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Psychoneuroendocrinology Dec 2023The underlying psychobiology that contributes to Anorexia Nervosa (AN) onset and disease progression remains unclear. New research is emerging suggesting a possible link...
INTRODUCTION
The underlying psychobiology that contributes to Anorexia Nervosa (AN) onset and disease progression remains unclear. New research is emerging suggesting a possible link between inflammation and a variety of mental illnesses. Alterations of cytokines may play a role in the pathogenesis of AN. Some studies have found differences in the cytokine profile of those with AN compared to healthy controls, but results are heterogeneous. The aim of this work was to systematically review existing studies investigating in-vivo cytokine production in those with AN before and after weight restoration compared to controls.
METHODS
A comprehensive literature search of four electronic databases (PubMed, PsychInfo, EMBASE and CINAH) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify human in-vivo studies investigating the relationship between AN and cytokine production. Data extracted from included studies related to population characteristics (e.g. age, gender, mean mBMI/%IBW), cytokine measurement and relevant findings. Confounding factors (e.g. smoking status, co-morbid mental illness, menstruation status) were also collected.
RESULTS
36 studies were eligible for this systematic review of which the majority were conducted in Europe (77.8%) and involved female subjects (97.2%). Those with AN ranged in age from 13 to 47 years and had an illness duration of 3 months to 24 years. 15 candidate cytokines and 3 receptors were identified (TNF-alpha, IL-6, IL-1B, CRP, IL-2, IL-7, IL-10, IFN-γ, TNF-R2, IL-1 α, IL-15, TNF-R1, IL-17, IL-18, TGF-B1, IL-12, IL-6R and TGF-B2) exploring in-vivo levels in patients with AN and comparing to controls. TNF-alpha and IL-6 were the most extensively studied with IL-6 being significantly elevated in 4 out of 8 (50%) of longitudinal studies when comparing AN patients at baseline compared to post weight restoration. Following weight restoration, there was no difference in IL-6 levels when comparing to HC in 7 of 8 (87.5%) longitudinal studies examined.
CONCLUSIONS
The most promising cytokine potentially involved in the pathogenesis of AN appears to be IL-6, and possibly TNF-alpha pathways. The heterogeneity of clinical and methodology factors impedes the generalizability of results. Future studies may wish to address these methodological shortcomings as alterations in cytokine levels in AN could act as therapeutic targets assisting with weight restoration and psychopathology and may offer diagnostic potential.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Anorexia Nervosa; Tumor Necrosis Factor-alpha; Interleukin-6; Cytokines; Longitudinal Studies
PubMed: 37769539
DOI: 10.1016/j.psyneuen.2023.106390 -
American Journal of Obstetrics and... May 2020Changes in menstrual bleeding concern many users of the 52 mg Levonorgestrel Intrauterine System. Prescribing information for Levonorgestrel Intrauterine System devices... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Changes in menstrual bleeding concern many users of the 52 mg Levonorgestrel Intrauterine System. Prescribing information for Levonorgestrel Intrauterine System devices describe an overall decrease in bleeding and spotting days over time; however, estimates derived from a variety of existing clinical data are currently unavailable.
OBJECTIVE
The objective of the study was to systematically calculate the mean days of bleeding-only, spotting-only, and bleeding and/or spotting experienced by a population of reproductive-aged Levonorgestrel Intrauterine System users with normal regular menses prior to insertion during the first year of use.
DATA SOURCES
We identified clinical trials, including randomized controlled trials and randomized comparative trials, as well as cohort studies published in English between January 1970 and November 2018 through searching 12 biomedical and scientific literature databases including MEDLINE and ClinicalTrials.gov.
STUDY ELIGIBILITY CRITERIA
We considered studies that reported data on Levonorgestrel Intrauterine System devices releasing 20 μg of levonorgestrel per day, collected daily menstrual bleeding data for at least 90 consecutive days, defined bleeding and spotting per World Health Organization standards and evaluated participants with normal regular menses prior to insertion.
STUDY APPRAISAL AND SYNTHESIS METHODS
We assessed study quality using established guidelines. Two reviewers independently conducted all review stages and rated the quality of evidence for each article; any disagreements were resolved by a third. Where possible, we pooled data using a random-effects model.
RESULTS
Among 3403 potentially relevant studies, we included 7 in our meta-analysis. We calculated the mean days of bleeding-only, spotting-only, and bleeding and/or spotting for the first four 90 day intervals after Levonorgestrel Intrauterine System insertion. Combined menstrual bleeding and/or spotting days gradually decreased throughout the first year, from 35.6 days (95% confidence interval, 32.2-39.1) during the first 90 day interval to 19.1 (95% confidence interval, 16.6-21.5), 14.2 (95% confidence interval, 11.7-16.8), and 11.7 days (95% confidence interval, 9.7-13.7) in the second, third, and fourth intervals. Measures for bleeding-only and spotting-only days similarly decreased throughout the first year, with the greatest decreases occurring between the first and second intervals.
CONCLUSION
Our study provides 90 day reference period measures that characterize menstrual patterns for Levonorgestrel Intrauterine System users with normal regular menses prior to insertion during the first year of use. Our findings provide broader generalizability and more detail than patterns described in the prescribing information. These findings quantify an overall decrease in menstrual bleeding days with longer duration of use, with the greatest decrease occurring between months 3 and 6. Accurately establishing expectations with the Levonorgestrel Intrauterine System may improve informed selection and decrease discontinuation.
Topics: Adult; Contraceptive Agents, Female; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Menstruation; Metrorrhagia; Time Factors
PubMed: 31589865
DOI: 10.1016/j.ajog.2019.09.044 -
BMC Pregnancy and Childbirth Mar 2023The aim of this systematic review and meta-analysis was to introduce the relatively novel method of ultrasound-guided local lauromacrogol injection (USG-LLI) followed by... (Meta-Analysis)
Meta-Analysis
Comparison of clinical safety and efficacy of ultrasound-guided local lauromacrogol injection versus uterine artery embolization in the treatment of caesarean scar pregnancy: a systematic review and meta-analysis.
BACKGROUND
The aim of this systematic review and meta-analysis was to introduce the relatively novel method of ultrasound-guided local lauromacrogol injection (USG-LLI) followed by dilatation and curettage for caesarean scar pregnancy (CSP) and to investigate the clinical safety and efficacy between uterine artery embolization (UAE) and USG-LLI in the treatment of CSP.
METHODS
The relevant literature and articles about USG-LLI, UAE and CSP published in eight electronic databases were searched to extract the primary outcomes for the selected articles. Review Manager Software(RevMan) V.5.2 was used for quantitative data synthesis and data analysis. Forest plots, sensitivity analysis and bias analysis were also performed on the included articles.
RESULTS
Of 10 studies included in our search, 623 patients were in the USG-LLI group and 627 patients were in the UAE groups. There were no significant differences between the two groups in terms of success rate, blood loss and time to human chorionic gonadotropin (hCG) normalization. However, USG-LLI group patients than UAE group patients had a shorter duration of hospital stay (mean difference [MD] = -1.97; 95% confidence intervals [CI] -2.63 to -1.31; P < 0.05; I = 95%), shorter restored menses (MD = -4.84; 95%CI -5.78 to -3.90; P < 0.05; I = 95%), and lower complication rates [odds ratio(OR) = 0.21; 95%CI:0.15 to 0.30; P < 0.05]; and cheaper on expenses of hospitalization (MD = -8028.29; 95%CI -10,311.18 to -5745.40; P < 0.05; I = 100%).
CONCLUSIONS
The results demonstrate that USG-LLI is comparable in curative effect and success rates with UAE in the therapy of CSP, but patients in the USG-LLI group seem to have fewer complications rates, shorter duration of hospital stays and lower costs.
Topics: Female; Pregnancy; Humans; Polidocanol; Cicatrix; Uterine Artery Embolization; Ultrasonography, Interventional; Cesarean Section
PubMed: 36882695
DOI: 10.1186/s12884-023-05455-2 -
Human Reproduction (Oxford, England) Dec 2016Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer? (Meta-Analysis)
Meta-Analysis Review
STUDY QUESTION
Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer?
SUMMARY ANSWER
Younger age and GnRH agonist (GnRHa) administration during chemotherapy were significantly associated with menses recovery, but this recovery was less likely in patients exposed to taxanes.
WHAT IS ALREADY KNOWN
To date, published meta-analyses have only assessed GnRHa administration as a possible factor for ovarian function recovery, and their results were conflicting. Current guidelines present distinct recommendations regarding the use of GnRHa for fertility preservation (FP) in women with breast cancer.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis of published studies in the English, Portuguese, French or Spanish languages (1990-2015), ongoing trials or completed trials (1990-2015) and conference proceedings (2000-2015) were performed.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We searched the MEDLINE, Embase, LILACS, Scielo, Toxline and DART databases, online trial registries and conference proceedings. Studies were eligible if they included premenopausal women with early breast cancer treated with chemotherapy, reported ovarian function recovery data and identified factor(s) associated with recovery. Two authors independently screened the studies, extracted data and assessed the risk of bias. An odds ratio (OR) was estimated from the number of recovery events. A meta-analysis was conducted using a random-effects model.
MAIN RESULTS AND THE ROLE OF CHANCE
Fifteen articles were included. Five different factors were analysed: younger age and baseline levels of anti-Müllerian hormone (patient-related factors), co-administration of GnRHa, addition of taxanes to anthracycline-based chemotherapy and addition of endocrine therapy to chemotherapy (treatment-related factors). Menses recovery was the most used marker. Younger age (≤40 years) and exposure to GnRHa were positively associated with menses recovery (OR 6.07 and 2.03, respectively) but exposure to taxanes adversely affected recovery (OR 0.49). Significant heterogeneity among studies was found.
LIMITATIONS, REASONS FOR CAUTION
A general limitation of the included studies is the use of menses as the main recovery marker. Regarding GnRHa, the substantial heterogeneity and conflicting results limit the interpretation of our results. Studies that use additional markers and have a longer follow-up are needed.
WIDER IMPLICATIONS OF THE FINDINGS
The decision for using chemotherapy regimens with taxanes must take into account their potential adverse effects on female fertility. Considering the conflicting results regarding GnRHa agonist use, other fertility preservation strategies should also be considered.
STUDY FUNDING/COMPETING INTERESTS
No external funding was received. There are no conflicts of interest to declare.
PROSPERO REGISTRATION NUMBER
This review was registered at PROSPERO (CRD42015013494).
Topics: Age Factors; Antineoplastic Agents; Breast Neoplasms; Female; Fertility Preservation; Humans; Ovary; Recovery of Function
PubMed: 27664208
DOI: 10.1093/humrep/dew224 -
The Cochrane Database of Systematic... Sep 2019Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies...
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
To determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.
SEARCH METHODS
We searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.
DATA COLLECTION AND ANALYSIS
We identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.
AUTHORS' CONCLUSIONS
NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral, Combined; Dysmenorrhea; Female; Humans; Menorrhagia; Naproxen; Progesterone; Randomized Controlled Trials as Topic
PubMed: 31535715
DOI: 10.1002/14651858.CD000400.pub4 -
Journal of Education and Health... 2021Recent studies have reported inconclusive results regarding the therapeutic effects of Rosa damascena on the outcomes of primary dysmenorrhea (PD) and premenstrual... (Review)
Review
Recent studies have reported inconclusive results regarding the therapeutic effects of Rosa damascena on the outcomes of primary dysmenorrhea (PD) and premenstrual syndrome (PMS). Hence, this study is aimed to summarize the findings of randomized controlled trials (RCTs) regarding the effects of this treatment on menstruation-related pain as the primary outcome and menstruation-related headache, fatigue, anxiety, and bloating as the secondary outcomes. This study evaluated parallel-group and cross-over RCTs on aromatherapy, topical treatment, or oral intake of R. damascena products for the treatment groups versus placebo, nontreated, or conventional treatment groups. Seven electronic databases (Web of Science Core Collection, Scopus, Embase, CENTRAL, CINAHL, SID, and MagIran) and one search engine (PubMed) were searched from inception to January 15, 2021. Of 1468 trials found in the initial search, 983 potentially relevant articles were screened by title and abstract. After examining the full-text of 13 studies for compliance with the inclusion criteria, seven studies were considered eligible for this review. A random-effects model was used to pool the data; otherwise, a narrative summary was presented. The retrieved studies were conducted on females with PD or PMS, aged 18-35 years. The total sample size of the intervention and comparator arms was 276 and 272. The results showed that R. damascena had a nonsignificant alleviating effect on the menstruation-related pain (weighted mean difference [WMD]: -0.47; 95% confidence interval [CI]: -1.25, 0.31; = 0.234). Such findings were also found for menstruation-related anxiety (WMD: -0.40; 95% CI: -0.91, 0.11; = 0.125). However, the treatment significantly reduced the menstruation-related headache (WMD: -0.42; 95% CI: -0.74, -0.11; = 0.008), fatigue (WMD: -0.48; 95% CI: -0.87, -0.09; = 0.015), and bloating (WMD: -0.72; 95% CI: -1.21, -0.22; = 0.005). Since R. damascena had no significant effects on menstruation-related pain and anxiety, further studies with improved methodological quality are suggested to evaluate the effects of the treatment on these symptoms, using different dosages and durations.
PubMed: 34485569
DOI: 10.4103/jehp.jehp_18_21 -
Annals of Allergy, Asthma & Immunology... Apr 2015To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE). (Review)
Review
OBJECTIVE
To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE).
DATA SOURCES
PubMed was searched with no time limitations using the keywords hereditary angioedema or angio-oedema combined with danazol, stanozolol, and androgen.
STUDY SELECTION
Qualifying articles were English-language reports of androgen use in patients with HAE, with relevant safety and/or efficacy information. Reports were categorized according to level of evidence (LOE).
RESULTS
The search process identified 153 citations, 63 of which contained relevant information; 2 additional publications were identified while other citations were being reviewed. Fifteen LOE 2 studies and multiple LOE 4 reports provided efficacy data, confirming a high level of prophylactic efficacy for androgen therapy in HAE, with occasional reports of poor prophylactic response. Common adverse events include weight gain, menstrual irregularities, virilization, headaches, myalgias or cramps, mood changes, and elevations in creatine phosphokinase level, liver function test results, and serum lipid level. The risk of adverse events is often correlated with dose and/or treatment duration. Rare cases of hepatic adenomas and hepatocellular carcinoma associated with long-term androgen use often had no preceding changes in liver function test results.
CONCLUSION
Androgen therapy may be effective for most patients with HAE; however, potential risks and adverse effects must be carefully considered and discussed with patients when considering options for long-term HAE prophylaxis.
Topics: Androgens; Angioedemas, Hereditary; Animals; Danazol; Drug Dosage Calculations; Female; Humans; Lipid Metabolism; Menstruation Disturbances; Obesity; Risk Assessment; Stanozolol; Time Factors; Virilism
PubMed: 25707325
DOI: 10.1016/j.anai.2015.01.003 -
Frontiers in Pharmacology 2022Motherwort injection (MI) is a modern patented injection extracted from motherwort (Leonurus japonicus Hoult). Empirical studies and systematic reviews have shown the...
Motherwort injection (MI) is a modern patented injection extracted from motherwort (Leonurus japonicus Hoult). Empirical studies and systematic reviews have shown the benefits of motherwort injection for preventing postpartum hemorrhage after vaginal delivery and cesarean section. This study was conducted to explore the efficacy and safety of motherwort injection for women with the prevention of post-abortion uterine hemorrhage. A comprehensive literature search was conducted to identify RCTs regarding the effect of the use of motherwort injection in women after abortion. Data from trials were pooled by meta-analysis and a random-effects model was used to calculate the summarized relative risks (RRs) and their 95% confidence intervals (CIs). The grading of recommendations assessment, development, and evaluation (GRADE) methodology was used to access the quality of the evidence. Nine trials with a total of 1,675 participants were identified. Overall, motherwort injection combined with oxytocin compared to oxytocin had a significantly lower blood loss within 2 hours (MD = -50.00, 95% CI -62.92 to -37.08, very low quality); lower blood loss within 24 h (MD = -50.00, 95% CI -62.92 to -37.08, very low quality); however, there was no significant difference between motherwort injection and oxytocin (24 h: MD: 0.72, 95% CI -7.76 to 9.20; 48 h: MD: -0.01, 95% CI -11.35 to 11.33; 72 h: MD: -1.12, 95% CI -14.39 to 12.15, very low quality). Compared with oxytocin or no intervention, both motherwort injection and motherwort injection combined with oxytocin had a significantly decreased duration of blood loss (MI vs. O: MD -2.59, 95% CI -4.59 to -0.60, very low quality; MI + O vs. O: MD -2.62, 95% CI -3.02 to -2.22, very low quality; MI + O vs. No intervention: MD: -1.80, 95% CI -2.28 to -1.33, low quality). Seven of nine included trials reported adverse event outcomes. Three cases were found in the motherwort injection group, and five induced abortion syndromes were found in the motherwort injection plus oxytocin group. 29 adverse events were reported in the oxytocin group instead. The recovery time of normal menstruation after abortion was significantly earlier in the group using motherwort injection compared with oxytocin (MDs -3.77, 95% CI -6.29 to -1.25, very low quality), and the endometrial thickness in the motherwort injection group was significantly different from that in the oxytocin group (MD: 2.24, 95% CI 1.58 to 2.90, very low quality). The results of this meta-analysis indicate prophylactic use of motherwort injection may reduce the risk of uterine hemorrhage in women after abortion, and more high-quality research is needed to confirm the efficacy and safety of motherwort injection in preventing uterine hemorrhage after abortion. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=274153, identifier CRD42021274153.
PubMed: 35935833
DOI: 10.3389/fphar.2022.916665 -
The Cochrane Database of Systematic... Mar 2017Premenstrual syndrome (PMS) is a psychological and somatic disorder of unknown aetiology, with symptoms typically including irritability, depression, mood swings,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premenstrual syndrome (PMS) is a psychological and somatic disorder of unknown aetiology, with symptoms typically including irritability, depression, mood swings, bloating, breast tenderness and sleep disturbances. About 3% to 10% of women who experience these symptoms may also meet criteria for premenstrual dysphoric disorder (PMDD). PMS symptoms recur during the luteal phase of the menstrual cycle and reduce by the end of menstruation. PMS results from ovulation and may be due to ovarian steroid interactions relating to neurotransmitter dysfunction. Premenstrual disorders have a devastating effect on women, their families and their work.Several treatment options have been suggested for PMS, including pharmacological and surgical interventions. The treatments thought to be most effective tend to fall into one of two categories: suppressing ovulation or correcting a speculated neuroendocrine anomaly.Transdermal oestradiol by patch, gel or implant effectively stops ovulation and the cyclical hormonal changes which produce the cyclical symptoms. These preparations are normally used for hormone therapy and contain lower doses of oestrogen than found in oral contraceptive pills. A shortened seven-day course of a progestogen is required each month for endometrial protection but can reproduce premenstrual syndrome-type symptoms in these women.
OBJECTIVES
To determine the effectiveness and safety of non-contraceptive oestrogen-containing preparations in the management of PMS.
SEARCH METHODS
On 14 March 2016, we searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register; Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; PsycINFO; CINAHL; ClinicalTrials.gov; metaRegister of Controlled trials (mRCT); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal. In addition, we checked the reference lists of articles retrieved.
SELECTION CRITERIA
We included published and unpublished randomized placebo or active controlled trials on the efficacy of the use of non-contraceptive oestrogen-containing preparations in the management of premenstrual syndrome in women of reproductive age with PMS diagnosed by at least two prospective cycles without current psychiatric disorder.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed risk of bias, extracted data on premenstrual symptoms and adverse effects and entered data into Review Manager 5 software. Where possible, intention-to-treat or modified intention-to-treat analysis was used. Studies were pooled using a fixed-effect model, analysing cross-over trials as parallel trials. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. The overall quality of the evidence was assessed using the GRADE working group methods.
MAIN RESULTS
The search resulted in 524 potentially relevant articles. Five eligible randomized controlled trials (RCTs) were identified (305 women). Trials using oral tablets, transdermal patches and implants were identified. No trial used gels.One small cross-over trial (11 women, effective sample size 22 women considering cross-over trials) compared oral luteal-phase oestrogen versus placebo. Data were very low quality and unsuitable for analysis, but study authors reported that the intervention was ineffective and might aggravate the symptoms of PMS. They also reported that there were no adverse events.Three studies compared continuous oestrogen with progestogen versus placebo (with or without progestogen). These trials were of reasonable quality, although with a high risk of attrition bias and an unclear risk of bias due to potential carry-over effects in two cross-over trials. Continuous oestrogen had a small to moderate positive effect on global symptom scores (SMD -0.34, 95% CI -0.59 to -0.10, P = 0.005, 3 RCTs, 158 women, effective sample size 267 women, I² = 63%, very low quality evidence). The evidence was too imprecise to determine if the groups differed in withdrawal rates due to adverse effects (RR 0.64, 95% CI 0.26 to 1.58, P = 0.33, 3 RCTs, 196 women, effective sample size 284 women, I² = 0%, very low quality evidence). Similarly, the evidence was very imprecise in measures of specific adverse events, with large uncertainties around the true value of the relative risk. None of the studies reported on long-term risks such as endometrial cancer or breast cancer.One study compared patch dosage (100 vs 200 µg oestrogen, with progestogen in both arms) and had a high risk of performance bias, detection bias and attrition bias. The study did not find evidence that dosage affects global symptoms but there was much uncertainty around the effect estimate (SMD -1.55, 95% CI -8.88 to 5.78, P = 0.68, 1 RCT, 98 women, very low quality evidence). The evidence on rates of withdrawal for adverse events was too imprecise to draw any conclusions (RR 0.70, 95% CI 0.34 to 1.46, P = 0.34, 1 RCT, 107 women, low-quality evidence). However, it appeared that the 100 µg dose might be associated with a lower overall risk of adverse events attributed to oestrogen (RR 0.51, 95% Cl 0.26 to 0.99, P = 0.05, 1 RCT, 107 women, very low quality evidence) with a large uncertainty around the effect estimate.The overall quality of the evidence for all comparisons was very low, mainly due to risk of bias (specifically attrition), imprecision, and statistical and clinical heterogeneity.
AUTHORS' CONCLUSIONS
We found very low quality evidence to support the effectiveness of continuous oestrogen (transdermal patches or subcutaneous implants) plus progestogen, with a small to moderate effect size. We found very low quality evidence from a study based on 11 women to suggest that luteal-phase oral unopposed oestrogen is probably ineffective and possibly detrimental for controlling the symptoms of PMS. A comparison between 200 µg and 100 µg doses of continuous oestrogen was inconclusive with regard to effectiveness, but suggested that the lower dose was less likely to cause side effects. Uncertainty remains regarding safety, as the identified studies were too small to provide definite answers. Moreover, no included trial addressed adverse effects that might occur beyond the typical trial duration of 2-8 months. This suggests the choice of oestrogen dose and mode of administration could be based on an individual woman's preference and modified according to the effectiveness and tolerability of the chosen regimen.
Topics: Administration, Oral; Drug Implants; Drug Therapy, Combination; Estrogens; Female; Humans; Luteal Phase; Premenstrual Dysphoric Disorder; Premenstrual Syndrome; Progestins; Randomized Controlled Trials as Topic; Transdermal Patch
PubMed: 28257559
DOI: 10.1002/14651858.CD010503.pub2 -
Fertility and Sterility Jun 2024Menstruation serves as an indicator of women's reproductive well-being and plays a pivotal role in their fertility; nevertheless, there remains an ongoing debate... (Review)
Review
IMPORTANCE
Menstruation serves as an indicator of women's reproductive well-being and plays a pivotal role in their fertility; nevertheless, there remains an ongoing debate regarding the epidemiological evidence linking menstrual characteristics and fertility.
OBJECTIVE
To explore the correlation between menstrual characteristics and fertility in women of reproductive age.
DATA SOURCES
A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and Cochrane libraries to identify research articles published up until 9 February 2024.
STUDY SELECTION AND SYNTHESIS
We included all studies in which the relationship between menstrual characteristics and pregnancy rates among women of reproductive age was investigated. We excluded studies involving the administration of oral contraceptives, application of assisted reproductive technologies, and individuals with a documented history of infertility or partners with a known history of infertility.
MAIN OUTCOMES
Clinical pregnancy and miscarriage.
RESULTS
This meta-analysis was composed of nine studies involving a total of 399,966 women, and the evidential quality derived from these studies was deemed to be high with a low risk of bias. Compared with a normal menstrual cycle length (2532 days), the impact of a short (<25 days) or long (>32 days) menstrual cycle on a woman's pregnancy was relatively insignificant (OR=0.81, CI [0.65, 1.01], I=68%; OR=0.89, CI [0.75, 1.06], I=60%, respectively); however, a change in cycle length may increase the risk of miscarriage (RR=1.87, CI [1.11, 3.15], I=0%; RR=1.66, CI [1.07, 2.57], I=43%, respectively). In comparison to women experiencing menarche at a typical age (1214 years), those with a late age at menarche (>14 years) exhibited a decreased likelihood of pregnancy (OR=0.92, CI [0.91, 0.93], I=0%); and compared with women experiencing a normal duration of menstrual bleeding (47 days), those with a short duration of menstrual bleeding (<4 days) exhibited reduced fertility potential (OR=0.86, CI [0.84, 0.88], I=29%).
CONCLUSION AND RELEVANCE
Short and long menstrual cycle lengths may elevate women's susceptibility to spontaneous abortion, whereas late age at menarche and short duration of menstrual bleeding appear to be linked to diminished fertility among women of reproductive age.
PubMed: 38936536
DOI: 10.1016/j.fertnstert.2024.06.016