Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study

B Formby, F SchmidtThe Rasmus Institute for Medical Research, Program in Reproductive Endocrinology, Santa Barbara, CA, USAObjective: To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base) to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.Design: An open, randomized, comparative, between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments. Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months. Pharmacokinetic data following transdermal administration of 17β-estradiol (0.3 mg, daily) and progesterone (100 mg, daily) were calculated from saliva levels using high-performance liquid chromatography analysis.Results: Improvement in climacteric symptoms was reported in 93% of women evaluated before and after 3 and 6 months of treatment. Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL, and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders, 88% characterized symptom relief as complete. No adverse health-related events were attributed to the bioidentical hormone therapy. Time to maximum saliva concentrations (Tmax), in all experimental cases, was observed after 6 hours. Baseline values were reached within 24 hours, indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period, ie, its daily biological rhythm.Conclusion: Percutaneous absorption of 17β-estradiol, as well as the absorption of progesterone, was associated with relief of climacteric symptoms. The cyclical transdermal delivery of combined bioidentical hormones may be advantageous because it mimics the secretory profiles of 17β-estradiol and progesterone in normally cyclic women over a 28-day period. Larger studies are needed to determine the long-term effects of our therapy.Keywords: menopause, transdermal, 17β-estradiol, circadian rhythms, estrogen homeostasi

Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis

Abstract Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. But the biologic mechanism of this inhibition remains to be determined. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis. Since p53, bcl-2 and survivin genetically control the apoptotic process, we investigated whether or not these genes could be involved in the progesterone-induced apoptosis. We found a maximal 90% inhibition of cell proliferation with T47-D breast cancer cells after exposure to 10 µM progesterone for 72 h. Control progesterone receptor negative MDA-231 cancer cells were unresponsive to 10 µM progesterone. The earliest sign of apoptosis is translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane and can be monitored by the calcium-dependent binding of annexin V in conjunction with flow cytometry. After 24 h of exposure to 10 µM progesterone, cytofluorometric analysis of T47-D breast cancer cells indicated 43% were annexin V-positive and had undergone apoptosis and no cells showed signs of cellular necrosis (propidium iodide negative). After 72 h of exposure to 10 µM progesterone, 48% of the cells had undergone apoptosis and 40% were annexin V positive/propidium iodide positive indicating signs of necrosis. Control untreated cancer cells did not undergo apoptosis. Evidence proving apoptosis was also demonstrated by fragmentation of nuclear DNA into multiples of oligonucleosomal fragments. After 24 h of exposure of T47-D cells to either 1 or 10 µM progesterone, we observed a marked down-regulation of protooncogene bcl-2 protein and mRNA levels. mRNA levels of survivin and the metastatic variant CD44 v7-v10 were also downregulated. Progesterone increased p53 mRNA levels. These results demonstrate that progesterone at relative high physiological concentrations, but comparable to those seen in plasma during the third trimester of human pregnancy, exhibited a strong antiproliferative effect on breast cancer cells and induced apoptosis. (Mol Cell Biochem 202: 53-61, 1999

If there’s going to be a subject that you don’t have to do …’ Findings from a mapping study of PSHE education in English secondary schools

This article discusses some key findings about secondary schools from a mapping study of Personal, Social, Health and Economic (PSHE) education in England. The secondary school elements of the study combined a nationally representative survey of 617 secondary schools with follow-up in-depth case studies in five of these schools. These case studies involved interviews and discussion groups with pupils, parents and key school staff members, as well as governors and school improvement partners, and local authority support staff. Results reported here relate to the models and methods of delivery; frequency and curriculum coverage; the purpose and value of schooling, and PSHE education, and issues about staffing, expertise and credibility. Where appropriate, comparisons are made with primary schools. In doing so, the article raises issues about the diminished status and priority of PSHE education in secondary as compared with primary schools, and how this may stem from the ways in which schools do/do not value the subject, and its relationship to broader attainment and education policy contexts

School toilets : queer, disabled bodies and gendered lessons of embodiment

In this paper we argue that school toilets function as one civilising site (Elias, 1978) in which children learn that disabled and queer bodies are out of place. This paper is the first to offer queer and crip perspectives on school toilets. The small body of existing school toilet literature generally works from a normative position which implicitly perpetuates dominant and oppressive ideals. We draw on data from Around the Toilet, a collaborative research project with queer, trans and disabled people (aroundthetoilet.wordpress.com) to critically interrogate this work. In doing this we consider ‘toilet training’ as a form of ‘civilisation’, that teaches lessons around identity, embodiment and ab/normal ways of being in the world. Furthermore, we show that ‘toilet training’ continues into adulthood, albeit in ways that are less easily identifiable than in the early years. We therefore call for a more critical, inclusive, and transformative approach to school toilet research

Sexualisation's four faces: sexualisation and gender stereotyping in the Bailey Review

This paper explores the considerations of sexualisation and gender stereotyping in the recent UK government report Letting Children be Children. This report, the Bailey Review, claimed to represent the views of parents. However, closer reading reveals that, while the parents who were consulted were concerned about both the sexualisation and the gender stereotyping of products aimed at children, the Bailey Review focuses only on the former and dismisses the latter. ‘Sexualisation’ has four faces in the Bailey Review: it is treated as a process that increases (1) the visibility of sexual content in the public domain, (2) misogyny, (3) the sexuality of children, and (4) the mainstream position of ‘deviant’ sexual behaviours and lifestyles. Through this construction of ‘sexualisation’, gendered relations of power are not only hidden from view but also buttress a narrative in which young women are situated as children, and their sexuality and desire rendered pathological and morally unacceptable as judged by a conservative standard of decency. Comparison of the treatment of sexualisation and gender stereotyping in the review is revealing of the political motivations behind it, and of wider discourse in these areas

Differences and Commonalities in Physical, Chemical and Mineralogical Properties of Zanzibari Geophagic Soils

The function of human geophagy has long been questioned. We sought to test hypotheses concerning its potential physiological effects through analysis of soils and patterns in geophagy behavior. Eleven samples of geophagic soils consumed by pregnant women on Pemba Island, Zanzibar, Tanzania, were characterized according to their color, texture, major element chemistry, trace element chemistry, bulk mineralogy, and clay mineralogy. An epidemiological study (N = 2367) and ethnographic interviews (N = 57) on Pemba yielded information about geophagic behaviors and socio-demographic and biological characteristics of those who consumed earth. The soils varied widely in color, ranging from light red to white through various shades of brown and yellow, and texture ranged from clay to sand. Major element chemistry of the soils also varied greatly; most were low in Fe and Ca. Trace elements, whether of biological or non-biological significance, were uniformly low when compared with normal ranges of mineral soils. The sole commonality among the samples is that all clay fractions were dominated by a kaolin mineral: kaolinite, halloysite, or a mixture of both. Geophagy behavior also varied greatly, with one major exception: a greater proportion of pregnant women (7.1%) and young children (4.5%) consumed earth than non-pregnant women (0.2%) or men (0%). The presence of kaolin mineral in all samples, its palliative and detoxifying properties, and the highest prevalence of geophagy among those most biologically vulnerable suggest that geophagy may be a protective behavior

Designing hate crime reporting devices: an exploration of young LGBT+ people's report needs

This paper reports on an exploratory study, which gathered LGBT+ young people’s (aged 15–22) experiences and perceptions of hate crime. Two design-led workshops were conducted in the North East of England, with the aim of identifying the reporting needs of LGBT+ young people. Participants in the first workshop were asked what types of ‘hate’ scenarios they would report to the police. Participants in the second workshop were asked to design hate crime reporting devices. Young people were ambivalent about reporting their experiences to the police as their victimization was intimately tied to people they were connected with (parents, school peers, and acquaintances). They highlighted a variety of response needs when reporting victimization. This article argues that acts of bullying and acts of antiLGBT+ hate crime are symmetrical in their tangibility. LGBT+ youth victimization is currently framed, within scholarly discourse, as a bullying issue involving peer victimization. However, the criminological discourse on LGBT+ adult victimization is framed as hate crime. The data provided bridges this gap by conceptualizing youth victimization as a form of hate crime, an important contribution in recognizing the report needs of young LGBT+ people