Endocrinopathies mimicking gene negative long QT syndrome

Ventricular repolarisation can be influenced by hormonal milieu which may mimic long QT syndrome. We describe a series of patients referred for genetic testing for diagnosed long QT syndrome where a detailed clinical workup demonstrated endocrinopathies as the cause of presumed “gene negative” long QT syndrome and QT prolongation.

266 Effects of Inflammatory States on Ovarian Biology and Oocyte Competence

Female fertility is dependent on estradiol concentrations which regulate a multitude of ovarian functions including follicle development and oocyte maturation leading to ovulation of a viable oocyte. Estradiol biosynthesis is regulated by coordinated actions of follicle-stimulating hormone and intra-ovarian control mechanisms including the co-transcription factor beta-catenin. Beta-catenin is a multi-faceted protein recognized for its role in granulosa cell steroid production and is shown to be modulated by lipopolysaccharide (LPS), the endotoxin responsible for stimulation of the immune system in infections caused by Gram-negative bacteria. Beef heifers treated with subacute concentrations of LPS during a synchronized follicular wave demonstrate a decline in serum estradiol concentrations 50 h after CIDR withdrawal, corresponding with dominant follicle maturation and preceding ovulation. The endotoxin exposure also resulted in increased LPS concentration and E2:P4 ratios in follicular fluid suggesting that low dose LPS modulates the intra-follicular hormonal milieu. Additionally, in a granulosa cell line, LPS treatment decreased mRNA expression of aromatase and beta-catenin. These data indicate that LPS alters E2 synthesis by modulating beta-catenin and subsequent steroidogenic enzyme expression. To further explore the contribution of naturally occurring LPS exposure on follicular steroid production and developing oocytes, bovine ovary pairs were collected from local abattoirs. Oocytes were aspirated from small follicles and matured in vitro to evaluate meiotic events related to nuclear maturation and spindle morphology. Small follicles from ovarian pairs were separated by the detectable LPS concentrations into high and low LPS groups. Oocytes matured from low LPS follicles demonstrated an increase in the percent of abnormal maturation events. Data indicate that induced or naturally occurring low doses of LPS can alter circulating and follicular estradiol concentrations impairing oocyte maturation. Perturbation to local ovarian signaling cascades from subclinical inflammatory disease may be an unappreciated factor altering fertility and leading to decreased cow retention.

The Male Reproductive System and Endocrine Disruptors

: The male reproductive system is exposed to a great number of chemical substances which can interfere with the normal hormonal milieu and reproductive function; these are called endocrine disruptors (EDs). Despite a growing number of studies evaluating the negative effects of EDs, their production is continuously growing although some of which have been prohibited. The prevalence of poor semen quality, hypospadias, cryptorchidism, and testicular cancer have increased in the last decades, and recently, it has been postulated that these could all be part of a unique syndrome called testicular dysgenesis syndrome. This syndrome could be related to exposure to a number of EDs which cause imbalances in the hormonal milieu and oestrogenic over-exposure during the foetal stage. The same EDs can also impair spermatogenesis in offspring and have epigenetic effects. Although studies on animal and in vitro models have raised concerns, data are conflicting. However, these studies must be considered as the basis for future research to promote male reproductive health.

Repercussions of Stress during Pregnancy and Beyond

Stress, anxiety and depression are the disorders of brain but these affect even unborn child (foetuses). Various phobias affect expecting mothers. All these happen due to stress hormone Cortisol which is secreted during stress. This along with cortisol and other stress hormones lead to endocrine disorders like Graves’ disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm. Stress during pregnancy changes hormonal milieu which affect the fetal environment and results in inflammatory conditions that have implications for maternal and infant health.

Recommendations and Nutritional Considerations for Female Athletes: Health and Performance

Optimal nutrition is an important aspect of an athlete’s preparation to achieve optimal health and performance. While general concepts about micro- and macronutrients and timing of food and fluids are addressed in sports science, rarely are the specific effects of women’s physiology on energy and fluid needs highly considered in research or clinical practice. Women differ from men not only in size, but in body composition and hormonal milieu, and also differ from one another. Their monthly hormonal cycles, with fluctuations in estrogen and progesterone, have varying effects on metabolism and fluid retention. Such cycles can change from month to month, can be suppressed with exogenous hormones, and may even be manipulated to capitalize on ideal timing for performance. But before such physiology can be manipulated, its relationship with nutrition and performance must be understood. This review will address general concepts regarding substrate metabolism in women versus men, common menstrual patterns of female athletes, nutrient and hydration needs during different phases of the menstrual cycle, and health and performance issues related to menstrual cycle disruption. We will discuss up-to-date recommendations for fueling female athletes, describe areas that require further exploration, and address methodological considerations to inform future work in this important area.

A practical guide to endocrine therapy in the management of estrogen receptor-positive male breast cancer

The majority (more than 90%) of male breast cancers (MaBCs) are estrogen receptor-positive, such that endocrine therapy is the mainstay of MaBC treatment. Endocrine therapy has been associated with improved overall survival in observational studies on MaBC, though large randomized clinical trials have never been completed to confirm this benefit in this population. Tamoxifen is currently the preferred drug for both metastatic and adjuvant treatment of MaBC. Known differences in treatment patterns and hormonal milieu between men and women may warrant a unique approach to the management of toxicities in men. This review provides a detailed discussion of endocrine therapy for MaBC.

Does Each Menstrual Cycle Elicit a Distinct Effect on Olfactory and Gustatory Perception?

The obesity pandemic has brought forth a scientific interest in food intake and sensory perception interactions. Olfactory perception and gustatory perception are very complex and under the influence of many factors, including the menstrual cycle. This study aims to clarify conflicting findings on the influence of the menstrual cycle on olfactory and gustatory perception. Women were assessed during four consecutive phases of one complete cycle (mid-follicular, ovulatory, mid-luteal, and late luteal phases (N = 21)), in contrast to women measured across the same phases belonging to two menstrual cycles (N = 29). Additional control groups were men (N = 17), postmenopausal women (N = 14), oral contraceptive users (N = 10), and women with an anovulatory cycle (N = 8). Olfactory threshold, odor discrimination, and identification were tested using the “Sniffin Sticks“ test kit. Suprathreshold intensity and hedonic ratings for sweet, salty, sour, and bitter solutions were assessed. One-way ANOVA and ANOVA for repeated measurements was applied in the analysis, along with linear and trigonometric data fitting and linear mixed models. Linear increases in olfactory discrimination, identification, and overall olfactory performance were observed only in women followed across a complete menstrual cycle. Compared to other groups, these women displayed a cyclic pattern characterized by a predilection for sweet solution; reduced distaste for salty and sour solutions; and increased intensity perception of salty, sour, and bitter solutions towards the end of the cycle. These results suggest that a distinct hormonal milieu of a complete menstrual cycle may be affecting both olfactory and gustatory perception.

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17β-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.

Pre-Menopausal Women With Breast Cancers Having High AR/ER Ratios in the Context of Higher Circulating Testosterone Tend to Have Poorer Outcomes

PurposeWomen with breast tumors with higher expression of AR are in general known to have better survival outcomes while a high AR/ER ratio is associated with poor outcomes in hormone receptor positive breast cancers mostly in post menopausal women. We have evaluated the AR/ER ratio in the context of circulating androgens specifically in patients younger than 50 years most of whom are pre-menopausal and hence have a high estrogenic hormonal milieu.MethodsTumor samples from patients 50 years or younger at first diagnosis were chosen from a larger cohort of 270 patients with median follow-up of 72 months. Expression levels of ER and AR proteins were detected by immunohistochemistry (IHC) and the transcript levels by quantitative PCR. Ciculating levels of total testosterone were estimated from serum samples. A ratio of AR/ER was derived using the transcript levels, and tumors were dichotomized into high and low ratio groups based on the third quartile value. Survival and the prognostic significance of the ratio was compared between the low and high ratio groups in all tumors and also within ER positive tumors. Results were further validated in external datasets (TCGA and METABRIC).ResultsEighty-eight (32%) patients were ≤50 years, with 22 having high AR/ER ratio calculated using the transcript levels. Circulating levels of total testosterone were higher in women whose tumors had a high AR/ER ratio (p = 0.02). Tumors with high AR/ER ratio had significantly poorer disease-free survival than those with low AR/ER ratio [HR-2.6 (95% CI-1.02–6.59) p = 0.04]. Evaluation of tumors with high AR/ER ratio within ER positive tumors alone reconfirmed the prognostic relevance of the high AR/ER ratio with a significant hazard ratio of 4.6 (95% CI-1.35–15.37, p = 0.01). Similar trends were observed in the TCGA and METABRIC dataset.ConclusionOur data in pre-menopausal women with breast cancer suggest that it is not merely the presence or absence of AR expression but the relative activity of ER, as well as the hormonal milieu of the patient that determine clinical outcomes, indicating that both context and interactions ultimately influence tumor behavior.