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JAMA Pediatrics Apr 2020The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first menstruation) to assess secular trends of pubertal timing, no systematic review has been conducted of secular trends of thelarche.
OBJECTIVES
To systematically evaluate published data on pubertal timing based on age at thelarche and evaluate the change in pubertal onset in healthy girls around the world.
DATA SOURCES
A systematic literature search was performed in PubMed and Embase of all original peer-reviewed articles published in English before June 20, 2019.
STUDY SELECTION
Included studies used clinical assessment of breast development in healthy girls and used adequate statistical methods, including the reporting of SEs or CIs. The quality of the articles was evaluated by assessing study design, potential sources of bias, main characteristics of the study population, and methods of statistical analysis.
DATA EXTRACTION AND SYNTHESIS
In accordance with PRISMA guidelines, all articles were assessed for eligibility independently by 2 authors. Weighted regression analysis was performed using a random-effects model.
MAIN OUTCOMES AND MEASURES
Studies examining age at thelarche (development of Tanner breast stage 2) in healthy girls.
RESULTS
The literature search resulted in a total of 3602 studies, of which 30 studies fulfilled the eligibility criteria. There was a secular trend in ages at thelarche according to race/ethnicity and geography. Overall, the age at thelarche decreased 0.24 years (95% CI, -0.44 to -0.04) (almost 3 months) per decade from 1977 to 2013 (P = .02).
CONCLUSIONS AND RELEVANCE
The age at thelarche has decreased a mean of almost 3 months per decade from 1977 to 2013. A younger age at pubertal onset may change current diagnostic decision-making. The medical community needs current and relevant data to redefine "precocious puberty," because the traditional definition may be outdated, at least in some regions of the world.
Topics: Adolescent; Age Factors; Breast; Child; Female; Humans; Puberty
PubMed: 32040143
DOI: 10.1001/jamapediatrics.2019.5881 -
PloS One 2020The need to control for the potential influence of menstrual cycle phase on resting metabolism (RMR) places a burden on research participants who must self-report onset... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The need to control for the potential influence of menstrual cycle phase on resting metabolism (RMR) places a burden on research participants who must self-report onset of menstruation and researchers who must schedule metabolic testing accordingly.
PURPOSE
To systematically review and analyze existing research to determine the effect of menstrual cycle on RMR.
METHODS
We searched PubMed, CINAHL, MEDLINE, SPORTDiscus, and Scopus databases using the search terms "menstrual cycle and metabolic rate" and "menstrual cycle and energy expenditure." Eligibility criteria were English language, single-group repeated measures design, and RMR as either a primary or secondary outcome. Risk of bias was assessed based on study sample, measurement, and control of confounders. Differences between the follicular and luteal phases of the menstrual cycle were analyzed using the standardized mean difference in effect size.
RESULTS
Thirty English-language studies published between 1930 and December 2019 were included in the systematic review, and 26 studies involving 318 women were included in the meta-analysis. Overall, there was a small but significant effect favoring increased RMR in the luteal phase (ES = 0.33; 95% CI = 0.17, 0.49, p < 0.001).
DISCUSSION
Limitations include risk of bias regarding measurement of both menstrual cycle and RMR. Sample sizes were small and studies did not report control of potential confounders. Sub-group analysis demonstrated that in more recent studies published since 2000, the effect of menstrual phase was reduced and not statistically significant (ES = 0.23; 95% CI = -0.00, 0.47; p = 0.055). Until larger and better designed studies are available, based on our current findings, researchers should be aware of the potential confounding influence of the menstrual cycle and control for it by testing consistently in one phase of the cycle when measuring RMR in pre-menopausal women.
Topics: Basal Metabolism; Female; Humans; Menstrual Cycle; Rest
PubMed: 32658929
DOI: 10.1371/journal.pone.0236025 -
BMC Women's Health Jul 2023Menopause is the time that marks passing 12 months after the last menstruation cycle in women between ages 40-50. Menopausal women often experience depression and...
BACKGROUND
Menopause is the time that marks passing 12 months after the last menstruation cycle in women between ages 40-50. Menopausal women often experience depression and insomnia that significantly impact their overall well-being and quality of life. This systematic review aims to determine the effects of different therapeutic physiotherapy modalities on insomnia and depression in perimenopausal, menopausal, and post-menopausal women.
METHODOLOGY
After identifying our inclusion/exclusion criteria, we conducted a database search in Ovid Embase, MIDRIS, PubMed, Cochrane, and ScienceOpen, where 4007 papers were identified. By using EndNote software, we excluded duplicates, unrelated, and non-full text papers. Adding more studies from manual search, we finally included 31 papers including 7 physiotherapy modalities: exercise, reflexology, footbath, walking, therapeutic and aromatherapy massage, craniofacial message, and yoga.
RESULTS
Reflexology, yoga, walking and aromatherapy massage showed an overall significant impact on decreasing insomnia and depression in menopausal women. Most of exercise and stretching interventions also showed improvement in sleep quality but inconsistent findings regarding depression. However, insufficient evidence was found regarding the effect of craniofacial massage, footbath, and acupressure on improving sleep quality and depression in menopausal women.
CONCLUSION
Using non-pharmaceutical interventions such as therapeutic and manual physiotherapy have an overall positive impact on reducing insomnia and depression in menopausal women.
Topics: Female; Humans; Sleep Initiation and Maintenance Disorders; Postmenopause; Perimenopause; Depression; Quality of Life; Menopause; Physical Therapy Modalities
PubMed: 37422660
DOI: 10.1186/s12905-023-02515-9 -
Human Reproduction Update May 2022Female patients undergoing anticancer treatment are at elevated risk of adverse ovarian outcomes including infertility and premature ovarian insufficiency (POI), which...
BACKGROUND
Female patients undergoing anticancer treatment are at elevated risk of adverse ovarian outcomes including infertility and premature ovarian insufficiency (POI), which is associated with short- and long-term health risks. Anti-Müllerian hormone (AMH) is a key biomarker of ovarian reserve, but its role prior to and after cancer treatment is less well understood.
OBJECTIVE AND RATIONALE
To conduct a systematic review evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment, which has become a pressing clinical issue in reproductive medicine. There are a large number of observational studies, but differences in patient groups, cancer diagnoses and study design make this a confusing field that will benefit from a thorough and robust review.
SEARCH METHODS
A systematic literature search for AMH in women with cancer was conducted in PubMed, Embase and Cochrane Central Register of Controlled Trials up to 1 April 2021. Bias review was conducted using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) protocol along with qualitative assessment of quality. Exploratory subgroups were established based on age, cancer type and length of follow-up.
OUTCOMES
Ninety-two publications (N = 9183 patients) were included in this analysis after quality and bias review. Reduced/undetectable AMH was consistently identified in 69/75 studies (92%) following chemotherapy or radiotherapy, with reductions ranging from 42% to concentrations below the limit of detection, and many reporting mean or median declines of ≥90%. Where longitudinal data were analysed (42 studies), a majority (33/42 (79%)) of studies reported at least partial recovery of AMH at follow-up, however, effect estimates were highly variable, reflecting that AMH levels were strongly impacted by anticancer treatment (i.e. the chemotherapy regimen used and the number of treatment cycles need), with recovery and its degree determined by treatment regimen, age and pre-treatment AMH level. In 16/31 (52%) publications, oligo/amenorrhoea was associated with lower post-treatment AMH consistent with impending POI, although menstruation and/or pregnancy were reported in patients with low or undetectable AMH. Long-term (>5 years) follow-up of paediatric patients following cancer treatment also found significantly lower AMH compared with control groups in 14/20 (70%) of studies, with very variable effect sizes from complete loss of AMH to full recovery depending on treatment exposure, as in adult patients.
WIDER IMPLICATIONS
AMH can be used to identify the damaging effect of cancer treatments on ovarian function. This can be applied to individual women, including pre-pubertal and adolescent girls, as well as comparing different treatment regimens, ages and pre-treatment AMH levels in populations of women. While there was evidence for its value in the diagnosis of POI after cancer treatment, further studies across a range of diagnoses/treatment regimens and patient ages are required to clarify this, and to quantify its predictive value. A major limitation for the use of AMH clinically is the very limited data relating post-treatment AMH levels to fertility, duration of reproductive lifespan or time to POI; analysis of these clinically relevant outcomes will be important in further research.
Topics: Adolescent; Adult; Anti-Mullerian Hormone; Biomarkers; Child; Female; Humans; Neoplasms; Observational Studies as Topic; Ovarian Reserve; Pregnancy; Primary Ovarian Insufficiency
PubMed: 35199161
DOI: 10.1093/humupd/dmac004 -
Reproductive Health Jan 2021Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators.
METHODS
The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD.
RESULTS
The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI.
CONCLUSION
ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.
Topics: Adolescent; Adult; Contraception Behavior; Contraceptive Agents, Female; Contraceptive Agents, Hormonal; Desogestrel; Female; Humans; Intrauterine Devices, Copper; Pregnancy; Treatment Outcome; Young Adult
PubMed: 33407632
DOI: 10.1186/s12978-020-01054-y -
Nutrients Jun 2023Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this... (Meta-Analysis)
Meta-Analysis Review
Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this study, we aimed to assess the effects of vitamin D (vit. D) supplementation in relieving the symptoms of primary dysmenorrhea. A comprehensive systematic database search of randomized controlled trials (RCTs) was performed. Oral forms of vit. D supplementation were included and compared with a placebo or standard care. The degree of dysmenorrhea pain was measured with a visual analogue scale or numerical rating scale. Outcomes were compared using the standardized mean difference (SMD) and 95% confidence intervals (CIs) in a meta-analysis. RCTs were assessed using the Cochrane risk-of-bias v2 (RoB 2) tool. The meta-analysis included 8 randomized controlled trials involving 695 participants. The results of the quantitative analysis showed a significantly lower degree of pain in the vit. D versus placebo in those with dysmenorrhea (SMD: -1.404, 95% CI: -2.078 to -0.731). The results of subgroup analysis revealed that pain lessened when the average weekly dose of vit. D was over 50,000 IU, in which dysmenorrhea was relieved regardless of whether vit. D was administered for more or less than 70 days and in any dose interval. The results revealed that vit. D treatment substantially reduced the pain level in the primary dysmenorrhea population. We concluded that vit. D supplementation is an alternative treatment for relieving the pain symptoms of dysmenorrhea.
Topics: Female; Humans; Dysmenorrhea; Randomized Controlled Trials as Topic; Menstruation; Vitamin D; Dietary Supplements
PubMed: 37447156
DOI: 10.3390/nu15132830 -
PloS One 2023Eumenorrheic women experience cyclic variations in sex hormones attributed to the menstrual cycle (MC) which can impact anterior cruciate ligament (ACL) properties, knee...
Effects of the menstrual cycle phase on anterior cruciate ligament neuromuscular and biomechanical injury risk surrogates in eumenorrheic and naturally menstruating women: A systematic review.
BACKGROUND
Eumenorrheic women experience cyclic variations in sex hormones attributed to the menstrual cycle (MC) which can impact anterior cruciate ligament (ACL) properties, knee laxity, and neuromuscular function. This systematic review aimed to examine the effects of the MC on ACL neuromuscular and biomechanical injury risk surrogates during dynamic tasks, to establish whether a particular MC phase predisposes women to greater ACL injury risk.
METHODS
PubMed, Medline, SPORTDiscus, and Web of Science were searched (May-July 2021) for studies that investigated the effects of the MC on ACL neuromuscular and biomechanical injury risk surrogates. Inclusion criteria were: 1) injury-free women (18-40 years); 2) verified MC phases via biochemical analysis and/or ovulation kits; 3) examined neuromuscular and/or biomechanical injury risk surrogates during dynamic tasks; 4) compared ≥1 outcome measure across ≥2 defined MC phases.
RESULTS
Seven of 418 articles were included. Four studies reported no significant differences in ACL injury risk surrogates between MC phases. Two studies showed evidence the mid-luteal phase may predispose women to greater risk of non-contact ACL injury. Three studies reported knee laxity fluctuated across the MC; two of which demonstrated MC attributed changes in knee laxity were associated with changes in knee joint loading (KJL). Study quality (Modified Downs and Black Checklist score: 7-9) and quality of evidence were low to very low (Grading of Recommendations Assessment Development and Evaluation: very low).
CONCLUSION
It is inconclusive whether a particular MC phase predisposes women to greater non-contact ACL injury risk based on neuromuscular and biomechanical surrogates. Practitioners should be cautious manipulating their physical preparation, injury mitigation, and screening practises based on current evidence. Although variable (i.e., magnitude and direction), MC attributed changes in knee laxity were associated with changes in potentially hazardous KJLs. Monitoring knee laxity could therefore be a viable strategy to infer possible ACL injury risk.
Topics: Humans; Female; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Menstruation; Joint Instability; Knee Joint; Menstrual Cycle; Biomechanical Phenomena
PubMed: 36701354
DOI: 10.1371/journal.pone.0280800 -
The Cochrane Database of Systematic... Dec 2021Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent,... (Review)
Review
BACKGROUND
Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent, cramping pelvic pain that occurs with periods, in the presence of a normal uterus, ovaries and fallopian tubes. It is thought to be caused by uterine contractions (cramps) associated with a high level of production of local chemicals such as prostaglandins. The muscle of the uterus (the myometrium) responds to these high levels of prostaglandins by contracting forcefully, causing low oxygen levels and consequently pain. Nifedipine is a calcium channel blocker in widespread clinical use for preterm labour due to its ability to inhibit uterine contractions in that setting. This review addresses whether this effect of nifedipine also helps with relief of the uterine contractions during menstruation OBJECTIVES: To assess the effectiveness and safety of nifedipine for primary dysmenorrhoea.
SEARCH METHODS
We searched for all published and unpublished randomised controlled trials (RCTs) of nifedipine for dysmenorrhoea, without language restriction and in consultation with the Cochrane Gynaecology and Fertility Group (CGF) Information Specialist. The following databases were searched to 25 November 2021: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. Also searched were the international trial registers: ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal, the Web of Science, OpenGrey, LILACS database, PubMed and Google Scholar. We checked the reference lists of relevant articles.
SELECTION CRITERIA
We included RCTs comparing nifedipine with placebo for the treatment of primary dysmenorrhoea.
DATA COLLECTION AND ANALYSIS
The primary outcomes to be assessed were pain, and health-related quality of life. Secondary outcomes were adverse effects, satisfaction, and need for additional medication. The two review authors independently assessed the included trials. There were insufficient data to allow meaningful meta-analysis.
MAIN RESULTS
The evidence assessed was of very low quality overall. We examined three small RCTs, with a total of 106 participants. Data for analysis could be extracted from only two of these trials (with a total of 66 participants); two trials were published in the 1980s, and the third in 1993. Nifedipine may be effective for "any pain relief" compared to placebo in women with primary dysmenorrhoea (odds ratio (OR) 9.04, 95% confidence interval (CI) 2.61 to 31.31; 2 studies, 66 participants; very low-quality evidence). The evidence suggests that if the rate of pain relief using placebo is 40%, the rate using nifedipine would be between 64% and 95%. For the outcome of "good" or "excellent" pain relief, nifedipine may be more effective than placebo; the confidence interval was very wide (OR 43.78, 95% CI 5.34 to 259.01; 2 studies, 66 participants; very low-quality evidence). We are uncertain if the use of nifedipine was associated with less requirement for additional analgesia use than placebo (OR 0.54, 95% CI 0.07 to 4.20, 1 study, 42 participants; very low-quality evidence). Participants indicated that they would choose to use nifedipine over their previous analgesic if the option was available. There were similar levels of adverse effects and menstruation-related symptoms in the placebo and intervention groups (OR 0.94, 95% CI 0.08 to 10.90; 1 study, 24 participants; very low-quality evidence); if the chance of adverse effects with placebo is 80%, the rate using nifedipine would be between 24% and 98%. There were no results regarding formal assessment of health-related quality of life.
AUTHORS' CONCLUSIONS
The evidence is insufficient to confirm whether nifedipine is a possible medical treatment for primary dysmenorrhoea. The trials included in this review had very low numbers and were of low quality. Notably, there was a large imbalance in numbers randomised between placebo and treatment groups in one of the two trials with data available for analysis. While there was no evidence of a difference noted in adverse effects between groups, more data from larger participant numbers are needed for this outcome. Larger, more well-conducted trials are required to elucidate the potential role of nifedipine in the treatment of this common condition, as it could be a useful addition to the therapeutic options available if shown to be well tolerated and effective. The safety of nifedipine in women of reproductive age is well established from trials of its use in preterm labour, and clinicians are accustomed to off-label use for this indication. The drug is inexpensive and readily available. Other options for relief of primary dysmenorrhoea are not suitable for all women; NSAIDs and the oral contraceptive pill (OCP) are contraindicated for some women, and the OCP is not suitable for women who are trying to conceive. In addition, the trials examined suggest there may be a participant preference for nifedipine.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Infant, Newborn; Menstruation; Nifedipine; Pelvic Pain; Pregnancy
PubMed: 34921554
DOI: 10.1002/14651858.CD012912.pub2 -
Journal of Lifestyle Medicine Feb 2023Primary Dysmenorrhea (PD) is characterized by painful cramps before or during menstruation. It is generally treated with nonpharmacological methods. However, with the... (Review)
Review
Primary Dysmenorrhea (PD) is characterized by painful cramps before or during menstruation. It is generally treated with nonpharmacological methods. However, with the advancement of research and the passage of time, physiotherapy plays an increasingly important role in treating patients with PD. Electrotherapy and exercise therapy are conservative methods to treat PD. Alternative methods to minimize reliance on medicinal-based treatments are the need of the hour. This review aims to determine the efficacy of exercise-based therapies and electrotherapy modalities in treating PD. Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards have been used in the present systematic review and meta-analysis. Cochrane, PubMed, and Google Scholar were searched to facilitate the same. The articles from 2011 to 2021 were included in this review. The quality of the review was assessed using the Cochrane risk of bias tool. The visual analog scale was taken as a measure of pain intensity in the meta-analysis, and other outcomes have been included in the systematic review discussed. A total of 15 publications have been included, with a meta-analysis of 7. All included studies were of high quality (PEDro ≥ 5), and demonstrated the efficacy of exercise-based therapies and electrotherapy modalities in treating pain in females with PD. This review aims to check the impact of exercise and electrotherapy in females suffering from PD.
PubMed: 37250278
DOI: 10.15280/jlm.2023.13.1.16 -
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