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1.
Per- and poly-fluoroalkyl substances (PFAS) and female reproductive outcomes: PFAS elimination, endocrine-mediated effects, and disease.
Rickard, BP, Rizvi, I, Fenton, SE
Toxicology. 2022;:153031
Abstract
Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants frequently detected in drinking water supplies worldwide that have been linked to a variety of adverse reproductive health outcomes in women. Compared to men, reproductive health effects in women are generally understudied while global trends in female reproduction rates are declining. Many factors may contribute to the observed decline in female reproduction, one of which is environmental contaminant exposure. PFAS have been used in home, food storage, personal care and industrial products for decades. Despite the phase-out of some legacy PFAS due to their environmental persistence and adverse health effects, alternative, short-chain and legacy PFAS mixtures will continue to pollute water and air and adversely influence women's health. Studies have shown that both long- and short-chain PFAS disrupt normal reproductive function in women through altering hormone secretion, menstrual cyclicity, and fertility. Here, we summarize the role of a variety of PFAS and PFAS mixtures in female reproductive tract dysfunction and disease. Since these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption, the role of PFAS in breast, thyroid, and hypothalamic-pituitary-gonadal axis function are also discussed as the interplay between these tissues may be critical in understanding the long-term reproductive health effects of PFAS in women. A major research gap is the need for mechanism of action data - the targets for PFAS in the female reproductive and endocrine systems are not evident, but the effects are many. Given the global decline in female fecundity and the ability of PFAS to negatively impact female reproductive health, further studies are needed to examine effects on endocrine target tissues involved in the onset of reproductive disorders of women.
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2.
Iron status in athletic females, a shift in perspective on an old paradigm.
Badenhorst, CE, Goto, K, O'Brien, WJ, Sims, S
Journal of sports sciences. 2021;(14):1565-1575
Abstract
Iron deficiency is a common nutrient deficiency within athletes, with sport scientists and medical professionals recognizing that athletes require regular monitoring of their iron status during intense training periods. Revised considerations for athlete iron screening and monitoring have suggested that males get screened biannually during heavy training periods and females require screening biannually or quarterly, depending on their previous history of iron deficiency. The prevalence of iron deficiency in female athletes is higher than their male counterparts and is often cited as being a result of the presence of a menstrual cycle in the premenopausal years. This review has sought to revise our current understanding of female physiology and the interaction between primary reproductive hormones (oestrogen and progesterone) and iron homoeostasis in females. The review highlights an apparent symbiotic relationship between iron metabolism and the menstrual cycle that requires additional research as well as identifying areas of the menstrual cycle that may be primed for nutritional iron supplementation.
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3.
Bidirectional Interactions between the Menstrual Cycle, Exercise Training, and Macronutrient Intake in Women: A Review.
Rocha-Rodrigues, S, Sousa, M, Lourenço Reis, P, Leão, C, Cardoso-Marinho, B, Massada, M, Afonso, J
Nutrients. 2021;(2)
Abstract
Women have a number of specificities that differentiate them from men. In particular, the role of sex steroid hormones and the menstrual cycle (MC) significantly impact women's physiology. The literature has shown nonlinear relationships between MC, exercise, and nutritional intake. Notably, these relationships are bidirectional and less straightforward than one would suppose. For example, the theoretical implications of the MC's phases on exercise performance do not always translate into relevant practical effects. There is often a disconnect between internal measures (e.g., levels of hormone concentrations) and external performance. Furthermore, it is not entirely clear how nutritional intake varies across the MC's phases and whether these variations impact on exercise performance. Therefore, a thorough review of the existing knowledge could help in framing these complex relationships and potentially contribute to the optimization of exercise prescription and nutritional intake according to the naturally occurring phases of the MC. Throughout this review, an emerging trend is the lack of generalizability and the need to individualize interventions, since the consequences of the MC's phases and their relationships with exercise and nutritional intake seem to vary greatly from person to person. In this sense, average data are probably not relevant and could potentially be misleading.
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4.
A new hypothesis linking oxytocin to menstrual migraine.
Bharadwaj, VN, Porreca, F, Cowan, RP, Kori, S, Silberstein, SD, Yeomans, DC
Headache. 2021;(7):1051-1059
Abstract
OBJECTIVE To highlight the emerging understanding of oxytocin (OT) and oxytocin receptors (OTRs) in modulating menstrual-related migraine (MRM). BACKGROUND MRM is highly debilitating and less responsive to therapy, and attacks are of longer duration than nonmenstrually related migraine. A clear understanding of the mechanisms underlying MRM is lacking. METHODS We present a narrative literature review on the developing understanding of the role of OT and the OTR in MRM. Literature on MRM on PubMed/MEDLINE database including clinical trials and basic science publications was reviewed using specific keywords. RESULTS OT is a cyclically released hypothalamic hormone/neurotransmitter that binds to the OTR resulting in inhibition of trigeminal neuronal excitability that can promote migraine pain including that of MRM. Estrogen regulates OT release as well as expression of the OTR. Coincident with menstruation, levels of both estrogen and OT decrease. Additionally, other serum biochemical factors, including magnesium and cholesterol, which positively modulate the affinity of OT for OTRs, both decrease during menstruation. Thus, during menstruation, multiple menstrually associated factors may lead to decreased circulating OT levels, decreased OT affinity for OTR, and decreased expression of the trigeminal OTR. Consistent with the view of migraine as a threshold disorder, these events may collectively result in decreased inhibition promoting lower thresholds for activation of meningeal trigeminal nociceptors and increasing the likelihood of an MRM attack. CONCLUSION Trigeminal OTR may thus be a novel target for the development of MRM therapeutics.
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5.
Plants used during maternity, menstrual cycle and other women's health conditions among Brazilian cultures.
Yazbek, PB, Tezoto, J, Cassas, F, Rodrigues, E
Journal of ethnopharmacology. 2016;:310-31
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE For innumerous clinical cases related to women's health and precarious medical care in developing countries, a large repertoire of plants have been used as popular medicines in order to fill this gap, which in a certain way creates health risks to users, since pharmacological and toxicological tests are still insufficient to guarantee their efficacy and safety. Besides therapeutic use, abortive plants are broadly used in countries where abortion is prohibited, increasing that risk even more. In this way, ethnopharmacological studies that register plants used for women's health can contribute not only to the selection of potential bioactives, enriching the repertoire of drugs available to females, above all in public health systems, but also questioning the safety of products that are used without prescription. AIMS AND OBJECTIVES This review aims at determining plants applied by Brazilian cultures in the treatment of conditions related to maternity, menstrual cycle and other women's health particularities, and to supplement the lack of epidemiological data available to assess the health of indigenous, rural and other populations of Brazilian women. MATERIALS AND METHODS A literature review was conducted of the collection at the Ethnobotanical and Ethnopharmacological Center of the Federal University of São Paulo (period covered: 1965 to 2012). All of the 343 articles were consulted and 31 articles mentioning therapeutic uses of interest were selected. Relevant information was extracted to compose Table 1 - Maternity, Table 2 - Menstrual Cycle and Table 3 - Other Conditions. Data was statistically analyzed in order to generate the discussion about plants used in healing contexts by different Brazilian ethnicities. A bibliographic review was performed using the Scopus database to collect the following information about the most cited plants: ethnobotany/ethnopharmacology of non-Brazilian cultures for women's health conditions, pharmacology, toxicology, and adverse reactions. RESULTS A total of 319 species were cited for 22 indications related to women's health. Ninety-seven species were indicated for conditions related to maternity, 94 to the menstrual cycle and 232 to others. The same species could be present in more than one of these three categories. The most cited family was Fabaceae (13.5%), and the species were Ruta graveolens L. (1.76%) and Strychnos pseudoquina A. St.-Hil (1.76%). The most frequent part utilized, mode of preparation and route of administration were leaves (2.0%), tea (73.38%) and oral (87. 2%), respectively. The indications that showed the highest number of species were: to treat venereal diseases (69 species), abortive (54) and anti-inflammatory for the ovaries and/or uterus (54). According to our bibliographic survey, among the 19 most indicated species in this review, only four are also used by non-Brazilian cultures for conditions related to women's health; 25% of them were pharmacologically investigated and it was possible to validate their ethnopharmacological/ethnobotanical use, 10.5% have presented well-described adverse reactions and for 42.1% of these species toxicological studies were performed. CONCLUSION The survey raised important data about plants implemented in healing related to women's health conditions by Brazilian cultures and their practices. The compilation presented in this study enables the realization of further investigation regarding the development of herbal medicines and contributes to the incrementation of policies focused on these cultures. Further phytochemical, pharmacological and toxicological studies should be conducted, which will allow the discovery of pharmacological properties, bioactive constituents, and moreover, adequate posology, manner of use and adverse events.
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6.
Systematic Review of Preventive and Acute Treatment of Menstrual Migraine.
Nierenburg, Hdel C, Ailani, J, Malloy, M, Siavoshi, S, Hu, NN, Yusuf, N
Headache. 2015;(8):1052-71
Abstract
OBJECTIVE The aim of this systematic review is to identify the efficacy of different categories of treatments for menstrual migraines as found in randomized controlled trials or open label studies with similar efficacy endpoints. BACKGROUND Menstrual migraine is very common and approximately 50% of women have increased risk of developing migraines related to the menstrual cycle. Attacks of menstrual migraine are usually more debilitating, of longer duration, more prone to recurrence, and less responsive to acute treatment than nonmenstrual migraine attacks. METHODS Search for evidence was done in 4 databases that included PubMed, EMBASE, Science Direct, and Web of Science. Eighty-four articles were selected for full text review by 2 separate readers. Thirty-six of the 84 articles were selected for final inclusion. Articles included randomized controlled and open label trials that focused on efficacy of acute and preventative therapies for menstrual migraine. Secondary analyses where excluded because the initial study population was not women with menstrual migraine. RESULTS After final screening, 11 articles were selected for acute and 25 for preventive treatment of menstrual migraine. These were further subdivided into treatment categories. For acute treatment: triptans, combination therapy, prostaglandin synthesis inhibitor, and ergot alkaloids. For preventive treatment: triptans, combined therapy, oral contraceptives, estrogen, nonsteroidal anti-inflammatory drug, phytoestrogen, gonadotropin-releasing hormone agonist, dopamine agonist, vitamin, mineral, and nonpharmacological therapy were selected. Overall, triptans had strong evidence for treatment in both acute and short term prevention of menstrual migraine. CONCLUSIONS Based on this literature search, of all categories of treatment for menstrual migraine, triptans have the most extensive research with strong evidence for both acute and preventive treatment of menstrual migraine. Further randomized controlled trials should be performed for other therapies to strengthen their use in the care of menstrual migraine patients.
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7.
Cyclic decidualization of the human endometrium in reproductive health and failure.
Gellersen, B, Brosens, JJ
Endocrine reviews. 2014;(6):851-905
Abstract
Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitment and renders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Here we review the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. We discuss how disorders that subvert the programming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure.
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8.
Endocrine disorders in adolescent and young female athletes: impact on growth, menstrual cycles, and bone mass acquisition.
Maïmoun, L, Georgopoulos, NA, Sultan, C
The Journal of clinical endocrinology and metabolism. 2014;(11):4037-50
Abstract
CONTEXT Puberty is a crucial period of dramatic hormonal changes, accelerated growth, attainment of reproductive capacity, and acquisition of peak bone mass. Participation in recreational physical activity is widely acknowledged to provide significant health benefits in this period. Conversely, intense training imposes several constraints, such as training stress and maintenance of very low body fat to maximize performance. Adolescent female athletes are therefore at risk of overtraining and/or poor dietary intake, which may have several consequences for endocrine function. The "adaptive" changes in the hypothalamic-pituitary-gonadal, -adrenal, and somatotropic axes and the secretory role of the adipose tissue are reviewed, as are their effects on growth, menstrual cycles, and bone mass acquisition. DESIGN A systematic search on Medline between 1990 and 2013 was conducted using the following terms: "intense training," "physical activity," or "exercise" combined with "hormone," "endocrine," and "girls," "women," or "elite female athletes." All articles reporting on the endocrine changes related to intense training and their potential implications for growth, menstrual cycles, and bone mass acquisition were considered. RESULTS AND CONCLUSION Young female athletes present a high prevalence of menstrual disorders, including delayed menarche, oligomenorrhea, and amenorrhea, characterized by a high degree of variability according to the type of sport. Exercise-related reproductive dysfunction may have consequences for growth velocity and peak bone mass acquisition. Recent findings highlight the endocrine role of adipose tissue and energy balance in the regulation of homeostasis and reproductive function. A better understanding of the mechanisms whereby intense training affects the endocrine system may orient research to develop innovative strategies (ie, based on nutritional or pharmacological approaches and individualized modalities of training and competition) to improve the medical care of these adolescents and protect their reproductive function.
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9.
Failure to consider the menstrual cycle phase may cause misinterpretation of clinical and research findings of cardiometabolic biomarkers in premenopausal women.
Schisterman, EF, Mumford, SL, Sjaarda, LA
Epidemiologic reviews. 2014;(1):71-82
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Abstract
Biomarker assessment plays a critical role in the study and prevention of disease. However, variation in biomarkers attributable to the menstrual cycle in premenopausal women may impair understanding the role of certain biomarkers in disease development and progression. Thus, in light of the recently increasing evidence of menstrual cycle variability in multiple cardiometabolic biomarkers, a reexamination of approaches for appropriately studying and diagnosing cardiovascular disease in premenopausal women is warranted. We reviewed studies (from 1934 through 2012) evaluating changes in cardiometabolic biomarkers across phases of the menstrual cycle, including markers of oxidative stress, lipids, insulin sensitivity, and systemic inflammation. Each was observed to vary significantly during the menstrual cycle. For example, nearly twice as many women had elevated cholesterol levels warranting therapy (≥200 mg/dL) during the follicular phase compared with the luteal phase (14.3% vs. 7.9%), with only 3% having consistently high levels during all phases of the cycle. Similarly, nearly twice as many women were classified as being at an elevated risk of cardiovascular disease (high sensitivity C-reactive protein >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%). Menstrual cycle-associated variability in cardiometabolic biomarkers is an important source of variability that should be accounted for in both research and clinical settings.
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Possible factors for altered energy balance across the menstrual cycle: a closer look at the severity of PMS, reward driven behaviors and leptin variations.
McNeil, J, Doucet, É
European journal of obstetrics, gynecology, and reproductive biology. 2012;(1):5-10
Abstract
This paper reviews the literature on the variations in energy intake (EI), energy expenditure (EE) and the factors which may affect the fluctuations in EI across the menstrual cycle. While no significant changes in body weight and body fat percentage have been noted across the cycle, increases in EI and EE have been well documented during the luteal phase in lean women. The occurrence and severity of the premenstrual syndrome (PMS) and food reinforcement are suggested to affect EI. It is not known, however, whether food reinforcement may affect EI across the menstrual cycle. These factors may also affect overweight/obese women differently than normal-weight women at times during which women may be more prone to episodes of overeating during the menstrual cycle. Certain studies have also noted fluctuations in leptin levels across the menstrual cycle, while others have not. It has also been suggested that variations in leptin levels may affect the rewarding value of food in order to maintain proper body weight and adiposity level. We emphasize that future studies should evaluate the variations in energy balance across the cycle in overweight/obese women, as well as the strength of the relationships between food reinforcement and the severity of PMS with energy and macronutrient intakes.