Moderate iodine deficiency among pregnant women in Hong Kong: revisit the problem after two decades.

INTRODUCTION: A survey conducted during 2005 to 2007 by the Centre for Food Safety in Hong Kong suggested that only 5% of the local population had a sufficient dietary intake of iodine. The study, however, was limited as biochemical data (ie urinary iodine concentration) were lacking. Pregnant women are vulnerable to iodine deficiency because of their increased requirement. Recent studies have shown that iodine deficiency in early pregnancy is associated with poorer cognitive development in early childhood. This study reports the iodine status of women during early gestation at an obstetric unit in Hong Kong. METHODS: Healthy pregnant women with no history of hyperemesis gravidarum were enrolled into a study when they first made a booking in an antenatal clinic of a public hospital to investigate their iodine status during early pregnancy. All subjects were asked to collect their morning urine for measurement of iodine and creatinine levels. Daily dietary intake of iodine was assessed in a subgroup of participants by structured interview using a standard food frequency questionnaire. RESULTS: A total of 600 pregnant women were enrolled at a median of 7.0 weeks of gestation. The median urinary iodine concentration and urinary iodine-to-creatinine ratio were 100 µg/L and 98 µg/g, respectively; 429 (71.5%) participants had iodine insufficiency according to the World Health Organization classification. Daily dietary intake of iodine was assessed in 146 participants. The median daily intake of iodine was 69.5 µg and 122 (83.6%) participants had an intake below the 250 µg recommended during pregnancy by the World Health Organization. CONCLUSIONS: Local pregnant women continue to have an inadequate dietary intake of iodine and remain iodine-deficient.

Non-linear relationship between birthweight and cardiometabolic risk factors in Chinese adolescents and adults.

AIM: To investigate the relationship between birthweight and cardiometabolic traits in two cohorts: one of Chinese adolescents and one of Chinese adults. METHODS: Birthweight and clinical data, including anthropometric traits, fasting plasma glucose and fasting plasma insulin levels, blood pressure and lipid profiles were collected from 2035 adolescents and 456 adults. A subset of 735 subjects underwent an oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents, birthweight showed U-shaped relationships with larger body size, obesity, abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 < P(quadratic) < 0.0499), as well as an inverse association with fasting plasma glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing birthweight was associated with elevated fasting plasma glucose levels, greater insulin resistance and worse lipid profiles (3.1 × 10⁻5 < P(linear) < 0.0058). Among adults, high birthweight was associated with larger body size and abdominal obesity in men, while low birthweight was associated with elevated glucose levels at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as well as with ß-cell dysfunction (6.5 × 10⁻5 < P(linear) < 0.0437). Adjustment for adult adiposity did not substantially change the relationships. There was significant interaction between birthweight and abdominal obesity in elevating fasting plasma insulin and homeostasis model assessment of insulin resistance (P > 0.05), with abdominally obese adolescents in the lowest birthweight category (≤ 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high and low birthweights are associated with an increased risk of cardiometabolic abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia and insulin resistance, as well as with ß-cell dysfunction.

Diabetes and pregnancy: perspectives from Asia.

There has been a marked increase in the prevalence of diabetes in Asia over recent years. Diabetes complicating pregnancy, in particular gestational diabetes, has also increased markedly in the region. Multi-ethnic studies have highlighted the increased risk of gestational diabetes mellitus among the different Asian populations. Prevalence of gestational diabetes in Asian countries varies substantially according to the screening strategy and diagnostic criteria applied, and ranges from 1% to 20%, with evidence of an increasing trend over recent years. The International Association for Diabetes in Pregnancy Study group criteria have been adopted by some Asian countries, although they present significant challenges in implementation, especially in low-resource settings. Studies on offspring of mothers with gestational diabetes have reported adverse cardiometabolic profiles and increased risk of diabetes and obesity. Gestational diabetes is likely to be a significant factor contributing to the epidemic of diabetes and other non-communicable diseases in the Asian region. In recognition of this, several large-scale prevention and intervention programmes are currently being implemented in different Asian countries in order to improve glucose control during pregnancy, as well as overall maternal health. Lessons emerging from gestational diabetes studies in Asia may help inform and provide insights on the overall burden and treatment strategies to target gestational diabetes, with the ultimate aim to reduce its adverse short- and long-term consequences.

The associations of pre-pregnancy BMI and gestational weight gain with maternal gut microbiota.

Previous studies reporting the association between gut microbiota dysbiosis and maternal obesity were mostly confined at the phylum level or at postpartum period. This study aimed to investigate the dynamic changes in gut microbial communities associated with maternal obesity at different time points of pregnancy. We performed 16S rRNA gene V3-V4 amplicon sequencing on stool samples from 110 women in all three trimesters and 1-month postpartum. Maternal gut microbial communities associated with maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) were explored. The influence of maternal obesity on gut microbiota trajectories was determined based on longitudinal shifts in community clusters across the trimesters. The richness index of alpha diversity decreased with the progression of pregnancy, particularly in women with excessive GWG. The evenness index in 2nd trimester was found inversely associated with GWG. Various taxonomic differences in 1st trimester were associated with excessive GWG, whereas limited taxonomic differences in 2nd and 3rd trimesters were associated with pre-pregnancy BMI or GWG. Meanwhile, the gut microbiota trajectory with especially depleted genus Faecalibacterium in 1st trimester was associated with excessive GWG (adjusted odds ratio 5.7, 95% confidence interval 1.2-28.1). Moreover, the longitudinal abundances of genus Lachnospiraceae ND3007 group across gestations were depleted in women with overweight/obese pre-pregnancy BMI, while genus Bifidobacterium enriched in women with excessive GWG. Our study shows that dysbiosis of the gut microbiota in early pregnancy may have a significant impact on excess GWG. The abundance of the genus Faecalibacterium in 1st trimester may be a potential risk factor. Clinical trial number: NCT03785093 (https://classic.clinicaltrials.gov/ct2/show/NCT03785093).

The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Effects of different inspired oxygen fractions on lipid peroxidation during general anaesthesia for elective Caesarean section.

BACKGROUND: During general anaesthesia (GA) for Caesarean section (CS), fetal oxygenation is increased by administering an inspired oxygen fraction (Fi(o(2))) of 1.0. However, it is unclear whether such high Fi(o(2)) will increase oxygen free radical activity. METHODS: We randomized 39 ASA I-II parturients undergoing elective CS under GA to receive 30% (Gp 30), 50% (Gp 50), or 100% (Gp 100) oxygen with nitrous oxide and sevoflurane adjusted to provide equivalent minimum alveolar concentration. Baseline maternal arterial blood before preoxygenation and maternal arterial, umbilical arterial and venous blood at delivery were sampled for assays of the by-product of lipid peroxidation, isoprostane, and for measurement of blood gases and oxygen content. RESULTS: Maternal and umbilical isoprostane concentrations were similar among the three groups at delivery, despite significantly increased maternal and fetal oxygenation in Gp 100. However, paired comparisons of maternal delivery vs baseline concentration of isoprostane showed an increase at delivery for all groups [Gp 30: mean 342 (sd 210) vs 154 (65) pg ml(-1), P=0.016; Gp 50: 284 (129) vs 156 (79) pg ml(-1), P=0.009; Gp 100: 332 (126) vs 158 (68) pg ml(-1), P<0.001]. The magnitude of increase was similar in all three groups and independent of the Fi(o(2)) or duration after induction. CONCLUSIONS: GA for CS is associated with a marked increase in free radical activity in the mother and baby. The mechanism is unclear but it is independent of the inspired oxygen in the anaesthetic mixture. Therefore, when 100% oxygen is administered with sevoflurane for GA, fetal oxygenation can be increased, without inducing an increase in lipid peroxidation.

Supplementary oxygen for emergency Caesarean section under regional anaesthesia.

BACKGROUND: Controversy still exists if the administration of supplementary oxygen to patients having emergency Caesarean section (CS) under regional anaesthesia is beneficial or potentially harmful. Therefore, in a prospective double-blinded study, we randomized patients having emergency CS under regional anaesthesia to receive either air or 60% oxygen until delivery and compared the effects on fetal oxygenation and lipid-peroxidation in the mother and baby. METHODS: We recruited 131 women having emergency CS under regional anaesthesia. Either 21% (air group) or 60% oxygen (oxygen group) was administered using a Venturi-type facemask until delivery. We compared the oxygen exposure duration, umbilical arterial (UA) and venous (UV) blood gases and oxygen content, and plasma concentration of 8-isoprostane. Subanalysis was performed according to whether or not fetal compromise was considered present. RESULTS: Data from 125 patients were analysed. For the oxygen group vs the air group, there were greater values for UA PO(2) [mean 2.2 (SD 0.5) vs 1.9 (0.6) kPa, P=0.01], UA O(2) content [6.6 (2.5) vs 4.9 (2.8) ml dl(-1), P=0.006], UV PO(2) [3.8 (0.8) vs 3.2 (0.8) kPa, P<0.0001], and UV O(2) content [12.9 (3.5) vs 10.4 (3.8) ml dl(-1), P=0.001]. There was no difference between the groups in maternal, UA, or UV 8-isoprostane concentration. Apgar scores and UA pH were similar between the groups. Similar changes were observed regardless of whether fetal compromise was considered present (n=37) or not (n=88). CONCLUSIONS: Breathing 60% oxygen during emergency CS under regional anaesthesia increased fetal oxygenation with no associated increase in lipid-peroxidation in the mother or fetus.

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women.

OBJECTIVE: To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. POPULATION: One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. METHODS: Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen. MAIN OUTCOME MEASURES: De novo endometrial pathology at 1 year of tamoxifen. RESULTS: Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year. CONCLUSION: LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.

Developmental origins of type 2 diabetes: a perspective from China.

There has been a marked increase in the prevalence of diabetes in Asia, including China, over the last few decades. While the increased prevalence of diabetes has often been attributed to the nutritional transition associated with recent economic development, emerging data suggest that early-life exposures also play a major role in shaping developmental trajectories, and contributes to alter an individual's susceptibility to diabetes and other non-communicable diseases (NCDs). Early-life exposures such as in utero exposure to undernutrition has been consistently linked with later risk of diabetes and obesity. Furthermore, in utero exposure to maternal hyperglycemia, maternal obesity and excess gestational weight gain are all linked with increased childhood obesity and later risk of diabetes. Emerging data have also highlighted the potential link between early-feeding practices, the role of one-carbon metabolism in metabolic programming and endocrine disrupting chemicals (EDCs) with later risk of diabetes. These different developmental exposures may all be highly relevant to the current epidemic of diabetes in China. For example, the prevalence of gestational diabetes has increased markedly over the last two decades, and may contribute to the diabetes epidemic by driving macrosomia, childhood obesity and later risk of diabetes. In order to address the current burden of diabetes, a lifecourse perspective, incorporating multisectoral efforts from public health policy down to the individuals, will be needed. Several major initiatives have been launched in China as part of its national plans for NCD prevention and treatment, and the experience from these efforts would be invaluable.

Steroid synthesis in vitro by the placenta of the guinea-pig, and progesterone concentrations in systemic and uterine plasma.

The spongy zone (SZ) syncytiotrophoblast has been identified as the prinicipal site of progesterone synthesis in the placenta of the guinea-pig. This was evident from the relatively large amounts of progesterone synthesized by the SZ from [7alpha-3H]pregnenolone and the exact correlation of SZ development and the estimated progesterone secretory activity of the placenta throughout gestation. Placental progesterone secretion started between days 20--25 of gestation when the SZ was being formed. Progesterone secretion rose to a maximum by day 30 and was maintained until at least day 53, reflecting the large amount of SZ tissue present in the placenta during this period. Secretory activity decreased simultaneously with decrease in SZ tissue, even though a decrease in progesterone concentration in systemic plasma was not evident. The results also suggested that the yolk sac was able to synthesize progesterone and metabolize steroids in vitro. Small quantities of 5-saturated C21 steroids were also synthesized by the placenta.

Metabolism of androgens by the active and inactive prostate gland, and the seasonal changes in systemic androgen levels in the grey squirrel (Sciurus carolinensis Gmelin).

The nuclear and cytoplasmic fractions derived from the actively secretory and inactive prostate of adult grey squirrels were incubated with radioactive testosterone and androstenedione. Testosterone was metabolized first to 5 alpha-dihydrotestosterone and then 5 alpha-androstane-3 alpha(beta), 17 beta-diols. Testosterone could also be transformed into androstenedione and then to androsterone, but no 5 alpha-dihydrotestosterone or diols could be synthesized from this pathway. Neither subcellular fraction of the inactive, non-secretory prostate could produce 5 alpha-androstane-3 alpha(beta), 17 beta-diols from testosterone either in the absence or presence of exogenous NADPH. The synthesis of androstenedione and 5 alpha-dihydrotestosterone by the nuclear and cytoplasmic fractions of the inactive gland were significantly increased compared to that in fractions of the active prostate. The increase was unaffected by exogenous NADPH. The concentration of androgen (testosterone plus 5 alpha-dihydrotestosterone) in systemic plasma was highest in December, the beginning of the breeding season. For the remainder of the breeding season, the androgen level was similar to that found in the non-breeding season. It is suggested that formation of 5 alpha-androstane-3 alpha(beta), 17 beta-diols was associated with the secretory activity of the prostate. The failure of the inactive prostate to synthesize these diols during sexual quiescence might be a means of ensuring the inactivity of the prostate.

Venous thromboembolism in pregnant Chinese women.

OBJECTIVE: To evaluate the incidence, disease pattern, and risk factors for thromboembolism in pregnant Chinese women. METHODS: We conducted a study from January 1998 to December 2000. Women with thromboembolic diseases were identified and their case records retrieved and reviewed. Demographic characteristics were compared between women with and without thromboembolism. RESULTS: Thirty-two women were diagnosed as having thromboembolic disease during the study period. The total number of deliveries over the study period was 16,993, giving an incidence of 1.88 per 1000 deliveries. There were two cases of pulmonary embolism and one resulted in a maternal death. The others had deep vein thrombosis of which over 80% were limited to calf veins only. The ultrasound examinations requested for suspected deep venous thrombosis before and after the event of maternal death were 1.62 and 10.7 per 1000 deliveries (P <.001); and the corresponding cases of deep venous thrombosis diagnosed were 0.29 and 2.94 per 1000 deliveries, respectively (P <.001). The majority (75%) of cases were diagnosed in the postpartum period, mainly after cesarean delivery. Women with venous thromboembolism were older, had higher body mass index, and a higher incidence of preeclampsia. CONCLUSION: Thromboembolic disease is not uncommon among pregnant Chinese women. The incidence was similar to that of the white population, although the sites of vascular occlusion were different. The long-standing belief that thromboembolism is rare among Chinese is at least partly because of underdiagnosis.

The incidence of pregnancy-induced hypertension among patients with carbohydrate intolerance.

OBJECTIVE: To determine the association between pregnancy-induced hypertension (PIH) and carbohydrate intolerance in pregnancy. METHODS: Data on singleton pregnancies were retrieved from the obstetric database of University Hospital, Kuala Lumpur. Gestational impaired glucose tolerance (GIGT) and gestational diabetes mellitus (GDM) were defined according to the World Health Organization criteria. Established diabetes mellitus (EDM) was defined as diabetes mellitus diagnosed prior to pregnancy. PIH was diagnosed according to the criteria of the International Society for the Study of Hypertension in Pregnancy. Maternal characteristics were compared between groups using analysis of variance (ANOVA) and incidence counts using the chi-squared test. Logistic regression analysis using the presence of PIH as the response variable was used to study the association among GDM, GIGT, EDM, and PIH, controlling for maternal factors. MAIN OUTCOME MEASURES: To determine the incidence of PIH among patients with glucose intolerance and the independent risk factors for the development of PIH. RESULTS: There were 24,290 singleton pregnancies retrieved from the database. Both the prevalence of carbohydrate intolerance and the incidence of PIH differed among the three principal ethnic groups (p < 0.0001). There was a significant association between PIH and both a higher maternal age (OR = 1.04, p < 0.0001) and a higher maternal body mass index (BMI) at delivery (OR = 1.14 per unit increment, p < 0.0001). After adjusting for maternal age, BMI, parity, and ethnic origin, using logistic regression, there was a significant residual risk of PIH among individuals with GIGT, GDM, or EDM. CONCLUSIONS: Patients with carbohydrate intolerance of varying severity are at increased risk of developing PIH. Our findings lend credence to the theory that carbohydrate intolerance and PIH share a common etiology.

PP103. Arterial stiffness in women with previous GDM - A follow up of Chinese HAPO study cohort.

INTRODUCTION: It is well known that women with history of gestational diabetes (GDM) are at risk of future DM. Whether they are at a higher risk of hypertension and cardiovascular risk remained to be determined. OBJECTIVES: To determine whether Chinese women who have been diagnosed GDM according to the new IADPSG criteria have a higher risk of hypertension & arterial stiffness than women with normal glucose tolerance (NGT) during pregnancy. METHODS: Chinese women who had participated in the HAPO study between 2001 and 2006 in Hong Kong were followed up at a median of 6years postpartum. All underwent anthropometric & BP measurements. Central systolic and diastolic blood pressures (SBP & DBP), augmentation index (AI) and pulse wave velocity (PWV) were assessed by using SphygmoCor(®) PVx.A total of 608 women (494 NGT, 114 GDM) were followed up till early 2012. RESULTS: Although there was no significant difference in the rate of hypertension, the central SBP (106±12 vs 102±13mmHg, p=0.03), AI (22.1±8.3 vs 18.9±8.5%, p<0.001) and PWV (6.8±1.0 vs 6.6±0.8, p=0.03) were all higher in women with history of GDM. CONCLUSION: The findings suggest a higher risk of subclinical atherosclerosis amongst women with GDM despite the blood pressure may appear normal at the time of follow up.

HPV vaccination in Hong Kong: implications for medical education.

OBJECTIVE: To explore the experience and attitudes of physicians in clinics, and to facilitate physicians' promotion of HPV vaccination. DATA SOURCES: Primary data collected from conducting semi-structural in-depth interviews from May to June 2010 with 12 physicians in one district in Hong Kong to understand their experience of providing HPV vaccines, the difficulties in promoting HPV vaccines, and their attitudes towards HPV vaccination. STUDY DESIGN: Physicians identified 4 categories of factors related to their experiences of and attitudes to providing HPV vaccination: (a) background information on HPV vaccination provided by physicians, (b) factors influencing women to receive vaccination, (c) physicians' recommendations to the public on HPV vaccines, and (d) physicians' perspectives on HPV vaccine promotion. CONCLUSIONS: Our findings show that public knowledge on HPV and cervical cancer is insufficient and the role of government in vaccine promotion is unclear. Promotion strategies such as physicians' recommendation, financial assistance and health education provided by the government will influence HPV vaccination and its promotion.

Sonographic measurement of mesenteric fat predicts presence of fatty liver among subjects with polycystic ovary syndrome.

OBJECTIVE: Visceral fat is believed to be important in the pathogenesis of metabolic syndrome and fatty liver. In this study, we examined the relationship between mesenteric fat thickness and other sonographic indices of adiposity and the presence of fatty liver among subjects with polycystic ovary syndrome (PCOS). SUBJECTS AND METHODS: A total of 117 Chinese subjects with PCOS were evaluated (mean age, 28.6 ± 6.5 yr; mean body mass index, 24.3 ± 5.3 kg/m(2)). Anthropometric measurements and metabolic risk profile, including a standard oral glucose tolerance test, were assessed in all subjects. All subjects underwent an ultrasound examination for measurement of thickness of mesenteric, preperitoneal, and sc fat as well as evaluation for fatty liver. RESULTS: Forty-six (39.3%) of the subjects had fatty liver. PCOS subjects with fatty liver had higher body mass index, waist circumference, waist-hip ratio, and systolic blood pressure; a more unfavorable lipid profile with higher triglyceride; lower high-density lipoprotein cholesterol; higher fasting glucose and insulin; higher 2-h glucose during oral glucose tolerance test; lower SHBG; and higher alanine aminotransferase. Subjects with fatty liver had increased thickness of preperitoneal, mesenteric, and sc fat, as well as increased carotid intima-media thickness. Abdominal fat thickness showed moderate correlation to alanine aminotransferase as well as fasting insulin. On multivariate logistic regression, fasting insulin and mesenteric fat thickness were identified as independent predictors of fatty liver among subjects with PCOS. CONCLUSION: Fatty liver is present in a significant proportion of Chinese patients with PCOS. Sonographic measurement of mesenteric fat is an independent determinant of fatty liver among subjects with PCOS and identifies subjects at increased cardiovascular risk.

Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.