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Journal of Clinical Medicine Jun 2022Researchers have been studying COVID-19 from day one, but not much is known about the impact of COVID-19 on the reproductive system, specifically the female reproductive... (Review)
Review
Researchers have been studying COVID-19 from day one, but not much is known about the impact of COVID-19 on the reproductive system, specifically the female reproductive system. There has been substantial anecdotal and media coverage on the effect of COVID-19 on the female reproductive system and changes in the menstrual cycle, but so far available data are not robust enough to draw firm conclusions about the topic. This article was carried out to present already published studies on the correlation between SARS-CoV-2 infection and menstrual cycle changes. A systematic literature search was conducted on the Medline, Scopus, and Cochrane Library databases in accordance with the PRISMA guidelines. Three studies were finally included in the review. The findings of the studies indicate changes in menstrual volume and changes in menstrual cycle length as consequences of SARS-CoV-2 infection; the latter was also the most common menstrual irregularity reported by the included studies. Women have mainly reported decreased menstrual volume and a prolonged cycle. The findings also indicate that the severity of COVID-19 does not play a role in menstrual cycle changes. However, the research on this topic is still too scarce to draw definitive conclusions, and there is a need for further research. The relevant conclusions, which could be drawn only from a well-constructed study, would have a major effect on defining the impact of SARS-CoV-2 infection on the menstrual cycle.
PubMed: 35807090
DOI: 10.3390/jcm11133800 -
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 -
Vacunas 2022The objective of this systematic review is to give a comprehensive interpretation of menstrual cycle changes after the COVID-19 vaccination. Additionally, it is... (Review)
Review
The objective of this systematic review is to give a comprehensive interpretation of menstrual cycle changes after the COVID-19 vaccination. Additionally, it is imperative to assess reports of menstrual changes following vaccination to dispel concerns that COVID-19 vaccines hinder the likelihood of pregnancy in the long run. A literature review was conducted using digital databases to systematically identify the studies reporting any menstrual abnormalities after the COVID-19 vaccine. Detailed patient-level study characteristics including the type of study, sample size, administered vaccines, and menstrual abnormalities were abstracted. A total of 78 138 vaccinated females were included in this review from 14 studies. Of these, 39 759 (52.05%) had some form of a menstrual problem after vaccination. Due to the lack of published research articles, preprints were also included in this review. Menorrhagia, metrorrhagia, and polymenorrhea were the most commonly observed problems and the overall study-level rate of menstrual abnormality ranged from 0.83% to 90.9%. Age, history of pregnancy, systemic side-effects of COVID-19, smoking, and second dose of COVID-19 vaccine were predictors of menstrual problems after vaccination.
PubMed: 35873308
DOI: 10.1016/j.vacun.2022.07.001 -
Human Reproduction Update Mar 2023Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations.
OBJECTIVE AND RATIONALE
We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers.
SEARCH METHODS
A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods.
OUTCOMES
Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36-1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90-1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52-0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38-0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26-0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53-1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low.
WIDER IMPLICATIONS
The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients' preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time.
Topics: Female; Humans; BRCA1 Protein; Breast Neoplasms; Contraceptive Agents; Genetic Predisposition to Disease; Mutation; Ovarian Neoplasms; Reproducibility of Results
PubMed: 36383189
DOI: 10.1093/humupd/dmac038 -
Reproductive Health Jun 2022Menstrual health and hygiene are a major public health and social issues in Nepal. Due to inadequate infrastructure to provide education, healthcare, and communication... (Review)
Review
Menstrual health and hygiene are a major public health and social issues in Nepal. Due to inadequate infrastructure to provide education, healthcare, and communication as well as religious teachings, women and girls are excluded from participation in many activities of daily living and community activities during menstruation. Evidence based research addressing menstrual health and hygiene in Nepal is scares. The objective of this paper is to review the current state of knowledge on menstrual health and hygiene in Nepal through a socio-ecological perspective. This systematic review identifies knowledge gaps and targets for future research and interventions. Studies from Nepal that examined factors contributing to menstrual health and hygiene were identified through searches across six databases (Medline, CINAHL, Web of Science, PsychInfo, Nepal Journals Online and Kathmandu University Medical Journal) in January 2019. The SEM is a public health framework that describes how health is impacted at multiple levels including the individual, interpersonal, community, organizational and policy levels. Key themes were identified, and factors contributing to menstrual health and hygiene were categorized as per the level of socio-ecological model (SEM). After a comprehensive literature review, twenty peer-reviewed publications, published between 2003 and January 2019 were included in this review. Eighteen studies were descriptive and two were interventional. The main outcomes reported were reproductive health concerns and menstrual hygiene practices. Nine studies focused on knowledge, attitude, and practices regarding menstruation, seven studies highlighted reproductive health issues, three studies focused on prevalence of culturally restrictive practices, and one on school absenteeism and intimate partner violence. Lack of awareness regarding menstrual health and hygiene, inadequate WASH facilities, no sex education and culturally restrictive practices makes menstruation a challenge for Nepali women. These challenges have negative implications on women and girls' reproductive as well as mental health and school attendance among adolescent girls. There are gaps in the evidence for high quality interventions to improve menstrual health and hygiene in Nepal. Future research and interventions should address needs identified at all levels of the SEM.
Topics: Activities of Daily Living; Adolescent; Female; Health Knowledge, Attitudes, Practice; Humans; Hygiene; Menstruation; Nepal; Schools
PubMed: 35773696
DOI: 10.1186/s12978-022-01456-0 -
PloS One 2021Disposal and washing facilities and services for menstrual materials are often designed based upon technical specifications rather than an in-depth understanding of what...
BACKGROUND
Disposal and washing facilities and services for menstrual materials are often designed based upon technical specifications rather than an in-depth understanding of what drives peoples' choices of practices.
OBJECTIVES AND DATA SOURCES
This systematic review identified and summarised the main behavioural drivers pertaining to the choice of disposal and washing practices of menstrual materials through the thematic content analysis and study appraisal of 82 publications (80 studies) on menstrual health and hygiene published since 1999, reporting the outcomes of primary research across 26 countries.
RESULTS
Disposal and washing behaviours are primarily driven by the physical state of sanitation facilities; however, this is intrinsically linked to taboos surrounding and knowledge of menstruation.
IMPLICATIONS
Using reasons given for disposal and washing practices by menstruators or those who know them well, or inferred by authors of the reviewed studies, we identify the key considerations needed to design facilities and services which best suit the desired behaviours of both planners and those who menstruate.
INCLUSIVITY
The term menstruators is used throughout to encompass all those mentioned in the studies reviewed (girls and women); although no studies explicitly stated including non-binary or transgender participants, this review uses inclusive language that represents the spectrum of genders that may experience menstruation.
REGISTRATION
The review protocol is registered on PROSPERO: 42019140029.
Topics: Adolescent; Adult; Developing Countries; Female; Health Knowledge, Attitudes, Practice; Humans; Hygiene; Menstrual Hygiene Products; Menstruation; Middle Aged; Sanitation
PubMed: 34860828
DOI: 10.1371/journal.pone.0260472 -
Frontiers in Global Women's Health 2021Women may be particularly vulnerable to alcohol harm, but many current theories fail to acknowledge the unique factors that influence female alcohol use. The biological...
Women may be particularly vulnerable to alcohol harm, but many current theories fail to acknowledge the unique factors that influence female alcohol use. The biological mechanisms underlying female alcohol consumption have largely been unexplored, although recently the menstrual cycle has been highlighted as a potentially important factor. This systematic review, using a narrative synthesis, examined the association between the menstrual cycle phases on alcohol consumption and aimed to determine whether hormonal contraception influences this association. The review follows PRISMA and SWiM guidelines, registration number: CRD42018112744. Electronic searches were conducted in the relevant databases with keyword (e.g., "menstrua"; "alcohol"). Thousand six hundred and sixty-two titles were identified, 16 of which were included in the review. Results were inconsistent regarding whether an association between menstrual cycle phase and alcohol consumption was found. Furthermore, there was inconsistency regarding which phase was associated with higher consumption, and different factors were reported to have moderated the direction, e.g., family history of alcohol use disorder (AUD), premenstrual syndrome (PMS). These conflicting results may be partly explained by variability in both study quality and design, and differences in measurement of cycle phase and alcohol consumption. More robust research is needed before conclusions can be drawn with regard to the role of the menstrual cycle and hormonal contraception on female drinking behavior. This review provides recommendations to strengthen research in this area.
PubMed: 34816249
DOI: 10.3389/fgwh.2021.745263 -
Journal of Ovarian Research Jul 2022Numerous studies have indicated that the level of the Anti-Müllerian hormone (AMH), one of the main markers for the ovarian reserve, does not fluctuate throughout a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Numerous studies have indicated that the level of the Anti-Müllerian hormone (AMH), one of the main markers for the ovarian reserve, does not fluctuate throughout a menstrual cycle, while some studies have rejected this finding. The purpose of this systematic and meta-analysis study is to consensus on all contradictory studies that have measured AMH levels throughout the menstrual cycle and to investigate the exact extent of AMH variation in a cycle.
METHODS
The protocol for this meta-analysis was registered at PROSPERO before data extraction. Relevant studies were identified by systematic search in PubMed, ScienceDirect, Embase, Cochrane Library, and Google Scholar with no limitation on publication date. Longitudinal studies which have evaluated AMH levels in the follicular and luteal phases of an unstimulated (natural) menstrual cycle in healthy women without endocrinology or ovarian disorders were included. We used the JBI Critical Appraisal Checklist for assessing the quality of studies found eligible for meta-analysis.
RESULTS
A total of 11 studies involving 733 women with regular menstrual cycles were included. The results showed that the AMH level in the follicular phase was significantly higher than in the luteal phase (95% Cl = 0.11 [0.01 to 0.21]; p < 0.05) and it varies about 11.5% from the luteal phase. The analysis of studies which had also examined the ovulatory phase (n = 380) showed that the serum levels of AMH in the ovulatory phase (about 2.02 ng/ml) did not significantly vary compared to follicular (95% Cl = 0.11 [-0.10 to 0.33]; p = 0.30) and luteal (95% Cl = 0.06 [-0.08 to 0.20]; p = 0.43) phases.
CONCLUSIONS
According to the results of this study, AMH levels differ between follicular and luteal phases which might be due to ovarian response to the gonadotropins. It seems the phase of AMH measurement needs to be considered for interpretation of the serum AMH test.
Topics: Anti-Mullerian Hormone; Female; Follicular Phase; Humans; Luteal Phase; Menstrual Cycle; Ovarian Reserve; Transforming Growth Factor beta
PubMed: 35778760
DOI: 10.1186/s13048-022-01006-z -
Biology of Sex Differences Jun 2022Relaxin is a hormone which peaks during the luteal phase of the menstrual cycle, and a known collagenolytic promoter that has been shown to avidly bind tissues... (Review)
Review
BACKGROUND
Relaxin is a hormone which peaks during the luteal phase of the menstrual cycle, and a known collagenolytic promoter that has been shown to avidly bind tissues supporting the trapeziometacarpal (TMC) joint in women. We hypothesize a causal linkage between cyclic binding of relaxin to the supporting tissues of the female TMC joint; and to the earlier onset of more severe TMC osteoarthritis (OA) commonly seen in women.
METHODS
A systematic literature review was performed per PRISMA guidelines, qualitatively and quantitatively assessing papers regarding relaxin-TMC joint stability interactions. The primary outcome variable was TMC joint degeneration/loss of function; the "late stage" consequences of relaxin-induced instability. The secondary outcome variable was presence of early signs of relaxin-induced instability; specifically asymptomatic TMC joint laxity in young women.
RESULTS
In healthy young women, menstrual cycle relaxin peaks corresponded with asymptomatic TMC joint instability. Immunohistochemical studies of TMC arthroplasty patients showed avidly increased relaxin binding to supporting tissues around the TMC joint in women but not men. Demographic analysis of patients from the TMC arthroplasty studies show a predominantly female cohort, who were on average significantly younger than the male surgical patients.
CONCLUSIONS
Each relaxin peak during the menstrual cycle can target receptors on the soft tissues supporting the TMC joint, including-critically-the main stabilizing ligament: the anterior oblique. The cyclic instability is typically asymptomatic for years after menarche, but causes cumulative chondral microtrauma. This likely causes the early-onset, high severity TMC joint OA clinically pervasive among female patients at orthopedic hand clinics. Further research is indicated to develop risk assessment strategies and potential interventional options before and after the onset of hormonal laxity-induced OA.
Topics: Case-Control Studies; Female; Humans; Joint Instability; Male; Menstrual Cycle; Osteoarthritis; Relaxin; Thumb
PubMed: 35725646
DOI: 10.1186/s13293-022-00438-y -
Sports Medicine - Open Jun 2021Despite an increasing rate of women participating in professional sports, emergency services, and military settings where they are exposed to exertional heat stress, our...
BACKGROUND
Despite an increasing rate of women participating in professional sports, emergency services, and military settings where they are exposed to exertional heat stress, our understanding of female thermoregulation and the detrimental effects of heat on women's performance, especially regarding the menstrual cycle, is limited. This review aimed to quantify the representation of women in exercise thermoregulation research between 2010 and 2019 and the frequency that these articles reported details pertaining to female participants' menstrual cycle to determine the volume of novel research that is directly relevant to this growing population.
METHODS
Original exercise thermoregulatory studies published in three major sports medicine databases (PubMed, MEDLINE, and SPORTDiscus) between 2010 and 2019 were surveyed. Articles were screened to determine the number of female and male participants in the study and whether studies involving women reported menstrual orientation or phase. Research involving healthy adult participants and an exercise protocol with a thermoregulatory outcome measure were included in the review.
RESULTS
A total of 1407 articles were included in the review, involving 28,030 participants. The annual representation of women ranged from a mean of 11.6% [95% credible interval (CI); 9.2, 14.3] to 17.8% [95% CI; 15.2, 20.6] across the 10 years, indicating studies predominantly included men. Nonetheless, there was a small statistical increase in the overall proportion of women, with a mean overall proportion change of 0.7% [95% CI; 0.2, 1.2] per year. The increase appeared to be driven by a reduction in the number of studies including only men, rather than studies including more women alongside men, or increased women-only studies. Less than one third of articles involving women reported the menstrual orientation of participants and less than one quarter reported both menstrual orientation and phase. This study shows that women were proportionally underrepresented in exercise thermoregulation research during the past decade and the majority of studies did not report menstrual cycle details of female participants. Researchers should consider including women in future work where their inclusion could contribute meaningful data that enhance the evidence-based and ultimately improves our comprehension of women's thermal physiology.
PubMed: 34156570
DOI: 10.1186/s40798-021-00334-6