Use of aromatase inhibitors to treat endometriosis-related pain symptoms: a systematic review

This systematic review aims to assess the efficacy of aromatase inhibitors (AIs) in treating pain symptoms caused by endometriosis. A comprehensive literature search was conducted to identify all the published studies evaluating the efficacy of type II nonsteroidal aromatase inhibitors (anastrozole and letrozole) in treating endometriosis-related pain symptoms. The MEDLINE, EMBASE, PubMed, and SCOPUS databases and the Cochrane System Reviews were searched up to October 2010. This review comprises of the results of 10 publications fitting the inclusion criteria; these studies included a total of 251 women. Five studies were prospective non-comparative, four were randomized controlled trials (RCTs) and one was a prospective patient preference trial. Seven studies examined the efficacy of AIs in improving endometriosis-related pain symptoms, whilst three RCTs investigated the use of AIs as post-operative therapy in preventing the recurrence of pain symptoms after surgery for endometriosis. All the observational studies demonstrated that AIs combined with either progestogens or oral contraceptive pill reduce the severity of pain symptoms and improve quality of life. One patient preference study demonstrated that letrozole combined with norethisterone acetate is more effective in reducing pain and deep dyspareunia than norethisterone acetate alone. However, letrozole causes a higher incidence of adverse effects and does not improve patients' satisfaction or influence recurrence of symptoms after discontinuation of treatment. A RCT showed that combining letrozole with norethisterone acetate causes a lower incidence of adverse effects and lower discontinuation rate than combining letrozole with triptorelin. Two RCTs demonstrated that, after surgical treatment of endometriosis, the administration of AIs combined with gonadotropin releasing hormone analogue for 6 months reduces the risk of endometriosis recurrence when compared with gonadotropin releasing hormone analogue alone. In conclusion, AIs effectively reduce the severity of endometriosis-related pain symptoms. Since endometriosis is a chronic disease, future investigations should clarify whether the long-term administration of AIs is superior to currently available endocrine therapies in terms of improvement of pain, adverse effects and patient satisfaction

Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin.</p> <p>Methods</p> <p>Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded.</p> <p>Results</p> <p>A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p = 0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p = 0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p = 0.018). During treatment, mineral bone density significantly decreased in group T but not in group N.</p> <p>Conclusions</p> <p>Aromatase inhibitors reduce the intensity of endometriosis-related pain symptoms. Combining letrozole with oral norethisterone acetate was associated with a lower incidence of adverse effects and a lower discontinuation rate than combining letrozole with triptorelin.</p

Characteristics of populations of granulosa cells from individual follicles in women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF

BACKGROUND: The aim of this study was to evaluate the functional characteristics of granulosa cell populations of individual follicles of women undergoing controlled ovarian stimulation (COS) for IVF/ICSI in whom gonadotrophin had been withheld (‘coasted’) for the prevention of OHSS. METHODS: Follicular fluid and granulosa cells were isolated from 224 individual follicles in 41 women who had been coasted and from 257 individual follicles in 50 women who had a ‘normal’ response to COS. Cells were cultured at 10 000 cells per well, to evaluate progesterone secretion. Follicular fluid was assayed for progesterone and estradiol (E2). RESULTS: No significant differences were observed between the two groups with respect to granulosa cell number or follicular fluid progesterone and E2 and follicle size, the retrieval of an oocyte and the subsequent fertilization of the oocyte. However, the granulosa cells derived from the coasted group showed a higher rate of progesterone secretion per cell at 72 h which was sustained for longer. Differences were also seen at 72 and 120 h of culture with a loss of correlation between progesterone secretion and follicle diameter in the coasted group. CONCLUSIONS: Our findings suggest that coasting has an effect on the functional capacity of the granulosa cells and the duration of their function. It is likely that in women at risk of OHSS who are not coasted, the granulosa cells have the capacity to produce significantly more chemical mediators per cell and for a more prolonged period of time

A Novel Diagnostic Aid for Detection of Intra-Abdominal Adhesions to the Anterior Abdominal Wall Using Dynamic Magnetic Resonance Imaging

Introduction. Abdominal adhesions can cause serious morbidity and complicate subsequent operations. Their diagnosis is often one of exclusion due to a lack of a reliable, non-invasive diagnostic technique. Development and testing of a candidate technique are described below. Method. During respiration, smooth visceral sliding motion occurs between the abdominal contents and the walls of the abdominal cavity. We describe a technique involving image segmentation and registration to calculate shear as an analogue for visceral slide based on the tracking of structures throughout the respiratory cycle. The presence of an adhesion is attributed to a resistance to visceral slide resulting in a discernible reduction in shear. The abdominal movement due to respiration is captured in sagittal dynamic MR images. Results. Clinical images were selected for analysis, including a patient with a surgically confirmed adhesion. Discernible reduction in shear was observed at the location of the adhesion while a consistent, gradually changing shear was observed in the healthy volunteers. Conclusion. The technique and its validation show encouraging results for adhesion detection but a larger study is now required to confirm its potential

The potential of vertical extension at the city scale

The UK construction sector is central to the climate and housing crises and must now deliver vast amounts of residential accommodation whilst reaching net zero emissions by 2050. Housing provision through the vertical extension of existing buildings offers opportunity to achieve this, reducing embodied carbon emissions and creating more efficient high-density settlements. In England, permitted development (PD) rights allow for residential vertical extensions without the requirement for conventional planning permission. Despite this, and due to limited uptake of PD rights and a lack of existing studies, the potential for housing provision through widespread extension is unknown. This paper develops a framework to assess the ability of vertical extensions in providing housing at different scales and applies this to Sheffield, England. The generation of new dwellings through PD vertical extension could house up to 175,000 in Sheffield, with detached buildings and those in residential use being most suited to extension. PD rights favour the enlargement of existing dwellings over the generation of new residential units, potentially limiting their effectiveness in tackling the housing crisis

Performance evaluation of a mechanically ventilated heat recovery (MVHR) system as part of a series of UK residential energy retrofit measures

This study involves a detailed analysis of a mechanically ventilated heat recovery (MVHR) system installed as a case study retrofit project in a UK test dwelling. Comparisons of predicted and in situ performance are made through the calculation of a theoretical and practical heat loss coefficient value (HLC). Analysis revealed underperformance in the installed MVHR system, as compared to predicted data. Issues were identified in the installation and function of the control unit and ductwork. Improvement work enabled the system to function more closely to optimum performance levels. However, discrepancies still existed between the predicted and actual HLC values, which were largely accounted for through theoretical heat loss calculations attributable to slight imbalances within the system supply and extract rates. When normalised, the data still showed an unaccounted heat loss of approximately 6 W/K in both MVHR tests. The study reinforces the need for high quality MVHR installation and commissioning work, which is critical to ensure that a system can perform to the optimum levels specified in manufacturer literature. Education and training throughout the supply chain is essential in achieving this, as system inefficiencies can lead to unnecessary heat losses resulting from increased levels of air infiltration or leakage

Thermal relaxation of magnetic clusters in amorphous Hf_{57}Fe_{43} alloy

The magnetization processes in binary magnetic/nonmagnetic amorphous alloy Hf_{57}Fe_{43} are investigated by the detailed measurements of magnetic hysteresis loops, temperature dependence of magnetization, relaxation of magnetization and magnetic ac susceptibility, including a nonlinear term. Blocking of magnetic moments at lower temperatures is accompanied with the slow relaxation of magnetization and magnetic hysteresis loops. All of the observed properties are explained with the superparamagnetic behaviour of the single domain magnetic clusters inside the nonmagnetic host, their blocking by the anisotropy barriers and thermal fluctuation over the barriers accompanied by relaxation of magnetization. From magnetic viscosity analysis based on thermal relaxation over the anisotropy barriers it is found out that magnetic clusters occupy the characteristic volume from 25 up to 200 nm3 . The validity of the superparamagnetic model of Hf_{57}Fe_{43} is based on the concentration of iron in the Hf_{100-x}Fe_{43} system that is just below the threshold for the long range magnetic ordering. This work throws more light on magnetic behaviour of other amorphous alloys, too

J D Bernal: philosophy, politics and the science of science

This paper is an examination of the philosophical and political legacy of John Desmond Bernal. It addresses the evidence of an emerging consensus on Bernal based on the recent biography of Bernal by Andrew Brown and the reviews it has received. It takes issue with this view of Bernal, which tends to be admiring of his scientific contribution, bemused by his sexuality, condescending to his philosophy and hostile to his politics. This article is a critical defence of his philosophical and political position