Uterine artery embolisation or myomectomy for women with uterine fibroids wishing to avoid hysterectomy: a cost-utility analysis of the FEMME trial.

OBJECTIVES: To assess the cost-effectiveness of uterine artery embolisation (UAE) and myomectomy for women with symptomatic uterine fibroids wishing to avoid hysterectomy. DESIGN: Economic evaluation alongside the FEMME randomised controlled trial. SETTING: 29 UK hospitals. POPULATION: Premenopausal women who had symptomatic uterine fibroids amenable to UAE or myomectomy wishing to avoid hysterectomy. 254 women were randomised to UAE (127) and myomectomy (127). METHODS: A within-trial cost-utility analysis was conducted from the perspective of the UK NHS. MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) measured using the EuroQoL EQ-5D-3L, combined with costs to estimate cost-effectiveness over 2 and 4 years of follow-up. RESULTS: Over a 2-year time horizon, UAE was associated with higher mean costs (difference £645; 95% CI -1381 to 2580) and lower QALYs (difference -0.09; 95% CI -0.11 to -0.04) when compared with myomectomy. Similar results were observed over the 4-year time horizon. Thus, UAE was dominated by myomectomy. Results of the sensitivity analyses were consistent with the base case results for both years. Over 2 years, UAE was associated with higher costs (difference £456; 95% CI -1823 to 3164) and lower QALYs (difference -0.06; 95% CI -0.11 to -0.02). CONCLUSIONS: Myomectomy is a cost-effective option for the treatment of uterine fibroids. The differences in costs and QALYs are small. Women should be fully informed and have the option to choose between the two procedures. TWEETABLE ABSTRACT: Fully informed women with uterine fibroids should have a choice between uterine artery embolisation or myomectomy.

Premature ovarian insufficiency: a toolkit for the primary care physician.

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.HIGHLIGHTSPremature 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.

Variation in menopausal vasomotor symptoms outcomes in clinical trials: a systematic review.

BACKGROUND: There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies. This has prevented meaningful comparisons between treatments and limited data synthesis. OBJECTIVES: To review systematically the outcome reporting and measures used to assess menopausal vasomotor symptoms from randomised controlled trials of treatments. SEARCH STRATEGY: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to May 2018. SELECTION CRITERIA: Randomised controlled trials with a primary outcome of menopausal vasomotor symptoms in women and a sample size of at least 20 women per study arm. DATA COLLECTION AND ANALYSIS: Data about study characteristics, primary vasomotor-related outcomes and methods of measuring them. MAIN RESULTS: The search identified 5591 studies, 214 of which were included. Forty-nine different primary reported outcomes were identified for vasomotor symptoms and 16 different tools had been used to measure these outcomes. The most commonly reported outcomes were frequency (97/214), severity (116/214), and intensity (28/114) of vasomotor symptoms or a composite of these outcomes (68/214). There was little consistency in how the frequency and severity/intensity of vasomotor symptoms were defined. CONCLUSIONS: There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials. Future studies should include standardised outcome measures which reflect the priorities of patients, clinicians, and researchers. This is most effectively achieved through the development of a Core Outcome Set. This systematic review is the first step towards development of a Core Outcome Set for menopausal vasomotor symptoms. TWEETABLE SUMMARY: Menopausal hot flushes and night sweats have been reported in 49 different ways in clinical research. A core outcome set is urgently required.

The evolution of the human menopause.

The females of most species die soon after ceasing to reproduce, their purpose in life being to ensure survival of their kin. Human females may live more than one-third of their lives after they cease to reproduce, a property shared by few species, one of which is Orca whales. Orcas have been extensively studied because families live together in stable units or pods and individual whales have distinctive markings, enabling them to be identified. The females survive long after the menopause, one possible reason for this being that the older females provide a survival advantage since they are seen to lead the pods more often than younger females or males, thus providing a survival advantage in times of food shortage. The female lifespan is increasing in most countries worldwide, principally due to decreased infection and maternal mortality. Women are now more active through middle and into older age. Whatever sort of life they wish to lead, women need to be as fit as possible to facilitate healthy aging. Chronic diseases that affect millions of women are cardiovascular disease, osteoporosis, cancer, and dementia. The incidence of all these is increased by obesity, the prevention of which is a major challenge in our society. Hormone therapy may have a place for some women but for many others taking control of their health by lifestyle intervention is a major contributor to disease prevention. It is our duty as doctors to encourage this at every opportunity to help all women live a fruitful and healthy old age.

Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause.

BACKGROUND: Vasomotor symptoms (VMSs) are the hallmarks of menopause, occurring in approximately 75% of postmenopausal women in the UK, and are severe in 25%. OBJECTIVES: To identify which treatments are most clinically effective for the relief of VMSs for women in natural menopause without hysterectomy. SEARCH STRATEGY: English publications in MEDLINE, Embase, and The Cochrane Library up to 13 January 2015 were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) of treatments for women with a uterus for the outcomes of frequency of VMSs (up to 26 weeks), vaginal bleeding, and discontinuation. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis (NMA) using mean ratios (MRs) and odd ratios (ORs). MAIN RESULTS: Across the three networks, 47 RCTs of 16 treatment classes (n = 8326 women) were included. When compared with placebo, transdermal estradiol and progestogen (O+P) had the highest probability of being the most effective treatment for VMS relief (69.8%; MR 0.23; 95% credible interval, 95% CrI 0.09-0.57), whereas oral O+P was ranked lower than transdermal O+P, although oral and transdermal O+P were no different for this outcome (MR 2.23; 95% CrI 0.7-7.1). Isoflavones and black cohosh were more effective than placebo, although not significantly better than O+P. Not only were selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) found to be ineffective in relieving VMSs, but they also had significantly higher odds of discontinuation than placebo. Limited data were available for bleeding, therefore no conclusions could be made. CONCLUSION: For women who have not undergone hysterectomy, transdermal O+P was the most effective treatment for VMS relief. TWEETABLE ABSTRACT: Which treatment best relieves menopause flushes? Results from the #NICE guideline network meta-analysis.

Abnormal uterine bleeding in perimenopause.

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

The menopausal hot flush: a review.

The hot flush is the most characteristic and often the most distressing symptom of the menopause. It is a unique feature and yet the mechanism and health implications are still not fully understood. This review summarizes some of the current thoughts on factors contributing to flushing, the physiological, vascular and neuroendocrine changes associated with flushing and the possible cardiovascular and other health implications for women experiencing hot flushes. Therapy is not discussed.

Individualized vaginal bleeding experience of women with uterine fibroids in the PEARL I randomized controlled trial comparing the effects of ulipristal acetate or placebo.

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).

Uterine artery embolization for symptomatic uterine fibroids.

BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence that is based on case controlled studies and case reports. This is an update of the review previously published in 2012. OBJECTIVES: To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched sources including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and trial registries. The search was last conducted in April 2014. We contacted authors of eligible randomised controlled trials to request unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. The primary outcomes of the review were patient satisfaction and live birth rate (among women seeking live birth). DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) independently selected studies, assessed quality and extracted data. Evidence quality was assessed using GRADE methods. MAIN RESULTS: Seven RCTs with 793 women were included in this review. Three trials compared UAE with abdominal hysterectomy, two trials compared UAE with myomectomy, and two trials compared UAE with either type of surgery (53 hysterectomies and 62 myomectomies).With regard to patient satisfaction rates, our findings were consistent with satisfaction rates being up to 41% lower or up to 48% higher with UAE compared to surgery within 24 months of having the procedure (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.59 to 1.48, 6 trials, 640 women, I(2) = 5%, moderate quality evidence). Findings were also inconclusive at five years of follow-up (OR 0.90; 95% CI 0.45 to 1.80, 2 trials, 295 women, I(2) = 0%, moderate quality evidence). There was some indication that UAE may be associated with less favourable fertility outcomes than myomectomy, but it was very low quality evidence from a subgroup of a single study and should be regarded with extreme caution (live birth: OR 0.26; 95% CI 0.08 to 0.84; pregnancy: OR 0.29; 95% CI 0.10 to 0.85, 1 study, 66 women).Similarly, for several safety outcomes our findings showed evidence of a substantially higher risk of adverse events in either arm or of no difference between the groups. This applied to intra-procedural complications (OR 0.91; 95% CI 0.42 to 1.97, 4 trials, 452 women, I(2) = 40%, low quality evidence), major complications within one year (OR 0.65; 95% CI 0.33 to 1.26, 5 trials, 611 women, I(2) = 4%, moderate quality evidence) and major complications within five years (OR 0.56; CI 0.27 to 1.18, 2 trials, 268 women). However, the rate of minor complications within one year was higher in the UAE group (OR 1.99; CI 1.41 to 2.81, 6 trials, 735 women, I(2) = 0%, moderate quality evidence) and two trials found a higher minor complication rate in the UAE group at up to five years (OR 2.93; CI 1.73 to 4.93, 2 trials, 268 women).UAE was associated with a higher rate of further surgical interventions (re-interventions within 2 years: OR 3.72; 95% CI 2.28 to 6.04, 6 trials, 732 women, I(2) = 45%, moderate quality evidence; within 5 years: OR 5.79; 95% CI 2.65 to 12.65, 2 trials, 289 women, I(2) = 65%). If we assumed that 7% of women will require further surgery within two years of hysterectomy or myomectomy, between 15% and 32% will require further surgery within two years of UAE.The evidence suggested that women in the UAE group were less likely to require a blood transfusion than women receiving surgery (OR 0.07; 95% CI 0.01 to 0.52, 2 trials, 277 women, I(2) = 0%). UAE was also associated with a shorter procedural time (two studies), shorter length of hospital stay (seven studies) and faster resumption of usual activities (six studies) in all studies that measured these outcomes; however, most of these data could not be pooled due to heterogeneity between the studies.The quality of the evidence varied, and was very low for live birth, moderate for satisfaction ratings, and moderate for most safety outcomes. The main limitations in the evidence were serious imprecision due to wide confidence intervals, failure to clearly report methods, and lack of blinding for subjective outcomes. AUTHORS' CONCLUSIONS: When we compared patient satisfaction rates at up to two years following UAE versus surgery (myomectomy or hysterectomy) our findings are that there is no evidence of a difference between the interventions. Findings at five year follow-up were similarly inconclusive. There was very low quality evidence to suggest that myomectomy may be associated with better fertility outcomes than UAE, but this information was only available from a selected subgroup in one small trial.We found no clear evidence of a difference between UAE and surgery in the risk of major complications, but UAE was associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. If we assume that 7% of women will require further surgery within two years of hysterectomy or myomectomy, between 15% and 32% will require further surgery within two years of UAE. This increase in the surgical re-intervention rate may balance out any initial cost advantage of UAE. Thus although UAE is a safe, minimally invasive alternative to surgery, patient selection and counselling are paramount due to the much higher risk of requiring further surgical intervention.

Prevention of diseases after menopause.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Femoral nerve block for pain relief in hip fracture: a dose finding study.

Hip fracture is the most common orthopaedic emergency. We investigated the concentration of 30 ml levobupivacaine that provided analgesia to 50% and 95% of patients with a hip fracture when injected around the femoral nerve under ultrasound guidance. We defined analgesia as a ≥ 20-point decrease on a 100-point pain scale with reduced cold sensation in the middle third of the anterior thigh 30 min after the nerve block. We increased the concentration of levobupivacaine if the preceding dose had been ineffective and decreased it if the preceding dose had been effective. Probit regression modelling estimated the effective (95% CI) concentration of 30 ml levobupivacaine in 50% and 95% of patients with a fractured hip to be 0.026 (0.023-0.028)% w/v and 0.036 (0.027-0.047)% w/v, respectively.

Non-hormonal management of vasomotor symptoms.

Vasomotor symptoms are the most common indication for the prescription of hormone replacement therapy since it is effective in over 80% of cases. In 1995, 37% of American women took hormone replacement therapy, principally for this purpose. However, following the publication of results from the Women's Health Initiative, as many as half of these women in the US and in the UK and New Zealand discontinued hormone therapy. Discontinuation of estrogen is often accompanied by a return of vasomotor symptoms; however, only a small number (18%) of women report restarting hormone therapy. Alternatives are available, but limited knowledge on etiology and mechanisms of hot flushing represents a major obstacle for the development of new, targeted, non-hormonal treatments, and no current alternatives are as effective as estrogen.

Uterine artery embolization for symptomatic uterine fibroids.

BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization (UAE) has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence based on case controlled studies and case reports. This is an update of the review previously published in 2006. OBJECTIVES: To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched the Cochrane Menstrual Disorders & Subfertility Group Trials register (searched November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, 4th Quarter 2011), MEDLINE (1950 to November 2011) and EMBASE (January 1980 to November 2011). We also contacted authors of eligible RCTs for unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) assessed the trials and extracted the data independently. MAIN RESULTS: Five RCTs were included in this review. Three trials compared UAE with abdominal hysterectomy in 291 women. A fourth trial included 157 women and compared UAE with surgery (43 hysterectomies and 8 myomectomies). The fifth trial included 121 women and compared UAE with myomectomy in women wishing to preserve fertility.There was moderately good evidence that there is no significant difference between UAE and surgery in patient satisfaction rates at two years (OR 0.69, 0.40 to 1.21, 516 women, 5 trials) nor at five years (OR 0.90, 95% CI 0.45 to 1.80, 295 women, 2 trials). There was very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but this analysis was restricted to the limited cohort of women (n=66) who tried to conceive in the single study of UAE versus myomectomy (live birth: OR 0.33, 95% CI 0.11 to 1.00; pregnancy: OR 0.29, 95% CI 0.10 to 0.85). There was no significant difference between the two interventions in the rate of major complications. Compared to surgery, UAE significantly reduced the length of the procedure, length of hospital stay and time to resumption of routine activities and also decreased the likelihood of needing a blood transfusion. However, UAE was associated with higher rates of minor short term and long term complications, more unscheduled readmissions after discharge and an increased surgical reintervention rate. This increase in the surgical reintervention rate may balance out the initial cost advantage of UAE (reinterventions within 2 years: OR 5.64, 95% CI 2.92 to 10.90, 486 women, 4 trials; within 5 years: OR 5.79, 95% CI 2.65 to 12.65. 289 women, 2 trials). There was no significant difference in ovarian failure rates at long term follow-up. AUTHORS' CONCLUSIONS: UAE appears to have an overall patient satisfaction rate similar to hysterectomy and myomectomy and offers an advantage with regards to a shorter hospital stay and a quicker return to routine activities. However, UAE is associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. There is very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but more research is needed.

Hot flushes, vascular reactivity and the role of the α-adrenergic system.

ABSTRACT Background Seventy percent of postmenopausal women suffer from hot flushes but the pathophysiology is poorly understood. Proposed mechanisms include altered peripheral vascular reactivity and a narrowed thermoneutral zone. A trigger has not yet been identified; however, the α-adrenergic system, and specifically noradrenaline, has been implicated. Aim To assess the role of the α-adrenergic system by studying the effect of clonidine (α-adrenergic agonist) on flushes and cutaneous microvascular perfusion. Methods Thirty-two postmenopausal women with severe flushing and 14 non-flushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine (ACh - endothelium-dependent) and sodium nitroprusside (SNP - endothelium-independent). In a double-blind, longitudinal, cross-over study, clonidine (an α-adrenergic agonist) was compared to placebo in its ability to modulate this response in the flushing group of women. Results The response of the subcutaneous vessels was greater in women who flushed than those who did not (ACh, p < 0.001 and SNP, p = 0.001). However, even though the intensity and number of flushes were decreased by clonidine, there was no difference compared to placebo (p = 0.21) and this 'placebo effect' was also noted in perfusion responses (ACh, p = 0.98; SNP, p = 0.50). Conclusion There was a significant 'placebo effect' for both clinical response and the reactivity of the subcutaneous vessels, making conclusions regarding the role of the α-adrenergic nervous system in hot flushing difficult to determine at a peripheral level. The mechanism for the change in vascular reactivity remains unclear.

Understanding weight gain at menopause.

OBJECTIVE: The aim of this review was to summarize the literature regarding the impact of the menopause transition on body weight and body composition. METHODS: We conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2012) for English-language studies that included the following search terms: 'menopause', 'midlife', 'hormone therapy' or 'estrogen' combined with 'obesity', 'body weight' or 'body composition'. RESULTS: Whereas weight gain per se cannot be attributed to the menopause transition, the change in the hormonal milieu at menopause is associated with an increase in total body fat and an increase in abdominal fat. Weight excess at midlife is not only associated with a heightened risk of cardiovascular and metabolic disease, but also impacts adversely on health-related quality of life and sexual function. Animal and human studies indicate that this tendency towards central abdominal fat accumulation is ameliorated by estrogen therapy. Studies mostly indicate a reduction in overall fat mass with estrogen and estrogen-progestin therapy, improved insulin sensitivity and a lower rate of development of type 2 diabetes. CONCLUSION: The hormonal changes across the perimenopause substantially contribute to increased abdominal obesity which leads to additional physical and psychological morbidity. There is strong evidence that estrogen therapy may partly prevent this menopause-related change in body composition and the associated metabolic sequelae. However, further studies are required to identify the women most likely to gain metabolic benefit from menopausal hormone therapy in order to develop evidence-based clinical recommendations.

Vascular function and cardiovascular risk factors in women with severe flushing.

BACKGROUND: Seventy per cent of postmenopausal women suffer from hot flushes causing significant morbidity in 25%. Oestrogen replacement provides symptom relief, but its use has declined following safety issues and there is, as yet, no good alternative. Pathophysiology is poorly understood, but one proposed mechanism is altered peripheral vascular reactivity. It has recently been suggested that the presence of flushing may be a marker of underlying cardiovascular risk. AIM: To measure (i) peripheral vascular reactivity in subcutaneous vessels (ii) routine and novel cardiovascular risk factors in postmenopausal women who flush, and compare results to a matched group of women who do not flush. METHODS: Thirty-two postmenopausal women with at least 20 flushes/week and 14 nonflushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging, and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine [Ach] (endothelial-dependent) and sodium nitroprusside [SNP] (endothelial independent). Blood samples for risk factors were taken following vascular assessment. RESULTS: Both study groups were well matched demographically. The response of the subcutaneous vessels was greater in women who flushed than those who did not, following administration of both the endothelium-dependent and independent vasodilators, (ACh, P ≤ 0·001, SNP, P = 0·001, 2-way anova). By contrast, levels of High Density Lipoprotein (HDL)-cholesterol and ApoA1 were significantly lower in the flushing women compared with the control women (P = 0·02 and 0·002, respectively), and levels of inter-cellular adhesion molecule-1 (ICAM-1) were higher (P = 0·03), findings robust to adjustment for confounders, suggesting an adverse cardiovascular risk profile. CONCLUSION: These results confirm a better vascular response in women but paradoxically, such women appear to have worse (not better) cardiovascular disease risk factors in particular lower HDL-cholesterol but also higher non-HDL-c to HDL-c ratio and increased ICAM-1. Further studies are needed to assess vascular risk factors in women who flush.

Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results.

OBJECTIVE: To compare the long-term results of uterine artery embolisation (UAE) with surgery for women with symptomatic uterine fibroids. DESIGN: Pragmatic, open, multicentre, randomised trial. SETTING: Twenty-seven participating UK secondary care centres. SAMPLE: Women aged ≥18 years with symptomatic fibroids who were considered to justify surgical treatment. METHODS: In total, 157 women were randomised (in a 2:1 ratio): 106 to UAE and 51 to surgery (hysterectomy 42; myomectomy nine). MAIN OUTCOME MEASURES: Quality of life at 5 years, as assessed by the Short Form General Health Survey (SF-36). Secondary measures included complications, adverse events and the need for further intervention. RESULTS: There were no significant differences between groups in any of the eight components of the SF-36 scores at 5 years (minimum P = 0.45). Symptom score reduction and patient satisfaction with either treatment was very high, with no group difference. Rates of adverse events were similar in both groups (19% embolization and 25% surgery; P = 0.40). The 5-year intervention rate for treatment failure or complications was 32% (UAE arm) and 4% (surgery arm), respectively. The initial cost benefit of UAE over surgery at 12 months was substantially reduced because of subsequent interventions, with treatments being cost neutral at 5 years. CONCLUSIONS: We have found that UAE is a satisfactory alternative to surgery for fibroids. The less invasive nature of UAE needs to be balanced against the need for re-intervention in almost a third of patients. The choice should lie with the informed patient.

Menopausal hot flushes and night sweats: where are we now?

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.