Результаты поиска

Gonadotropin suppression in men leads to a reduction in claudin-11 at the Sertoli cell tight junction.

STUDY QUESTION: Are Sertoli cell tight junctions (TJs) disrupted in men undergoing hormonal contraception? SUMMARY ANSWER: Localization of the key Sertoli cell TJ protein, claudin-11, was markedly disrupted by 8 weeks of gonadotropin suppression, the degree of which was related to the extent of adluminal germ cell suppression. WHAT IS KNOWN ALREADY: Sertoli cell TJs are vital components of the blood-testis barrier (BTB) that sequester developing adluminal meiotic germ cells and spermatids from the vascular compartment. Claudin-11 knockout mice are infertile; additionally claudin-11 is spatia

Oral contraceptives containing drospirenone for premenstrual syndrome.

BACKGROUND: Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception. OBJECTIVES: To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another comb

Targeting the RANKL/RANK/OPG Axis for Cancer Therapy.

RANKL and RANK are expressed in different cell types and tissues throughout the body. They were originally described for their essential roles in bone remodeling and the immune system but have subsequently been shown to provide essential signals from regulating mammary gland homeostasis during pregnancy to modulating tumorigenesis. The success of RANKL/RANK research serves as a paragon for translational research from the laboratory to the bedside. The case in point has been the development of Denosumab, a RANKL-blocking monoclonal antibody which has already helped millions of patients sufferin

Совпадение в полном тексте источника
… Progesterone, as well as synthetic progestins, up-regulate RANKL expression in PR + luminal breast epithelial cells which stimulates RANK-mediated cell proliferation of adjacent progenitor cells as discussed in (A) . … Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature. (2010) 468:98–102. 10.1038/nature09387 85. Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson R, Schmidt EV, et al. …

European guidance for the diagnosis and management of osteoporosis in postmenopausal women.

UnlabelledGuidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis.IntroductionThe European Foundation for Osteoporosis and Bone disease (subsequently the International Osteoporosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting.MethodsThe following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of oste

The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review.

STUDY QUESTION: Can controlled ovarian hyperstimulation (COH) for fertility preservation be effectively conducted in women with breast cance … lize to individual cases. The implication of alterations in other hormone levels such as androgens, progestins or vascular endothelial growth factor secondary to COH in women with breast cancer has not been quantified. WIDER IMPLICATIONS OF THE FINDINGS: The co-administration of 5 mg of letrozole daily commencing on Day 2 and continuing throughout COH is re …

Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis.

Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals

Совпадение в полном тексте источника
… For patients who are unresponsive to progestin-based therapies, low estrogen regimens serve as an effective second-line alternative. … Medically, because EM growth is estrogen-dependent, therapies that counteract endometrial proliferation are prioritized: progestins and oestro-progestins are widely used to alleviate EM-associated pain by suppressing endometrial growth and inducing secretory transformation [ 69 ], although a subset of …

Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E(2) and P4, and cyclic adenosine monophosphate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING P

Contraceptive sales in the setting of the Zika virus epidemic.

STUDY QUESTION: Has there been any influence of the Zika virus (ZIKV) outbreak on the sales of contraceptive methods in Brazil? SUMMARY ANSWER: Contraceptive sales in the 24 months of evaluation showed little variation and no significant change has been observed since the ZIKV outbreak. WHAT IS KNOWN ALREADY: Transmission of ZIKV is primarily by Aedes aegypti mosquitoes; however, sexual transmission has also been described. The association of several birth defects and the ZIKV infection during pregnancy has been established, and it was estimated in Bahia, Brazil that the infection rate could

Mechanisms of action of endocrine treatment in breast cancer.

Endocrine treatment plays an important role in the therapy of breast cancer. While the basic mechanisms are understood, additional mechanisms may be of importance to their action and they may also contribute to the mechanism(s) of acquired resistance. Currently, several novel drugs are entering into clinical trials. Observations of the absence or presence of cross resistance to novel 'pure' steroidal antiestrogens and the non-steroidal tamoxifen may add important information to our understanding of the mechanisms of action of both classes of drugs. Similarly, exploration of different aromatase

Sex- and Gender-Related Differences in Obesity: From Pathophysiological Mechanisms to Clinical Implications.

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue wei

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales.

BackgroundHormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives

Guidelines on deep vein thrombosis of the Brazilian Society of Angiology and Vascular Surgery.

Deep vein thrombosis is one of the main causes of inpatient and outpatient morbidity, both in medical and surgical patients, significantly impacting mortality statistics and requiring prompt diagnosis so that treatment can be initiated immediately. This document was prepared and reviewed by 11 specialists certified by the Brazilian Society of Angiology and Vascular Surgery, who searched the main databases for the best evidence on the diagnostic (physical examination, imaging) and therapeutic approaches (heparin, coumarins, direct oral anticoagulants, fibrinolytics) to the disease.

Совпадение в полном тексте источника
… However, no risk reduction was confirmed with OCs containing 20 μg of ethinyl estradiol compared with those containing 30 μg of ethinyl estradiol. 122 The type of progestin also influences the risk of VTE, where second-generation progestins (levonorgestrel [LNG] and norethisterone) are safer than third … - and fourth-generation progestins. 122 The OC-related risk of VTE is associated with increasing body weight and age and with the reintroduction or change of OC after discontinuation exceeding 4 weeks. …

Glanzmann's thrombasthenia: pathogenesis, diagnosis, and current and emerging treatment options.

Glanzmann's thrombasthenia (GT) is a genetic platelet surface receptor disorder of GPIIb/IIIa (ITG αIIbβ3), either qualitative or quantitative, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes. Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa (rFVIIa

Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL) pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in thre

Cost-effectiveness of preventative therapies for postmenopausal women with osteopenia.

BackgroundLimited data are available regarding the cost-effectiveness of preventative therapies for postmenopausal women with osteopenia. The objective of the present study was to evaluate the cost-effectiveness of raloxifene, alendronate and conservative care in this population.MethodsWe developed a microsimulation model to assess the incremental cost and effectiveness of raloxifene and alendronate relative to conservative care. We assumed a societal perspective and a lifetime time horizon. We examined clinical scenarios involving postmenopausal women from 55 to 75 years of age with bone mine

Safety and continued use of the levonorgestrel intrauterine system as compared with the copper intrauterine device among women living with HIV in South Africa: A randomized controlled trial.

BACKGROUND: Women living with HIV (WLHIV) have lower rates of contraceptive use than noninfected peers, yet concerns regarding contraceptive efficacy and interaction with antiretroviral therapy (ART) complicate counseling. Hormonal contraceptives may increase genital tract HIV viral load (gVL) and sexual transmission risk to male partners. We compared gVL, plasma VL (pVL), and intrauterine contraceptive (IUC) continuation between the levonorgestrel intrauterine system (LNG-IUS) and copper intrauterine device (C-IUD) in Cape Town, South Africa. METHODS AND FINDINGS: In this double-masked, rand

Ectopic uterine tissue as a chronic pain generator.

While chronic pain is a main symptom in endometriosis, the underlying mechanisms and effective therapy remain elusive. We developed an animal model enabling the exploration of ectopic endometrium as a source of endometriosis pain. Rats were surgically implanted with autologous uterus in the gastrocnemius muscle. Within two weeks, visual inspection revealed the presence of a reddish-brown fluid-filled cystic structure at the implant site. Histology demonstrated cystic glandular structures with stromal invasion of the muscle. Immunohistochemical studies of these lesions revealed the presence of

The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.

Menopause impacts 25 million women world wide each year, and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030. Menopause has been associated with symptoms of hot flashes, night sweats, dysphoric mood, sleep disturbance, and conditions of cardiovascular disease, depression, osteoporosis, osteoarthritis, depression, dementia, and frailty. Conventional hormone replacement therapy results in increased thrombotic events, and an increased risk of breast cancer and dementia as evidenced in large prospective clinical trials including Heart and Estrogen/Progestin

Immune system and bone microenvironment: rationale for targeted cancer therapies.

Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator of NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune s