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The Cochrane Database of Systematic... Sep 2021This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening 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. Women may not receive 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 aims to address these issues 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 and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included RCTs and quasi-RCTs of blinded or open-label 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. We included the following types of interventions: 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 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
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 change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for 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 a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group. The results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or 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 were reported from the norethisterone RCTs. 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 for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to 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 highlights 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 women who do not have regular menses. Further clinical trials are needed in this area.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Menstruation; Middle Aged; Randomized Controlled Trials as Topic; Seizures; Young Adult
PubMed: 34528245
DOI: 10.1002/14651858.CD013225.pub3 -
Advances in Nutrition (Bethesda, Md.) Jul 2023Breast cancer (BC) poses an important burden of disease, which probably could be reduced by adopting healthy lifestyles like healthy body weight, healthy diet, and... (Meta-Analysis)
Meta-Analysis Review
Breast cancer (BC) poses an important burden of disease, which probably could be reduced by adopting healthy lifestyles like healthy body weight, healthy diet, and physical activity, among others. Many studies have reported that adherence to healthy lifestyles may decrease BC risk. The main objective of this study was to estimate a summary association of studies evaluating a healthy lifestyle index and BC risk. A systematic review and meta-analysis following the Cochrane methodology were carried out. Observational studies, including healthy lifestyle indices and their association with BC, were searched from 4 databases. For the meta-analysis, random-effects model was used to evaluate overall BC risk, BC by molecular subtype and menopausal status. Thirty-one studies were included in the systematic review, and 29 studies in the meta-analysis. When the highest vs. the lowest category to a healthy lifestyle index were compared, the study identified a 20% risk reduction for BC in prospective studies (hazard ratio [HR] 0.80 95% CI: 0.78, 0.83) and an odds ratio (OR) of 0.74 (95% CI: 0.63, 0.86) for retrospective studies. The inverse association remained statistically significant when stratified by menopausal status, except for premenopausal BC in prospective studies. Furthermore, an inverse association was found for molecular subtypes estrogen receptor (ER+)/progesterone receptor (PR+): HR = 0.68 (95%CI: 0.63, 0.73), ER+/PR-: HR = 0.78 (95% CI: 0.67, 0.90) and ER-/PR-: HR = 0.77 (95% CI: 0.64, 0.92). Most studies scored at a low risk of bias and a moderate score for the certainty of the evidence. Adherence to a healthy lifestyle reduces the risk of BC, regardless of its molecular subtypes, which should be considered a priority to generate recommendations for BC prevention at a population level. International prospective register of systematic reviews (PROSPERO) ID: CRD42021267759.
Topics: Humans; Female; Breast Neoplasms; Prospective Studies; Retrospective Studies; Risk; Life Style; Risk Factors
PubMed: 37085092
DOI: 10.1016/j.advnut.2023.04.007 -
Journal of Assisted Reproduction and... Mar 2023To investigate the possibility that altered actions of endogenous progesterone affect receptivity and contribute to unexplained infertility (UI). (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the possibility that altered actions of endogenous progesterone affect receptivity and contribute to unexplained infertility (UI).
METHODS
Two authors electronically searched MEDLINE, CINAHL and Embase databases from inception to 6 July 2022 and hand-searched according to Cochrane methodology. We included all published primary research reporting outcomes related to endogenous progesterone in natural cycles in women with UI. Studies were assessed for risk of bias using a modified Newcastle-Ottawa Score or NHLBI Score. We pooled results where appropriate using a random-effects model. Findings were reported as odds ratios or mean differences.
RESULTS
We included 41 studies (n = 4023). No difference was found between the mid-luteal serum progesterone levels of women with UI compared to fertile controls (MD 0.74, - 0.31-1.79, I 36%). Women with UI had significantly higher rates of 'out-of-phase' endometrium than controls. Nine out of 10 progesterone-mediated markers of endometrial receptivity were significantly reduced in women with UI compared to fertile controls (the remaining 1 had conflicting results). Resistance in pelvic vessels was increased and perfusion of the endometrium and sub-endometrium reduced in UI compared to fertile controls in all included studies. Progesterone receptor expression and progesterone uptake were also reduced in women with unexplained infertility.
CONCLUSIONS
End-organ measures of endogenous progesterone activity are reduced in women with UI compared to fertile controls. This apparently receptor-mediated reduction in response affects endometrial receptivity and is implicated as the cause of the infertility. Further research is required to confirm whether intervention could overcome this issue, offering a new option for treating unexplained infertility.
TRIAL REGISTRATION
PROSPERO registration: CRD42020141041 06/08/2020.
Topics: Female; Humans; Progesterone; Infertility, Female; Endometrium; Corpus Luteum
PubMed: 36572790
DOI: 10.1007/s10815-022-02689-5 -
Sleep Medicine Reviews Dec 2022Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly... (Review)
Review
Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly understood, making it challenging to provide appropriate therapy. Our goal was to i) review the literature about the influence of ovarian hormones on sleep in perimenopausal women, ii) summarize the potential underlying pathophysiology of menopausal sleep disturbances and iii) evaluate the implications of these findings for the therapeutic approach to sleep disturbances in the context of menopause. A systematic literature search using the databases Embase, MEDLINE and Cochrane Library was conducted. Keywords relating to ovarian hormones, sleep disturbances and menopause were used. Ultimately, 86 studies were included. Study Quality Assessment Tools of the National Institutes of Health were used for quality assessment. Results from good-quality studies demonstrated that the postmenopausal decline in estrogen and progesterone contributes to sleep disturbances in women and that timely treatment with estrogen and/or progesterone therapy improved overall sleep quality. Direct and indirect effects of both hormones acting in the central nervous system and periphery, as well as via secondary effects (e.g. reduction in vasomotor symptoms), can contribute to improvements in sleep. To strengthen external validity, studies examining neurobiological pathways are needed.
Topics: United States; Female; Humans; Progesterone; Sleep; Estrogens
PubMed: 36356400
DOI: 10.1016/j.smrv.2022.101710 -
European Review For Medical and... Jan 2017Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general... (Review)
Review
OBJECTIVE
Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general population - approximately 27% and 8%, respectively. This is extremely important in young women, because both disorders are connected with fertility problems. As HT and PCOS occur together, fertility problems may become a serious clinical issue in these patients.
MATERIALS AND METHODS
A systematic literature review in PubMed of PCOS- and HT-related articles in English, published until December 2015 was conducted.
RESULTS
The reasons for joint prevalence still remain unclear. Genetic and autoimmune backgrounds are recognized to be possible common etiological factors. Three genetic polymorphisms have been described to play a role in PCOS as well as in HT. They are polymorphism of the gene for fibrillin 3 (FBN3) regulating the activity of transforming growth factor-b (TGF-b) and regulatory T cell levels, gonadotropin-releasing hormone receptor (GnRHR) polymorphism and CYP1B1 polymorphism standing for estradiol hydroxylation. High estrogen-to-progesterone ratios owing to anovulatory cycles, as well as high estrogen levels during prenatal life, disrupt development of the thymus and its function in maintaining immune tolerance, and are suspected to enhance autoimmune response in PCOS. Vitamin D deficiency could be also involved in the pathogenesis of HT and PCOS.
CONCLUSIONS
The above-mentioned common etiological factors associated with fertility problems in HT and PCOS require further research.
Topics: Cytochrome P-450 CYP1B1; Female; Fibrillins; Hashimoto Disease; Humans; Polycystic Ovary Syndrome; Receptors, LHRH; Transforming Growth Factor beta
PubMed: 28165551
DOI: No ID Found -
Neuro-oncology Advances 2021Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of... (Review)
Review
BACKGROUND
Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients.
METHODS
Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates.
RESULTS
15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordant on ER, 23.0% (95% CI: 18.0%-30.0%) discordant on PR, and 12.0% (95% CI: 8.0%-16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%).
CONCLUSIONS
BCBM exhibits significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.
PubMed: 33898990
DOI: 10.1093/noajnl/vdab010 -
Systematic Reviews Jul 2016Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model.
RESULTS
We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81.
CONCLUSIONS
Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.
Topics: Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Humans; Observational Studies as Topic; Progesterone; Progesterone Congeners; Progestins; Risk Factors
PubMed: 27456847
DOI: 10.1186/s13643-016-0294-5 -
Ultrasound in Obstetrics & Gynecology :... Aug 2016To compare the effects of dydrogesterone and progesterone for luteal-phase support (LPS) in women undergoing assisted reproductive techniques (ART). (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
To compare the effects of dydrogesterone and progesterone for luteal-phase support (LPS) in women undergoing assisted reproductive techniques (ART).
METHODS
We performed a systematic review to identify relevant randomized controlled trials (RCTs) by searching the following electronic databases: Cochrane CENTRAL, PubMed, Scopus, Web of Science, ClinicalTrials.gov, ISRCTN Registry and WHO ICTRP.
RESULTS
The last search was performed in October 2015. Eight RCTs were considered eligible and were included in the review and meta-analyses. There was no relevant difference between oral dydrogesterone and vaginal progesterone for LPS with respect to rate of ongoing pregnancy (risk ratio (RR), 1.04 (95% CI, 0.92-1.18); I(2) , 0%; seven RCTs, 3134 women), clinical pregnancy (RR, 1.07 (95% CI, 0.93-1.23); I(2) , 34%; eight RCTs, 3809 women) or miscarriage (RR, 0.77 (95% CI, 0.53-1.10); I(2) , 0%; seven RCTs, 906 clinical pregnancies). Two of the three studies reporting on dissatisfaction of treatment identified lower levels of dissatisfaction among women using oral dydrogesterone than among women using vaginal progesterone (oral dydrogesterone vs vaginal progesterone capsules: 2/79 (2.5%) vs 90/351 (25.6%), respectively; oral dydrogesterone vs vaginal progesterone gel: 19/411 (4.6%) vs 74/411 (18.0%), respectively). The third study showed no difference in dissatisfaction rate (oral dydrogesterone vs vaginal progesterone capsules: 8/96 (8.3%) vs 8/114 (7.0%), respectively).
CONCLUSIONS
Oral dydrogesterone seems to be as effective as vaginal progesterone for LPS in ART cycles, and appears to be better tolerated . Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Administration, Intravaginal; Administration, Oral; Dydrogesterone; Female; Humans; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Treatment Outcome
PubMed: 26577241
DOI: 10.1002/uog.15814 -
Reviews in Endocrine & Metabolic... Apr 2023Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity... (Review)
Review
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Leptin; C-Reactive Protein; Obesity, Maternal; Adiponectin; Progesterone; Obesity; Biomarkers; Insulin; Chorionic Gonadotropin; Carbon
PubMed: 36520252
DOI: 10.1007/s11154-022-09762-5 -
BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331