Hormone replacement therapy | EPFL Graph Search

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal atrophy, accelerated skin aging, vaginal dryness, decreased muscle mass, sexual dysfunction, and bone loss or osteoporosis. They are in large part related to the diminished levels of sex hormones that occur during menopause. Estrogens and progestogens are the main hormone drugs used in HRT. Progesterone is the main female sex hormone that occurs naturally and is also manufactured into a drug that is used in menopausal hormone therapy. Although both classes of hormones can have symptomatic benefit, progestogen is specifically added to estrogen regimens, unless the uterus has been removed, to avoid the increased risk of endometrial cancer. Unopposed estrogen therapy

Tissue Factor-Independent Coagulation Correlates with Clinical Phenotype in Factor XI Deficiency and Replacement Therapy

Alessandro Aliotta, Vanessa Carle, Christian Heinis

Background In factor XI (FXI) deficiency, bleeding cannot be predicted by routine analyses. Since FXI is involved in tissue factor (TF)-independent propagation loop of coagulation, we hypothesized that investigating the spatiotemporal separated phases of coagulation (TF-dependent and -independent) could improve diagnostics. Objectives This article investigates the correlation of parameters describing TF-dependent and -independent coagulation with the clinical phenotype of FXI deficiency and their ability to assess hemostasis after FXI replacement. Methods We analyzed: (1) plasma from healthy controls ( n =53); (2) normal plasma ( n =4) spiked with increasing concentrations of a specific FXI inhibitor (C7P); (3) plasma from FXI-deficient patients ( n =24) with different clinical phenotypes (13 bleeders, 8 non-bleeders, 3 prothrombotics); (4) FXI-deficient plasma spiked with FXI concentrate ( n =6); and (5) plasma from FXI-deficient patients after FXI replacement ( n =7). Thrombin generation was measured with the reference method calibrated automated thrombogram and with Thrombodynamics (TD), a novel global assay differentiating TF-dependent and -independent coagulation. Results C7P dose-dependently decreased FXI activity, prolonged activated partial thromboplastin time, and hampered TF-independent coagulation. In FXI-deficient bleeders, TD parameters describing TF-independent propagation of coagulation and fibrin clot formation were reduced compared with controls and FXI-deficient nonbleeders and increased in FXI-deficient patients with prothrombotic phenotype. Receiver operating characteristic analysis indicated that TF-independent parameters were useful for discriminating FXI-deficient bleeders from non-bleeders. In FXI-deficient plasma spiked with FXI concentrate and in patients receiving FXI replacement, TD parameters were shifted toward hypercoagulation already at plasma FXI levels around 20%. Conclusion TF-independent coagulation parameters assessed by TD have the potential to identify the clinical phenotype in FXI-deficient patients and to monitor FXI replacement therapy.

GEORG THIEME VERLAG KG2020

A high resolution LC-MS targeted method for the concomitant analysis of 11 contraceptive progestins and 4 steroids

Alexandre Béguin, Cathrin Brisken, Fabio De Martino, Csaba Ferenc László, Marc Moniatte, Jonathan Paz Montoya, Marie Shamseddin

In the context of hormonal contraception and hormone replacement therapy (HRT), many women are exposed to exogenous hormones. Current use of hormonal contraception with combined ethinyl estradiol and different progestins bestows a breast cancer relative risk (RR) of 1.2-while combined HRT has a RR of 2. Although these exposures present an important public health issue, little is known about the effects of individual progestins on the breast and other tissues. Increasing availability of large scale biobanks, high throughput analyses and data management tools enable ever expanding, sophisticated population studies. In order to address the impact of distinct progestins on various health indicators, it is desirable to accurately quantify progestins in clinical samples. Here we have developed and validated a high resolution liquid chromatography mass spectrometry (LC-MS) targeted method for the simultaneous quantification of 11 synthetic progestins widely used in oral contraceptives, gestodene, levonorgestrel, etonogestrel, chlormadinone acetate, cyproterone acetate, drospirenone, desacetyl norgestimate, medroxyprogesterone acetate, norethindrone, dienogest, nomegestrol acetate, and 4 endogenous steroid hormones, progesterone, testosterone, androstenedione, and cortisol in blood samples. This highly specific quantitative analysis with high resolution Orbitrap technology detects and quantifies 15 compounds using their internal standard counterparts in a single 12 min LC-MS run. Sensitivity is attained by the use of the instrument in targeted selected ion monitoring mode. Lower limit of quantitation ranges from 2.4 pg/ml for drospirenone to 78.1 pg/ml for chlormadinone acetate. The method provides comprehensive progestin panel measurements with as little as 50 pi of murine or human plasma. (C) 2019 The Authors. Published by Elsevier B.V.

2019

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids

Frédéric Bruno Martin Gachon, Cédric Gobet, Benjamin Dieter Weger, Meltem Weger

Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism.