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Reproductive Sciences (Thousand Oaks,... Feb 2024In the last four decades, advances in assisted reproductive technology (ART) have offered hope to individuals with fertility problems to conceive. However, a closer... (Review)
Review
In the last four decades, advances in assisted reproductive technology (ART) have offered hope to individuals with fertility problems to conceive. However, a closer examination of the clinical outcomes of ART shows a stark contrast in Asian women compared to Caucasians, with majority of studies reporting lower reproductive success among Asian women. We performed a systematic review to elucidate the genes associated with ART clinical outcomes, with a focus on Asian ethnicities. We completed a database search to identify all studies associated with reproductive outcomes in women of different ethnic backgrounds. Following PRISMA, 128 studies were analyzed. Pathway analysis of gene sets was done using Cytoscapev3.4.0. We observed that age at menarche (AAM) was correlated with the timing of the first pregnancy, with Hawaiians having the lowest age (22.2 years) and Japanese the highest age (25.0 years). LIN28 mutations were associated with AAM and prevalent in both Chinese and American populations. FMR1 was most associated with ovarian reserve. Network analysis highlighted a close association between FMR1, FSHR, ESR1, BMP15, and INHA, through biological functions affecting menstrual cycle and hypothalamic-pituitary axis and therefore ovarian follicle development. Leveraging these findings, we propose the development of a personalized, ethnic-specific biomarker panel which would enhance patient stratification to address every woman's unique reproductive potential.
Topics: Pregnancy; Humans; Female; United States; Young Adult; Adult; Reproductive Health; Reproduction; Menstrual Cycle; Asian; Reproductive Techniques, Assisted; Fragile X Mental Retardation Protein; Native Hawaiian or Other Pacific Islander
PubMed: 37524971
DOI: 10.1007/s43032-023-01311-y -
Biomedicines Jul 2023A better understanding of interindividual differences and the development of targeted therapies is one of the major challenges of modern medicine. The sex of a person... (Review)
Review
A better understanding of interindividual differences and the development of targeted therapies is one of the major challenges of modern medicine. The sex of a person plays a crucial role in this regard. This systematic review aimed to summarise and analyse available evidence on the mutual interactions between non-invasive brain stimulation and sex/polypeptide hormones. The PubMed database was searched from its inception to 31 March 2023, for (i) studies that investigated the impact of sex and/or polypeptide hormones on the effects induced by non-invasive brain stimulation, or (ii) studies that investigated non-invasive brain stimulation in the modulation of sex and/or polypeptide hormones. Eighteen studies (319 healthy and 96 disabled participants) were included. Most studies focused on female sex hormone levels during the menstrual cycle. The later follicular phase is associated with a weak between hemispheric and intracortical inhibition, strong intracortical facilitation, and high stimulation-induced neural and behavioural changes. The opposite effects are observed during the luteal phase. In addition, the participant's sex, presence and/or absence of real ovulation and increase in oestradiol level by chorionic gonadotropin injection influence the stimulation-induced neurophysiological and behavioural effects. In Parkinson's disease and consciousness disorders, the repetitive application of non-invasive brain stimulation increases oestradiol and dehydroepiandrosterone levels and reduces disability. To date, male hormones have not been sufficiently included in these studies. Here, we show that the sex and/or polypeptide hormones and non-invasive brain stimulation methods are in reciprocal interactions. This may be used to create a more effective and individualised approach for healthy individuals and individuals with disabilities.
PubMed: 37509620
DOI: 10.3390/biomedicines11071981 -
BMC Women's Health Jul 2023Given the increase in the incidence of breast cancer during the past decades, several studies have investigated the effects of variables on breast cancer, especially... (Meta-Analysis)
Meta-Analysis
Given the increase in the incidence of breast cancer during the past decades, several studies have investigated the effects of variables on breast cancer, especially obesity. This systematic review and meta-analysis aims to evaluate any effects of obesity on breast cancer risk in women, before and after menopause, and in different continents.All forms of relevant literature examining any association between obesity and breast cancer, including cohort, case-control, and cross-sectional studies, were identified in the PubMed, Scopus, EMBASE, and Web of Science databases from January 1, 1990 until January 13, 2023. Body mass index (BMI) > 30 was used to indicate obesity. Every type of breast cancer was examined as outcome factors. The quality of the papers was evaluated using the Newcastle-Ottawa scale checklist. The Egger and Begg test was used to evaluate publication bias. To assess any extra impact of each research on the final measurement, a sensitivity analysis was carried out.One hundred and two studies were included in this meta-analysis. Respectively, 48 and 67 studies reported associations between obesity and breast cancer in pre and post menopausal women. Combining all studies, the pooled OR of the association between obesity and breast cancer in pre-menopausal women was OR = 0.93 CI: (0.85-1.1), (I = 65.4%), and for post-menopausal woman, OR = 1.26 CI: (1.19-1.34), (I = 90.5%).Obesity has a protective role in breast cancer among pre-menopausal women, but this relationship is statistically significant only in European women. The chance of developing breast cancer increases in post-menopausal women who are obese. This relationship is significant among Asian, North American, African and European women.
Topics: Female; Humans; Breast Neoplasms; Risk Factors; Cross-Sectional Studies; Menstruation; Obesity
PubMed: 37496015
DOI: 10.1186/s12905-023-02543-5 -
Heliyon Jun 2023To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on O in physically...
OBJECTIVE
To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on O in physically active women.
METHODS
This systematic review and meta-analysis conforms to the PRISMA statement guidelines. Four (sub-)meta-analyses were performed. Two focused on longitudinal studies examining the same women several times to compare the O during the different menstrual phases or oral contraceptive (OC) use and withdrawal. Two meta-analyses examined if there is a difference in O between OC users and normally menstruating women by analyzing cross-sectional studies assigning physically active women to one of these two groups as well as intervention-based studies (cross-over studies, randomized controlled trials considering only the data of the intervention group) comparing women intra-individually with and without OCs.
RESULTS
Nine of the included studies (107 women) evaluated the influence of the MC, five studies (69 women) the impact of OCs on O, and six studies investigated both topics (88 women). A mean difference of O -0.03 ml/kg/min (95%CI -1.06 to 1.01) between the early follicular and luteal menstrual phase was observed. Between the active and inactive phases of OCs, a mean difference of -0.11 ml/kg/min (95%CI -2.32 to 2.10) was found. The inter-individual comparison of naturally menstruating women and OC users showed a mean difference in O of 0.23 ml/kg/min (95% CI -2.33 to 2.79) in favor of OC use. The intra-individual comparison of the same women showed a mean decrease in O of -0.84 ml/kg/min (95% CI -2.38 to 0.70) after a new start with OCs.
CONCLUSIONS
Our meta-analyses showed no effects of the MC or the OCs on O. More high-quality studies are needed determining the MC phases more precisely, including OCs with the current standard formulations and comparing the influence of different progestins.
PubMed: 37484400
DOI: 10.1016/j.heliyon.2023.e17049 -
Climacteric : the Journal of the... Oct 2023A systematic review with meta-analysis was conducted to establish the impact of menopause health education on quality of life (QoL) among menopausal women. Research... (Meta-Analysis)
Meta-Analysis Review
A systematic review with meta-analysis was conducted to establish the impact of menopause health education on quality of life (QoL) among menopausal women. Research suggests that specific educational programs can support and enable women during the physical and emotional transition through menopause. The CINAHL, Medline, APA, Embase and Google Scholar databases were searched between 30 November 2021 and 9 January 2022 using the PRISMA guidelines. The Cochrane risk of bias tool was used to critically evaluate the included studies. Review Manager software was used to conduct the meta-analysis of suitable studies. Eight papers were eligible for this review. The participants were aged between 40 and 60 years, with diagnosis of menopause stemming from changes in the menstrual cycle to a last menstrual period of 7 years. Follow-up data were collected between 1 and 4 months post education. Meta-analysis of both the primary outcome (QoL) and secondary outcome (symptom control) demonstrated statistically significant improvements post intervention. Papers not suitable for meta-analysis were reviewed narratively; two papers assessing the primary outcome (QoL) demonstrated an improvement, but only one to a statistically significant level. Secondary outcomes revealed improvements, with all bar one paper doing so to statistical significance. Menopause health education demonstrated an improvement in both QoL and symptom control in menopausal women; however, given some weaknesses in the included studies, further research is justified. Limitations include participants' level of education, geographical location, risk of bias, that only half of the papers addressed participant use of hormone replacement therapy and length of follow-up.
Topics: Humans; Female; Adult; Middle Aged; Quality of Life; Menopause; Hormone Replacement Therapy
PubMed: 37477236
DOI: 10.1080/13697137.2023.2226318 -
The Cochrane Database of Systematic... Jul 2023Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary... (Review)
Review
BACKGROUND
Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels. This is an update of a Cochrane Review first published in 2011.
OBJECTIVES
To assess the efficacy and safety of statin therapy in women with PCOS who are not actively trying to conceive.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHLs, and four ongoing trials registers on 7 November 2022. We also handsearched relevant conference proceedings and the reference lists of relevant trials for any additional studies, and we contacted experts in the field for any further ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated the effects of statin therapy in women with PCOS not actively trying to conceive. Eligible comparisons were statin versus placebo or no treatment, statin plus another agent versus the other agent alone, and statin versus another agent. We performed statistical analysis using Review Manager 5, and we assessed the certainty of the evidence using GRADE methods.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. Our primary outcomes were resumption of menstrual regularity and resumption of spontaneous ovulation. Our secondary outcomes were clinical and physiological measures including hirsutism, acne severity, testosterone levels, and adverse events.
MAIN RESULTS
Six RCTs fulfilled the criteria for inclusion. They included 396 women with PCOS who received six weeks, three months, or six months of treatment; 374 women completed the studies. Three studies evaluated the effects of simvastatin and three studies evaluated the effects of atorvastatin. We summarised the results of the studies under the following comparisons. Statins versus placebo (3 RCTs) One trial measured resumption of menstrual regularity as menstrual cycle length in days. We are uncertain if statins compared with placebo shorten the mean length of the menstrual cycle (mean difference (MD) -2.00 days, 95% confidence interval (CI) -24.86 to 20.86; 37 participants; very low-certainty evidence). No studies reported resumption of spontaneous ovulation, improvement in hirsutism, or improvement in acne. We are uncertain if statins compared with placebo reduce testosterone levels after six weeks (MD 0.06, 95% CI -0.72 to 0.84; 1 RCT, 20 participants; very low-certainty evidence), after 3 months (MD -0.53, 95% CI -1.61 to 0.54; 2 RCTs, 64 participants; very low-certainty evidence), or after 6 months (MD 0.10, 95% CI -0.43 to 0.63; 1 RCT, 28 participants; very low-certainty evidence) Two studies recorded adverse events, and neither reported significant differences between the groups. Statins plus metformin versus metformin alone (1 RCT) The single RCT included in this comparison measured resumption of menstrual regularity as the number of spontaneous menses per six months. We are uncertain if statins plus metformin compared with metformin improves resumption of menstrual regularity (MD 0.60 menses, 95% CI 0.08 to 1.12; 69 participants; very low-certainty evidence). The study did not report resumption of spontaneous ovulation. We are uncertain if statins plus metformin compared with metformin alone improves hirsutism measured using the Ferriman-Gallwey score (MD -0.16, 95% CI -0.91 to 0.59; 69 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.31, 95% CI -0.67 to 0.05; 69 participants; very low-certainty evidence), or testosterone levels (MD -0.03, 95% CI -0.37 to 0.31; 69 participants; very low-certainty evidence). The study reported that no significant adverse events occurred. Statins plus oral contraceptive pill versus oral contraceptive pill alone (1 RCT) The single RCT included in this comparison did not report resumption of menstrual regularity or spontaneous ovulation. We are uncertain if statins plus the oral contraceptive pill (OCP) improves hirsutism compared with OCP alone (MD -0.12, 95% CI -0.41 to 0.17; 48 participants; very low-certainty evidence). The study did not report improvement in acne severity. We are also uncertain if statins plus OCP compared with OCP alone reduces testosterone levels, because the certainty of the evidence was very low (MD -0.82, 95% CI -1.38 to -0.26; 48 participants). The study reported that no participants experienced significant side effects. Statins versus metformin (2 RCTs) We are uncertain if statins improve menstrual regularity compared with metformin (number of spontaneous menses per six months) compared to metformin (MD 0.50 menses, 95% CI -0.05 to 1.05; 1 RCT, 61 participants, very low-certainty evidence). No studies reported resumption of spontaneous ovulation. We are uncertain if statins compared with metformin reduce hirsutism measured using the Ferriman-Gallwey score (MD -0.26, 95% CI -0.97 to 0.45; 1 RCT, 61 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.18, 95% CI -0.53 to 0.17; 1 RCT, 61 participants; very low-certainty evidence), or testosterone levels (MD -0.24, 95% CI -0.58 to 0.10; 1 RCT, 61 participants; very low-certainty evidence). Both trials reported that no significant adverse events had occurred. Statins versus oral contraceptive pill plus flutamide (1 RCT) According to the study report, no participants experienced any significant side effects. There were no available data for any other main outcomes.
AUTHORS' CONCLUSIONS
The evidence for all main outcomes of this review was of very low certainty. Due to the limited evidence, we are uncertain if statins compared with placebo, or statins plus metformin compared with metformin alone, improve resumption of menstrual regularity. The trial evaluating statin plus OCP versus OCP alone reported neither of our primary outcomes. No other studies reported resumption of spontaneous ovulation. We are uncertain if statins improve hirsutism, acne severity, or testosterone. All trials that measured adverse events reported no significant differences between the groups.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hirsutism; Metformin; Acne Vulgaris; Contraceptives, Oral; Testosterone
PubMed: 37462232
DOI: 10.1002/14651858.CD008565.pub3 -
Sports Medicine (Auckland, N.Z.) Oct 2023
PubMed: 37458980
DOI: 10.1007/s40279-023-01893-2 -
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 -
Obstetrics and Gynecology Sep 2023The diagnosis of endometriosis, a common gynecologic condition, is characterized by delays of up to 11 years. During this time, women may experience persistent symptoms...
OBJECTIVE
The diagnosis of endometriosis, a common gynecologic condition, is characterized by delays of up to 11 years. During this time, women may experience persistent symptoms that affect their quality of life, productivity, and relationships, and the disease may progress. It is therefore a priority to understand the factors that contribute to this delay to help improve the diagnostic pathway. Our objective was to describe the diagnosis barriers of endometriosis from the patient and health care professional perspectives using a qualitative evidence synthesis.
DATA SOURCES
We searched MEDLINE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature using combinations of the synonyms of endometriosis, diagnosis, and qualitative research. The search was restricted to English-language articles from database creation until May 2022.
METHODS OF STUDY SELECTION
The initial search yielded 899 articles. Studies were included if they explored the experiences or views of affected women or health care professionals on the diagnosis of endometriosis and used qualitative methods for data collection and data analysis. Risk of bias was assessed with the Critical Appraisal Skills Programme checklist.
TABULATION, INTEGRATION, AND RESULTS
Thirty-seven articles were considered for full review, with 13 eligible articles identified for inclusion. Thematic synthesis was used to identify four key themes: 1) individual factors (n=6), 2) interpersonal influences (n=6), 3) health system factors (n=13), and 4) factors specific to endometriosis (n=13). These encompassed 12 subthemes that represented barriers to the diagnosis of endometriosis: 1) difficulty establishing pathologic symptoms from normal menstruation and the use of self-care techniques; 2) menstrual stigma and the normalization of menstrual pain; 3) attitudes and lack of training for health care professionals, delayed referrals to specialist services, and poor explanation of oral contraceptive pill use in the diagnostic process; and 4) variability in presenting symptoms, overlap with other conditions, lack of a noninvasive method of diagnosis, and concerns about the value of a diagnosis.
CONCLUSION
This review identified barriers to the timely diagnosis of endometriosis from the perspective of affected individuals and health care professionals. It highlights areas for improvement along the diagnostic pathway, which may guide future strategies to reduce delays.
Topics: Humans; Female; Endometriosis; Quality of Life; Menstruation; Dysmenorrhea; Health Personnel
PubMed: 37441792
DOI: 10.1097/AOG.0000000000005255 -
Sports Medicine (Auckland, N.Z.) Oct 2023Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in...
BACKGROUND
Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in sports continues to increase, understanding the prevalence of a range of MC disorders and MC-related symptoms may guide preventive strategies to protect the health and optimise the performance of female athletes.
OBJECTIVE
To examine the prevalence of MC disorders and MC-related symptoms among female athletes who are not using hormonal contraceptives and evaluate the assessment methods used to identify MC disorders and MC-related symptoms.
METHODS
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Six databases were searched until September 2022 for all original research that reported the prevalence of MC disorders and/or MC-related symptoms in athletes not using hormonal contraceptives, which included the definitions of the MC disorders examined, and the assessment methods used. MC disorders included amenorrhoea, anovulation, dysmenorrhoea, heavy menstrual bleeding (HMB), luteal phase deficiency (LPD), oligomenorrhoea, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). MC-related symptoms included any affective and physical symptoms related to the MC that do not cause significant personal, interpersonal or functional impairment. The prevalence data across eligible studies were combined, and all studies were qualitatively synthesised to evaluate the assessment methods and tools used to identify MC disorders and MC-related symptoms. The methodological quality of studies was assessed using a modified Downs and Black checklist.
RESULTS
Sixty studies involving 6380 athletes were included. A wide range of prevalence was observed for all types of MC disorders, with a dearth of data on anovulation and LPD. Based on pooled data, dysmenorrhoea (32.3%; range 7.8-85.6%) was the most prevalent MC disorder. Studies reporting MC-related symptoms mostly examined the premenstrual and menstruation phases, where affective symptoms appeared more prevalent than physical symptoms. A larger proportion of athletes reported symptoms during the initial days of menstruation compared with the premenstrual phase. MC disorders and MC-related symptoms were retrospectively assessed using self-report methods in 90.0% of studies. Most studies (76.7%) in this review were graded as moderate quality.
DISCUSSION
MC disorders and MC-related symptoms are commonplace among female athletes, warranting further research examining their impact on performance and preventive/management strategies to optimise athlete health. To increase the quality of future studies, researchers should adopt standardised definitions of MC disorders and assessment methods such as a combination of calendar counting, urinary ovulation tests and a mid-luteal phase serum progesterone measurement when assessing menstrual function. Similarly, standardised diagnostic criteria should be used when examining MC disorders such as HMB, PMS and PMDD. Practically, implementing prospective cycle monitoring that includes ovulation testing, mid-luteal blood sampling (where feasible) and symptom logging throughout the MC could support athletes and practitioners to promptly identify and manage MC disorders and/or MC-related symptoms.
TRIAL REGISTRATION
This review has been registered in the PROSPERO database (CRD42021268757).
Topics: Female; Humans; Dysmenorrhea; Prevalence; Prospective Studies; Anovulation; Retrospective Studies; Menstrual Cycle; Premenstrual Syndrome; Menstruation Disturbances; Premenstrual Dysphoric Disorder; Athletes; Contraceptive Agents
PubMed: 37389782
DOI: 10.1007/s40279-023-01871-8