Role Of Female Sex Hormones Research Articles

Diabetes Abolishes the Cardioprotective Effect of Estrogen on Systolic Cardiac Function

The present study evaluated the role of female sex hormones on the adverse effects of diabetes in cardiac function. Adult female Sprague‐Dawley rats (10 weeks‐old) were submitted to ovariectomy. One week later, diabetes was induced with a single dose of streptozotocin (65 mg/kg, i.p) without insulin replacement. After 4 weeks cardiac function was evaluated by echocardiography (Vevo 2100, VisualSonics, Toronto, Ontario, Canada) in intact controls (CTL); diabetics (STZ); ovariectomized (OVX); and OVX with diabetes (OVX‐STZ). Diabetes and OVX alone or in combination did not affect systolic blood pressure. While OVX animals exhibited a higher LV weight: tibia length ratio (LVW/TL; 18%; vs CTL; p<0.05), LVW/TL was particularly reduced in the diabetic animals (STZ: 14%; OVX‐STZ: 11%; vs CTL; p<0.05). However, the relative wall thickness was decreased in OVX and diabetic animals (STZ: 21%; OVX: 18%; OVX‐STZ: 21%; vs CTL; p<0.05). The ejection fraction (EF) and fractional shortening (FS) were decreased in OVX, respectively (65% ± 1% vs 72 % ± 2% in CTL; 37± 1% vs 43 ± 2% in CTL). The systolic function was markedly reduced by the same magnitude in both STZ (EF: 66± 1%; FS: 38 % ± 1%) and OVX‐STZ (EF: 65± 2%; FS: 37± 1%) relative to CTL. These data indicate that diabetes removes the cardioprotective effect of estrogen on cardiac function independently of alterations in blood pressure.

The Role of Plasma Female Sex Hormones on Gingivitis in Pregnancy: A Clinicobiochemical Study

To correlate the changes in the level of female sex hormones (progesterone, estrogen) in plasma with the changes in severity of gingivitis in various trimesters of pregnancy till the postparturition. This study comprised of 20 pregnant women with good oral hygiene who were followed up in each trimester till 3rd month of postpartum by screening their oral hygiene status following OHI-S index by Greene and Vermillion. Clinically to correlate gingivitis, gingival index by Loe and Sillness was carried out in each trimester till postpartum. For hormonal assay, blood sampling by venipuncture was done and quantative analysis of the hormones was done by ELISA test. The severity of gingivitis gradually increased and reached its peak in 3rd trimester followed by sudden decline in the severity in postpartum which correlated with gradual increase in the plasma level of progesterone and estrogen levels to reach their peak in the 3rd trimester and sudden fall after the postpartum. This study shows the role of female sex hormones in aggravating gingivitis to its peak in the 3rd trimester, even though the oral hygiene remains fairly good constantly. This study signifies the gingivitis status during different trimesters of pregnancy and postpartum indicating the general practitioner to take appropriate oral hygiene measures.

Symptomatic Changes of Oral Mucosa during Normal Hormonal Turnover in Healthy Young Menstruating Women

Changes in hormonal levels, such as those that occur during puberty, pregnancy, menstruation and menopause, have varying effects on oral cavity. Many researchers have proposed a direct link between changing hormonal status and oral health among females. To study the various symptoms and clinical manifestations of oral cavity during normal course of menstrual cycle in healthy women. Our study comprised of forty healthy young women volunteers with normal menstrual cycle of 28 to 30 days. A proper menstrual history was recorded from the study subjects. The entire cycle was divided into four phases comprising of bleeding, proliferative, ovulation and secretory. All the study subjects had a menstrual cycle of 28 to 30 days. Thorough recording of oral discomforts during various phases of the cycle was done during the study period. 30% of study subjects complained of aphthous ulcers, 5% had herpes labialis, 25% of them complained of depression, 8% showed gingival bleeding. Complaints, like oral ulcerations, mood variations, recurrent herpetic lesions, gingival bleeding in females during normal menstrual period, are attributed to the role of female sex hormones. Lesions, like oral ulcers, recurrent herpetic lesions and increased gingival bleeding, seen in females during normal menstrual periods, could be related to hormonal turnover and therefore treated accordingly.

Role of female sex hormones, estradiol and progesterone, in mast cell behavior

Female sex hormones have long been suspected to have an effect on mast cell (MC) behavior. This assumption is based on the expression of hormone receptors in MCs as well as on the fact that many MC-related pathophysiological alterations have a different prevalence in females than in males. Further, serum IgE levels are much higher in allergic female mice compared to male mice. Ovariectomized rats developed less airway inflammation compared to sham controls. Following estrogen replacement ovariectomized rats re-established airway inflammation levels’ found in intact females. In humans, a much higher asthma prevalence was found in women at reproductive age as compared to men. Serum levels of estradiol and progesterone have been directly correlated with the clinical and functional features of asthma. Around 30–40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma. Beside, estrus cycle dependent changes on female sex hormones are related to changes on MC number in mouse uterine tissue and estradiol and progesterone were shown to induce uterine MC maturation and degranulation. We will discuss here the currently available information concerning the role of these female sex hormones on MC behavior.

Gender Differences in Age-Related Changes in Cardiac Autonomic Nervous Function

Ageing is associated with changes in cardiac autonomic control as measured by Heart Rate Variability (HRV). Not many studies have explored the influence of gender on age-related changes in cardiac autonomic regulation. This study evaluated the gender differences in age-associated changes in cardiac autonomic nervous activity by assessing HRV using frequency domain analysis of short-term stationary R-R intervals. HRV was studied in healthy males and females ranging in age from 6 to 55 years. Total power and absolute power in High-Frequency (HF) and Low-Frequency (LF) components as well as HF in normalized unit declined significantly with ageing. The HF/LF ratio was significantly higher in the adolescent and adult females compared to male of these age groups. This study suggests that gender differences exist in age-related changes in HRV. The finding that gender differences are limited to adolescent and adult age groups may indicate a role for female sex hormones in cardiac autonomic modulation.

Hormonal and reproductive factors and risk of postmenopausal thyroid cancer in the NIH-AARP Diet and Health Study

Background: Worldwide, thyroid cancer incidence rates are higher among women than men. While this suggests a possible etiologic role of female sex hormones, clear associations between hormonal and reproductive factors and thyroid cancer have not been observed. However, few large prospective studies have been conducted. Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) for hormonal and reproductive factors and incident thyroid cancer were estimated using Cox regression methods in the prospective US NIH-AARP Diet and Health Study. Between 1995 and 2006, 312 first primary incident thyroid cancers were diagnosed among 187,865 postmenopausal women ages 50–71 at baseline. Results: Thyroid cancer was not associated with ages at menarche or menopause, menopause type, or parity. Oral contraceptive use for ≥10 years (vs. never use) was inversely associated with thyroid cancer risk (HR, 0.48; 95%CI, 0.28–0.84; Ptrend=0.01). Women who reported current menopausal hormone therapy at baseline had an increased thyroid cancer risk vs. never users (HR 1.38; 95% CI: 1.07–1.79) but there was no trend with increasing duration of use. Women with benign breast disease (BBD) had a significantly higher thyroid cancer risk vs. women without BBD (HR, 1.47; 95% CI, 1.09–1.99). Conclusions: Our results do not support a strong role for female hormonal and reproductive factors including ages at menarche and menopause, type of menopause or parity, in thyroid cancer etiology among postmenopausal women. Compared with previous studies, no clear patterns emerge for exogenous hormone use but further analysis in large, prospective populations may be informative. The HR for BBD is consistent with the one previous prospective analysis that examined this association.

Population based epidemiology of amyotrophic lateral sclerosis using capture–recapture methodology

BackgroundVariation in the incidence rate in epidemiological studies on amyotrophic lateral sclerosis (ALS) may be due to a small population size and under ascertainment of patients. The previously reported incidence...

Giant liver hemangioma

Hepatic hemangiomas are the most common focal liver lesions and are especially prevalent in women. Giant hemangiomas are defined as hemangiomas of at least 4 cm in diameter and the majority remains stable in size over time. However, in some cases hemangiomas display growth and give rise to symptoms because of their space-occupying effect. Causes for the enlargement of the tumors are unknown, but a role of female sex hormones has been suggested. Therefore, hormone therapy should be avoided in patients who became symptomatic. In patients with important symptoms, disease control can be obtained by transcatheter arterial embolization. In selected patients, especially in case of Kasabach-Merritt syndrome, there is a good indication for liver transplantation.

Increased prevalence of sexually transmitted viral infections in women: the role of female sex hormones in regulating susceptibility and immune responses

Sexually transmitted infections (STIs) caused by viruses, including HSV-2, HIV-1, HPV, are among the most prevalent infectious diseases worldwide and a major cause of morbidity and mortality. Despite decades of effort, the attempts to develop efficacious vaccines against viral STIs have failed repeatedly, with the exception of the recent HPV vaccine. Given the higher prevalence rates of STIs in women, it is becoming clear that a better understanding of gender-specific differences in STIs may be critical for the development of preventative strategies for these diseases. In order to gain this insight, it is important to examine the distinct microenvironment of the female reproductive tract, the site of primary infection, since it can significantly influence the outcome of infection. An important biological factor in the female reproductive tract is the presence of female sex hormones, estrogen and progesterone, which are produced endogenously primarily by the ovaries and commonly provided exogenously via the use of hormonal contraceptives. Here we review our current knowledge of the role played by the female sex hormones in regulating susceptibility and immune responses to viral sexually transmitted infections and whether this could contribute to higher prevalence of STIs in women. Manipulating the microenvironment of the female genital tract with sex hormones may contribute to the development of improved immunization strategies against sexually transmitted infections.

Reproductive Immunology: a Focus on the Role of Female Sex Hormones and Other Gender-Related Factors

Reproductive immunology has attracted the attention of researchers interested in fertility and pregnancy as well as those interested in immunity and autoimmunity. Over the past couple of decades, a wealth of data on the immune-reproductive interactions has been generated. This issue of the Journal will examine several topics including the role of immune factors in the induction of anti-Ro antibody-mediated autoimmunity in neonates and the immunological effects of gender and sex hormones. The possible implications of the research reviewed here for the development of novel therapeutic approaches are also addressed.

Genetics of Menstrual Migraine: The Molecular Evidence

Migraine is considered to be a multifactorial disorder in which genetic, environmental, and, in the case of menstrual and menstrually related migraine, hormonal events influence the phenotype. Certainly, the role of female sex hormones in migraine has been well established, yet the mechanism behind this well-known relationship remains unclear. This review focuses on the potential role of hormonally related genes in migraine, summarizes results of candidate gene studies to date, and discusses challenges and issues involved in interpreting hormone-related gene results. In light of the molecular evidence presented, we discuss future approaches for analysis with the view to elucidate the complex genetic architecture that underlies the disorder.

Factor Seven Activating Protease (FSAP) levels during normal pregnancy and in women using oral contraceptives

Introduction Factor seven activating protease (FSAP) is a plasma serine protease involved in haemostasis and remodeling processes. We have investigated whether pregnancy or the use of oral contraceptives (OCs) influences circulating FSAP levels. The effect of female sex hormones on FSAP expression in cultured cells was also determined. Materials and Methods FSAP levels and activity was measured in plasma samples obtained at different gestation stages from healthy pregnant women (n = 101), from non-pregnant women, pre-menopausal women who currently use OCs (n = 48), and non-pregnant women who did not use OCs (n = 69). Results In late pregnancy the plasma FSAP antigen (median 2.28 PEU/ml [range 1.11 to 2.62 PEU/ml]; p < 0.001 vs control group) and activity (median 2.98 PEU/ml [range 1.05 to 4.24 PEU/ml]; p < 0.001 vs control group) was significantly higher compared with levels in non-pregnant women and remained elevated after delivery. Plasma FSAP levels in women using OCs was also significantly elevated compared to the control group. Ex vivo experiments demonstrated enhanced FSAP expression in monocytes isolated from women using OCs. In vitro experiments showed that FSAP mRNA levels were strongly induced by estradiol in monocytes but not in hepatocytes. Conclusions Increased levels of circulating FSAP in pregnancy and in women using OCs indicate that hormonal status critically influences FSAP expression. Hormonal influences could be observed in monocytes in vivo and ex-vivo but not in hepatocytes indicating cell-specific regulation. Future studies designed to investigate the role of FSAP in haemostasis and remodeling processes should consider the role of female sex hormones on FSAP expression.

Abstract 4919: Contradictive Estrogen Effects on BMP Signaling in Pulmonary Artery Depend on Oxygen Concentration

Epidemiologic studies have shown that the female predominance in the morbidity of Idiopathic PAH (pulmonary arterial hypertension) in the world, which suggests a role of female sex hormones in the pathogenesis of PAH. Our previous study demonstrated the contradictory effects of estrogen on pulmonary arterial endothelial cells (PAEC) via BMP (Bone Morphogenetic Protein) signaling depend on cellular oxygen environment. This study is to investigate the mechanism of the contradictory effect of β -estradiol (E2) upon BMP signaling in PAEC. &lt;MATERIALS and METHODS&gt; Human and rat PAEC were cultured and the expression of BMPR2, Smad1/5/8, and Id1 were examined under 21%O 2 (normoxic; N) or 1%O 2 (hypoxic; H) condition in the presence of E2. We investigated the effect of estrogen receptor antagonist (ICI 182.780.) and searched for an evidence of binding interaction between estrogen receptor (ER) and Smad. In the presence of E2 (10 −7 M), the expression of BMPR2, phosphorylated Smad (p-Smad)1/5/8 proteins, Id1 mRNA was augmented under N and suppressed under H. We confirmed same phenomena by using Id1 promoter assay. These alterations of BMPR signal expression were inhibited by ICI182.780. An Immunoprecipitation experiment demonstrated a direct binding interaction between ER and p-Smad1/5/8 proteins only under H, whereas estrogen response activity measured by luciferase assay was increased by E2 only under N. In addition, HIF-1 α augmentation by cobalt chloride suppressed BMP signaling, whereas HIF-1 α inhibition by YC-1 augmented those expression. By inhibiting de novo synthesis by administration of cycloheximide, p-Smad1/5/8 were suppressed under N, but could not change under H. We demonstrated that the alteration of BMP signaling in PAEC under different O 2 condition was associated with HIF-1 α expression and the presence of E2. This alteration may also relate to an interaction between BMP signaling and receptor-mediated estrogen pathway under hypoxia, and to de novo synthesis under normoxia. Our observations provide the new mechanism how sex hormone affects on BMP signaling, a key signal pathway for PAH, which can offer novel therapeutic targets in the treatment of PAH.

The effects of previous hysterectomy on lupus

Hysterectomy is one of the most common surgical procedures performed in United States, and currently, one in three women in United States has had a hysterectomy by the age of 60 years. Systemic lupus erythematosus (SLE) is a common autoimmune disease and especially targets women of childbearing age at least 10 times higher than men, which reflects the major role of female sex hormones. In this retrospective study, we evaluate the potential effects of previous hysterectomy in our lupus cohort. Data collected from study subject questionnaires were obtained from the Lupus Family Registry and Repository (LFRR) at the Oklahoma Medical Research Foundation. Hysterectomy data were available from 3389 subjects. SLE patients with a positive history of hysterectomy have been selected and compared with matched lupus patients with a negative history of hysterectomy and healthy controls. Association analyses were performed, and the P values and adjusted odds ratios (ORs) were calculated. SLE patients with a negative history of hysterectomy more likely had kidney nephritis or positive anti-dsDNA than age-matched SLE patients with a history of hysterectomy before disease onset. This effect was independent of ethnicity with an OR of 6.66 (95% CI = 3.09-14.38, P = 1.00 x 10(-8)) in European patients and 2.74 (95% CI = 1.43-5.25, P = 0.001) in African-Americans. SLE patients with a positive history of hysterectomy before disease onset also had a later age of disease onset (P = 0.0001) after adjustment for age and race. Our findings support the notion that the influence of female sex hormones in SLE and various clinical findings are tremendous and that surgical menopause such as this could significantly affect the outcome of disease and clinical manifestations.

The role of female sex hormones in the development and severity of allergic and non‐allergic asthma

Allergic asthma is usually diagnosed by the presence of variable airway obstruction, bronchial hyperresponsiveness, and allergy. However, a significant proportion of adult asthma patients (up to 40%) are non-allergic. Patients with non-allergic asthma often have a later disease onset and greater disease severity, as reflected by more severe airway obstruction and bronchial hyperresponsiveness. Furthermore, females have a higher risk of developing non-allergic asthma. The latter suggests that hormone-related events play an important role in the development and severity of adult-onset non-allergic asthma. This paper describes the associations between asthma and hormonal changes throughout the female life-span, such as those associated with the monthly cycle of menstruation and menopausal hormonal changes.

Lung Function in Korean Adolescent Girls: in Association with Obesity and the Menstrual Cycle

Gender differences in asthma have been observed with a preponderance of boys affected before puberty and girls during and after puberty. The known influences of the menstrual cycle on asthma support a role for female sex hormones on the changing expression of asthma during adolescence. The purpose of this study was to investigate obesity, the menstrual cycle and lung function in adolescent girls. One hundred and three female high school girls (mean age: 15.9±0.8 yr) were enrolled. The investigation was performed using a questionnaire that included history of asthma, the menstrual cycle, other combined allergic disease and obesity. The skin prick and pulmonary function test during menstruation period and non-menstruation period. Analyses of these factors were compared. The forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was significantly lower in the obese group compared to the non-obese group (99.8±13.8 vs. 107.1±10.2, p=0.03). The FEV1 was significantly lower in the girls during menstruation period than in the girls who were not on menstruation (77.5±10.2 vs. 80.4±8.6, p=0.03). Our results showed that changes of pulmonary function were related to menstrual cycle and obesity in Korean adolescent girls.

Estrone and progesterone inhibit the growth of murine MC38 colon cancer line

The unsatisfactory effectiveness of reference chemotherapy in colon cancer (fluorouracil – FU) results in continuous search for agents, which could enhance the action of FU. Some epidemiological data such as a decreased risk of colorectal cancer among menopausal women receiving hormonal replacement therapy indicate the role of female sex hormones in the pathogenesis of this disease. The aim of this study was to examine the direct effects of various concentrations of estrone and progesterone (10 −4 to 10 −12 M) applied alone or together with FU on the growth of murine MC38 colon cancer in vitro. Estrone inhibited MC38 cancer growth in a wide range of concentrations (10 −12 to 10 −4 M) with similar potency and at some concentrations (10 −6 and 10 −4 M) augmented also the cytotoxic action of FU. Progesterone induced MC38 cancer growth inhibition at high concentrations (10 −5 to 10 −4 M) in dose- and time-dependent manner but it did not intensify antineoplastic effect of FU. A weak inhibitory effect of progesterone was also observed for lower concentrations (10 −5 to 10 −10 M) in long lasting cultures (72 h). The results indicate that estrone and progesterone inhibit the MC38 cancer growth and that estrone increases also the cytotoxic effect of FU, what confirms the role of female sex steroids in modulation of colon cancer growth.

Abstract 1636: Adverse Effect of Estrogen on Bone Morphogenetic Protein Receptor Signal Pathway in Pulmonary Arterial Endothelial Cells

Gender differences in the development of Pulmonary Artery Hypertension (PAH) have been documented in both human and animal studies. In human, idiopathic PAH is predominantly a disease of young women in their child-bearing years, which suggests a role of female sex hormones in the pathogenesis of PAH. However, the effect of sex hormones on pulmonary vasculatures and the development of PAH has not been fully understood. Recent researches have revealed genetic predisposition such as BMPR (Bone Morphogenetic Protein Receptor). The aim of the present study is to investigate the effect of β-estradiol (E2) and oxygen concentration upon BMPR signal pathway in pulmonary arterial endothelial cells (PAEC) in vitro. Human and rat PAEC were cultured and we examined the expression of BMPR2, BMP-regulated Smads, and Id1 under 21% or 1% O 2 with BMP2 stimulation. Then, we investigate changes in the expression of these molecules in the presence of E2 with or without estrogen receptor antagonist (ICI 182.780.). First, we confirmed that estrogen receptor α and β were expressed in both PAECs. Second, we demonstrated that the expression of mRNA transcripts for BMPR2 and Id1 in PAEC was reduced after exposure to 24 hours’ hypoxia. In addition, E2 decreased the expression of phosphorylated Smad (p-Smad)1/5/8 in a dose-dependent manner (10 −10 M-10 −7 M) and p-Smad1/5/8 expression were decreased about 80% by 10 −7 M of E2. These attenuation of p-Smad1/5/8 expression were rescued by ICI182.780. Third, under normoxic condition with cobalt chloride or deferoxamine to prevent the degradation of HIF (hypoxia-inducible factor)-1α, the presence of E2 decreased the expression of p-Smad1/5/8 like under hypoxia. Conversely, administration of HIF-1α inhibitor (YC-1) canceled the reduced expression of p-Smad1/5/8 like under normoxia. Under hypoxia, the presence of E2 attenuates the BMPR signal pathway in PAEC in vitro. Our data indicated that the advance effect of E2 on BMPR signal pathway was associated with HIF-1α and estrogen receptor. Our observations provide the first evidence that female sex hormone affects on BMPR signal pathway, which can offer new strategies for the treatment of PAH.

Sex differences in a transgenic rat model of Huntington's disease: decreased 17β-estradiol levels correlate with reduced numbers of DARPP32+ neurons in males

Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal DARPP32(+) medium-sized spiny neurons (MSNs) and dopamine receptor autoradiography) and (iii) peripheral sex hormone levels as well as striatal estrogen receptor expression. Independent of their sex, tgHD rats exhibited increased levels of food intake, elevated home-cage activity scores and anxiolytic-like behavior, whereas only males showed an impairment of motor function. In line with the latter finding, loss and atrophy of DARPP32(+) MSNs were apparent only in male tgHD rats. This result was associated with a decreased striatal dopamine D1 receptor density and lower plasma levels of 17beta-estradiol at the age of 14 months. As DARPP32(+) MSNs expressed both alpha- and beta-estrogen receptors and showed a correlation between cell numbers and 17beta-estradiol levels, our findings suggest sex-related differences in the HD phenotype pointing to a substantial neuroprotective effect of sex hormones and opening new perspectives on the therapy of HD.

Analysis of estrogen binding sites of the posterior ligament of the human TMJ

Conflicting results have been reported regarding the presence or absence of estrogen-binding sites (EBS) in the human temporomandibular joint (TMJ). The possible role of female sex hormones in the pathophysiology of internal derangement of the TMJ has been suggested to explain the prevalence of TMJ symptoms in female patients. Posterior bilaminar tissue excised during TMJ articular disc repositioning and posterior ligament repair was taken from 28 patients (26 female, 2 male) for evaluation. Cryosections were stained using a monoclonal antibody (Mab) against EBS. To ensure efficacy of the antibody staining procedure, an internal positive control consisting of human breast tissue previously proven EBS-positive was used. No asymptomatic control TMJ tissue was available for our study. None (0%) of 28 TMJ tissue specimens showed nuclear-staining positive for the presence of EBS in the posterior bilaminar tissue of the TMJ. However, estrogen-binding sites associated with probable inflammatory cells were observed. Our results are consistent with the probability of positives as high as 0.1234 using a 95% confidence interval. The lack of EBS of the posterior ligament of the TMJ suggests that the role of estrogen contributing to internal derangement of the TMJ appears not to be significant.