To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.
Attempting an update of the epidemiology of schizophrenia, it is pointed out that schizophrenia seems to occur with the same core symptoms and almost at the same frequency in all countries and cultures studied. Methodologically sound studies have failed to produce evidence for a secular trend of the morbid risk. The genotype of schizophrenia is expressed as psychosis, personality disorders and non-specific disorders or it goes without manifest psychopathology. Minor brain anomalies are present in most cases. The British Child Development Study showed that behavioural, cognitive, emotional and neuromotor antecedents occur in 50% of cases, thus pointing to disordered brain development, very likely not specific to schizophrenia, since found in many other mental disorders as well. A look into the hidden early course of schizophrenia revealed a significant sex difference in age of onset and a prodromal phase of some 3 to 4 years throughout the cases. A case-control study showed that it is mainly during this early course before first admission that social disadvantage in schizophrenia arises. In the prephase a disease-related lack of social ascent plays a greater role than steps of social decline. The early social course differs between the sexes mainly due to an earlier onset of the disorder in males. The actual disease variables, that is, core symptoms and type of course, do not show any essential differences between males and females. These results indicate that schizophrenia is one of the rare uniform patterns of response of the brain, capable of being triggered by a large number of causes or favoured by non-specific risk factors. In this context the protective effect of estrogens will be discussed.
Four pregnancies in three panic disorder patients are described. In three pregnancies panic symptoms improved initially, but worsened in the second half. One patient developed panic disorder in the second half of her pregnancy. Changes in balance between progesterone and estrogen could explain this clinical course.
– Earlier studies on the influence of pregnancy and postpartum period on the course of panic disorder have been inconsistent. The present study aims to quantify panic manifestations in these periods in large sample of women.
– Panic manifestations, including exacerbations and new manifestations of panic disorder, were assessed retrospectively in a sample of 128 women with panic disorder with or without agoraphobia, 93 of whom had had 195 pregnancies.
– Panic manifestations were fewer during pregnancy and more frequent in the postpartum period when compared with the control period. Women who had never been pregnant had significantly more panic manifestations than women with prior pregnancies. Breastfeeding and miscarriages did not have a significant effect. Women with postpartum panic reported more psychosocial stress events during this period.
– Possible reasons for postpartum panic and the protective effects of pregnancy are discussed, including psychosocial or hormonal factors and other neurobiological changes. Postpartum panic coincides with a sudden drop of hormones after delivery.
Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.
Maternal high-fat diet (HFD) alters hypothalamic programming and disrupts offspring energy homeostasis in rodents. We previously reported that the loss of ERα signaling partially blocks the effects of maternal HFD in female offspring fed a standard chow diet. In a companion study, we determined if the effects of maternal HFD were magnified by an adult obesogenic diet in our transgenic mouse models. Heterozygous ERα knockout (wild-type (WT)/KO) dams were fed a control breeder chow diet (25% fat) or a semipurified HFD (45% fat) 4 weeks prior to mating with heterozygous males (WT/KO or WT/ knockin) to produce WT, ERα KO, or ERα knockin/knockout (KIKO) (no estrogen response element (ERE) binding) female offspring, which were fed HFD for 20 weeks. Maternal HFD potentiated the effects of adult HFD on KIKO and KO body weight due to increased adiposity and decreased activity. Maternal HFD also produced KIKO females that exhibit KO-like insulin intolerance and impaired glucose homeostasis. Maternal HFD increased plasma interleukin 6 and monocyte chemoattractant protein 1 levels and G6pc and Pepck liver expression only in WT mice. Insulin and tumor necrosis factor α levels were higher in KO offspring from HFD-fed dams. Arcuate and liver expression of Esr1 was altered in KIKO and WT, respectively. These data suggest that loss of ERE-dependent ERα signaling, and not total ERα signaling, sensitizes females to the deleterious influence of maternal HFD on offspring energy and glucose potentially through the control of peripheral inflammation and hypothalamic and liver gene expression. Future studies will interrogate the tissue-specific mechanisms of maternal HFD programming through ERα signaling.
Historically, pre-pubertal development of the bovine mammary gland (MG) has received little attention compared to later development. Recent evidence suggests not only that this period represents a very active time in the development of the MG but also that the first 90 days of life can partially dictate future productivity of the lactating cow. The MG, often considered quiescent during early life (first 3 months), is now known to increase in size by over 60-fold in the same period. The importance of sex steroids in MG development is well classified, but a complex signaling network exists among estrogen, progesterone and other growth factors and hormones. Complicating our understanding of this developmental period further is the discovery that pre-weaning nutrition of the calf not only influences the growth of the mammary parenchyma but may also alter the way in which it responds to mammogenic stimuli. Recent data suggest that feeding calves a higher plane of nutrition improves the ability of the mammary epithelium to respond to estradiol and also alters the way in which the mammary parenchyma and fat pad communicate. It is clear that early life nutrition, although able to influence the MG, is still poorly understood mechanistically. For example, additional evidence suggests that increased feeding rates in early life alter the morphology of myoepithelial cells in the mammary epithelium. Further data have also suggested a role for other cell types, such as immune cells, in the penetration of the mammary parenchyma into the fat pad during the early life development of the MG suggesting that mammary development is not only controlled by the local tissue population (parenchyma and fat pad) but perhaps systemically by other tissue types (i.e., immune system). Understanding the roles of these various stimuli and signaling pathways as they relate to the development of the MG in early life may hold the key to unlocking the potential for the optimal development of this crucial organ and, in turn, may lead to improvements in other phases of mammary development and milk yield potential.
In addition to being associated with a higher risk of complications during pregnancy, twinning may also be a proxy for altered hormonal exposure for mothers and twin offspring, with implications for their health later in life. We compared maternal and fetal steroid hormone and insulin-like growth factor concentrations between singleton (n=62) and twin (n=41) pregnancies. Maternal concentrations of androgens, estrogens, insulin-like growth factor (IGF)-1, IGF-binding protein (BP)-3 and prolactin were quantified during the third trimester and at delivery, as well as in the fetal circulation at birth. Geometric means accounting for gestational age were calculated for hormone concentrations and compared between matched twin and singleton pregnancies. Most maternal hormone concentrations were modestly higher in twin than in singleton pregnancies in the third trimester (ranging from 8.3% for IGF-1 to 17.1% for estradiol) and at delivery (ranging from 11.1% for IGFBP-3 to 15.2% for estriol). Cord serum hormones were generally similar in twin and singleton pregnancies, except for IGFBP-3, which was 200% lower in twins. The modest differences in maternal hormones in late gestation seem unlikely to explain alterations in hormonally related disease risk in mothers of twins compared with singletons. The large deficit of IGFBP-3 in the fetal circulation of twins at birth may allow for sufficient concentrations of IGF-2 for growth and development in an environment of shared nutritional resources.
It is important to identify molecular candidates involved in morphological and functional changes in the female reproductive system. We have discovered several candidate genes that were significantly altered in chick oviducts by exogenous estrogen and those candidates included dexamethasone (DEX)-induced RAS-related protein 1 (RASD1). RAS-related protein 1, a member of the Ras family of monomeric G proteins, is involved in various cellular processes including cell growth, proliferation and differentiation, as well as a cell-signaling protein regulating hormonal actions. Although the RASD1 gene was first identified as a DEX (a corticosteroid) inducible gene, there is evidence that it is also an estrogen-responsive gene. However, hormone-mediated expression and biological functions of RASD1 in the avian female reproductive system are poorly understood. Therefore, we tested the hypothesis that RASD1 may be involved in the development and remodeling of the chicken reproductive system as an estrogen-responsive gene. Here we demonstrate differential expression of RASD1 gene and candidate microRNAs (miRNAs) targeting chicken RASD1 transcripts in chicken oviducts in response to diesthylstilbestrol (DES, a synthetic non-steroidal estrogen) and the estrogen-mediated molting process. Result of the present study indicated that expression of RASD1 messenger RNA (mRNA) increased in the developing oviducts of chicks treated with DES, particularly in the glandular (GE) and luminal (LE) epithelia of the magnum and the shell gland. Also, during induced molting by zinc feeding, RASD1 expression changed in concert with changes in concentrations of estrogen in blood of laying hens. Our results revealed that expression of RASD1 mRNA decreased as the oviduct regressed and then increased as the oviduct underwent re-growth and recrudescence in hens. Furthermore, RASD1 mRNA was expressed predominantly in GE and LE of the oviduct of laying hens during regeneration of the oviduct after induced molting, but not during the period of regression of the oviduct during molting. In addition, the relative expression of candidate miRNAs (miR-30a-5p, miR-30b-5p, miR-30c-5p and miR-30d) regulating RASD1 transcripts changed in response to estrogen stimulation of chick oviducts. These results indicate that transcription of the RASD1 gene and miRNAs regulating post-transcriptional aspects of expression of RASD1 are modulated by estrogen which is critical for growth, development, remodeling and maintenance of function of the chicken oviduct.
Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r2 = 0.30, p = .030), percentage total body (r2 = 0.43, p = .014), and thigh (r2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r2 = 0.27, p = .020) and thigh muscle area (r2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.
Although the expression of estrogen and progesterone receptors within porcine ovary and cumulus–oocyte complexes (COCs) is well recognized, still little information is known regarding expression of the progesterone receptor (PGR), PGR membrane component 1 (PGRMC1) and of estrogen-related receptors (ERRγ and ERRβ/γ) in separated cumulus cells in relation to real-time proliferation. In this study, a model of oocytes-separated cumulus cells was used to analyze the cell proliferation index and the expression PGR, PGRMC1 and of ERRγ and ERRβ/γ during 96-h cultivation in vitro using real-time quantitative PCR (qRT-PCR) and confocal microscopic observation. We found that PGR protein expression was increased at 0 h, compared with PGR protein expression after 96 h of culture (P < 0.001). The expression of PGRMC1, ERRγ and ERRβ/γ was unchanged. After using qRT-PCR we did not found statistical differences in expression of PGR, PGRMC1, ERRγ and ERRβ/γ during 96 h of cumulus cells in vitro culture (IVC). We supposed that the differential expression of the PGR protein at 0 h and after 96 h is related to a time-dependent down-regulation, which may activate a negative feedback. The distribution of PGR, PGRMC1 proteins may be linked with the translocation of receptors to the cytoplasm after the membrane binding of respective agonists and intra-cytoplasmic signal transduction. Furthermore, cumulus cells analyzed at 0 h were characterized by decreased proliferation index, whereas those after 96 h of culture revealed a significant increase of proliferation index, which may be associated with differentiation/luteinization of these cells during real-time proliferation.
Despite decades of research aimed at identifying the causes of postpartum depression (PPD), PPD remains common, and the causes are poorly understood. Many have attributed the onset of PPD to the rapid perinatal change in reproductive hormones. Although a number of human and nonhuman animal studies support the role of reproductive hormones in PPD, several studies have failed to detect an association between hormone concentrations and PPD. The purpose of this review is to examine the hypothesis that fluctuations in reproductive hormone levels during pregnancy and the postpartum period trigger PPD in susceptible women. We discuss and integrate the literature on animal models of PPD and human studies of reproductive hormones and PPD. We also discuss alternative biological models of PPD to demonstrate the potential for multiple PPD phenotypes and to describe the complex interplay of changing reproductive hormones and alterations in thyroid function, immune function, hypothalamic–pituitary–adrenal (HPA) axis function, lactogenic hormones, and genetic expression that may contribute to affective dysfunction. There are 3 primary lines of inquiry that have addressed the role of reproductive hormones in PPD: nonhuman animal studies, correlational studies of postpartum hormone levels and mood symptoms, and hormone manipulation studies. Reproductive hormones influence virtually every biological system implicated in PPD, and a subgroup of women seem to be particularly sensitive to the effects of perinatal changes in hormone levels. We propose that these women constitute a “hormone-sensitive” PPD phenotype, which should be studied independent of other PPD phenotypes to identify underlying pathophysiology and develop novel treatment targets.
Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort.
We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R.
We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD.
These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.
To investigate the aetiology of rhinitis occurring in pregnancy, by (1) describing the relationship between pregnancy rhinitis and serum oestrogen, progesterone, placental growth hormone and insulin-like growth factor, and (2) assessing the prevalence of pregnancy rhinitis among Malaysian women.
Prospective study involving 30 pregnant women followed at an ante-natal clinic for 14 months. Hormone levels were analysed during pregnancy and the post-partum period.
Levels of all four hormones were elevated in the third trimester, compared with first trimester and post-partum values. Rhinitis patients had higher levels of oestrogen and insulin-like growth factor 1 in the third trimester than non-rhinitis patients, although these differences were not statistically significant. The prevalence of rhinitis was 53.3 per cent, with most cases occurring in the third trimester. Patients with pregnancy rhinitis had a higher prevalence of female babies, compared with non-rhinitis patients (p = 0.003).
Pregnancy rhinitis was significantly more common in women giving birth to female babies. Women with pregnancy rhinitis had a non-significant elevation in oestrogen and insulin-like growth factor 1 levels, compared with those without rhinitis.
The objective of the present study was to investigate the effect of Gram-negative bacteria infection on ovarian steroid receptors, i.e. progesterone receptor (PR) and estradiol receptor (ER) during preimplantation days of pregnancy. A well established mouse model of Gram-negative bacteria infection was used to test this objective. Mice were treated with normal saline or lipopolysaccharide (LPS) on day 0.5 of pregnancy and used to collect embryos and uterine horns on day 1.5 to day 4.42 preimplantation day of pregnancy. Total RNA was extracted and reverse-transcription polymerase chain reaction (PCR) was performed to check the expression of PR and ER genes. The mRNA expression of PR and ER was altered in embryos and uterus of LPS-treated animals during preimplantation days of pregnancy studied. These results suggest that PR and ER play an important role in Gram-negative bacteria infection and induced implantation failure in mouse.
We describe the case of a 56-year old woman with no prior psychiatric history who was diagnosed with hormone receptor positive early-stage breast cancer and who developed severe mood changes after administration of anastrozole, which resolved after discontinuation of treatment. Aromatase inhibitors (AIs) are the preferred hormonal approach for postmenopausal women with estrogen hormone sensitive breast cancer. The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen. Treatment strategies with these agents include the use of an AI as an upfront strategy for 5 years, as a sequential approach after 2–3 years of tamoxifen, or as extended use after the classical 5 years of tamoxifen. The side effects of AIs, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen. However, the use of AIs have been associated with loss of bone density, arthralgia, myalgia, a negative effect on lipid metabolism, and cardiovascular risk (Tomao et al., 2011). Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy.
This chapter describes the diagnosis, surgical intervention, and prognosis for breast cancer in pregnancy. Estrogen receptor-negative and progesterone receptor-negative tumors, which correlate with poor prognoses, are more common among pregnant women than among age-matched controls, possibly due to receptor down-regulation in pregnancy. The rate of mastectomy among pregnant women is higher than the rate of lumpectomy due to large tumor size and avoidance of adjuvant radiation, but breast-conserving surgery is becoming more frequent. Radiation therapy administered either to complete breast-conserving surgery, as postmastectomy adjuvant treatment in high-risk patients or as a palliative treatment for metastatic cancer, is contra-indicated during pregnancy because of fetal exposure. Chemotherapy should be avoided four weeks before the anticipated delivery date to reduce the risk for infection, or hemorrhage due to pancytopenia. Comparisons between pregnant and nonpregnant women of matched age, nodal status, estrogen receptor status, and tumor histopathology and size yielded no differences in prognosis.
Several medications have been found to increase implantation rates with in vitro fertilization (IVF) when given as adjuncts to follicle stimulating hormone (FSH) stimulation of the ovaries in preparation for oocyte retrieval. Gonadotropin-releasing hormone (GnRH) agonists, oral contraceptives (OCs), and estrogen pretreatment help to synchronize the follicular cohort resulting in an improved ovarian response. Metformin (MET) increases implantation in PCOS women having IVF and dramatically reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in these women. Growth hormone (GH) markedly increases implantation in poor-responding women having IVF. Small doses of human chorionic gonadotropin (hCG) are used to provide LH activity allowing use of pure FSH products and the pen devices that deliver graduated FSH doses. Low-dose aspirin (ASA) increases ovarian response and implantation, and reduces the incidence of severe OHSS. Drugs such as letrozole that increase androgens may prove to be useful agents to increase ovarian response in poor responders.
This chapter covers issues most likely to be raised by young women who have been diagnosed with breast cancer or those at high risk of the disease contemplating assisted fertility procedures. The type of adjuvant regimen selected for an individual woman is determined by menopause status, biological characteristics of the tumor and risk of relapse. Large meta-analyses of multiple trials with longterm follow-up have been used to assess the effects of systemic therapy on breast cancer outcomes. Achievement of amenorrhea appears to be associated with a reduction in relapse and improvement in survival in premenopausal women with estrogen receptor positive (ER+) tumors. There are three main barriers to implementing fertility preservation in women with breast cancer: cost; concern about treatment delays; and concern that increasing sex hormones as a result of controlled ovarian stimulation (COS) protocols will stimulate proliferation in ER+ tumors.
The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial. With the initial dose of GnRHa, the pituitary gland releases endogenous gonadotropins. This initial follicle stimulating hormone (FSH) release stimulates the ovary. After continued GnRHa exposure, further FSH release is prevented. Gonadotropin-releasing hormone analogues can be administered in many formulations with different durations of action. The most common side effects of GnRH analogues are related to the subsequent estrogen deprivation. Vasomotor symptoms, hot flushes, night sweats, vaginal dryness and headaches can occur. Cotherapy of a GnRHa during chemotherapy has been under investigation since the mid 1990s. If prolonged GnRHa administration decreases ovarian blood flow, then less chemotherapy may reach the ovary. Direct effects of GnRHa or FSH on ovarian tissue may influence ovarian response to chemotherapy. For GnRHa to be of benefit to fertility preservation, they would likely need to spare both oocyte quantity and quality.