Explore the vast range of titles available.

In women with hormone-receptor–positive metastatic breast cancer that had progressed after endocrine therapy, palbociclib plus fulvestrant was associated with progression-free survival of more than 9 months, as compared with less than 4 months with fulvestrant alone. Approximately 80% of breast cancers express estrogen receptors, progesterone receptors, or both. Endocrine therapies are the mainstay of treatment for these hormone-receptor–positive cancers, substantially reducing the relapse rate after presentation with early-stage cancer. 1 Despite advances in endocrine therapy, many women have a relapse during or after completing adjuvant therapy. The care of these women remains a considerable clinical challenge. Single-agent treatment with an aromatase inhibitor or tamoxifen has shown limited clinical benefit. 2 , 3 The selective estrogen-receptor degrader fulvestrant has modest activity in this population of patients, 4 , 5 and the development of effective therapies that can reverse resistance to endocrine therapy . . .

This study, designed to determine the relative degree of testosterone deficiency, estradiol deficiency, or both at which undesirable bodily changes occur, showed that some features of male hypogonadism are due to both androgen deficiency and estrogen deficiency. Testosterone therapy is prescribed for millions of men each year, and the number is increasing rapidly. Prescription sales of testosterone increased by 500% in the United States between 1993 and 2000. 1 Most testosterone prescriptions are written to treat nonspecific symptoms, such as fatigue or sexual dysfunction, when accompanied by testosterone levels below the laboratory reference range. Currently, testosterone levels that are at least 2 SD below the mean value for healthy young adults are classified as low. 1 , 2 Although convenient, this classification fails to consider the physiological consequences of specific testosterone levels. More than 80% of circulating estradiol in men . . .

The addition of palbociclib to fulvestrant prolonged overall survival among women with hormone receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous hormonal therapy. In the entire trial group, survival differences were not significant.

Background: A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance. Objective: The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel. Study Design: Healthy women aged 18–50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2mg/dienogest 2 mg, 17 days estradiol valerate 2mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03mg/levonorgestrel 0.15mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three. Results: Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/ levonorgestrel. Conclusion: The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/ levonorgestrel.

Menopause predisposes women to osteoporosis due to declining estrogen levels. This results in a decrease in bone mineral density (BMD) and an increase in fractures. Osteoporotic fractures lead to substantial morbidity and mortality, and are considered one of the largest public health priorities by the World Health Organization (WHO). It is therefore essential for menopausal women to receive appropriate guidance for the prevention and management of osteoporosis. The Women’s Health Initiative (WHI) randomized controlled trial first proved hormonal therapy (HT) reduces the incidence of all osteoporosis-related fractures in postmenopausal women. However, the study concluded that the adverse effects outweighed the potential benefits on bone, leading to a significant decrease in HT use for menopausal symptoms. Additionally, HT was not used as first-line therapy for osteoporosis and fractures. Subsequent studies have challenged these initial conclusions and have shown significant efficacy of HT in various doses, durations, regimens, and routes of administration. These studies support that HT improves BMD and reduces fracture risk in women with and without osteoporosis. Furthermore, the studies suggest that low-dose and transdermal HT are less likely associated with the adverse effects of breast cancer, endometrial hyperplasia, coronary artery disease (CAD), and venous thromboembolism (VTE) previously observed in standard-dose oral HT regimens. Given the need for estrogen in menopausal women and evidence supporting the cost effectiveness, safety, and efficacy of HT, we propose that HT should be considered for the primary prevention and treatment of osteoporosis in appropriate candidates. HT should be individualized and the once “lowest dose for shortest period of time” concept should no longer be used. This review will focus on the prior and current studies for various HT formulations used for the prevention and treatment of osteoporosis, exploring the safety profile of low-dose and transdermal HT that have been shown to be safer than oral standard-dose HT.

Background and Objective: The hormonal components of combined oral contraceptives (COCs) have various metabolic and haemostatic effects. The objective of this study was to compare the metabolic and haemostatic effects of a novel COC comprising estradiol valerate/dienogest (E 2 V/DNG) with ethinylestradiol/levonorgestrel (EE/LNG). Methods: In a randomized, open-label study conducted in Germany over seven cycles, healthy women aged 18–50 years received E 2 V/DNG (E 2 V 3 mg on days 1–2, E 2 V 2 mg/DNG 2 mg on days 3–7, E 2 V 2 mg/DNG 3 mg on days 8–24, E 2 V 1 mg on days 25–26, placebo on days 27–28; n = 30) or EE/LNG (EE 0.03 mg/LNG 0.05 mg on days 1–6, EE 0.04 mg/LNG 0.075 mg on days 7–11, EE 0.03 mg/LNG 0.125 mg on days 12–21, placebo on days 22–28; n = 28). The primary variables were the mean intraindividual relative changes from baseline to cycle 7 in high-density lipoprotein ( HDL) and low-density lipoprotein (LDL) cholesterol levels. Changes in other lipid parameters, haemostatic parameters, sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), carbohydrate metabolism parameters, blood pressure and body weight were also assessed. Results: Mean ± SD HDL cholesterol increased by 7.9%±21.8% with E 2 V/DNG and decreased by 2.3%±14.4% with EE/LNG. Mean ± SD LDL cholesterol decreased by 6.5% ±15.9% with E 2 V/DNG and by 3.0% ±17.4% with EE/LNG. Mean ± SD prothrombin fragment 1+2 and D-dimer levels remained essentially unchanged in the E 2 V/DNG group (−0.6% ± 30.3% and −2.1% ± 43.5%, respectively), but increased in the EE/LNG group (by 117.3% ± 358.0% and 62.9% ± 99.5%, respectively). Changes in other hepatic-induced arameters (SHBG, CBG) and carbohydrate metabolism were generally less pronounced with E 2 V/DNG versus EE/LNG. Body weight and blood pressure remained stable throughout the study in both treatment groups. Both formulations were well tolerated, with no serious adverse events reported. Conclusion: E 2 V/DNG had a minimal impact on metabolic and haemostatic parameters, and a more favourable effect than EE/LNG on lipid markers. Trial registration:} ClinicalTrials.gov Identifier: NCT00185224

Mutations in ESR1 have been associated with resistance to aromatase inhibitor (AI) therapy in patients with ER+ metastatic breast cancer. Little is known of the impact of these mutations in patients receiving selective oestrogen receptor degrader (SERD) therapy. In this study, hotspot mutations in ESR1 and PIK3CA from ctDNA were assayed in clinical trial samples from ER+ metastatic breast cancer patients randomized either to the SERD fulvestrant or fulvestrant plus a pan-PI3K inhibitor. ESR1 mutations are present in 37% of baseline samples and are enriched in patients with luminal A and PIK3CA -mutated tumours. ESR1 mutations are often polyclonal and longitudinal analysis shows distinct clones exhibiting divergent behaviour over time. ESR1 mutation allele frequency does not show a consistent pattern of increases during fulvestrant treatment, and progression-free survival is not different in patients with ESR1 mutations compared with wild-type patients. ESR1 mutations are not associated with clinical resistance to fulvestrant in this study. Fulvestrant degrades the oestrogen receptor. Here, the authors report on a clinical trial using fulvestrant and show that mutations in the oestrogen receptor alpha gene are prevalent in circulating tumour DNA and do not influence the clinical outcome of patients to fulvestrant.

The estrogens estrone (E1), 17α-estradiol (E2α), 17β-estradiol (E2β), and estriol (E3) are natural sex hormones produced by humans and animals. In addition, there are some synthetic estrogens, such as 17α-ethinylestradiol (EE2), used for contraception purposes. These compounds are able to produce endocrine disruption in living organisms at nanogram-per-liter levels. In both humans and animals, estrogens are excreted in urine and feces, reaching the natural environment through discharge from sewage treatment plants (STP) and manure disposal units. In STPs, hormone removal depends on the type of treatment process and on different parameters such as the hydraulic and sludge retention times. Thus, hormone elimination rates vary from 0% to 90% in different STPs. Animals are also an important source of estrogens in the environment. Indeed, animals produce high concentrations of hormones which will end up in manure which is typically spread on land. Hence, waste-borne animal hormones may transfer these pollutants to the soil. The purpose of this review is to highlight the significance for both health and the environment of pollution by estrogens and critically review the existing knowledge on their fate and removal in different treatment processes. Relevant information on the microbial degradation of hormones and metabolic pathways is also included.

Estradiol valerate (Progynova ) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including C , AUC , and AUC , were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.