The average age of menopause in the United Kingdom is 51 years, although 1% of women experience premature ovarian insufficiency (menopause before the age of 40 years). Eight out of 10 women ...experience perimenopausal symptoms, most commonly hot flushes and night sweats (figure?), which typically last about four years.1 Quality of life may be severely affected.2
The origin of the superconducting state in the recently discovered Fe-based materials is the subject of intense scrutiny. Neutron scattering and NMR (ref. 8) measurements have already demonstrated a ...strong correlation between magnetism and superconductivity. A central unanswered question concerns the nature of the normal-state spin fluctuations that may be responsible for the pairing. Here we present inelastic neutron scattering measurements from large single crystals of superconducting and non-superconducting Fe1+yTe1−xSex. These measurements indicate a spin fluctuation spectrum dominated by two-dimensional incommensurate excitations extending to energies greater than 250 meV. Most importantly, the spin excitations in Fe1+yTe1−xSex have four-fold symmetry about the (1, 0) wavevector (square-lattice (π,π) point). Moreover, the excitations are described by the identical wavevector and can be characterized by the same model as the normal-state spin excitations in the high-TC cuprates. These results demonstrate commonality between the magnetism in these classes of materials, which perhaps extends to a common origin for superconductivity.
Premature ovarian insufficiency (POI) refers to the loss of ovarian activity before the age of 40 years, which leads to hypoestrogenism and amenorrhea. The diagnosis of POI in a young woman has ...potentially life-changing physical and emotional consequences for both the patient and her family. Therefore, it is very important that the diagnosis is correct and that it is made in a timely manner. Unfortunately, the diagnosis and therefore the effective treatment of POI are often delayed, which underlines the need for education of the broad medical community on the issue. A panel of menopause experts reviewed and critically appraised the literature, and present: (1) the diagnostic approach to POI, (2) the investigation of the etiology of this condition, (3) the therapeutic strategy regarding both hormone replacement therapy and fertility, and (4) the long-term follow-up and management for ensuring quality of life, as well as urogenital, cardiovascular, bone and mental health. The ultimate goal of this article is to provide a complete toolkit for the primary care physician to have easy access to all the information needed for the optimal management of women with POI, in the context of evidence-based and personalized medicine.
HIGHLIGHTS
Premature ovarian insufficiency occurs in 1% of the female population of reproductive age, yet the diagnosis is often delayed, with severe physical and emotional consequences for the patient.
Primary care physicians should be aware of the possibility of premature ovarian insufficiency in young women presenting with menstrual irregularity.
Prompt initiation of hormone replacement therapy ensures quality of life and prevents osteoporosis and cardiovascular disease.
Women seeking fertility should be referred to specialists to discuss assisted reproduction options.
Please cite this paper as: Rashid S, Khaund A, Murray L, Moss J, Cooper K, Lyons D, Murray G, Lumsden M. The effects of uterine artery embolisation and surgical treatment on ovarian function in women ...with uterine fibroids. BJOG 2010;117:985–989.
Objective The aim of this study was to evaluate and compare both ovarian function and menstrual characteristics following uterine artery embolisation (UAE) and surgery.
Design Subgroup of women from a randomised controlled trial.
Setting Gynaecology and radiology units in Scotland, UK.
Population Ninety‐six women from the randomised controlled trial comparing embolisation with surgery as a treatment for fibroids (REST), which recruited 157 patients (106 UAE; 51 surgery).
Methods Seventy‐three women undergoing UAE and 23 women undergoing surgery (with ovarian conservation) had serum follicle‐stimulating hormone (FSH) measurements taken on day 3 of the menstrual cycle prior to treatment, and at 6 and 12 months post‐treatment. Data on menstrual cycle characteristics was also collected.
Main outcome measures Ovarian failure, as defined by an FSH level of >40 iu/l, and change in duration of menses and length of menstrual cycle.
Results There was no significant difference in the rate of ovarian failure at 12 months between UAE (11%) and surgical patients (18%) (P = 0.44). This finding was not influenced by age. The mean duration of menstrual flow decreased significantly, from baseline to 12 months, by 1.7 days (SD 3.8), (95% CI 0.8–2.6). There was no statistically significant change in mean cycle length at 12 months (0.7 days SD 4.9; 95% CI −0.5, 1.9).
Conclusions There is no evidence for UAE accelerating a deterioration in ovarian function at 1 year, when compared with surgery. UAE is associated with a decrease in the duration of menstrual flow at 1 year.
Uterine fibroids cause heavy and prolonged bleeding, pain, pressure symptoms and subfertility but are mostly benign. The traditional method of treatment has been surgery as long term medical ...therapies have not shown to be effective. Uterine artery embolization (UAE - complete occlusion of both the uterine arteries with particulate emboli) has been reported to be an effective and safe alternative in the treatment of menorrhagia and other fibroid-related symptoms in women not desiring future fertility, but thus far this evidence is based on case controlled studies and case reports.
To review the benefits and/or harms from randomised controlled trials (RCTs) of uterine artery embolization (UAE) versus other interventions for symptomatic uterine fibroids.
We searched the Cochrane Menstrual Disorders & Subfertility Group Trials register (searched 10 August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, Issue 3, 2004), MEDLINE (January 1966 to November 2005) and EMBASE (January 1980 to November 2005). We also contacted authors of potential ongoing studies.
RCTs of UAE versus any medical or surgical therapy for symptomatic uterine fibroids.
Two of the authors (AS and JKG) assessed the trials and extracted the data independently. They also contacted the investigators of eligible RCTs for unpublished data.
Three trials were included in this review. Two RCTs compared UAE with abdominal hysterectomy in 234 women. Although the follow-up period was intended for two years, the available published results was only for six months follow-up. The second trial included 63 women comparing UAE with myomectomy in women who wished to preserve their fertility. The minimum follow-up reported was six months with a mean of 17 (+/- 9.3) months. The clinical success rate measured by improvement in fibroid-related symptoms e.g. menstrual loss was at least 85% in the UAE group from both trials. The mean dominant fibroid volume decreased by 30 to 46% in two trials. UAE significantly reduces length of hospital stay compared to surgery for either hysterectomy or myomectomy. Women undergoing UAE resumed routine activities sooner than those undergoing surgery. UAE was associated with a higher rate of minor post procedural complications such as vaginal discharge, post puncture haematoma and post embolization syndrome (pain, fever, nausea, vomiting), as well as higher unscheduled visits and readmission rates after discharge, compared with hysterectomy. There were no major complication differences between the two groups. Three women in the myomectomy trial had elevated FSH levels post UAE indicating possible ovarian dysfunction.
UAE offers an advantage over hysterectomy with regards to a shorter hospital stay and a quicker return to routine activities. There is no evidence of benefit of UAE compared to surgery (hysterectomy / myomectomy) for satisfaction. The higher minor complications rate after discharge in the UAE group as well as the unscheduled visits and readmission rates require more longer term follow-up trials to comment on its effectiveness and safety profile. There is currently an ongoing trial (REST, U. K.) and EMMY trial yet to report on the long term follow up, the results of which are awaited with interest.
ABSTRACT
Objective An overview of the current knowledge on the etiology and treatment of vasomotor symptoms in postmenopausal women.
Materials and methods Acknowledged experts in the field ...contributed a brief assessment of their areas of interest which were combined and edited into the final manuscript.
Results Women around the world experience vasomotor symptoms as they enter and complete the menopause transition. Vasomotor symptoms, specifically hot flushes, are caused by a narrowing of the thermoneutral zone in the brain. This effect, although related to estrogen withdrawal, is most likely related to changes in central nervous system neurotransmitters. Peripheral vascular reactivity is also altered in symptomatic women. Estrogen replacement therapy is the most effective treatment for hot flushes. Of the other interventions investigated, selective serotonin and selective norepinephrine reuptake inhibitors and gabapentin show efficacy greater than placebo. Objective monitoring of hot flushes indicates a robust improvement with hormone replacement therapy but little to no change with placebo. These data suggest that the subjective assessment of responses to therapy for vasomotor symptom results in inaccurate data. Hot flushes have recently been associated with increased cardiovascular risks and a lower incidence of breast cancer, but these data require confirmation.
Conclusions Vasomotor symptoms are experienced by women of all ethnic groups. They are caused by changes in the central nervous system associated with estrogen withdrawal and are best treated with estrogen replacement therapy. Objective monitoring of hot flushes indicates that placebo has little to no effect on their improvement. Subjective assessments of hot flushes in clinical trials may be inaccurate based on objective measurement of the frequency of hot flushes. Based on preliminary reports, women experiencing hot flushes have an increased risk of cardiovascular disease and a reduced incidence of breast cancer.
It is shown that attempts to accurately deduce the magnetic penetration depth λ of overdoped BaFe(1.82)Co(0.18)As₂ single crystals by transverse-field muon spin rotation (TF μSR) are thwarted by ...field-induced magnetic order and strong vortex-lattice disorder. We explain how substantial deviations from the magnetic field distribution of a nearly perfect vortex lattice by one or both of these factors is also significant for other iron-arsenic superconductors, and this introduces considerable uncertainty in the values of λ obtained by TF μSR.
Summary
Background A clear‐cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin’s mechanism of action ...has hampered progress in this area. Recently, the protein neutrophil gelatinase‐associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes.
Objectives To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes.
Methods Methods were developed to isolate and quantify skin‐surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin.
Results Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB‐1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)‐1β. In patients, isotretinoin increases NGAL levels by 2·4‐fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts.
Conclusions These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin.
RESEARCH QUESTION
What is the individualized bleeding experience of women with fibroids and anaemia in a 3 month randomized placebo controlled trial (PEARL I) of the selective progesterone receptor ...modulator (SPRM), ulipristal acetate (UPA)?
SUMMARY ANSWER
In contrast to continuing excessive regular menstruation in the placebo group, a majority of women treated with UPA (63.1% of those on 5 mg/day and 71.3% of those on 10 mg/day) experienced the rapid onset of amenorrhoea or minimal blood loss pictorial blood loss assessment chart (PBAC) < 12. The remainder experienced various patterns of bleeding and intensity of blood loss that are described for the first time, including an association of irregular bleeding on UPA with sub-mucous fibroids.
WHAT IS KNOWN ALREADY
The majority experience on UPA is amenorrhoea but the bleeding experience of the others has not been characterized.
STUDY DESIGN, SIZE, DURATION
A 13 week randomized controlled trial in women, eligible for surgery for uterine fibroids and anaemia, comparing placebo (n = 48), UPA 5 mg (n = 95) or UPA 10 mg (n = 94). The treatment aim was fibroid shrinkage and the primary definitions and outcomes are published elsewhere; here the secondary outcome measure of vaginal bleeding pattern is described.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women, 18–50 years old, with fibroids and haemoglobin ≤10.2 g/dl, justifying surgery. At least one fibroid was 3–10 cm diameter and uterus ≤16 weeks pregnancy size. All used the daily PBAC methodology in a screening cycle (Ps) and throughout treatment, and for the 4 weeks preceding Week 26 and Week 38 in those who did not have surgery. An excessive menstruation is PBAC > 100. The bleeding patterns were characterized using the classification of Belsey, developed under auspices of WHO.
MAIN RESULTS AND THE ROLE OF CHANCE
In the placebo group, all women had an excessive screening PBAC median 376; interquartile range (IQR) 241–574; 81.3% of them had regular menstrual bleeding and the intensity of bleeding remained similar, so that the median PBAC in the next three periods was 90, 92 and 93% of the screening value. Four of the 48 women had spontaneous improvement in bleeding and one developed amenorrhoea and elevation of gonadotrophins. In the placebo group, 22 women provided Week 26 and 21 women provided Week 38 PBAC data. The median Week 26 PBAC (312: IQR 102–524) and Week 38 PBAC (236; IQR 103–465) indicated ongoing excessive bleeding. In the UPA group, screening PBAC confirmed excessive bleeding (UPA 5 mg, median 358; IQR 232–621; UPA 10 mg, median 330; IQR 235–542). UPA was initiated from the start of a menstruation (P1) and no women had regular periods on treatment. Following P1 through the whole of the remaining 13 weeks of UPA treatment amenorrhoea or minimal loss (PBAC < 12 for whole phase) occurred in 63.1% (UPA 5 mg) or 71.3% (UPA 10 mg). The characterization of the individualized bleeding experience of the remaining women on 5 mg and 10 mg UPA, respectively, were infrequent bleeding in 17.9 and 12.8%; frequent or prolonged bleeding or both in 12.7 and 11.7% and irregular bleeding in 5.3 and 3.2%. In those with prolonged, frequent or irregular bleeding there was a high chance that sub-mucous fibroids were present (UPA 5 mg 100% and UPA 10 mg 78.6%) but no correlation with progesterone receptor modulator-associated endometrial changes.
LIMITATIONS, REASONS FOR CAUTION
The follow-up PBAC data at Week 26 and Week 38 are only valid for women who did not have surgical intervention. These groups may not be representative of the groups at screening.
WIDER IMPLICATIONS OF THE FINDINGS
This first detailed description of these SPRM bleeding patterns provides clinicians with an indication of potential responses in women using the SPRM UPA and provides an extended definition of bleeding in untreated women with excessive bleeding and fibroids.
STUDY FUNDING/COMPETING INTEREST(S)
Funded by PregLem/Gedeon Richter. D.H.B. is a member of the Scientific Advisory Board of PregLem, and in this role participated in the study design and supervision. Stock originally held in PregLem was given up when PregLem was incorporated into Gedeon Richter; D.H.B. does not currently hold stock. M.A.L. has received payment from Gideon Richter to attend a meeting to present these data (Barcelona, April 2013) but no financial support in preparing the manuscript. B.C.J.M.F. is a member of the Scientific Advisory Board of PregLem and has received fees and grant support from the following companies: Andromed, Ardana, Auxogyn, Ferring, Genovum, Gedeon Richter, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Roche, Schering, Schering Plough, Serono, Watson Laboratories and Wyeth. P.T. is a paid statistical consultant for PregLem SA. E.B. is a full time employee of PregLem and received payment from stocks sold in October 2010 from the company's full acquisition by Gedeon Richter Group.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov Identifier: NCT00755755 (PEARL I).
Menopausal symptoms can disrupt a woman's personal and social life. Vasomotor symptoms (hot flushes and night sweats) are the most common symptoms and can be treated very effectively with ...oestrogen-based hormone therapy. The decision to use oestrogen (often simply termed hormone therapy or hormone replacement therapy or HT) therapy involves balancing the potential benefits against the potential risks. Most agree that short-term oestrogen therapy, using the lowest effective dose, is a reasonable option for recently menopausal women with moderate-to-severe symptoms who are in good cardiovascular health (Martin and Manson. 2008. J. Clin. Endocrinol. Metab. 93, 4567-75). Whilst effective and safe in most instances, HT is not suitable for all women or for all menopause-related symptoms when alternatives are available. The role of HRT in chronic disease prevention is also discussed.
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