Objective:
The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause.
Participants:
The Treatment of Symptoms of the Menopause ...Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society.
Evidence:
The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials.
Consensus Process:
Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft.
Conclusions:
Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures.
•A BC/OC occurring at a young age and/or in a family with preexisting cases, suggests screening for mutations.•If no genetic susceptibility has been identified, lifetime BC risk can be calculated ...with tools estimating a woman’s lifetime risk of BC.•Screening strategy will depend on the level of individual risk.•Triple negative BC and medullary BC are suggestive of BRCA mutation carriers if occurring before menopause.•Guidelines for genetic screening and management of high risk women may vary between the US, the UK and France.
A breast or an ovarian cancer occurring at a young age and/or in a family where other cases preexist suggests that those patients should be candidates for screening for mutations. Despite decades of medical research, less than 30% of cases with a suggestive personal and/or family history of hereditary breast cancer have an identified causative gene mutation.
The vast majority of these cases are due to a mutation in one of the highly penetrant breast cancer genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11) and various guidelines direct the management of these patients. A minority of cases are due to mutations in moderate-penetrance genes (PALB2, ATM, BRIP1, and CHEK2).
A small number of low-penetrance alleles have been identified using advanced genetic testing methods. While these may contribute to risk in a polygenic fashion, this is likely to be relevant to a minority of cases and their identification should not be considered routine practice. Mutation testing currently requires a high index of suspicion for a specific contributing etiology, but next-generation sequencing may improve the identification of such genes and the clinical management of these cases.
Where no genetic susceptibility is identified, lifetime breast cancer risk can be calculated with standard tools. Breast cancer risk management then depends on the calculated lifetime risk. The psychological consequences of such screening for mutation carriers and non-carriers are discussed.
Pain management in the Ehlers–Danlos syndromes Chopra, Pradeep; Tinkle, Brad; Hamonet, Claude ...
American journal of medical genetics. Part C, Seminars in medical genetics,
March 2017, Volume:
175, Issue:
1
Journal Article
Progesterone and endometrial cancer Gompel, Anne
Best practice & research. Clinical obstetrics & gynaecology,
November 2020, 2020-11-00, 20201101, Volume:
69
Journal Article
Peer reviewed
It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin ...resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.
•Throughout women’s life, respect the balance between estrogen and progestogen.•Use combined contraception or progestin in anovulatory premenopausal women.•Prevent hyperplasia in obese women, women with polycystic ovary syndrome (PCOS), metabolic syndrome.•In MHT, adapt the dose of progestogen to dose/duration of estrogen treatment.•Inform the woman of the importance of taking the progestogen pill and check the compliance.•In menopause hormonal treatment (MHT), prefer continous treatment than sequential.
The high affinity receptor 1 (NTSR1) and its agonist, neurotensin (NTS), are correlated with tumor cell aggressiveness in most solid tumors. As chemoresistance and tumor aggressiveness are often ...related, we decided to study the role of the NTSR1 complex within platinum-based chemotherapy responses. In an ovarian model, we studied carboplatin because it is the main standard of care for ovarian cancer.
Experimental tumors and
studies were performed using SKOV3 and A2780 cells treated with carboplatin, with or without a very specific NTSR1 antagonist, SR48692. We measured the effects of these treatments on cell apoptosis and apoptosis-related proteins, platinum accumulation in the cell and nucleus, and the expression and localization of platinum transporters. NTS and NTSR1 labeling was measured in patients with ovarian cancer.
SR48692 enhanced the response to carboplatin in ovarian cancer cells and experimental tumors. When SR48692 is combined with carboplatin, we noted a major improvement of platinum-induced DNA damage and cell death, as well as a decrease in tumor growth. The relationship of these results to clinical studies was made by the detection of NTS and NTSR1 in 72% and 74% of ovarian cancer, respectively. Furthermore, in a large series of high-grade ovarian cancer, NTSR1 mRNA was shown to correlate with higher stages and platinum resistance.
This study strongly suggests that the addition of NTSR1 inhibitor in combination with platinum salt-based therapy will improve the response to the drug.
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Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has ...been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.
Background There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). ...Objective We sought to elaborate guidelines for optimizing the management of gynecologic/obstetric events in female patients with HAE-C1-INH. Methods A roundtable discussion took place at the 6th C1 Inhibitor Deficiency Workshop (May 2009, Budapest, Hungary). A review of related literature in English was performed. Results Contraception : Estrogens should be avoided. Barrier methods, intrauterine devices, and progestins can be used. Pregnancy : Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid or virally inactivated fresh frozen plasma can be used for long-term prophylaxis if human plasma-derived C1-INH is not available. No safety data are available on icatibant, ecallantide, or recombinant human C1-INH (rhC1INH). Parturition : Complications during vaginal delivery are rare. Prophylaxis before labor and delivery might not be clinically indicated, but pdhC1INH therapeutic doses (20 U/kg) should be available. Nevertheless, each case should be treated based on HAE-C1-INH symptoms during pregnancy and previous labors. pdhC1INH prophylaxis is advised before forceps or vacuum extraction or cesarean section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer : Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer. Conclusions A consensus for the management of female patients with HAE-C1-INH is presented.
A growing challenge in medicine today, is the need to improve the suitability of drug treatments for cancer patients. In this field, biomarkers have become the “flags” to provide additional ...information in tumor biology. They are a relay between the patient and practitioner and consequently, aid in the diagnosis, providing information for prognosis, or in some cases predicting the response to specific therapies. In addition to being markers, these tumor “flags” can also be major participants in the process of carcinogenesis.
Neurotensin receptor 1 (NTSR1) was recently identified as a prognosis marker in breast, lung, and head and neck squamous carcinomas. Neurotensin (NTS) was also shown to exert numerous oncogenic effects involved in tumor growth and metastatic spread. These effects were mostly mediated by NTSR1, making the NTS/NTSR1 complex an actor in cancer progression. In this review, we gather information on the oncogenic effects of the NTS/NTSR1 complex and its associated signaling pathways in order to illuminate its significant role in tumor progression and its potential as a biomarker and a therapeutic target in some tumors.
► Biomarkers act as relays between patients and practitioners. ► They help define the diagnosis, the prognosis, and to condition patient therapies. ► NTS/NTSR1 exerts a significant role in tumor progression. ► NTS/NTSR1 is a potential biomarker for tumor aggressiveness.
Most of breast cancers are hormonedependent. Hormone treatment (contraception and menopause hormone treatment) has a promoter effect on preexisting lesions: the increase in risk decreases after ...stopping treatment. Hormonal contraception increases modestly the risk in current users but the amplitude of the risk remains low up to 40 years when this increase is more significant due of the number of breast cancer occurring at that age. Pregnancy decreases the risk if at a young age but after 25 years may increase the risk. Combined menopause hormone treatment is associated to a greater risk than estrogens alone. Breast cancer associated with hormone treatment is estradiol receptor positive. There is an increase in the risk with duration. Combining the hormone treatment with an anti-estrogen could decrease the risk of breast cancer and help to keep the benefits of estrogens.
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