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Acta Physiologica (Oxford, England) Aug 2023The immune system plays an important role in mediating exercise responses and adaptations. However, whether fluctuating hormone concentrations across the menstrual cycle... (Meta-Analysis)
Meta-Analysis Review
The immune system plays an important role in mediating exercise responses and adaptations. However, whether fluctuating hormone concentrations across the menstrual cycle may impact these processes remains unknown. The aim of this systematic review with meta-analysis was to compare baseline concentrations as well as exercise-induced changes in immune and inflammatory parameters between menstrual cycle phases. A systematic literature search was conducted according to the PRISMA guidelines using Pubmed/MEDLINE, ISI Web of Science, and SPORTDiscus. Of the 159 studies included in the qualitative synthesis, 110 studies were used for meta-analysis. Due to the designs of the included studies, only the follicular and luteal phase could be compared. The estimated standardized mean differences based on the random-effects model revealed higher numbers of leukocytes (-0.48 [-0.73; -0.23], p < 0.001), monocytes (-0.73 [-1.37; -0.10], p = 0.023), granulocytes (-0.85 [-0.1.48; -0.21], p = 0.009), neutrophils (-0.32 [-0.52; -0.12], p = 0.001), and leptin concentrations (-0.37 [-0.5; -0.23], p = 0.003) in the luteal compared to the follicular phase at rest. Other parameters (adaptive immune cells, cytokines, chemokines, and cell adhesion molecules) showed no systematic baseline differences. Seventeen studies investigated the exercise-induced response of these parameters, providing some indications for a higher pro-inflammatory response in the luteal phase. In conclusion, parameters of innate immunity showed cycle-dependent regulation at rest, while little is known on the exercise responses. Due to a large heterogeneity and a lack of cycle phase standardization among the included studies, future research should focus on comparing at least three distinct hormonal profiles to derive more specific recommendations for exercise prescription.
Topics: Female; Humans; Menstrual Cycle; Follicular Phase; Exercise; Inflammation; Immunity
PubMed: 37309068
DOI: 10.1111/apha.14013 -
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 -
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 -
BMC Medicine Oct 2022Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
METHODS
We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
RESULTS
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
CONCLUSIONS
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Topics: Elafin; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins; Immunologic Factors; Interferons; Interleukin 1 Receptor Antagonist Protein; Interleukin-16; Interleukin-1alpha; Interleukin-6; Interleukins; Lactoferrin; Menstrual Cycle; Muramidase; Progesterone; beta-Defensins
PubMed: 36195867
DOI: 10.1186/s12916-022-02532-9 -
Frontiers in Neuroendocrinology Jul 2022Differential HPA axis function has been proposed to underlie sex-differences in mental disorders; however, the impact of fluctuating sex hormones across the menstrual... (Meta-Analysis)
Meta-Analysis Review
Differential HPA axis function has been proposed to underlie sex-differences in mental disorders; however, the impact of fluctuating sex hormones across the menstrual cycle on HPA axis activity is still unclear. This meta-analysis investigated basal cortisol concentrations as a marker for HPA axis activity across the menstrual cycle. Through a systematic literature search of five databases, 121 longitudinal studies were included, summarizing data of 2641 healthy, cycling participants between the ages of 18 and 45. The meta-analysis showed higher cortisol concentrations in the follicular vs. luteal phase (d = 0.12, p =.004, [0.04 - 0.20]). Comparisons between more precise cycle phases were mostly insignificant, aside from higher concentrations in the menstrual vs. premenstrual phase (d = 0.17, [0.02 - 0.33], p =.03). In all included studies, nine samples used established cortisol parameters to indicate HPA axis function, specifically diurnal profiles (k = 4) and the cortisol awakening response (CAR) (k = 5). Therefore, the meta-analysis highlights the need for more rigorous investigation of HPA axis activity and menstrual cycle phase.
Topics: Adolescent; Adult; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Menstrual Cycle; Middle Aged; Pituitary-Adrenal System; Saliva; Young Adult
PubMed: 35597328
DOI: 10.1016/j.yfrne.2022.100998 -
International Journal of Women's Health 2021Recently, adipose tissue has been identified as endocrine organ in addition to its action as energy store; it produces a large number of biologically active mediators... (Review)
Review
Recently, adipose tissue has been identified as endocrine organ in addition to its action as energy store; it produces a large number of biologically active mediators known as adipocytokines. Significantly, adipocytokines were found to be involved in the physiology of many body functions, including reproduction. The role of body weight, body fat compositions, and nutrition has been largely investigated using animal models and human studies. Malnutrition and/or abnormal body weight may induce disturbances in fertility, puberty, pregnancy, and menstrual cycles. Leptin was the first discovered adipocytokine, and a large body of data over the last 25 years has shown that leptin is not only a molecule that reflects energy stores in the body, but is also an important cytokine involved in many physiological functions, such as inflammatory response, insulin sensitivity, bone metabolism, immunity, and most importantly, reproductive function. Leptin controls the normal physiology of the female reproductive system; it interacts with the hypothalamic-pituitary-gonadal (HPG) axis by a complex mechanism that connects energy homeostasis with reproduction. However, observational studies have demonstrated inconsistent results about leptin variation during normal menstrual cycle, and the mechanisms involved in the interplay between leptin and the hormones of the HPG axis are largely unknown. This review focuses on leptin variation during normal menstrual cycles and its relation to the hypothalamic-pituitary-gonadal axis, and the effect of overweight/obesity on leptin during menstrual cycle is further reviewed.
PubMed: 34007218
DOI: 10.2147/IJWH.S309299 -
JAMA Nov 2022Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the...
IMPORTANCE
Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years.
OBJECTIVE
To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause.
POPULATION
Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions.
EVIDENCE ASSESSMENT
The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit.
RECOMMENDATION
The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).
Topics: Female; Humans; Chronic Disease; Estrogens; Postmenopause; Primary Prevention; Progestins; Hormone Replacement Therapy; Hormones
PubMed: 36318127
DOI: 10.1001/jama.2022.18625 -
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 -
American Journal of Physiology. Heart... Dec 2020Fluctuations in endogenous hormones estrogen and progesterone during the menstrual cycle may offer vasoprotection for endothelial and smooth muscle (VSM) function. While... (Meta-Analysis)
Meta-Analysis Review
Fluctuations in endogenous hormones estrogen and progesterone during the menstrual cycle may offer vasoprotection for endothelial and smooth muscle (VSM) function. While numerous studies have been published, the results are conflicting, leaving our understanding of the impact of the menstrual cycle on vascular function unclear. The purpose of this systematic review and meta-analysis was to consolidate available research exploring the role of the menstrual cycle on peripheral vascular function. A systematic search of MEDLINE, Web of Science, and EMBASE was performed for articles evaluating peripheral endothelial and VSM function across the natural menstrual cycle: early follicular (EF) phase versus late follicular (LF), early luteal, mid luteal, or late luteal. A meta-analysis examined the effect of the menstrual cycle on the standardized mean difference (SMD) of the outcome measures. Analysis from 30 studies ( = 1,363 women) observed a "very low" certainty of evidence that endothelial function increased in the LF phase (SMD: 0.45, = 0.0001), with differences observed in the macrovasculature but not in the microvasculature (SMD: 0.57, = 0.0003, I = 84%; SMD: 0.21, = 0.17, I = 34%, respectively). However, these results are partially explained by differences in flow-mediated dilation [e.g., discrete (SMD: 0.86, = 0.001) vs. continuous peak diameter assessment (SMD: 0.25, = 0.30)] and/or menstrual cycle phase methodologies. There was a "very low" certainty that endothelial function was largely unchanged in the luteal phases, and VSM was unchanged across the cycle. The menstrual cycle appears to have a small effect on macrovascular endothelial function but not on microvascular or VSM function; however, these results can be partially attributed to methodological differences.
Topics: Adult; Endothelium, Vascular; Female; Gonadal Steroid Hormones; Hemodynamics; Humans; Menstrual Cycle; Microcirculation; Muscle, Smooth, Vascular; Premenopause; Signal Transduction; Young Adult
PubMed: 33064553
DOI: 10.1152/ajpheart.00341.2020