title: Population-based cohort study of injuries. The pilot study. A longitudinal study of the effect of subcutaneous estrogen replacement on bone in young women with Turner's syndrome. Insulin resistance and body composition in Turner syndrome: Effect of sequential change in the route of estrogen administration Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone Decreased bone mass despite long-term estrogen replacement therapy in young women with Turner's syndrome and previously normal bone density. A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism Comparison of Transdermal and Oral Estrogen Therapy in Girls with Turner's Syndrome Androgen replacement therapy in Turner syndrome: a pilot study. Choosing an oestrogen replacement therapy in young adult women with Turner syndrome* Growth hormone and 17 beta-oestradiol treatment of Turner girls--2-year results. Nonoptimal Lipids Commonly Present in Young Adults and Coronary Calcium Later in Life: The CARDIA (Coronary Artery Risk Development in Young Adults) Study Estrogen Deficiency in Adolescents and Young Adults: Impact on Bone Mineral Content and Effects of Estrogen Replacement Therapy [The effect of primary lack of estrogens and the influence of the age at the beginning of estrogen therapy on bone mineral density in patients with Turner's syndrome]. Mortality ratios, life expectancy, and causes of death in patients with Turner's syndrome.
abstract: A population -based cohort study was done to estimate the incidence of different types of injuries and to evaluate certain risk factors in an urban slum ; 4333 slum dwellers in Madras city in India were r and omly selected by cluster sampling  , of whom 1.7 per cent were lost during the 12 months of follow up . The cumulative injury incidence for 12 months for all injuries was 127 per 1000 persons ( 95 per cent confidence interval 117 - 137 ) ; for males 137 per 1000 and for females 118 per 1000 . Incidence of unintentional injury was 121 per 1000 persons . The incidence for road traffic injury was 16 per 1000 persons , for household injuries 57 per 1000 persons and for injury at place of work 19 per 1000 persons . The relative risk of males to females for traffic injuries was 3.04 and for household injuries was 0.39 . The relative risk of traffic injuries among adult males who reported daily alcohol consumption was 2.26 . The incidence of injury is high in an urban slum and it is a priority health problem . This study has identified groups of people who are at high risk for injuries and who may need specific protective measures This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer It is desirable that young women with primary ovarian failure achieve normal peak bone mass to reduce the subsequent risk of osteoporosis , and that there are management strategies to replace bone that is already lost . While estrogen ( E2 ) is generally considered to prevent bone loss by suppressing bone resorption , it is now recognized that estrogen also exerts an anabolic effect on the human skeleton . In this study , we tested whether estrogen could increase bone mass in women with primary ovarian failure . We studied the mechanism underlying this by analyzing biochemical markers of bone turnover and iliac crest biopsy specimens obtained before and 3 years after E2 replacement .  Twenty-one women with Turner 's syndrome , aged 20 - 40 years , were studied . The T scores of bone mineral density at lumbar spine and proximal femur at baseline were -1.4 and -1.1 , respectively . Hormone replacement was given as subcutaneous E2 implants ( 50 mg every 6 months ) with oral medroxy progesterone .  Serum E2 levels increased incrementally from 87.5 pM at baseline to 323 , 506 , 647 , and 713 pM after 6 months and 1 , 2 , and 3 years of hormone replacement therapy ( HRT ) , respectively . The bone mineral density at the lumbar spine and proximal femur increased after 3 years to T scores of -0.2 and -0.4 , respectively . The cancellous bone volume increased significantly from 13.4 % to 18.8 % . There was a decrease in activation frequency , but the active formation period was increased by HRT . There was a significant increase in the wall thickness from 33.4 microm at baseline to 40.9 microm after 3 years of HRT , reflecting an increase in bone formed at individual remodeling units . Although there was an early increase in biochemical markers of bone formation , these declined thereafter . Our results show that estrogen is capable of exerting an anabolic effect in the skeleton of young women with Turner 's syndrome and low bone mass The aim of the present study was to examine the impact of sequential change in the route of estrogen administration on body composition and insulin resistance in patients with Turner syndrome ( TS ) using  cyclical hormone replacement therapy ( HRT ) with conjugated equine estrogens ( CEE ) plus medroxyprogesterone acetate ( MPA ) . We carried out a self-controlled study of nine non-obese patients with TS , with an average age of 23 ± 4.9 years .  Body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , fasting glycemia , insulin tolerance ( glucose disappearance constant during an insulin tolerance test , kITT ) and body composition ( dual-energy X-ray absorptiometry ) were studied after 1 year 's use of CEE plus MPA and repeated after 1 year 's use of 17β-estradiol gel with the same schedule of MPA administration . We did not observe any difference between the oral and percutaneous HRT with regard to BMI , WHR and insulin tolerance ( kITT : 4.9 ± 1.5 vs. 5.3 ± 1.5%/min , p = 0.8 ) . During administration of the 17β-estradiol gel a tendency to increased total lean mass ( p = 0.054 ) was observed . We conclude that sequential change in the route of estrogen administration in TS patients using cyclical HRT with CEE and MPA does not affect insulin resistance , although use of percutaneous 17β-estradiol gel seems to exert favorable changes in body composition Background There are limited long-term r and omized controlled trials of growth hormone ( GH ) supplementation to adult height and few published reports of the health-related quality of life ( HRQOL ) following treatment . The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome ( TS ) yielded data to examine whether GH supplementation result ed in a higher HRQOL ( either due to taller stature or from the knowledge that active treatment and not placebo had been received ) or alternatively a lower HRQOL ( due to medicalization from years of injections ) . Methods The original trial r and omized 154 Canadian girls with TS aged 7 - 13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections ; estrogen prescription for induction of puberty was st and ardized . Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up . The instrument used to study HRQOL was the SF-36 , summarized into physical and mental component scales ( PCS and MCS ) ; higher scores indicate better HRQOL . Results Thirty-four of the 48 eligible participants ( 71 % ) consented to participate ; data were missing for one patient . Both groups ( GH and no treatment ) had normal HRQOL at this post-treatment assessment . The GH group had a ( mean ± SD ) PCS score of 56 ± 5 ; the untreated group 58 ± 4 ; mean score for 16 - 24 year old females in the general population 53.5 ± 6.9 . The GH group had a mean MCS score of 52 ± 6 ; the untreated group 49 ± 13 ; mean score for 16 - 24 year old females in the general population 49.6 ± 9.8 . Secondary analyses showed no relationship between HRQOL and height . Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term r and omized controlled trial , confirming larger observational studies . We suggest that it remains ethically acceptable as well as necessary to maintain a long-term untreated control group to estimate the effects of pharmacological agents to manipulate adult height . Young adult women with TS have normal HRQOL suggesting that they adjust well to their challenges in life . Trial Registration Clinical Trials.gov Identifier NCT00191113 OBJECTIVE To determine whether young women with Turner 's syndrome who had normal bone mineral density ( BMD ) before the induction of puberty maintain normal BMD in young adulthood . DESIGN Controlled clinical study . SETTING A private hospital clinical research setting . PATIENTS Young women with Turner 's syndrome in Tanner stage V of puberty with previously normal BMD . INTERVENTIONS Oral conjugated estrogens and progesterone acetate were administered continuously for a mean ( + /-SD ) of 4.1+/-1.0 years . Bone mineral densities and blood sample s were evaluated . MAIN OUTCOME MEASURE(S ) The BMD of the lumbar spine and the femoral neck was determined during young adulthood . The change in BMD over the previous 6 years also was evaluated . Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured . RESULT ( S ) The BMD of the lumbar spine was reduced significantly in our patients . There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years . Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased , whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased . CONCLUSION ( S ) Young women with Turner 's syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence . Their low BMD seems to be due to decreased bone formation and increased bone resorption Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects . Currently , health care providers have varying practice s without evidence -based st and ards , thus investigating potential differences between oral and transdermal preparations is essential . The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen ( OCEE ) , oral 17β estradiol ( OBE ) , or transdermal 17β estradiol ( TBE ) on biochemical profiles and feminization in girls with ovarian failure . Study design 20 prepubertal adolescent females with ovarian failure , ages 12–18 years , were r and omized to OCEE ( n = 8) , OBE ( n = 7 ) , or TBE ( n = 5 ) for 24 months .  Estrogen replacement was initiated at a low dose ( 0.15 mg OCEE , 0.25 mg OBE , or 0.0125 mg TBE ) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE , 1 mg/d OBE , or 0.05 mg/d TBE . At 18 months , micronized progesterone was added to induce menstrual cycles . Biochemical markers including sex hormones , inflammatory markers , liver enzymes , coagulation factors , and lipids were obtained at baseline and 6 month intervals . Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance ( ANOVA ) . The effect of progesterone on biochemical markers was evaluated with the paired t-test . Results Mean ( ±SE ) estradiol levels at maximum estrogen dose ( 18 months ) were higher in the TBE group ( 53 ± 19 pg/mL ) compared to OCEE ( 14 ± 5 pg/mL ) and OBE ( 12 ± 5 pg/mL ) ( p ≤ 0.01 ) . The TBE and OBE groups had more effective feminization ( 100 % Tanner 3 breast stage at 18 months ) . There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone . Conclusions Treatment with transdermal 17β estradiol result ed in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients . OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls , but larger prospect i ve r and omized trials are required . Trial registration Clinical Trials Identifier : NCT01023178 Eight girls with Turner 's syndrome were given low dose oral ethinyl estradiol or transdermal 17 beta-estradiol in order to compare the effect of the route of administration on selected markers of hepatic metabolism , and various hormonal concentrations . Oral estrogen was given at a dose of 100 ng/kg/day and transdermal estrogen via adhesive skin patch at 0.0125 mg/kg/day . The subjects received one form of estradiol for one month , and after a one month washout period , received the other form . Both oral and transdermal estradiol caused a significant decrease in FSH while only transdermal result ed in a significant decrease in LH . Oral estradiol , though not transdermal estradiol , increased serum high density lipoprotein , thyroxine binding protein and growth hormone binding protein . Urinary growth hormone excretion increased after both forms of therapy , while insulin-like growth factor-I and insulin-like growth factor binding protein-3 remained unchanged . Thus , in girls with Turner 's syndrome , estrogen replacement by the transdermal route may have less deleterious effect on hepatic metabolism than oral estrogen CONTEXT Women with Turner syndrome ( TS ) have reduced levels of and rogens due to ovarian failure . HYPOTHESES Morbidity associated with TS , such as bone fragility , metabolic changes , obesity , neurocognitive profile , and sexual problems may partly relate to and rogen insufficiency and improve on and rogen replacement therapy ( ART ) . OBJECTIVES The objective of the study was to determine the effect of and rogens on morbidity in TS . DESIGN Fourteen TS women ( aged 17 - 27 yr ) participated in a r and omized , double-blind , placebo-controlled crossover pilot . The study was conducted in a hospital outpatient clinic between December 2001 and July 2004 . INTERVENTION TS patients were on estrogen/progestin replacement therapy .  Subjects received oral 1.5 mg methyl testosterone ( ART ) or placebo for 1 yr and the alternative for another year . MAIN OUTCOME MEASURES The study compared body composition as a primary outcome , and physiology , biochemistry , visceral fat , cognition , and quality of life ( QOL ) as secondary outcomes . RESULTS ART as compared with placebo reduced total cholesterol , triglycerides , and high-density lipoprotein cholesterol . It improved bone mineral density , increased lean body mass , and decreased fat mass .  ART improved attention , reaction time , and verbal memory and had no effect on executive functions and spatial cognition . Patients reported improved QOL , including general health , coping with stress , and sexual desire . CONCLUSIONS And rogen insufficiency plays a role in TS-impaired body composition , neurocognition , and QOL , and these aspects improve with ART , which was safe and effective when given for 1 yr OBJECTIVE Hormone replacement therapy ( HRT ) is prescribed to most patients with Turner syndrome ( TS ) although its use in adult TS patients has not been scientifically evaluated . The present study was performed to compare the short‐term effects in adult women with Turner syndrome of  low‐dose oral conjugated oestrogen (  0·625  mg , CE ) with relatively high dose ethinyl oestradiol ( 30 µg , EE2 ) ; both combined with an oral progestin Girls with Turner syndrome are mainly characterized by growth retardation and gonadal insufficiency . In order to evaluate the effect of growth hormone ( GH ) and /or low dose 17 beta-oestradiol ( E2 ) on growth and pubertal development , 39 Turner girls with a chronological age ( CA ) of 7.6 - 18.1 years were divided into three groups depending on pretreatment bone age ( BA ) . They were treated with either GH 0.1 IE/kg per day ( n = 13 , BA 7.1 - 10.2 ) , peroral E2 0.01 mg/kg per day ( n = 8 , BA 8.5 - 12.7 ) or both ( n = 18 , BA 10.5 - 15.3 ) . In the 2nd year the E2 group also received GH , while the E2 dose was reduced 30 % . In the 1st year height velocity ( HV ) expressed as st and ard deviation scores ( SDS ) increased in all groups ( mean ) : from -0.4 to 3.3 ( P < 0.01 ) in the GH group , -0.5 to 2.7 ( P < 0.01 ) in the E2 group , and -0.8 to 4.6 ( P < 0.001 ) in the GH+E2 group . A possible synergistic effect from combination therapy was seen , as HV increase was higher in group 3 than groups 1 and 2 ( P < 0.05 ) . In the 2nd year HV was unchanged in groups 1 and 2 , while a clear decrease was seen in the GH+E2 group ( P < 0.001 ) . In the 1st year BA progression in the E2 group was rapid ( 1.9 BA/CA year ) and higher than in the other groups ( P < 0.05 ) . In the 2nd year progression slowed down -- particularly in the E2 group ( 0.7 BA/CA year , P = 0.07 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Dyslipidemia causes coronary heart disease in middle-aged and elderly adults , but the consequences of lipid exposure during young adulthood are unclear . OBJECTIVE To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age . DESIGN Prospect i ve cohort study . SETTING 4 cities in the United States . PARTICIPANTS 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA ( Coronary Artery Risk Development in Young Adults ) study . MEASUREMENTS  Low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol , triglycerides , and coronary calcium .  Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study ; these measurements were then related to coronary calcium scores assessed later in life ( 45 years [ SD , 4 ] ) . RESULTS 2824 participants ( 87 % ) had nonoptimal levels of LDL cholesterol ( > or=2.59 mmol/L [ > or=100 mg/dL ] ) , HDL cholesterol ( < 1.55 mmol/L [ < 60 mg/dL ] ) , or triglycerides ( > or=1.70 mmol/L [ > or=150 mg/dL ] ) during young adulthood . Coronary calcium prevalence 2 decades later was 8 % in participants who maintained optimal LDL levels ( < 1.81 mmol/L [ < 70 mg/dL ] ) , and 44 % in participants with LDL cholesterol levels of 4.14 mmol/L ( 160 mg/dL ) or greater ( P < 0.001 ) . The association was similar across race and sex and strongly grade d , with odds ratios for coronary calcium of 1.5 ( 95 % CI , 0.7 to 3.3 ) for LDL cholesterol levels of 1.81 to 2.56 mmol/L ( 70 to 99 mg/dL ) , 2.4 ( CI , 1.1 to 5.3 ) for levels of 2.59 to 3.34 mmol/L ( 100 to 129 mg/dL ) , 3.3 ( CI , 1.3 to 7.8 ) for levels of 3.37 to 4.12 mmol/L ( 130 to 159 mg/dL ) , and 5.6 ( CI , 2.0 to 16 ) for levels of 4.14 mmol/L ( 160 mg/dL ) or greater , compared with levels less than 1.81 mmol/L ( < 70 mg/dL ) , after adjustment for lipid exposure after age 35 years and other coronary risk factors . Both LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinical ly abnormal lipid levels were excluded . LIMITATION Coronary calcium , although a strong predictor of future coronary heart disease , is not a clinical outcome . CONCLUSION Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later . PRIMARY FUNDING SOURCE National Heart , Lung , and Blood Institute Because the long-term effects of estrogen replacement in adolescents with ovarian failure and hypothalamic amenorrhea have not been previously studied , we conducted a 2-year study of 35 patients to determine factors contributing to baseline bone density measures ( bone density , bone mineral content , and bone width ) and the response to estrogen therapy . Estrogen-deficient patients were often profoundly osteopenic by single-photon absorptiometry of the radius and dual-photon absorptiometry of the spine , despite estrogen replacement . Variables that were significant predictors of better initial single-photon absorptiometry measurements included increased age , increased body mass index , spontaneous pubertal development , lack of radiation therapy , and lower serum osteocalcin . Patients treated with estrogen/progestin had stable cortical bone mineral content and bone density at the distal one-third of the radius , a slight improvement in bone density at the distal one-tenth of the radius , and an encouraging , but marginal , improvement in the z score ( st and ard deviation from the mean ) of bone mineral content at the distal onetenth . The z scores for cortical bone width and bone density decreased , suggesting a possible relative worsening over time . In untreated estrogen-deficient girls , bone mineral content and bone density decreased ( but not significantly ) ; the z score of cortical bone width showed a significant decrease . Using dual-photon absorptiometry , a history of radiation therapy was found to be a predictor of lower bone density compared with age-matched controls . Estrogen/ progestin therapy did not result in changes in serum levels of lipids and antithrombin HI , weight , or blood pressure . This study suggests that because most adolescent/young adult patients with estrogen deficiency may not achieve normal bone density with current therapy , earlier and more aggressive intervention may be necessary Lumbar spine bone mineral density ( BMD ) values were measured in women with Turner 's syndrome ( TS ) and the influence of primary ovarian failure as well as the age at the start of estroprogestins ( EP ) therapy were considered . EP treatment with 2 mg of estradiol ( E2 ) and BMD monitoring were started in 72 and finally continued for 5 years in 34 patients with TS , aged 12 - 38 years , previously not treated with growth hormone or anabolic steroids .  The mean total BMD gain ( deltaBMD ) was 20 % and the most significant increase was observed after the first ( 7.5 % ) and the second ( 6.6 % ) year of the therapy . Before the start and during EP treatment E2 levels were evaluated : they increased from 9.2pg/ml to the values observed in the controls ( C ) but positive correlation with BMD was not observed . Analysis of TS patients in age brackets ( < 15 years , 15 - 20 years , 21 - 25 years , > 25 years ) showed that only in the group that started EP treatment before the age of 15 every year significant deltaBMD was observed . The group that started EP therapy after the age of 20 did n't achieve significant deltaBMD . Patients wit TS had significantly higher levels of bone metabolism markers ( Ntx and BALP ) than the controls and in both groups negative correlation with age was found . On the basis of the results the conclusion was made that in hypoestrogenic women , not exclusively TS , the age when estrogen therapy is started may determine the effects in relation to bone mass . The administered E2 doses may also be important In a prospect i ve study of 156 female patients with Turner 's syndrome who had survived infancy and been followed up for an average of 17 years there were 15 deaths . The expected mortality was 3.6 . Sixteen of the patients had a congenital heart anomaly and five of the deaths occurred in this group . The 10 deaths in the remaining 140 were three times as many as expected . The reduction in life expectation was 12.5 years at age 1 year , 11 years at age 20 , and 10 years at age 40 . Deaths were due to a broad spectrum of diseases . In the sample as a whole there were eight deaths from diseases of the circulatory system . This number is significantly greater than expected , but four were due to congenital heart disease . When patients with congenital heart disease were omitted from the sample the mortality from circulatory disorders was not significantly increased . Within the category of circulatory disorders there were three deaths from dissection of the aorta , a number which is greatly in excess of the expected . Two of these patients had no previous evidence of heart disease
target: Using r and om-effects models , estrogen replacement therapy showed an increase in bone mineral density [ weighted mean change from baseline 0.09 g/cm2 ( 0.04–0.14 ) ] that differed by type of estrogen but not route of administration .
  Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [ weighted mean difference 9.33 mg/dl ( 4.82–13.85 ) ] with no significant effect on other lipid fractions .
  The current evidence suggests possible benefit of estrogen replacement therapy  on bone mineral density and high density lipoprotein cholesterol .
background: Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency .
  Hence , long-term estrogen replacement therapy is the cornerstone treatment .
  The estimates of its effect and optimal use , however , remain uncertain .
  We aim ed to summarize the benefits and harms of estrogen replacement therapy on bone , cardiovascular , vasomotor and quality of life outcomes in patients with Turner syndrome .