Hormonal Intake Research Articles

Influence of steroid hormones on ventricular repolarization.

QT interval prolongation, corrected for heart rate (QTc), either spontaneous or drug-induced, is associated with an increased risk of torsades de pointes and sudden death. Women have longer QTc than men and are at higher risk of torsades de pointes, particularly during post-partum and the follicular phase. Men with peripheral hypogonadism have longer QTc than healthy controls. The role of the main sex steroid hormones has been extensively studied with inconsistent findings. Overall, estradiol is considered to promote QTc lengthening while progesterone and testosterone shorten QTc. New findings suggest more complex regulation of QTc by sex steroid hormones involving gonadotropins (i.e. follicle-stimulating hormone), the relative concentrations of sex steroid hormones (which depends on gender, i.e., progesterone/estradiol ratio in women). Aldosterone, another structurally related steroid hormone, can also prolong ventricular repolarization in both sex. Better understanding of pathophysiological hormonal processes which may lead to increased susceptibility of women (and possibly hypogonadic men) to drug-induced arrhythmia may foster preventive treatments (e.g. progesterone in women). Exogenous hormonal intake might offer new therapeutic opportunities or, alternatively, increase the risk of torsades de pointes. Some exogenous sex steroids may also have paradoxical effects on ventricular repolarization. Lastly, variations of QTc in women linked to the menstrual cycle and sex hormone fluctuations are generally ignored in regulatory thorough QT studies. Investigators and regulatory agencies promoting inclusion of women in thorough QT studies should be aware of this source of variability especially when studying drugs over several days of administration.

Evaluación clínica de dos preparados bifásicos y un trifásico a base de norgestrel/etinilestradiol

458 mujeres fueron evaluadas durante 3585 ciclos en un estudio controlado randomizado y abierto, diseñado para comparar dos preparados bifásicos y un trifásico a base de Norgestrel/Etilnilestradiol. Los tres preparados son anticonceptivos efectivos y no se registraron gestaciones. El control del ciclo fue bueno con los tres, pero la incidencia de sangrado intermensual fue ayor con el trifásico. Con este preparado la ingesta hormonal total está bien por debajo de la dosis fija más baja de Norgestrel/Etinilestradiol como preparación combinada (300 mcg. Norgestrel más 30 mcg. EE) en la proporción original 10:1. Se concluye que el tambaleo de dosis hormonales abre la posibilidad de anticoncepción con menor ingesta hormonal de lo que es posible cuando se utiliza un regimen a dosis fija.

The protective effect of hormonal intake on risk of hepatocellular carcinoma in the United States.

4019 Background: In the United States, the incidence of hepatocellular carcinoma (HCC) has been tripled over the last two decades. Despite the overwhelming effect of several environmental risk fact...

The effects of hormonal contraceptives on glycemic regulation.

A number of side effects have been linked to the use of hormonal contraceptives, among others, alterations in glucose levels. Hence, the objective of this mini-review is to show the main effects of hormonal contraceptive intake on glycemic regulation. First, the most relevant studies on this topic are described, then the mechanisms that might be accountable for this glycemic regulation impairment as exerted by hormonal contraceptives are discussed. Finally, we briefly discuss the ethical responsibility of health professionals to inform about the potential risks on glycemic homeostasis regarding hormonal contraceptive intake.

Factors associated with sexual function in Iranian women with type 2 diabetes mellitus: partner relationship as the most important predictor.

Background:No comprehensive study has been conducted on risk factors of sexual dysfunction in women with diabetes mellitus.Objectives:The aim of this study was to consider all possible influencing variables including hormonal, physical and, psychological status, socioeconomic status, and dietary intake to get more accurate and reliable results.Patients and Methods:Sexual function was assessed by Iranian validated female sexual function index (FSFI).The variables of the study were demographic and diabetes-related factors, stress-depression, physical activity, blood pressure, anthropometric measurements, lipid profile, cortisol, sex and thyroid hormones, 25-hydroxy vitamin D, and dietary intake.Results:Among all investigated variables, partner relationship showed a strong positive association with FSFI (β = 1.93 ± 0.41, P < 0.0001). In addition, not considering partner relationship, FSFI showed a significant negative association with age (β = -0.19 ± 0.20, P = 0.04), stress-depression score (β = -0.08 ± 0.04, P = 0.04), DD (β = -0.03 ± 0.01, P = 0.04), and systolic blood pressure (β = -0.14 ± 0.06, P = 0.03). Significant associations between FSFI and serum sex hormones and other biochemical were found in neither postmenopausal nor non-menopausal women. The means of SFSI in postmenopausal women were greater than non-menopausal (P = 0.02).Conclusions:It seems that in our population, female sexual function was much more than just a hormonal or physical problem and psychological factors, especially partner relationship and stress-depression, are the most determinants. In addition, age, duration of challenging with disease, and the lack of controlling systolic blood pressure were common factors that decreased sexual function.

Hormonal responses and test meal intake among obese teenagers before and after laparoscopic adjustable gastric banding

Relatively little is known about changes in eating behavior or hormonal responses to food after bariatric surgery in adolescents. This study compared eating behavior and hormones among adolescents in a bariatric surgery program with those in nonoverweight control adolescents and evaluated changes before and after laparoscopic adjustable gastric banding (LAGB). Fasting leptin, peptide YY (PYY), and ghrelin concentrations were obtained, and postprandial ghrelin and PYY area under the curve (AUC) were assessed after a single-item breakfast. Intake from an ad libitum lunchtime multi-item meal was measured. Compared with controls (n = 9), all presurgical candidates (n = 20) had significantly greater fasting leptin, lower fasting ghrelin, and lower AUC ghrelin but similar PYY and AUC PYY. Preoperative candidates did not differ from controls in total energy consumed during the test meal. Postoperatively, among the 11 participants with data both before and after surgery, BMI (in kg/m(2)) decreased by 3.5 (P < 0.001), significantly less energy was consumed in the test meal, and a smaller number of foods were selected. AUC ghrelin and PYY did not significantly change before or after LAGB. Few significant short-term changes were observed in appetitive hormones after LAGB. It is unclear whether objective measures of eating behavior will prove useful in evaluating the impact of bariatric surgery on outcomes. This trial was registered at clinicaltrials.gov as CT00764127.

Marked increase of breast density due to a levonorgestrel-releasing intrauterine device

A 44- year old woman presented with bilateral breat pain and a feeling of increasing “tenderness” over the last year. Clinical examination as well as ultrasound performed by her obsterician was unremarkable. Mammography was performed at our department. No suspicious mass or microcalcifications were found. A marked increase in breast density (ACR 4) compared to the previous exam two years previously (ACR 2) was evident (Fig. A, B). The patient reported about the insertion of a levonorgestel-relasing intrauterine device about one an a half year ago (Mirena®, Bayer Healthcare, Leverkusen, Germany). No systemic hormonal intake was reported (oral or transdermal) and clinical history was unremarkable. Especially there were no pathologies with a possible increase in breast density (radiation therapy to the chest, diabetes, congestive heart failure). There was no recent pregnancy.

Pregnancy, maternal exposure to hair dyes and hair straightening cosmetics, and early age leukemia

ObjectiveTo investigate the association between maternal exposure to hair dyes and hair straightening cosmetics (HDSC) during pregnancy and leukemia at an early age (<2yr., EAL). MethodsA multicenter hospital-based case-control study was carried out in 13 states in Brazil between 1999 and 2007. Mothers of 176 ALL (acute lymphocytic leukemia) and 55 AML (acute myeloid leukemia) cases and 419 controls were enrolled and interviewed. Data on maternal exposure to HDSC occurring 3months before pregnancy, during pregnancy and during breastfeeding were obtained. Data were also gathered on paternal exposure to HDSC before pregnancy. Unconditional logistic regression was performed and odds ratios (OR) on the association between HDSC use and EAL were obtained after adjustment for hormonal intake during pregnancy, maternal age, education, birth weight, and the child skin color. ResultsAn adjusted OR of 1.78 (95% C.I. 1.13–2.81) was observed between maternal exposure to HDSC in the first trimester of pregnancy and ALL. Regarding AML, an adjusted OR of 2.43 (95% C.I. 1.13–5.22) was found for maternal exposure to HDSC during breastfeeding. No association between maternal exposure to HDSC during pregnancy and ALL or AML was observed in children with MLL (Mixed Lineage Leukemia) gene rearrangement. ConclusionsResults in this study seem to support the hypothesis that maternal exposure to HDSC during pregnancy may be involved in the etiology of leukemia in children under 2years of age.

Characterisation of the pharmacokinetics of ethinylestradiol and drospirenone in extended-cycle regimens: population pharmacokinetic analysis from a randomised Phase III study

ObjectivesThe primary objective of this analysis was to characterise the steady-state pharmacokinetics (PK) of ethinylestradiol (EE) and drospirenone (DRSP) in a randomised Phase III study that investigated the contraceptive efficacy...

Editorial: Molecular Endocrinology Articles in the Spotlight for October 2012

The October issue of Molecular Endocrinology is packed with excellent science. I would like to highlight a few articles especially recommended for your reading. In the article, “Cell-Autonomous Regulation of Brown Fat Identity Gene UCP1 by Unliganded Vitamin D Receptor,” Malloy et al demonstrate that regulation of the critical brown fat gene UCP1 by vitamin D receptor (VDR), which regulates brown fat identity genes in human cells is direct, resulting in cell autonomous control of this mediator of energy metabolism. The regulation of UCP1 by VDR is ligand independent, suggesting that hormonal intake or stores of vitamin D are unlikely to impact the beiging phenotype of adipocyte tissue. The ligand independence of the regulation will stimulate development of selective VDR antagonists (SVDRMs) that promote cellular beiging but do not impair other VDR activities like the regulation of calcium homeostasis. This study also suggests that mutations or polymorphisms in the VDR gene could impact the amount of beige or brown fat in humans and may therefore be worthy of investigation. “Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)” by Lai et al describes the first stromal fibromuscular androgen receptor (AR) knockout, which used a probasin promoter driven prolactin transgenic (Pb-PRL tg) mouse, to study stromal AR function in BPH development. Specifically, elimination of stromal fibromuscular AR led to reduced prostate size, diminished epithelial/stromal cell proliferation, and alleviated microenvironmental changes including extracellular matrix remodeling and immune cells infiltration. Furthermore, stromal fibromuscular AR was able to modulate an epithelial-stromal interaction through the epithelial prolactin/prolactin receptor-granulocyte macrophage-colony stimulating factor-stromal signal transducer and activator of transcription 3 axes to facilitate the stromal cell growth. The report by Laryea et al, “Disrupting Hypothalamic Glucocorticoid Receptors Causes HPA Axis Hyperactivity and Excess Adiposity” (freely available at http://mend. endojournals.org/) demonstrates the essential role of glucocorticoid receptor-mediated negative feedback regulation in the paraventricular nucleus of the hypothalamus. Although chronic exposure to elevated glucocorticoids is often associated with anxiety and despair-related behavioral changes, the elevation resulting from disrupted paraventricular nucleus (PVN) glucocorticoid receptor (GR) does not. This may reflect adaptive mechanisms in other brain regions that attenuate glucocorticoid receptor activation. Alternatively, the normal circadian rhythm that is maintained in these animals may allow compensation to occur. Importantly, the loss of GR in the PVN is somehow protective against high circulating glucocorticoid levels. This study highlights the substantial differences in phenotypes that can emerge with conditional deletion of different versions of the same gene. Congratulations to all the authors in this issue for their fine work and research. Donald B. DeFranco, PhD Editor-in-Chief, Molecular Endocrinology E D I T O R I A L

Contraceptive efficacy and tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study

BackgroundThe contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough)...

Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study

BackgroundThis study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic...

P4-11-15: Increased Propability of Triple Negative Breast Cancer (TNBC) in Premenopausal Patients after Exogenous Hormonal Intake (EHI).

Abstract Purpose: HRT is a known risk factor for breast cancer (BC) among post-menopausal women. Our knowledge in relation to EHI (estrogens and/or progestin) and BC among pre-menopausal women is scarce. We have studied whether previous EHI influences BC phenotype, clinical and pathologic characteristics and correlation with other known BC risk factors. Patients and methods: A prospective analysis (data recorded upon patients first presentation) of an electronic database at a tertiary cancer centre was performed. Patients’ demographics, risk factors for BC (smoking, alcohol use, obesity, family history), clinical profile, EHI parameters (duration, cause) and the tumors’ histopathology (type, grade,ER/PgR and HER2 by IHC and FISH) were analyzed. Premenopausal patients without an EHI history consisted control group. Results: Out of 938 patients treated for BC between 2006 and 2010, 333(35,5%) were premenopausal and 131(39%) of them reported any use of hormones. Median age was identical (43 years,range:20–57) among premenopausal patients with and without EHI history. Mean duration of use was 28 months (range:1–180). Causes of EHI were contraception (35%), pregnancy(17%), menstrual abnormalities(17%) and medically assisted fertilization(17%). Smoking, alcohol use and obesity didn't differ among two groups. Family history for BC was more common (31, 3% vs. 22,8%, p=0,08)among women with EHI. No correlation was found among duration of use and the time of cancer diagnosis, while the mean time from the cessation of hormones to cancer diagnosis was 13 years(range:1–32). Only 18% of breast cancers were diagnosed within the first 5 years after exogenous hormones cessation. TNBC was found to be significantly increased among premenopausal women with a history for EHI (23,6% vs. 13,4%, p=0,016). This increase was independent of the existence of positive family history for BC (p=0,61). EHI conferred a twofold increase in the risk for a TNBC (OR=1,99 p=0,019). No other clinical or histopathologic parameter showed any difference among the two groups. Conclusion: Prior use of exogenous hormones, for any cause and irrespective of the coexistence of other risk factors and family history, increases the probability of a triple negative breast cancer diagnosis by twofold. Whether this represents a trend of a changing epidemiology in the types of BC in prior hormone users vs. nonusers, poses an extremely challenging hypothesis to be verified in large epidemiologic studies — given the young age and the treating difficulties of this patient population. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-15.

PREGNANCY, EXPOSURE TO PESTICIDES AND INFANT LEUKEMIA IN BRAZIL

Background and Aims: Infant leukemia (IL) is a rare hematological neoplasm associated with MLL gene rearrangements. Maternal exposures during pregnancy to pesticides, hormones, dipyrone, and topoisomerase-II DNA inhibitors and high birth weight were associated risk factors. Methods: This is a hospital-based multicenter case-control study. Mothers of 252 IL cases and 423 controls were interviewed and data were obtained regarding environmental maternal exposure during periconceptional, pregnancy and breast-feeding periods, including exposure to pesticides. Unconditional logistic regression was performed and odds ratios (OR) on the association between maternal pesticides exposure and IL, including their 95% confidence intervals (CI), were ascertained after adjustment to hormonal intake during pregnancy, mother’s age, mother’s level of education, birth weight and infant’s skin color. Results: An adjusted OR, 2.39, 95% CI, 1.63-3.51 was observed for the association between IL and maternal exposure to pesticides during pregnancy, being higher for acute myeloid leukemia (adjusted OR 3.50, 95% CI, 2.01-6.11). The use of pyrethroids during pregnancy revealed an OR 2.18 (95% CI, 1.44-3.29), while the use of other pesticides showed an OR 3.61 (95% CI, 1.69-7.73). The reported household use of pesticides revealed an adjusted OR 2.25 (95% CI, 1.48-3.43), and agriculture exposure showed an adjusted OR 9.26, (95% CI, 2.82-30.4). According to frequency of exposure, an adjusted OR, 2.48 (95% CI, 1.50 - 4.00) was seem among those reporting up to 1 contact weekly, and an adjusted OR 2.34 (95% CI, 1.30– 4.21) among those with &gt; 1 contact (p-trend &lt; 0.0001). Mixed exposure to different pesticides showed an adjusted OR, 3.83 (95% CI, 1.33-11.0) and the exposure to different chemical classes revealed an adjusted OR, 8.87 (95% CI, 1.55-50.6). Conclusions: The observed results seem to support the hypothesis that mothers’ household use of pesticides and other contaminants may be involved in the etiology of infant leukemia.

SP1-6 No effect of hormonal exposures on uveal melanoma

IntroductionSeveral studies suggest that hormonal mechanisms may be associated with the development of uveal melanoma.ObjectivesTo study the association between the risk of uveal melanoma and exposure to hormonal exposures in...

P2-82 Pregnancy, exposure to pesticides and infant leukaemia in Brazil

Infant Leukaemia is a rare haematological neoplasm associated with MLL gene rearrangements. Maternal exposure during pregnancy to pesticides, hormones, dipyrone, and topoisomerase-II DNA inhibitors and birth weight were associated risk...

The Effect of Eating Frequency on Appetite Control and Food Intake: Brief Synopsis of Controlled Feeding Studies ,

Increased eating frequency is postulated to increase metabolism, reduce hunger, improve glucose and insulin control, and reduce body weight, making it an enticing dietary strategy for weight loss and/or the maintenance of a healthy body weight. Because past research has primarily focused on the effects of eating frequency on changes in energy expenditure and body weight, limited data exist surrounding the impact of eating frequency on appetite control and energy intake. We provide a brief review of the controlled-feeding studies that primarily targeted the appetitive, hormonal, and food intake responses potentially altered with eating frequency. The 3 meal/d pattern served as the reference for defining increased or reduced eating frequency. In general, increased eating frequency led to lower peaks (P< 0.05) in perceived appetite, satiety, glucose, insulin, ghrelin, and PYY responses compared with reduced eating frequency. However, when examining these responses over the course of the day (i.e. using area under the curve assessments), no differences in any of these outcomes were observed. The rate of gastric emptying also appears to be unaltered with increased eating frequency. Subsequent food intake was examined in several studies with conflicting results. Regarding the effect of reduced eating frequency, several studies indicate significant increases in perceived appetite and reductions in perceived satiety when 1 or 2 meals were eliminated from the daily diet. Taken together, these findings suggest that increased eating frequency (>3 eating occasions/d) has minimal, if any, impact on appetite control and food intake, whereas reduced eating frequency(<3 eating occasions/d) negatively effects appetite control.

Hormonal exposures and the risk of uveal melanoma

Several studies suggest that hormonal mechanisms may be associated with the development of uveal melanoma. Therefore, the association between the risk of uveal melanoma and exposure to hormonal exposures was investigated in a case-control study from nine European countries. Incident cases of uveal melanoma were frequency-matched to population and hospital controls by country, age, and sex. Female subjects were asked about their reproductive history, use of menopausal hormone replacement therapy and oral contraceptives. Among men, occupational handling of oils while working with transformers or capacitors which contain polychlorinated biphenyls (PCB) was solicited. Unconditional logistic regression analyses were calculated, adjusting for several potential confounders. Analyses were stratified by sex. Two hundred and ninety-three cases (165 men, 128 women) and 3,198 control subjects (2,121 men, 1,077 women) were interviewed. Among women, no associations were observed with hormonal status variables, intake of hormonal therapy or intake of oral contraceptives. Men showed an increased risk with occupational exposure to transformer/capacitor oils (OR=2.74; Bonferroni-corrected 99.3% CI 1.07-7.02). However, these results were based on few exposed subjects only. The results of this study do not support the hypothesis of a hormonal influence in the carcinogenesis of uveal melanoma. Our finding of a potentially increased risk with PCB-containing oils requires further research.

Arias-Stella reaction in upper genital tract in pregnant and non-pregnant women: a study of 120 randomly selected cases

1. To study the diagnostic importance of the Arias-Stella reaction. 2. To study tubal epithelial changes in ectopic pregnancy. 3. To study the occurrence of Arias-Stella reaction in non-pregnant women receiving hormonal treatment. A prospective study was conducted on 120 patients who underwent endometrial curettage and/or salpingectomy. The patients were divided into four groups, each comprising of 30 patients. Groups 1 and 4 included non-pregnant patients who were being evaluated for infertility and dysfunctional uterine bleeding respectively, while pregnant patients were included in Group 2 (intra-uterine abortions) and Group 3 (ectopic tubal gestation). The endometrial curettings and fallopian tube lining epithelial cells were examined for the changes described by Arias-Stella. Cases which showed the presence of the Arias-Stella reaction were further classified. The changes of the Arias-Stella reaction in endometrial glands were observed in 80% cases of intra-uterine abortions. Secretory/hypersecretory pattern was the most commonly observed type (36.67%). The reaction was seen in 3.33% each of patients evaluated for infertility and patients on hormonal therapy with oral progestational agents for the management of dysfunctional uterine bleeding. Although uncommon, the Arias-Stella reaction was noted in the epithelium of fallopian tubes (16.67%) from patients with ectopic tubal gestation. The findings of the present study emphasize the diagnostic importance of the Arias-Stella reaction. The changes of the reaction are a histological clue to the presumptive diagnosis of the presence of chorial tissue in cases in which the chorionic material is not found in the endometrial biopsy. The morphological features can be mistaken for malignancy if the pathologist is not aware of the patient's pregnancy or history of hormonal intake.

Determinação de desmineralização óssea em gatos após tirotoxicose experimental

O hipertiroidismo é capaz de proporcionar efeitos sobre o metabolismo ósseo tanto em humanos como em animais. Para melhor avaliar este fato em gatos, em 16 animais foram induzidos a tirotoxicose a partir da administração oral de 150 µg/kg de levotiroxina sódica a cada 24 horas durante 42 dias. Os níveis hormonais foram avaliados por radioimunoensaio e a densidade mineral óssea da extremidade distal do rádio direito foi mensurada através de densitometria óptica radiográfica. Foi possível observar, a partir da primeira semana de experimento, significativa elevação sérica de T4 livre e T4 total acompanhada de desmineralização óssea do rádio.