Search

Thymidine analogs such as ethynyl deoxyuridine (EdU) or bromodeoxyuridine (BrdU) can be used to label mitosis of mammary epithelial cells (MEC) and to quantify their proliferation. However, labeling cells in larger animals requires considerable amounts of chemical that can be costly and hazardous. We developed a strategy to infuse EdU into the mammary glands of ewes to directly label mitotic MEC. First, each udder half of nulliparous ewes (n = 2) received an intramammary infusion of one of four different concentrations of EdU (0, 0.1, 1.0 or 10 mM) which was compared to BrdU IV (5 mg/kg) 24 h later. Tissues were analyzed by immunofluorescent histochemistry to detect EdU, BrdU, and total MEC. Of the EdU doses tested, 10 mM EdU yielded the greatest labeling index, while a proportion of MEC were labeled by both EdU and BrdU. We next sought to establish whether intramammary labeling could detect the induction of mitosis after exposure to exogenous estrogen and progesterone (E + P). We first infused EdU (10 mM) into the right udder half of ewes (n = 6) at t 0, followed by thymidine (100 mM) 24 h later to prevent further labeling. Three ewes were then administered E + P for 5 d, while n = 3 ewes served as controls. On d 5, EdU was infused into the left udder half of all mammary glands alongside BrdU IV (5 mg/kg). By the time of necropsy 24 h later an average MEC labeling index of 2.9% resulted from EdU delivered at t 0. In the left half of the udder on d 5, CON glands had a final EdU labeling index of 3.4% while glands exposed to E + P had a labeling index of 4.6% (p = 0.05). The corresponding degree of labeling with BrdU was 5.6% in CON glands, and 12% following E + P (p

PURPOSE: Treatment guidelines for gender-affirming hormone therapy with estrogen (GAHT-E) recommend specific dosing regimens based on limited data. Well-controlled efficacy trials are essential to tailoring treatment to patient goals as the guidelines recommend. The goal of this study was to take a foundational step toward designing community-centered effectiveness trials for gender-diverse individuals seeking GAHT-E. METHODS: Our team developed a cross-sectional survey based on broad clinical experience and consultation with our community advisory board. The survey included 60 items covering demographics, transition history, goals and priorities for treatment, indicators of treatment success, sexual function goals, and future research priorities. The survey was distributed during the summer of 2021, primarily through social networks designed for gender-expansive individuals seeking treatment with estrogen. RESULTS: A total of 1270 individuals completed the survey. Overall treatment goals most frequently rated extremely important or very important were the following: (1) improved satisfaction with life (81%), (2) appearing more feminine (80%), (3) appearing less masculine (77%), (4) improved mental health (76%), and (5) being seen as your true gender by others (75%). The three body characteristics most frequently rated highest priority or high priority among changes were the following: (1) facial hair (85%), (2) breast shape or size (84%), and (3) body shape (80%). The highest-rated research priority was comparing feminization with different routes of estrogen administration. CONCLUSION: The goals and experiences of individuals seeking GAHT-E are diverse. Future clinical trials of GAHT-E should be grounded in the needs and priorities of community stakeholders.

The injectable progestin depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in sub-Saharan Africa although mouse models indicate it weakens genital epithelial integrity and barrier function and increases susceptibility to genital infection. The intravaginal ring NuvaRing® is another contraceptive option that like DMPA suppresses hypothalamic pituitary ovarian (HPO) axis function with local release of progestin (etonogestrel) and estrogen (ethinyl estradiol). As we previously reported that treating mice with DMPA and estrogen averts the loss of genital epithelial integrity and barrier function induced by DMPA alone, in the current investigation we compared genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and genital epithelial permeability in rhesus macaques (RM) treated with DMPA or a NuvaRing®re-sized for RM (N-IVR). While these studies demonstrated comparable inhibition of the HPO axis with DMPA or N-IVR, DMPA induced significantly lower genital DSG1 levels and greater tissue permeability to intravaginally administered low molecular mass molecules. By identifying greater compromise of genital epithelial integrity and barrier function in RM administered DMPA vs. N-IVR, our results add to the growing body of evidence that indicate DMPA weakens a fundamental mechanism of anti-pathogen host defense in the female genital tract.

Introduction: Melasma is a common acquired disorder of melanogenesis that predominately affects women and presents as hyperpigmented skin lesions mainly located on the face. The study aims to investigate the epidemiologic characteristics and hormonal profiles in melasma patients. Methods: One hundred fifty patients were enrolled in this study in a tertiary care hospital. Clinical patterns, pigment depth, disease severity, underlying conditions, and heredity were recorded. Endocrinologic profile and vitamin D levels were assessed. Results: On clinical examination, the condition indicated a centrofacial localization in 74% of the patients. Extra facial melasma was noticed in 10 patients who had centrofacial melasma to begin with. Wood's lamp examination showed the dermal type as the most common. A family history of melasma was noted in 38% of the patients. Melasma Area and Severity Index (MASI) score ranged from 0.3 to 10.8, with a mean score of 4.12 ± 2.06. Pregnancy-induced melasma was reported in 36.1% of the patients. In 17.4% of women, melasma was related to using oral contraceptives. In 22% of patients, mild vitamin D deficiency was detected, while 21% had thyroid disorders. Conclusion: There is a strong correlation between family history and prevalence of melasma. Sun exposure is a major precipitating factor and should be carefully addressed in Mediterranean countries like Greece. However, other factors such as concomitant medication, multiple pregnancies, use of oral contraceptives, thyroid disorders and vitamin D deficiency might precipitate melasma. [ABSTRACT FROM AUTHOR]

Context Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. Objective To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. Methods Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started GH replacement in 1995 to 2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol, and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Results Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone, and estradiol showed similar patterns. Women with HH and ACTH deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. Conclusion This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study, and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes (T2D) are widespread metabolic disorders that significantly impact global health today, affecting approximately 17% of adults worldwide with obesity and 9.3% with T2D. Both conditions are closely linked to disruptions in lipid metabolism, where peroxisomes play a pivotal role. Mitochondria and peroxisomes are vital organelles responsible for lipid and energy regulation, including the β-oxidation and oxidation of very long-chain fatty acids (VLCFAs), cholesterol biosynthesis, and bile acid metabolism. These processes are significantly influenced by estrogens, highlighting the interplay between these organelles' function and hormonal regulation in the development and progression of metabolic diseases, such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and T2D. Estrogens modulate lipid metabolism through interactions with nuclear receptors, like peroxisome proliferator-activated receptors (PPARs), which are crucial for maintaining metabolic balance. Estrogen deficiency, such as in postmenopausal women, impairs PPAR regulation, leading to lipid accumulation and increased risk of metabolic disorders. The disruption of peroxisomal–mitochondrial function and estrogen regulation exacerbates lipid imbalances, contributing to insulin resistance and ROS accumulation. This review emphasizes the critical role of these organelles and estrogens in lipid metabolism and their implications for metabolic health, suggesting that therapeutic strategies, including hormone replacement therapy, may offer potential benefits in treating and preventing metabolic diseases. [ABSTRACT FROM AUTHOR]

Estrogens, widely used for therapeutic or contraceptive purposes, act as endocrine disruptors in aquatic systems and have adverse effects on a wide range of living organisms. Wastewater insufficiently treated by conventional methods is the main way for estrogens to enter aquatic systems. Therefore, the purpose of this paper is to develop a novel photocatalytic system for the removal of the estrogenic mixture estradiol valerate/norgestrel from wastewater. The photocatalytic modules are operated in a plug flow reactor system under a UV-A radiation field, and the photocatalyst (TiO2, ZnO or TiO2/ZnO) is immobilized on an inert support of glass balls that are strung on stainless-steel wire and arranged in rows along the photocatalytic modules. The photocatalysts were synthesized by the sol–gel method and then deposited on the inert glass support by the hot method, after which it was calcined for two hours at a temperature of 500 °C. The experimental results showed that the efficiency of photocatalytic degradation largely depends on the dose of photocatalyst. The dose of photocatalyst can be adjusted by adding or removing photocatalytic modules, each of which have an approximately equal amount of photocatalyst. The best result was obtained for the TiO2/ZnO photocatalyst, the organic substrate being practically mineralized in 120 min, for which only two photocatalytic modules are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: As women transition to menopause (i.e., perimenopause), they become more susceptible to hypertension. Animal studies using a mouse model of peri-menopause (peri-AOF) have revealed that hypertension susceptibility is associated with increased postsynaptic glutamatergic NMDA receptor plasticity in the paraventricular hypothalamic nucleus (PVN), a brain area critical for blood pressure regulation. The aim of this study was to determine if presynaptic NMDA receptors also play a role in neural plasticity in peri-AOF hypertension susceptibility. For comparison, males were also studied. Following slow pressor Angiotensin II (AngII), both peri-AOF and male mice became hypertensive; however, peri-AOF females showed higher cytoplasmic NMDA receptor levels. To determine the involvement of estrogen signaling in AngII-induced hypertension, an estrogen receptor beta (ERß) agonist was co-administered. In peri-AOF females, but not males, activation of ERß blocked hypertension and increased NMDA receptors on the membrane of axon terminals where it would be more available for binding of glutamate. These results indicate that sex-dependent recruitment of presynaptic NMDA receptors in the PVN is influenced by ERß signaling in a mouse model of perimenopause. Women become susceptible to hypertension as they transition to menopause (i.e., perimenopause); however, the underlying mechanisms are unclear. Animal studies using an accelerated ovarian failure (AOF) model of peri-menopause (peri-AOF) demonstrate that peri-AOF hypertension is associated with increased postsynaptic NMDA receptor plasticity in the paraventricular hypothalamic nucleus (PVN), a brain area critical for blood pressure regulation. However, recent evidence indicates that presynaptic NMDA receptors also play a role in neural plasticity. Here, using immuno-electron microscopy, we examine the influence of peri-AOF hypertension on the subcellular distribution of the essential NMDA GluN1 receptor subunit in PVN axon terminals in peri-AOF and in male mice. Hypertension was produced by 14-day slow-pressor angiotensin II (AngII) infusion. The involvement of estrogen signaling was investigated by co-administering an estrogen receptor beta (ERß) agonist. Although AngII induced hypertension in both peri-AOF and male mice, peri-AOF females showed higher cytoplasmic GluN1 levels. In peri-AOF females, activation of ERß blocked hypertension and increased plasmalemmal GluN1 in axon terminals. In contrast, stimulation of ERß did not inhibit hypertension or influence presynaptic GluN1 localization in males. These results indicate that sex-dependent recruitment of presynaptic NMDA receptors in the PVN is influenced by ERß signaling in mice during early ovarian failure. [ABSTRACT FROM AUTHOR]

It has now been about a century since a flurry of discoveries identified first the pituitary, then more specifically the anterior pituitary and soon thereafter the central nervous system as components regulating gonadal and downstream reproductive functions. This was an era of ablation/replacement designs using at first rudimentary and then increasingly pure preparations of gonadal and pituitary "activities" or transplanting actual glands, whole or homogenized, among subjects. There was, of course, controversy as is typical of lively and productive scientific debates to this day. The goals of this commentary are to briefly review the history of this work and how the terms referring to interactions among the components of the hypothalamo (as the central neural component was soon associated with)–pituitary–gonadal (HPG) axis evolved, and then to question if the current terms used have kept up with our understanding of the system. The focus in this review will be the actions of estradiol primarily upon the hypothalamus. Important actions of progesterone on the hypothalamus as well as both steroids on the pituitary response to hypothalamic factors are both acknowledged and largely ignored in this document, as are any sex differences as we focus on females. [ABSTRACT FROM AUTHOR]

The estrous cycle regulates rhythms of locomotor activity, body temperature, and circadian gene expression. In female mice, activity increases on the night of proestrus, when elevated estrogens cause ovulation. Exogenous estradiol regulates eating behavior rhythms in female mice fed a high-fat diet, but it is unknown whether endogenous estrogens regulate eating rhythms. In this study, we investigated whether diurnal and circadian eating behavior rhythms change systematically across the estrous cycle. We first studied diurnal eating behavior rhythms in female C57BL/6J mice in 12L:12D. Estrous cycle stages were determined by vaginal cytology while eating behavior and wheel revolutions were continuously measured. The mice had regular 4- to 5-day estrous cycles. Consistent with prior studies, the greatest number of wheel revolutions occurred on the night of proestrus into estrus when systemic levels of estrogens peak. The amplitude, or robustness, of the eating behavior rhythm also fluctuated with 4- to 5-day cycles and peaked primarily during proestrus or estrus. The phases of eating behavior rhythms fluctuated, but not at 4- or 5-day intervals, and phases did not correlate with estrous cycle stages. After ovariectomy, the eating behavior rhythm amplitude fluctuated at irregular intervals. In constant darkness, the amplitude of the circadian eating behavior rhythm peaked every 4 or 5 days and coincided with the circadian day that had the greatest number of wheel revolutions, a marker of proestrus. These data suggest that fluctuations of ovarian hormones across the estrous cycle temporally organize the robustness of circadian eating behavior rhythms so that it peaks during ovulation and sexual receptivity. [ABSTRACT FROM AUTHOR]

Purpose: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization. Results: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district. Conclusion: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance. [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying alcohol‐induced breast carcinogenesis are not fully understood but may involve hormonal changes. Methods: Cross‐sectional associations were investigated between self‐reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta‐analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984). Results: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two‐sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6–7.6) and free testosterone (7.8%; 4.1–11.5), and an inverse association with SHBG (–8.1%; –11.3% to –4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively). Conclusions: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk. Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions. Sex hormones are therefore likely to be part of the mechanism through which alcohol increases breast cancer risk. [ABSTRACT FROM AUTHOR]

Mounting evidence indicates that whereas some fundamental aspects of bone cell differentiation and function are similar in females and males, there is a clear contribution of sex/gender on the effects of signaling molecules on bone mass and strength and, consequently, on the effects of pharmacologic approaches to treat skeletal disorders. However, until recently, most studies were designed and performed using only 1 sex, resulting in a scarcity of published information on sexual dimorphism of the musculoskeletal system, including the mandible/masticatory muscles and the axial and appendicular bones and skeletal muscles. Further, it is now recognized that scientific rigor requires the study of both males and females. Therefore, there is an increasing need to understand the molecular and cellular basis for the differential outcomes of genetic manipulations and therapeutic agent administration depending on the sex of the experimental animals. Studies have shown higher muscle mass, cancellous bone mass, and long bone width in males compared with females as well as different traits in the pelvis and the skull, which are usually used for gender identification in forensic anthropology. Yet, most reports focus on the role of sex hormones, in particular, the consequences of estrogen deficiency with menopause in humans and in ovariectomized animal models. In addition, emerging data is starting to unveil the effects of gender-affirming hormonal therapy on the musculoskeletal system. We summarize here the current knowledge on the sex/gender-dependent phenotypic characteristics of the bone and skeletal muscles in humans and rodents, highlighting studies in which side by side comparisons were made. [ABSTRACT FROM AUTHOR]

Fish are exposed to increased water temperatures and aquatic pollutants, including endocrine-disrupting compounds (EDCs). Although each stressor can disturb fish liver metabolism independently, combined effects may exist. To unveil the molecular mechanisms behind the effects of EDCs and temperature, fish liver cell lines are potential models needing better characterisation. Accordingly, we exposed the rainbow trout RTL-W1 cells (72 h), at 18 °C and 21 °C, to ethynylestradiol (EE2), levonorgestrel (LNG), and a mixture of both hormones (MIX) at 10 µM. The gene expression of a selection of targets related to detoxification (CYP1A, CYP3A27, GST, UGT, CAT, and MRP2), estrogen exposure (ERα, VtgA), lipid metabolism (FAS, FABP1, FATP1), and temperature stress (HSP70b) was analysed by RT-qPCR. GST expression was higher after LNG exposure at 21 °C than at 18 °C. LNG further enhanced the expression of CAT, while both LNG and MIX increased the expressions of CYP3A27 and MRP2. In contrast, FAS expression only increased in MIX, compared to the control. ERα, VtgA, UGT, CYP1A, HSP70b, FABP1, and FATP1 expressions were not influenced by the temperature or the tested EDCs. The RTL-W1 model was unresponsive to EE2 alone, sensitive to LNG (in detoxification pathway genes), and mainly insensitive to the temperature range but had the potential to unveil specific interactions. [ABSTRACT FROM AUTHOR]

Estrogens in river systems can significantly impact aquatic ecosystems. This study aimed to investigate the multiphase partitioning of estrogens in Wulo Creek, Taiwan, which receives animal feedlot wastewater, to understand their distribution and potential environmental implications. Water samples were separated into suspended particulate matter (SPM), colloidal, and soluble phases using centrifugation and cross-flow ultrafiltration. Concentrations of estrone (E1), 17β-estradiol (E2), and estriol (E3) in each phase were analyzed using LC/MS/MS. Partition coefficients were calculated to assess estrogen distribution among phases. Estrogens were predominantly found in the soluble phase (85.8–87.3%). The risk assessment of estrogen equivalent (EEQ) values suggests that estrogen concentration in water poses a higher risk compared to SPM, with a majority of the samples indicating a high risk to aquatic organisms. The colloidal phase contained 12.7–14.2% of estrogens. The log KCOC values (4.72–4.77 L/kg-C) were significantly higher than the log KOC and log KPOC values (2.02–3.40 L/kg-C) for all estrogens. Colloids play a critical role in estrogen distribution in river systems, potentially influencing their fate, transport, and biotoxicity. This finding highlights the importance of considering colloidal interactions in assessing estrogen behavior in aquatic environments. [ABSTRACT FROM AUTHOR]

17 β‐Estradiol is produced by animals, and humans and excreted through excreta, and has endocrine‐disrupting activity. Bacterial degradation is one of the suitable methods used for the removal of 17 β‐estradiol (E2) from the natural environment. In this study, E2‐degrading bacteria were screened from the enriched sediment sample from the wastewater environment. Two bacterial strains of E2‐degrading bacteria (Stenotrophomonas maltophilia MN08 and Pseudomonas aeruginosa KL10) were determined and >70% of E2‐degradation was achieved. The strain MN08 could rapidly remove approximately 86.5% ± 1.3% of E2 within 7 days of treatment. In addition, the strain KL10 removed 79.5% ± 1% of E2 within the same period. Optimized culture temperature and pH of the medium could improve E2‐degradation. The results demonstrated that the strain MN08 exhibited maximum E2‐degradation activity at 35°C, and pH 8.0. The optimal pH for strain KL10 to degrade E2 ranged from 7.0 to 9.0. The E2‐degradation level for the mixture culture systems can exhibit synergistic E2‐degradation activity. The degradation of the MN08 and KL10 individual strains was 87.3% ± 1.2% and 81.4% ± 1.5%, respectively. The E2‐degradation potential for the mixed culture system was 91.3% ± 2.9% under optimized conditions in which 100 mg/L of E2 served as the sole source of carbon and energy. The present finding demonstrates that the co‐culture of S. maltophilia MN08 and P. aeruginosa KL10 may provide a promising bio‐treatment strategy for the removal of steroids from wastewater. [ABSTRACT FROM AUTHOR]

Abstract Introduction Melasma is a common acquired disorder of melanogenesis that predominately affects women and presents as hyperpigmented skin lesions mainly located on the face. The study aims to investigate the epidemiologic characteristics and hormonal profiles in melasma patients. Methods One hundred fifty patients were enrolled in this study in a tertiary care hospital. Clinical patterns, pigment depth, disease severity, underlying conditions, and heredity were recorded. Endocrinologic profile and vitamin D levels were assessed. Results On clinical examination, the condition indicated a centrofacial localization in 74% of the patients. Extra facial melasma was noticed in 10 patients who had centrofacial melasma to begin with. Wood's lamp examination showed the dermal type as the most common. A family history of melasma was noted in 38% of the patients. Melasma Area and Severity Index (MASI) score ranged from 0.3 to 10.8, with a mean score of 4.12 ± 2.06. Pregnancy-induced melasma was reported in 36.1% of the patients. In 17.4% of women, melasma was related to using oral contraceptives. In 22% of patients, mild vitamin D deficiency was detected, while 21% had thyroid disorders. Conclusion There is a strong correlation between family history and prevalence of melasma. Sun exposure is a major precipitating factor and should be carefully addressed in Mediterranean countries like Greece. However, other factors such as concomitant medication, multiple pregnancies, use of oral contraceptives, thyroid disorders and vitamin D deficiency might precipitate melasma.

Pathologic pain is a serious chronic disease, including inflammatory pain, neuropathic pain and cancer pain. Previous studies have proved a close correlation of estrogen and its receptors with pathologic pain, which plays an important role in its occurrence and development, therefore, it has attracted the attention of many researchers at home and abroad. Combining the relevant literature at home and abroad in recent years, this paper reviews the relevant research progress of the mechanism of estrogen and its receptors in pathologic pain, in order to provide a theoretical basis for the prevention and treatment of pathologic pain, as well as the guidance for future research.

Aim: systemically assessed characteristics of intestinal microbiota taxonomic composition in relation to parameters of hormonal and immune status in patients with external genital endometriosis (EGE).Materials and Methods. The controlled cross-sectional study included 33 patients with EGE comprising main group, and 30 healthy women enrolled to control group. All women underwent assessment of hormonal status and cytokine expression levels in peripheral blood. Level of blood hormones estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) was carried out using enzyme-linked immunosorbent and chemiluminescent assays. Expression levels of cytokines such as interleukin (IL) IL-6, IL-8, tumor necrosis factor alpha (TNF-α) were analyzed by an enzyme-linked immunosorbent assay. Taxonomic composition of intestinal microbiota at the level of phyla and genera was carried out by 16S ribosomal RNA gene sequencing. Microbial community a-diversity, the Chao1, ACE, and Sobs indices were used.Results. The concentration of blood E2 in main group was significantly higher compared to control group. Also, women with EGE had higher plasma concentrations for IL-6, IL-8, IL-17 and TNF-a compared to those in control group (p < 0.001). While analyzing bacterial community a-diversity in main group, Chao1 index was found to be significantly decreased. At the phylum level, the Firmicutes/Bacteroidetes ratio was increased in patients with EGE compared with that in control group. Among the 20 largest genera in patients with EGE, significant abundance was observed for Lachnospira, Blautia, Dorea, Streptococcus, Eubacterium hallii_group paralleled with significant decline in Bifidobacterium and Eubacterium eligens_group. A positive correlation was obtained between estrogen levels and the number of representatives from the genera Eubacterium hallii_group and Streptococcus, IL-8 and Streptococcus, TNF-α and Streptococcus and Lachnospira, as well as a negative correlation between TNF-α and Bifidobacterium.Conclusion. A relation between dysbiotic intestinal alterations and developing endometriosis was found. The identified correlations between altered taxonomic composition of the intestinal microflora and parameters of hormonal and immune status in patients with EGE suggest that intestinal microbiota is involved in pathophysiology of endometriosis.

BACKGROUND: In ovulating psychiatric patients experiencing suicidality, suicidal ideation (SI) often peaks perimenstrually. Our recent double-blind, placebo-controlled, crossover randomized clinical trial (RCT; NCT03720847) showed that perimenstrual administration of estradiol and progesterone (EP) can prevent this peak in SI and depressed mood. In this pre-registered follow-up analysis, we studied how the menstrual cycle and experimental manipulation affected two neurobiological systems associated with the menstrual cycle and suicide risk: GABAergic neuroactive steroids (NAS) and peripheral cytokines. METHODS: In 26 psychiatric outpatients with natural menstrual cycles and past-month SI, we analyzed serum samples from three blood draws (midluteal, perimenstrual, midfollicular) per experimental condition (EP vs placebo) timed to a luteinizing hormone-surge ovulation test. Using gas chromatography/mass spectrometry (GC/MS), we measured the progesterone (P4)-derived pregnane NAS (3α,5α)- 3-hydroxypregnan20-one (3α,5α-THP), (3α,5β)- 3-hydroxypregnan-20-one (3α,5β-THP), (3α,5α)- 3,21-dihydroxypregnan-20-one (3α,5α-THDOC), (3α,5α)- 3-hydroxyandrostan-17-one (3α,5α-A), the androstane NAS (3α,5β)- 3-hydroxyandrostan-17-one (3α,5β-A), (3α,5α,17β)-androstane-3,17-diol (3α,5α-A-diol), (3α,5β,17β)-androstane-3,17-diol (3α,5β-A-diol), and their precursor pregnenolone. High sensitivity multiplex assay kits quantified peripheral cytokines IL-1β, IL-6, and TNF-α. RESULTS: P4-derived NAS fluctuated in parallel with P4 and increased with exogenous perimenstrual administration of EP. Conversely, androstane NAS either did not fluctuate or fluctuated inversely from P4, and these NAS decreased with exogenous EP. Peripheral cytokines did not show cyclical patterns, but each significantly predicted SI, depressed mood, or anxiousness. Concomitant SSRI medication use predicted lower androstane NAS. CONCLUSIONS: While preliminary and exploratory, our findings provide critical descriptive context for future studies. Further, our work presents menstrual cycle-related patterns for ten frequently-studied biomarkers, allowing for improved quality of comparisons involving naturally-cycling populations in research.

PURPOSE: Recent guidelines defined a new reporting category of ER-low-positive breast cancer based on immunohistochemistry (IHC). While low positivity of either hormone receptor is uncommon in invasive lobular carcinoma (ILC), we sought to investigate whether relatively low hormone receptor positivity was associated with tumor characteristics and patient outcomes in a single institutional cohort. METHODS: We searched an institutional database for cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, ER was classified as low, medium, or high as defined by ER staining of 10-69%, 70-89%, and ≥ 90% respectively. PR low and high tumors were defined by

BackgroundBreast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention.MethodsThis study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression.Results7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density.ConclusionsThe associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.