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Neurology Oct 2021Endogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
Endogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to nonperimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms. We compared perimenstrual and nonperimenstrual migraine attack characteristics and assessed premenstrual syndrome (PMS) in women with migraine.
METHODS
Women with migraine were invited to complete a headache e-diary. Characteristics of perimenstrual attacks and nonperimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake, and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in patients without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and nonmenstrually related migraine (non-MRM) and women with a natural menstrual cycle and women using hormonal contraceptives.
RESULTS
A representative group of 500 participants completed the e-diary for at least 1 month. Perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with longer duration (20.0 vs 16.1 hours, 95% confidence interval 0.2-0.4), higher recurrence risk (odds ratio [OR] 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3 to -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]), and less aura (OR 0.8 [0.6-1.0]). In total, 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs 15%).
DISCUSSION
The longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.
Topics: Adult; Female; Humans; Medical Records; Menstruation; Middle Aged; Migraine Disorders; Prevalence; Tryptamines
PubMed: 34493613
DOI: 10.1212/WNL.0000000000012723 -
Contraception Nov 2023To assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm IUD (Cu380-IUD). (Comparative Study)
Comparative Study Randomized Controlled Trial
Bleeding profile and safety of a levonorgestrel 13.5 mg intrauterine device versus Nova T copper 380 mm intrauterine device: Results of a 3-year, single-center, randomized phase 4 study.
OBJECTIVE
To assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm IUD (Cu380-IUD).
STUDY DESIGN
Single-center, evaluator-masked, randomized study conducted in women aged 18-45 years starting these methods. Primary outcomes were number of bleeding days, self-reported bleeding intensity, Pictorial Blood Assessment Chart (PBAC) score, and blood biochemical values at baseline, months 3, 6, 12, 24, and 36 per 90-day reference periods except for PBAC (months). Secondary objectives were presence/duration/intensity of dysmenorrhea and tolerability.
RESULTS
We included 106 women aged 32.5 ± 6.7 years: 55 with LNG13.5-IUD and 51 with Cu380-IUD. Data for LNG13.5-IUD versus Cu380-IUD at baseline and month 36 (both respectively) were as follows: (1) median (25th; 75th percentile) number of bleeding days: 12 (9.0; 15.0) versus 12 (9.0; 15.0), p = 0.82, and 4 (0; 13.7) versus 15 (14.2; 20.0), p < 0.001; (2) mean bleeding intensity: 1.7 for both, p = 0.66, and 0.7 and 2.2, p < 0.001. Forty percent versus 0% presented with amenorrhea at month 36; (3) mean PBAC score (95% Confidence interval (CI): 50.7 (16.6; 84.7) versus 130.4 (95.7; 165.0) at month 1, and 7.9 (-26.7; 42.6) versus 126 (90.7; 161.2), p < 0.001; (4) median (25th; 75th percentile) ferritin levels (Ug/L) 33 (19; 53) versus 30 (19; 45), p = 0.70, and 59 (42; 84) versus 21 (8; 39). We did not observe changes or differences between groups in hemoglobin and hematocrit. The duration and intensity of dysmenorrhea were significantly lower with LNG13.5-IUD versus Cu380-IUD. Adverse events were those expected.
CONCLUSIONS
LNG13.5-IUD is associated with a significant reduction in blood loss and dysmenorrhea compared with Cu380-IUD.
IMPLICATIONS
Women eligible for a levonorgestrel 13.5 mg intrauterine device (IUD) or a copper 380 mm IUD should be informed of the differences in bleeding profiles-one of the main causes for IUD discontinuation-so they can compare this information against their bleeding expectations.
Topics: Female; Humans; Contraceptive Agents, Female; Copper; Dysmenorrhea; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Adult; Menstruation Disturbances; Menstruation
PubMed: 37487868
DOI: 10.1016/j.contraception.2023.110127 -
Headache Jul 2021To highlight the emerging understanding of oxytocin (OT) and oxytocin receptors (OTRs) in modulating menstrual-related migraine (MRM). (Review)
Review
OBJECTIVE
To highlight the emerging understanding of oxytocin (OT) and oxytocin receptors (OTRs) in modulating menstrual-related migraine (MRM).
BACKGROUND
MRM is highly debilitating and less responsive to therapy, and attacks are of longer duration than nonmenstrually related migraine. A clear understanding of the mechanisms underlying MRM is lacking.
METHODS
We present a narrative literature review on the developing understanding of the role of OT and the OTR in MRM. Literature on MRM on PubMed/MEDLINE database including clinical trials and basic science publications was reviewed using specific keywords.
RESULTS
OT is a cyclically released hypothalamic hormone/neurotransmitter that binds to the OTR resulting in inhibition of trigeminal neuronal excitability that can promote migraine pain including that of MRM. Estrogen regulates OT release as well as expression of the OTR. Coincident with menstruation, levels of both estrogen and OT decrease. Additionally, other serum biochemical factors, including magnesium and cholesterol, which positively modulate the affinity of OT for OTRs, both decrease during menstruation. Thus, during menstruation, multiple menstrually associated factors may lead to decreased circulating OT levels, decreased OT affinity for OTR, and decreased expression of the trigeminal OTR. Consistent with the view of migraine as a threshold disorder, these events may collectively result in decreased inhibition promoting lower thresholds for activation of meningeal trigeminal nociceptors and increasing the likelihood of an MRM attack.
CONCLUSION
Trigeminal OTR may thus be a novel target for the development of MRM therapeutics.
Topics: Estrogens; Female; Humans; Menstrual Cycle; Menstruation Disturbances; Migraine Disorders; Oxytocin; Receptors, Oxytocin
PubMed: 34125955
DOI: 10.1111/head.14152 -
JNCI Cancer Spectrum Jul 2022Hormone-replacement therapy (HRT) is associated with lower colorectal cancer (CRC) risk among postmenopausal women. However, little is known about the effects of...
BACKGROUND
Hormone-replacement therapy (HRT) is associated with lower colorectal cancer (CRC) risk among postmenopausal women. However, little is known about the effects of lifetime exposure of women to varying levels of estrogen and progesterone through reproductive factors such as parity, use of oral contraceptives (OC), breastfeeding, and menstruation on CRC risk.
METHODS
We assessed associations between reproductive factors and CRC risk among 2650 female CRC patients aged 30+ years and 2175 matched controls in a population-based study in Germany, adjusting for potential confounders by multiple logistic regression.
RESULTS
Inverse associations with CRC risk were found for numbers of pregnancies (odds ratio [OR] per pregnancy = 0.91, 95% confidence interval [CI] = 0.86 to 0.97), breastfeeding for 12 months and longer (OR = 0.74, 95% CI = 0.61 to 0.90), and use of either OC or HRT (OR = 0.75, 95% CI = 0.64 to 0.87) or both (OR = 0.58, 95% CI = 0.48 to 0.70). Similar results were found for postmenopausal women only and when adjusting for number of pregnancies and for all reproductive factors analyzed together. Breastfeeding duration of 12 months and longer was associated with lower risk of cancer only in the proximal colon (OR = 0.58, 95% CI = 0.45 to 0.74).
CONCLUSIONS
Several reproductive factors were associated with lower CRC risk in women, including number of pregnancies, breastfeeding duration, and use of OC and HRT. This suggests that women's exposure to female reproductive hormones plays a key role in the difference in CRC risk between women and men and in site-specific CRC risk.
Topics: Case-Control Studies; Colorectal Neoplasms; Contraceptives, Oral; Female; Humans; Male; Odds Ratio; Pregnancy; Reproductive History; Risk Factors
PubMed: 35642982
DOI: 10.1093/jncics/pkac042 -
RMD Open 2019Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and... (Review)
Review
Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and when the duration of amenorrhoea is long. The mechanisms underlying bone loss in anorexia are complex. Oestrogen deficiency has long been considered as the main factor, but cannot explain the phenomenon on its own. The essential role of nutrition-related factors-especially leptin and adiponectin-has been reported in recent studies. Therapeutic strategies to mitigate bone involvement in anorexia are still a matter for debate. Although resumption of menses and weight recovery appear to be essential, they are not always accompanied by a total reversal of bone loss. There are no studies in the literature demonstrating that oestrogen treatment is effective, and the best results seem to have been obtained with agents that induce bone formation-such as IGF-1-especially when associated with oestrogen. As such, bone management in anorexia remains difficult, hence, the importance of early detection and multidisciplinary follow-up.
Topics: Absorptiometry, Photon; Adiponectin; Amenorrhea; Anorexia Nervosa; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Estrogens; Exercise; Female; Humans; Insulin-Like Growth Factor I; Leptin; Lipolysis; Osteoporosis; Recombinant Proteins; Treatment Outcome; Weight Gain
PubMed: 31798952
DOI: 10.1136/rmdopen-2019-001009 -
The Cochrane Database of Systematic... Oct 2019Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the... (Review)
Review
BACKGROUND
Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses.Catamenial epilepsy and seizure exacerbation is common in women with epilepsy, and may have a significant negative impact on quality of life. Women may not be receiving appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aimed to address these issues in order to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases to 10 January 2019: Cochrane Register of Studies (CRS Web; includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE (Ovid: 1946 to 9 January 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials (RCTs) of blinded or opeṉlabel design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. Types of interventions included: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and mean change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
We identified 62 records from the databases and search strategies. Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses.Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for mean change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results on the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported that the decrease in seizure frequency from baseline in the progesterone group was significantly higher than the decrease in seizure frequency from baseline in the placebo group.Results of secondary efficacy outcomes showed no significant difference in terms of treatment withdrawal for any reason in the pooled progesterone RCTs when compared to placebo (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or for treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals from the norethisterone RCTs were reported. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life.We judged the evidence from the included progesterone RCTs to be of low to moderate certainty due to risk of bias and from the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out.Our review highlighted an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those patients who do not have regular menses. Further clinical trials are needed in this area.
PubMed: 31608992
DOI: 10.1002/14651858.CD013225.pub2 -
Human Reproduction (Oxford, England) Sep 2022Is it possible to use free and extracellular vesicle-associated microRNAs (miRNAs) from human endometrial fluid (EF) samples as non-invasive biomarkers for implantative...
STUDY QUESTION
Is it possible to use free and extracellular vesicle-associated microRNAs (miRNAs) from human endometrial fluid (EF) samples as non-invasive biomarkers for implantative endometrium?
SUMMARY ANSWER
The free and extracellular vesicle-associated miRNAs can be used to detect implantative endometrium in a non-invasive manner.
WHAT IS KNOWN ALREADY
miRNAs and extracellular vesicles (EVs) from EF have been described as mediators of the embryo-endometrium crosstalk. Therefore, the analysis of miRNA from this fluid could become a non-invasive technique for recognizing implantative endometrium. This analysis could potentially help improve the implantation rates in ART.
STUDY DESIGN, SIZE, DURATION
In this prospective study, we first optimized different protocols for EVs and miRNA analyses using the EF of a setup cohort (n = 72). Then, we examined differentially expressed miRNAs in the EF of women with successful embryo implantation (discovery cohort n = 15/validation cohort n = 30) in comparison with those for whom the implantation had failed (discovery cohort n = 15/validation cohort n = 30). Successful embryo implantation was considered when pregnancy was confirmed by vaginal ultrasound showing a gestational sac 4 weeks after embryo transfer (ET).
PARTICIPANTS/MATERIALS, SETTING, METHODS
The EF of the setup cohort was obtained before starting fertility treatment during the natural cycle, 16-21 days after the beginning of menstruation. For the discovery and validation cohorts, the EF was collected from women undergoing frozen ET on Day 5, and the samples were collected immediately before ET. In this study, we compared five different methods; two of them based on direct extraction of RNA and the other three with an EV enrichment step before the RNA extraction. Small RNA sequencing was performed to determine the most efficient method and find a predictive model differentiating between implantative and non-implantative endometrium. The models were confirmed using quantitative PCR in two sets of samples (discovery and validation cohorts) with different implantation outcomes.
MAIN RESULTS AND THE ROLE OF CHANCE
The protocols using EV enrichment detected more miRNAs than the methods based on direct RNA extraction. The two most efficient protocols (using polymer-based precipitation (PBP): PBP-M and PBP-N) were used to obtain two predictive models (based on three miRNAs) allowing us to distinguish between an implantative and non-implantative endometrium. The first Model 1 (PBP-M) (discovery: AUC = 0.93; P-value = 0.003; validation: AUC = 0.69; P-value = 0.019) used hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-148b-3p. Model 2 (PBP-N) (discovery: AUC = 0.92; P-value = 0.0002; validation: AUC = 0.78; P-value = 0.0002) used hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-99b-5p. Functional analysis of these miRNAs showed strong association with key implantation processes such as in utero embryonic development or transforming growth factor-beta signaling.
LARGE SCALE DATA
The FASTQ data are available in the GEO database (access number GSE178917).
LIMITATIONS, REASONS FOR CAUTION
One important factor to consider is the inherent variability among the women involved in the trial and among the transferred embryos. The embryos were pre-selected based on morphology, but neither genetic nor molecular studies were conducted, which would have improved the accuracy of our tests. In addition, a limitation in miRNA library construction is the low amount of input RNA.
WIDER IMPLICATIONS OF THE FINDINGS
We describe new non-invasive protocols to analyze miRNAs from small volumes of EF. These protocols could be implemented in clinical practice to assess the status of the endometrium before attempting ET. Such evaluation could help to avoid the loss of embryos transferred to a non-implantative endometrium.
STUDY FUNDING/COMPETING INTEREST(S)
J.I.-P. was supported by a predoctoral grant from the Basque Government (PRE_2017_0204). This study was partially funded by the Grant for Fertility Innovation (GFI, 2011) from Merck (Darmstadt, Germany). It was also supported by the Spanish Ministry of Economy and Competitiveness MINECO within the National Plan RTI2018-094969-B-I00, the European Union's Horizon 2020 research and innovation program (860303), the Severo Ochoa Centre of Excellence Innovative Research Grant (SEV-2016-0644) and the Instituto de Salud Carlos III (PI20/01131). The funding entities did not play any role in the study design, collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication. The authors declare no competing interests.
Topics: Biomarkers; Endometrium; Female; Humans; MicroRNAs; Polymers; Pregnancy; Prospective Studies; Transforming Growth Factors
PubMed: 36029522
DOI: 10.1093/humrep/deac184 -
Frontiers in Surgery 2023To compare the efficacy of transvaginal repair and hysteroscopic resection in improving niche associated postmenstrual spotting.
OBJECTIVE
To compare the efficacy of transvaginal repair and hysteroscopic resection in improving niche associated postmenstrual spotting.
METHODS
The improvement rate of postmenstrual spotting in women who underwent transvaginal repair or hysteroscopic resection treatment was assessed retrospectively in patients accepted at the Niche Sub-Specialty Clinic in International Peace Maternity and Child Health Hospital between June 2017 and June 2019. Postoperative spotting symptom within one year after surgery, pre- and postoperative anatomical indicators, women' satisfaction with menstruation and other perioperative parameters were compared between the two groups.
RESULTS
68 patients in the transvaginal group and 70 patients in the hysteroscopic group were included for analysis. The improvement rate of postmenstrual spotting in the transvaginal group at the 3rd, 6th, 9th, and 12th months after surgery was 87%, 88%, 84%, and 85%, significantly higher than 61%, 68%, 66%, and 68% in the hysteroscopic group, respectively ( < 0.05). The total days of spotting improved significantly at the 3rd month after surgery but did not change over time within one year in each group ( > 0.05). After surgery, the disappearance rates of the niche are 68% in transvaginal group and 38% in hysteroscopic group, however, hysteroscopic resection had shorter operative time and hospitalization duration, less complications, and lower hospitalization costs.
CONCLUSION
Both treatments can improve the spotting symptom and anatomical structures of uterine lower segments with niches. Transvaginal repair is better in thickening the residual myometrium than hysteroscopic resection, however, hysteroscopic resection has shorter operative time and hospitalization duration, less complications, and lower hospitalization costs.
PubMed: 36843994
DOI: 10.3389/fsurg.2023.1019237 -
International Journal of Environmental... Jul 2021: The aim of the study was to assess the influence of both physical activity, such as running and dancing, and the personal characteristics of the studied women on the...
: The aim of the study was to assess the influence of both physical activity, such as running and dancing, and the personal characteristics of the studied women on the occurrence and progression of premenstrual disorder (PMD). : We surveyed 414 women aged 22-48 who were experiencing the menstrual cycle but not using hormonal contraception. There were two physically active groups, runners ( = 215) and Argentine tango dancers ( = 94), and there was one group not undertaking any physical activity-the control group ( = 104). The research was conducted using the researchers' own questionnaire. : The number of days of PMD symptoms in the tango vs. runner vs. control groups are as follows: pre-bleeding (mean: 4.14 vs. 4.86 vs. 4.85; = 0.024), after the onset of bleeding (mean: 1.76 vs. 2.39 vs. 2.16; = 0.001), and in total (mean: 5.94 vs. 7.25 vs. 7.01; < 0.001). The regression analysis results without grouping results are as follows: the number of days of symptoms before bleeding and menarche (B: -0.16; 95% CIs: from -0.29 to -0.04; = 0.011), the total duration of symptoms and menarche (B: -0.17; 95% CIs: from -0.32 to -0.01; = 0.036), lower abdominal pain and age (B: -0.05; 95% CIs: 0.92-0.98; = 0.002), diarrhoea (B: -0.08; 95% CIs: 0.88-0.97; < 0.001), tearfulness, depressive states and age (B: -0.06; 95% CIs: 0.91-0.97; < 0.001), skin problems and age (B: -0.05; 95% CIs: 0.92-0.98; = 0.004), joint pain and age (B: -0.09; 95% CIs: 0.86-0.96; = 0.001), pain in the lumbar spine (B: -0.06, 95% CIs: 0.91-0.98; = 0.001), water retention and BMI (B: 0.09; 95% CIs: 0.92-0.98; = 0.007), and water retention and menarche (B: -0.19; 95% CIs: 0.73-0.94; = 0.003). : generally there is one regression model, we have several here, we have a bit the description. : Physical activity such as dancing (tango) shortens the duration of PMD symptoms but does not completely eliminate them. Running does not have as beneficial an effect on symptom relief as dancing. Current age, age when menstruation began (menarche), and BMI were revealed to be important factors influencing the symptoms of premenstrual disorders.
Topics: Female; Humans; Menarche; Menstrual Cycle; Menstruation; Menstruation Disturbances; Premenstrual Syndrome; Running
PubMed: 34360242
DOI: 10.3390/ijerph18157946 -
The Cochrane Database of Systematic... Aug 2022Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual... (Review)
Review
BACKGROUND
Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non-steroidal anti-inflammatory drugs (NSAIDs), anti-fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use.
OBJECTIVES
To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021.
SELECTION CRITERIA
We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE.
MAIN RESULTS
This review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding. Treatment of heavy menstrual bleeding Cu IUD Vitamin B1 resulted in fewer pads used per day (mean difference (MD) -7.00, 95% confidence interval (CI) -8.50 to -5.50) and fewer bleeding days (MD -2.00, 95% CI -2.38 to -1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence). Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD -64.26, 95% CI -105.65 to -22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI -0.27 to 0.42, 2 trials, 152 women; low-certainty evidence). LNG IUD The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD -9.30 days, 95% CI -26.76 to 8.16; 1 trial, 24 women; low-certainty evidence). Unknown IUD type Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD -2.40, 95% CI -13.77 to 8.97; 1 trial; 84 women; low-certainty evidence). Treatment of pain Cu IUD Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence). Unknown IUD type Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence). Prevention of heavy menstrual bleeding Cu IUD We found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD -14.11, 95% CI -36.04 to 7.82) and duration of bleeding (MD -0.2 days, 95% CI -1.40 to 1.0; 1 trial, 28 women, low-certainty evidence). Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD -0.30, 95% CI -26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence). LNG IUD Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B. There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol. Prevention of pain Cu IUD There was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence).
AUTHORS' CONCLUSIONS
Findings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.
Topics: Acetaminophen; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Ibuprofen; Intrauterine Devices, Medicated; Mefenamic Acid; Menorrhagia; Middle Aged; Naproxen; Thiamine; Tranexamic Acid; Young Adult
PubMed: 36017945
DOI: 10.1002/14651858.CD006034.pub3