Margaret Rees

Revised Global Consensus Statement on Menopausal Hormone Therapy

The following Consensus Statement is endorsed by The International Menopause Society, The North American Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The...

Global Consensus Statement on menopausal hormone therapy.

MediClinic Panorama and Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa; * Department of Surgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, OH, USA; † Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR; ‡ Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; * * Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA; † † University of Geneva, Switzerland; ‡ ‡ Reader Emeritus, University of Oxford, UK

Revised global consensus statement on menopausal hormone therapy

The following Consensus Statement is endorsed by The International Menopause Society, The North American Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The Asia Pacific Menopause Federation, The International Osteoporosis Foundation and The Federation of Latin American Menopause Societies.

Adrenomedullin Haploinsufficiency Predisposes to Secondary Lymphedema

Secondary lymphedema is a debilitating condition, and genetic factors predisposing to its development remain largely unknown. Adrenomedullin (AM) is peptide encoded, together with proadrenomedullin N-terminal peptide (PAMP), by the Adm gene (adrenomedullin gene). AM and its putative receptor calcitonin receptor–like receptor (CLR) are implicated in angiogenesis and lymphangiogenesis during embryogenesis and wound healing, suggesting their possible involvement in secondary lymphedema. To investigate whether AM deficiency predisposes to secondary lymphedema, we used heterozygous adult mice with Adm gene-knockin stop mutation, which selectively abrogated AM, but preserved PAMP, expression (AdmAM+/Δ animals). After hind limb skin incision, Adm messenger RNA expression was upregulated in wounded tissue of both AdmAM+/+ and AdmAM+/Δ mice. However, only AdmAM+/Δ animals developed limb swelling and histopathological lymphedematous changes, including epidermal thickening, elevated collagen fiber density, and increased microvessel diameter. Secondary lymphedema was prevented when circulating AM levels in AdmAM+/Δ mice were restored by systemic peptide delivery. In human skin, CLR was expressed in tissue components affected by lymphedema, including epidermis, lymphatics, and blood vessels. Our study identified a previously unrecognized role for endogenous AM as a key factor in secondary lymphedema pathogenesis and provided experimental in vivo evidence of an underlying germ-line genetic predisposition to developing this disorder.

The G-Protein–Coupled Receptor CLR Is Upregulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis

Purpose: The G-protein–coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) and its ligand peptide adrenomedullin (encoded by ADM gene) are implicated in tumor angiogenesis in mouse models but poorly defined in human cancers. We therefore investigated the diagnostic/prognostic use for CLR in human tumor types that may rely on adrenomedullin signaling and in clear cell renal cell carcinoma (RCC), a highly vascular tumor, in particular. Experimental Design: In silico gene expression mRNA profiling microarray study (n = 168 tumors) and cancer profiling cDNA array hybridization (n = 241 pairs of patient-matched tumor/normal tissue samples) were carried out to analyze ADM mRNA expression in 13 tumor types. Immunohistochemistry on tissue microarrays containing patient-matched renal tumor/normal tissues (n = 87 pairs) was conducted to study CLR expression and its association with clinicopathologic parameters and disease outcome. Results: ADM expression was significantly upregulated only in RCC and endometrial adenocarcinoma compared with normal tissue counterparts (P < 0.01). CLR was localized in tumor cells and vessels in RCC and upregulated as compared with patient-matched normal control kidney (P < 0.001). Higher CLR expression was found in advanced stages (P < 0.05), correlated with high tumor grade (P < 0.01) and conferred shorter overall survival (P < 0.01). Conclusions: In human tissues ADM expression is upregulated in cancer type–specific manner, implicating potential role for adrenomedullin signaling in particular in RCC, where CLR localization suggests autocrine/paracrine mode for adrenomedullin action within the tumor microenvironment. Our findings reveal previously unrecognized CLR upregulation in an autocrine loop with adrenomedullin in RCC with potential application for this GPCR as a target for future functional studies and drug development. Clin Cancer Res; 19(20); 5740–8. ©2013 AACR.

Information giving and involvement in treatment decisions:Is more really better? Psychological effects and relation with adherence

Objectives : The aim of this study is to improve our understanding of the ways in which a medical consultation style relates to satisfaction and adherence. Design : Participants completed questionnaires about preferred and perceived consultation styles; psychological variables such as satisfaction, anxiety and depression; and questions about taking medication. Questionnaires were completed prior to the consultation, immediately after, three months later and one year later. Doctors also completed a scale on completion of the consultation. The decisions in question related to women seeking advice about Hormone Replacement Therapy (HRT) and decisions about pain management. Results : Patients expressed preferences for information about the treatment options and for active involvement in the decision process. The extent to which patients perceived themselves as having received information about the treatment options was a particularly consistent predictor of satisfaction. The extent to which patients perceived themselves as having been prepared for the side effects of HRT was a consistent predictor of anxiety. Conclusions : Perceptions of the amount of information received about medical options, including information preparing individuals for potential side effects of medication, appears to be more important to satisfaction and anxiety, than actual involvement in the decision.

Emerging Facade of Menopausal Hormone Therapy

Menopausal hormone therapy (HT) has been around for 70 years, and in the 1980s and 1990s was considered a universal panacea for womens problems from midlife onward. However, this concept was challenged by the results of the Womens Health Initiative (WHI) and the Million Women Study (MWS) that were first published in 2002 and 2003. Since the publication of these studies, prescriptions of HT have markedly declined and there have been many media scares. An unfortunate sequel was an extrapolation of the observations from women in their 50s and older to those with early ovarian failure. This article discusses the WHI and the MWS with a focus on differences between HT regimens including doses, formulations, and routes, timing, and duration of HT. It addresses practical issues such as strategies for stopping HT, and discusses bioidentical hormones. The specialist knowledge now required to deliver post-reproductive health service has led to considerations that menopause management should be now the responsibility of a specialist and not a general gynecologist.

Low calcitonin receptor like receptor expression in endometrial vessels from women with unexplained infertility.

Adrenomedullin (AM) and its receptor subunit, calcitonin receptor-like receptor (CLR) are known to be important for endothelial function. The genotypes and phenotypes of AM and CLR in the endometrium were studied in relation to unexplained infertility. Endometrial biopsies from 12 fertile and 11 infertile women and blood samples from 156 fertile and 106 infertile women were collected. Protein and mRNA expression of AM and CLR was determined using immunohistochemistry and real time PCR. Allele and genotype frequencies in the AM (rs4399321 and rs7944706) and CLR genes (rs696574, rs1528233 and rs3771073) were performed using Taqman genotyping assays. Unexplained infertility was characterised by lower number of vessels stained with CLR in endometrium compared to fertile controls. There was no difference in AM expression. This could not be explained by SNP analysis in the AM or CLR genes. Imbalance in the AM/CLR system might alter endothelial function in women with unexplained infertility.

Adrenomedullin and its receptor, calcitonin receptor-like receptor, are aberrantly expressed in women with idiopathic menorrhagia

The human endometrium undergoes a unique process of benign angiogenesis under the control of ovarian steroids during reproductive life. Aberrant angiogenesis has been implicated in idiopathic menorrhagia, a common gynaecological complaint. One of the key factors involved in endometrial angiogenesis is adrenomedullin (AM), a multifunctional 52-amino acid peptide. AM mediates the activities of endometrial angiogenesis via calcitonin receptor-like receptor (CLR). The objective of the present study was to compare the endometrial expression of AM and CRL in women with and without idiopathic menorrhagia. Endometrial biopsies were obtained from 9 women with menorrhagia (≥80 ml per menstruation) and 12 women with normal blood loss (<80 ml per menstruation). Protein and mRNA expression levels of AM and CLR were determined using immunohistochemistry and real-time PCR. Compared to the controls, patients with menorrhagia exhibited low immunostaining intensity of AM, while high CLR staining was observed in the epithelium (p<0.05). No difference in mRNA expression was observed between the groups. These data suggest that an imbalance in the AM/CLR system might alter endometrial angiogenesis in menorrhagia.

Gender and ageing in the 21st century: Special issue

This theme issue covers the multifaceted aspects of gender and geing in the 21st century and includes both original papers and eview articles. The idea to dedicate an issue to this topic was based n the implications of increasing longevity, especially in women, so hat centenarians will no longer be exceptions [1]. Also as more omen are entering medicine, career progression over the past entury is explored. Unfortunately, the glass ceiling still exists, hankfully not to the extent endured in the early 20th century, hich means that women are currently under represented in senior ositions and certain specialities [2,3]. How does one measure health in ageing populations? Shroufi t al. examine this highly practical problem [4]. Different techiques and approaches, such as DALYs (Disability Adjusted Life ears), have been used to measure health in populations. Howver, these techniques all have the disadvantage of incorporating ndividual biases (derived from particular characteristics specific to ndividuals or populations) into the process through which health tate valuations are derived. Thus health states cannot be directly ompared between populations as factors such as nationality and thnicity can affect results. Also people of different ages can judge ealth differently. The authors conclude that objective measures f health should be comparable to those acquired in other poplations, irrespective of age, gender, disease status, ethnicity and eographical location. As populations age the number of centenarians is growing and here is increased interest as to why some people are long lived 1]. Hausman and colleagues review studies of dietary intake and atterns of long-lived people as well as current knowledge of utritional status of centenarians. The studies indicate that body ass index and nutritional status as indicated by circulating levls of antioxidant vitamins, vitamin B12, folate, homocysteine and 5(OH)vitamin D of centenarians is quite heterogeneous and influnced by region of residency and many of the demographic, dietary nd lifestyle factors that influence nutritional status in other older dults. Thus, it seems unlikely that there is one particular dietary attern that promotes exceptional longevity.The theme of dietary atterns is continued by Bountziouka and colleagues [5]. They evalate the short-term stability (repeatability) of dietary patterns erived using a priori and a posteriori approaches in two samles from a Mediterranean (Greek) community population. A priori ethods seek to determine a person’s adherence to a pre-specified usually ‘healthy’ diet), whereas a posteriori methods are used to ecord a person’s (or more generally a population’s) actual diet. he study found that both a priori and a posteriori procedures an be trusted to define stable dietary patterns, and the choice of hich approach to use should be based on the information that