnomedicine as well as current pharmacological data on their inhibition of myometrial contractility led us to hypothesize that this medicinal plant might be a new treatment option for dysmenorrhea. In the first part of the present work, clinical, and studies on the anti-nociceptive and anti-inflammatory, as well as on myometrium relaxing properties of are reviewed. In the second part, cases of five women with dysmenorrhea who were tentatively treated with a product are described. The review revealed thirty-three experimental and studies, but no clinical study, reporting anti-nociceptive and anti-inflammatory effects of extracts and compounds in a wide range of conditions. Moreover, sixteen publications on smooth muscle contractility revealed relaxing effects. The latter consisted of clinical evidence, as well as of and data. The evidence reviewed therefore provided a rational basis for the use of in the treatment of dysmenorrhea. We subsequently set out to tentatively treat patients with a well-tolerated product that is registered (without indication) and commonly used in obstetrics and gynecology in Switzerland. All five treated patients reported a reduction in pain symptoms and 4 out of 5 indicated a reduced intake of painkillers during menstruation. Taken together, the reviewed information on the pharmacological properties and clinical evidence of extracts and compounds as well as the outcomes of all five patients in the case series support our hypothesis in favor of as a new, well-tolerated therapeutic approach for dysmenorrhea. Prospective clinical studies are urgently needed.
PubMed: 38130407
DOI: 10.3389/fphar.2023.1292919 -
The Cochrane Database of Systematic... Dec 2021Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent,... (Review)
Review
BACKGROUND
Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent, cramping pelvic pain that occurs with periods, in the presence of a normal uterus, ovaries and fallopian tubes. It is thought to be caused by uterine contractions (cramps) associated with a high level of production of local chemicals such as prostaglandins. The muscle of the uterus (the myometrium) responds to these high levels of prostaglandins by contracting forcefully, causing low oxygen levels and consequently pain. Nifedipine is a calcium channel blocker in widespread clinical use for preterm labour due to its ability to inhibit uterine contractions in that setting. This review addresses whether this effect of nifedipine also helps with relief of the uterine contractions during menstruation OBJECTIVES: To assess the effectiveness and safety of nifedipine for primary dysmenorrhoea.
SEARCH METHODS
We searched for all published and unpublished randomised controlled trials (RCTs) of nifedipine for dysmenorrhoea, without language restriction and in consultation with the Cochrane Gynaecology and Fertility Group (CGF) Information Specialist. The following databases were searched to 25 November 2021: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. Also searched were the international trial registers: ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal, the Web of Science, OpenGrey, LILACS database, PubMed and Google Scholar. We checked the reference lists of relevant articles.
SELECTION CRITERIA
We included RCTs comparing nifedipine with placebo for the treatment of primary dysmenorrhoea.
DATA COLLECTION AND ANALYSIS
The primary outcomes to be assessed were pain, and health-related quality of life. Secondary outcomes were adverse effects, satisfaction, and need for additional medication. The two review authors independently assessed the included trials. There were insufficient data to allow meaningful meta-analysis.
MAIN RESULTS
The evidence assessed was of very low quality overall. We examined three small RCTs, with a total of 106 participants. Data for analysis could be extracted from only two of these trials (with a total of 66 participants); two trials were published in the 1980s, and the third in 1993. Nifedipine may be effective for "any pain relief" compared to placebo in women with primary dysmenorrhoea (odds ratio (OR) 9.04, 95% confidence interval (CI) 2.61 to 31.31; 2 studies, 66 participants; very low-quality evidence). The evidence suggests that if the rate of pain relief using placebo is 40%, the rate using nifedipine would be between 64% and 95%. For the outcome of "good" or "excellent" pain relief, nifedipine may be more effective than placebo; the confidence interval was very wide (OR 43.78, 95% CI 5.34 to 259.01; 2 studies, 66 participants; very low-quality evidence). We are uncertain if the use of nifedipine was associated with less requirement for additional analgesia use than placebo (OR 0.54, 95% CI 0.07 to 4.20, 1 study, 42 participants; very low-quality evidence). Participants indicated that they would choose to use nifedipine over their previous analgesic if the option was available. There were similar levels of adverse effects and menstruation-related symptoms in the placebo and intervention groups (OR 0.94, 95% CI 0.08 to 10.90; 1 study, 24 participants; very low-quality evidence); if the chance of adverse effects with placebo is 80%, the rate using nifedipine would be between 24% and 98%. There were no results regarding formal assessment of health-related quality of life.
AUTHORS' CONCLUSIONS
The evidence is insufficient to confirm whether nifedipine is a possible medical treatment for primary dysmenorrhoea. The trials included in this review had very low numbers and were of low quality. Notably, there was a large imbalance in numbers randomised between placebo and treatment groups in one of the two trials with data available for analysis. While there was no evidence of a difference noted in adverse effects between groups, more data from larger participant numbers are needed for this outcome. Larger, more well-conducted trials are required to elucidate the potential role of nifedipine in the treatment of this common condition, as it could be a useful addition to the therapeutic options available if shown to be well tolerated and effective. The safety of nifedipine in women of reproductive age is well established from trials of its use in preterm labour, and clinicians are accustomed to off-label use for this indication. The drug is inexpensive and readily available. Other options for relief of primary dysmenorrhoea are not suitable for all women; NSAIDs and the oral contraceptive pill (OCP) are contraindicated for some women, and the OCP is not suitable for women who are trying to conceive. In addition, the trials examined suggest there may be a participant preference for nifedipine.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Infant, Newborn; Menstruation; Nifedipine; Pelvic Pain; Pregnancy
PubMed: 34921554
DOI: 10.1002/14651858.CD012912.pub2 -
Frontiers in Psychiatry 2021Women with primary dysmenorrhea are vulnerable to develop a depressive disorder, which is a common form of psycho-disturbance. However, clinical findings are...
Women with primary dysmenorrhea are vulnerable to develop a depressive disorder, which is a common form of psycho-disturbance. However, clinical findings are inconsistent across studies, and the evidence has not been previously synthesized. This study aims to investigate whether primary dysmenorrhea is associated with a higher risk of depression via a cumulative analysis. Four electronic databases were systematically searched for the eligible studies. The combined effect was assessed by analyzing the relative risk (RR) and standard mean differences (SMD) with a 95% confidence interval (CI). This cumulative analysis was registered on the PROSPERO (ID: CRD42020169601). Of 972 publications, a total of 10 studies involving 4,691 participants were included. Pooled results from six included studies showed that primary dysmenorrhea was associated with a significant depressive disorder ( = 1.72, 95%CI: 1.44 to 2.0, < 0.001; heterogeneity: = 0%, = 0.544). In addition, synthesis results from two studies provided the BDI scores suggested that dysmenorrhea had significantly higher scores when compared to non-dysmenorrhea ( = 0.47, 95% CI: 0.31-0.62, < 0.001; heterogeneity: = 0%, = 0.518). However, in the two studies providing the PROMIS T-Score, the pooled result showed that there was no significant difference between women with dysmenorrhea and those without dysmenorrhea ( = 0.466). The overall quality of the evidence in our study was judged to MODERATE. The present study has confirmed the positive relationship between primary dysmenorrhea and depression. Social supports and medical help from pain management physicians or psychologists are important interventions for women with dysmenorrhea-suffering depressive disorder.
PubMed: 34421672
DOI: 10.3389/fpsyt.2021.686514 -
Evidence-based Complementary and... 2016Primary dysmenorrhea (PD) is one of the most common diseases in gynecology at present. Some clinical trials have reported the effects of moxibustion and confirmed... (Review)
Review
Primary dysmenorrhea (PD) is one of the most common diseases in gynecology at present. Some clinical trials have reported the effects of moxibustion and confirmed temporal factors are the important elements influencing the efficacy of moxibustion. However, no systematic review has yet been conducted. In this study, we assessed the effects of moxibustion in patients with PD enrolled in randomized controlled trials (RCTs) and the difference among different intervention times to start moxibustion. We extracted data for studies searched from 10 electronic databases and evaluated the methodological quality of the included studies. We discussed three outcomes: effective rate, pain remission, and the level of PGF2 in serum. Current clinical researches showed that, compared with nonmoxibustion treatments for PD, moxibustion leads to higher effective rate and lower level of PGF2 in serum. However, there was no difference in using moxibustion to treat PD at different intervention times. Based on the theory of Chinese medicine and the results of this study, choosing 5 ± 2 days before menstruation to start moxibustion can achieve good efficacy for PD patients. However, more high-quality RCTs are needed to confirm the conclusions.
PubMed: 28115970
DOI: 10.1155/2016/6706901 -
Frontiers in Global Women's Health 2022To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with systemic medication or blank control in the treatment of dysmenorrhea. (Review)
Review
Levonorgestrel-releasing intrauterine system vs. systemic medication or blank control for women with dysmenorrhea: Systematic review and meta-analysis of randomized controlled trials.
AIMS
To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with systemic medication or blank control in the treatment of dysmenorrhea.
METHODS
PubMed, EMBASE, the China National Knowledge Infrastructure (CNKI) and Wanfang Data were searched to collect randomized controlled trials (RCTs) comparing LNG-IUS with systemic medication or blank control among women diagnosed with primary dysmenorrhea or secondary dysmenorrhea (adenomyosis or endometriosis) from inception to 2020.04. Der Simonian-Laird random-effect model was used to pool data.
RESULTS
Seventy-one RCTs (6551 patients) were included. Overall bias risk was medium. Sixty-two articles enrolled patients with adenomyosis; LNG-IUS significantly reduced the visual analogue scale (VAS) score compared with the systemic medication group among adenomyosis women at 3 months (standardized mean difference (SMD) = -0.81, 95% confidence interval (CI) -1.22 to -0.40); 6 months (SMD = -1.25, 95%CI: -1.58 to -0.92); 9 months (SMD = -1.23, 95%CI: -1.63 to -0.83); 12 months (SMD = -1.66, 95%CI: -2.14 to -1.18). No difference was found in the incidence of irregular vaginal bleeding (16 RCTs; RR = 0.91, 95%CI: 0.62-1.33, = 0.63, = 4%) and other adverse outcomes. Sensitivity analysis regarding randomization methods was robust. Nine RCTs enrolled endometriosis women. Pooling results showed no significant difference between LNG-IUS and systemic medication treatment in terms of VAS at 6 months (SMD = -0.27, 95% CI: -0.97-0.43). Moreover, LNG-IUS was associated with higher risk of irregular vaginal bleeding (26.8% vs. 0).
CONCLUSIONS
LNG-IUS was associated with a reduced severity of dysmenorrhea compared with systemic medication; it was also beneficial for better control of menstrual blood loss and fewer adverse outcomes. Owing to small sample sizes, further well-designed RCTs are warranted to confirm these findings and long-term effects of LNG-IUS in the treatment of dysmenorrhea.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.
PubMed: 36405811
DOI: 10.3389/fgwh.2022.1013921 -
Korean Journal of Family Medicine Mar 2024Dysmenorrhea and premenstrual syndrome (PMS) are common periodic and frequent complications in women of reproductive age that can negatively affect health and quality of...
BACKGROUND
Dysmenorrhea and premenstrual syndrome (PMS) are common periodic and frequent complications in women of reproductive age that can negatively affect health and quality of life. The present study examined the effects of curcumin on the severity of dysmenorrhea and PMS symptoms.
METHODS
A systematic review and meta-analysis of randomized controlled trials was conducted by searching databases such as the Cochrane Library, EMBASE, Scopus, PubMed, and Web of Science from inception to January 2023. Article screening was performed using Endnote ver. X8 (Clarivate). Review Manager (RevMan ver. 5.3; Cochrane) was used for the quality assessment and meta-analysis. A total of 147 studies were screened, of which five were finally selected for quantitative and qualitative analyses. The studies were conducted between 2015 and 2021, and a total of 379 participants with a mean age of 23.33±5.54 years had been recruited in these studies.
RESULTS
The meta-analysis showed that curcumin consumption could significantly reduce the severity of dysmenorrhea (mean difference, -1.25; 95% confidence interval [CI], -1.52 to -0.98; three studies; I2=31%) and the overall score of PMS (standardized mean difference, -1.41; 95% CI, -1.81 to -1.02; two studies; I2=0%).
CONCLUSION
The reduction in the severity of PMS and dysmenorrhea has been attributed to curcumin's anti-inflammatory and antidepressant activities. Although the findings suggest that curcumin may be an effective treatment for reducing the severity of PMS and dysmenorrhea, further research with a larger number of participants from various socioeconomic levels and a longer duration of treatment is needed to evaluate the effective dose of curcumin.
PubMed: 38266637
DOI: 10.4082/kjfm.23.0184 -
Obstetrics & Gynecology Science Mar 2024This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain...
The effect of antioxidant supplementation on dysmenorrhea and endometriosis-associated painful symptoms: a systematic review and meta-analysis of randomized clinical trials.
This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain symptoms. The PubMed/Medline, Scopus, and Web of Science databases were searched until April 2022. Additionally, we manually searched the reference lists. Endpoints were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) in a random-effects model. The I2 statistic was used to assess heterogeneity. Ten RCTs were included in this meta-analysis. Overall, 10 studies were related to dysmenorrhea, four to dyspareunia, and four to pelvic pain. Antioxidants significantly reduced dysmenorrhea (SMD, -0.48; 95% CI, -0.82 to -0.13; I2=75.14%). In a subgroup analysis, a significant reduction of dysmenorrhea was observed only in a subset of trials that administered vitamin D (SMD, -0.59; 95% CI, -1.13 to -0.06; I2=69.59%) and melatonin (SMD, -1.40; 95% CI, -2.47 to -0.32; I2=79.15%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, -1.51; 95% CI, -2.74 to -0.29; I2=93.96%), although they seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea (with an emphasis on vitamin D and melatonin) and pelvic pain. However, due to the relatively small sample size and high heterogeneity, the findings should be interpreted cautiously, and the importance of further well-designed clinical studies cannot be overstated.
PubMed: 38221738
DOI: 10.5468/ogs.23210 -
Ginekologia Polska Oct 2023Endometriosis is a chronic inflammatory disease affecting approximately 10% of women. It is defined as endometrial tissue outside of the uterus and produces a variety of...
Endometriosis is a chronic inflammatory disease affecting approximately 10% of women. It is defined as endometrial tissue outside of the uterus and produces a variety of symptoms including pelvic pain, dysmenorrhea, dyspareunia, and intermenstrual bleeding. Although several theories have been postulated regarding the pathogenesis of endometriosis, no theory has provided a complete explanation, therefore limiting our progress in diagnostic tools and management of endometriosis. Recently, much attention has been paid to the importance and role of the gut microbiome in endometriosis. As defined by Joshua Lederberg - microbiome is a set of the genome of microorganisms inhabiting a human body, including commensal, symbiotic and pathogenic microorganisms. The aim of this systematic review was to conduct a search in the Embase, Medline, and PubMed databases for literature from July 2013 to July 2023 regarding the relationship between the gut microbiome and endometriosis. 147 records were screened, of which 26 met the eligibility criteria, and 16 were included in this review. Our review concludes that patients with endometriosis show an altered gut microbiome, and that this has the potential to provide insight for pathogenesis, markers for diagnosis, as well as therapeutic options for treatment of endometriosis. Future research is necessary to confirm this and further investigate the relationship between the gut microbiome and endometriosis.
PubMed: 37772919
DOI: 10.5603/gpl.97581 -
PloS One 2021Chinese herbal footbaths are an external therapy of traditional Chinese medicine that has been widely used to treat dysmenorrhea. This review aims to systematically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chinese herbal footbaths are an external therapy of traditional Chinese medicine that has been widely used to treat dysmenorrhea. This review aims to systematically evaluate its efficacy and safety for the treatment of dysmenorrhea.
METHODS
Databases of PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Database (VIP), Wanfang Database, China Biomedical Literature Database(CBM), and Chinese Biomedical Literature Service System (SinoMed) will be searched from the inception to September 30, 2020. The eligible randomized controlled trials (RCTs) will be identified and included. The primary outcomes include pain intensity measured by validated scales of visual analog scale, numeric rating scale, and response rate of symptom reduction. The secondary outcomes are scores on validated pain questionnaires, quality of life measured by SF-36 or other validated scales, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted by two reviewers independently. RevMan software (V.5.3.5) will be utilized to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of the evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System.
RESULTS
A high-quality synthesis of current evidence of Chinese herbal footbaths for patients with dysmenorrhea will be provided in this study.
CONCLUSION
This systematic review will provide evidence of whether Chinese herbal footbaths are an effective and safe intervention for the treatment of dysmenorrhea.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020188256.
Topics: Baths; Drugs, Chinese Herbal; Dysmenorrhea; Female; Foot; Humans
PubMed: 33939740
DOI: 10.1371/journal.pone.0250685