title: A longitudinal study of the treatment of hot flushes: the population study of women in Gothenburg during a quarter of a century Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. The prevalence of hot flash and associated variables among perimenopausal women. Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. Prevalence of menopausal symptoms in different ethnic groups of Asian women and responsiveness to therapy with three doses of conjugated estrogens/medroxyprogesterone acetate: the Pan-Asia Menopause (PAM) study. Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women. Urogenital Prolapse and Atrophy at Menopause: A Prevalence Study Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. Effects of bazedoxifene in nonflushing postmenopausal women: a randomized phase 2 trial Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women Bazedoxifene/conjugated estrogens and quality of life in postmenopausal women. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent. Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: a randomized, controlled trial Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy.
abstract: Objective To describe the prevalence and treatment of hot flushes in premenopausal and postmenopausal women from the 1960s to the 1990s . Design This prospect i ve study , based on a r and om sample of the total female population of 430,000 in Gothenburg , Sweden , was started in 1968 , with follow-ups in 1974 , 1980 , and 1992 . The participants were 1,462 women born in 1930 , 1922 , 1918 , 1914 , and 1908 ( participation rate 90.1 % ) who were representative of women of the same age in the general population . For the purpose of analyzing secular trends , we included 122 participants who were 38 years old and 47 who were 50 years old in 1980–1981 .  Results The prevalence of hot flushes increased from ∼11 % at 38 years to a maximal prevalence of ∼60 % at 52 to 54 years of age , then declined successively from ∼30 % at 60 years of age to ∼15 % at 66 years of age , and then to ∼9 % at 72 years of age . The predominant type of medication being prescribed changed during the observation period from sedatives/anticholinergic drugs in the 1960s to hormone replacement therapy in the 1980s . Hormone replacement therapy was considered to be an effective form of treatment for hot flushes by 70 % to 87 % of the women . Conclusions Hot flushes were a common symptom , with a maximal prevalence of 64 % at 54 years of age . Medical consultation and treatment did not increase in 50-year-old women from 1968–1969 to 1980–1981 . Treatment changed and became more effective during the observation period Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk . Greater decreases in bone resorption markers were associated with greater decreases in vertebral ( and nonvertebral ) fractures . Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density . Early decreases in bone resorption may also play a role . We tested this hypothesis by measuring two bone resorption markers , the C-telopeptide of type I collagen ( CTX ) and the N-telopeptide of type I collagen ( NTX ) , in osteoporotic patients in risedronate vertebral fracture trials . We studied 693 women with at least one vertebral deformity ( mean age , 69 + /- 7 years ) who received calcium ( and vitamin D if required ) and placebo or risedronate 5 mg daily for 3 years . The reductions in urinary CTX ( median , 60 % ) and NTX ( 51 % ) at 3 - 6 months with risedronate therapy were significantly associated ( p < 0.05 ) with the reduction in vertebral fracture risk ( 75 % over 1 year and 50 % over 3 years ) . The changes in both CTX and NTX accounted for approximately one-half ( CTX , 55 % ; NTX , 49 % ) of risedronate 's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds ( CTX , 67 % ; NTX , 66 % ) over 3 years compared with placebo . The changes in CTX and NTX accounted for 77 % and 54 % , respectively , of risedronate 's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo . The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear ( p < 0.05 ) . There was little further improvement in fracture benefit below a decrease of 55 - 60 % for CTX and 35 - 40 % for NTX . The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk . There may be a level of bone resorption reduction below which there is no further fracture benefit A  telephone survey of a r and om sample of 594 perimenopausal women was done to study the prevalence of hot flashes , use of estrogen , age of menopause onset , and , among those subjects experiencing hot flashes , the frequency of occurrence and number of years of hot flashes . The prevalence of hot flashes was 88 % . Surgical menopause women had a prevalence rate of 92 % and had the highest estrogen utilization rate . The median age of onset for natural menopause women was 49 years . The frequency of occurrence and number of years of hot flash experience was variable across all groups The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism .  Eighty-one postmenopausal women ( 1.5 - 3 years after menopause ) were r and omly divided into three groups . The first two groups received sequential estrogen treatment with either transdermal estradiol ( Estraderm TTS , Ciba Geigy ; 50 micrograms/day ; 24 women ) or 0.625 mg/day conjugated estrogens ( Premarin , Wyeth ; 20 subjects ) , respectively . In both groups medroxyprogesterone ( 10 mg/day per os ) was added for 12 days of each cycle . Thirty-five subjects served as control group without therapy  . No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up . Serum triglycerides decreased significantly ( -10.9 + /- 26 % S.D. ; P < 0.05 ) in transdermal treated women , whereas it slightly rose in oral estrogen group . Comparable significant decreases in total and low density lipoprotein ( LDL ) cholesterol ( mean range -6.5/-18.0 % ) were observed in women on estrogen replacement therapy . High density lipoprotein ( HDL ) cholesterol significantly diminished in transdermal estradiol group , but it rose slightly in the oral estrogen group . Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens . It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases UNLABELLED We used data from the Fracture Intervention Trial to assess the relationship change in bone turnover after 1 year of alendronate or placebo treatment and subsequent hip , non-spine , and spine fracture risk among 6186 postmenopausal women . In the alendronate group ( n = 3105 ) , greater reductions in one or more biochemical marker were associated with a lower risk of fracture . INTRODUCTION There are few data on the relationship between short-term change in biochemical markers of bone turnover and non-spine fracture risk among bisphosphonate-treated women , and the clinical use of such measurements is unknown . MATERIAL S AND METHODS We measured biochemical markers of bone turnover ( bone-specific alkaline phosphatase [ bone ALP ] , intact N-terminal propeptide of type I collagen , and C-terminal crosslinked telopeptide of type 1 collagen ) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo . During a mean follow-up of 3.6 years , 72 hip , 786 non-spine , and 336 vertebral fractures were documented . RESULTS AND CONCLUSIONS Each 1 SD reduction in 1-year change in bone ALP was associated with fewer spine ( odds ratio = 0.74 ; CI : 0.63 , 0.87 ) , non-spine ( relative hazard [ RH ] = 0.89 ; CI : 0.78 , 1.00 ; p < 0.050 ) , and hip fractures ( RH = 0.61 ; CI : 0.46 , 0.78 ) . Alendronate-treated women with at least a 30 % reduction in bone ALP had a lower risk of non-spine ( RH = 0.72 ; CI : 0.55 , 0.92 ) and hip fractures ( RH = 0.26 ; CI : 0.08 , 0.83 ) relative to those with reductions < 30 % . We conclude that greater reductions in bone turnover with alendronate therapy are associated with fewer hip , non-spine , and vertebral fractures , and the effect is at least as strong as that observed with 1-year change in BMD OBJECTIVE To survey the prevalence of 18 menopausal symptoms in nine ethnic groups of Asian women . To evaluate responsiveness of symptoms to three estrogen/progestin doses in Asian women . DESIGN A prospect i ve , r and omized , double-blind multinational clinical trial in 1028 healthy postmenopausal women from 11 Asian countries/regions . Following 2 weeks of baseline observations , the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate ( MPA ) doses ( in mg ) daily for 24 weeks : 0.625/2.5 ; 0.45/1.5 ; or 0.3/1.5 . At baseline and throughout the study period , the women were asked to record each symptom daily on diary cards translated into 10 language s. RESULTS The number of women in the different ethnic groups ranged from 24 ( Malay ) to 248 ( Chinese ) . The overall prevalence of symptoms differed among the groups , with Vietnamese women generally reporting the highest rates . Within each ethnic group , the prevalence of individual symptoms varied substantially . Only 5 % of Indonesian women , for example , reported hot flushes but 93 % complained of body or joint aches/pains . Overall , body or joint aches/pains was the most prevalent symptom , ranging from 76 % in Korean women to 96 % in Vietnamese women . Therapy result ed in a significant decline in all symptoms . The decline was observed with all three doses after 4 weeks of treatment and continued throughout the 6-month study period . CONCLUSION The prevalence of individual menopausal symptoms differed among ethnic groups of Asian women . Within each ethnic group the percentage of women reporting each symptom varied substantially . Symptoms declined after 4 weeks of hormone therapy and thereafter throughout the study . The effect of the lowest dose of CE/MPA ( 0.3/1.5 mg/day ) was comparable to that of the higher doses Objective To evaluate the effects of the tissue selective estrogen complex ( TSEC ) pairing bazedoxifene ( BZA ) with conjugated estrogens ( CE ) on sexual function and quality of life in postmenopausal women . Methods In this 12-week , double-blind , placebo-controlled study , postmenopausal , non-hysterectomized women ( n = 652 ) with symptoms of moderate to severe vulvar/vaginal atrophy were r and omized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg , BZA 20 mg , or placebo . The Arizona Sexual Experiences ( ASEX ) Scale , Menopause-Specific Quality of Life ( MENQOL ) question naire , and Menopause Symptoms Treatment Satisfaction Question naire ( MS-TSQ ) were secondary measures used to assess the effects of BZA/CE on sexual function , menopausal symptoms , and satisfaction with treatment , respectively . Results At week 12 , both BZA/CE doses were associated with significant improvement in ease of lubrication score from baseline compared with placebo ( p < 0.05 ) on the ASEX scale , although there was no difference in the change in total score . The MENQOL question naire results at week 12 showed significant improvements in vasomotor function , sexual function and total scores with both BZA/CE doses vs. placebo or BZA 20 mg ( p < 0.001 ) . The MS-TSQ results showed that BZA/CE-treated subjects reported significantly greater overall satisfaction with treatment , as well as satisfaction with control of hot flushes during the day and night , effect on quality of sleep , and effect on mood or emotions , compared with subjects treated with placebo or BZA 20 mg ( all p < 0.05 ) . Conclusion Treatment with BZA/CE for 12 weeks was shown to significantly improve sexual function and quality -of-life measures in symptomatic postmenopausal women OBJECTIVE To determine the relation between estrogen replacement therapy and fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore County , Maryl and ; Minneapolis , Minnesota ; Portl and , Oregon ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 9704 ambulatory , nonblack women 65 years of age or older . MEASUREMENTS  Estrogen use , medical history , and anthropometric data  were obtained by question naire , interview , and examination . Appendicular bone mass was measured by single-photon absorptiometry .  Incident fractures were vali date d by radiographic report . RESULTS After adjustment for potential confounders , current estrogen use was associated with a decrease in the risk for wrist fractures ( relative risk [ RR ] , 0.39 ; 95 % CI , 0.24 to 0.64 ) and for all nonspinal fractures ( RR , 0.66 ; CI , 0.54 to 0.80 ) when compared with no estrogen use . Results were similar for women using unopposed estrogen or estrogen plus progestin , for women younger or older than 75 years of age , and for current smokers or nonsmokers . The effect of estrogen remained after adjustment was made for appendicular bone mass . The relative risk for hip fracture tended to be lower among current users ( RR , 0.60 ; CI , 0.36 to 1.02 ) than among never-users . Estrogen was most effective in preventing hip fracture among those older than 75 years . Current users who started estrogen within 5 years of menopause had a decreased risk for hip fractures ( RR , 0.29 ; CI , 0.09 to 0.92 ) , wrist fractures ( RR , 0.29 ; CI , 0.13 to 0.68 ) , and all nonspinal fractures ( RR , 0.50 ; CI , 0.36 to 0.70 ) when compared with women who had never used estrogen . Previous use of estrogen for more than 10 years or use begun soon after menopause had no substantial effect on the risk for fractures . CONCLUSIONS Current use of estrogen appears to decrease the risk for fracture in older women . These results suggest that for protection against fractures , estrogen should be initiated soon after menopause and continued indefinitely CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women .  All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD ABSTRACT Objectives Bazedoxifene/conjugated estrogens ( BZA/CE ) has demonstrated efficacy in improving vasomotor and vulvar/vaginal atrophy symptoms in postmenopausal women . This study evaluated the endometrial safety of BZA/CE and effects on bone mineral density ( BMD ) compared with CE/medroxyprogesterone acetate ( MPA ) and placebo . Methods The Selective estrogens , Menopause , And Response to Therapy (SMART)-4 trial was a 1-year , multicenter , double-blind , r and omized , placebo– and active-controlled , phase-3 study in non-hysterectomized , postmenopausal women ( n = 1061 ; aged 40 − < 65 years ) . Subjects received BZA 20 mg/CE 0.45 or 0.625 mg , CE 0.45 mg/MPA 1.5 mg , or placebo daily . Primary endpoints were the incidence of endometrial hyperplasia and the change in lumbar spine BMD at 1 year . Secondary endpoints included the change in total hip BMD and rates of amenorrhea and breast pain . Results At 1 year , no cases of endometrial hyperplasia were identified in the BZA 20-mg/CE 0.45-mg group , while three cases ( 1.1 % ) were confirmed for the BZA 20-mg/CE 0.625-mg group ( 95 % one-sided confidence interval upper limit < 4 % ) . Both BZA/CE doses significantly increased lumbar spine and total hip BMD versus placebo ( p ≤ 0.001 ) and showed low incidences of bleeding and breast tenderness , similar to placebo and significantly lower than for CE 0.45 mg/MPA 1.5 mg ( p < 0.05 ) . BZA/CE treatment was generally safe and well tolerated . Conclusions BZA 20 mg/CE 0.45 and 0.625 mg significantly improved BMD while maintaining endometrial safety and showed a favorable safety/tolerability profile over 1 year . BZA/CE may be a promising therapy for treating menopausal symptoms and preventing osteoporosis in non-hysterectomized , postmenopausal women OBJECTIVE To evaluate the efficacy of lower doses of conjugated equine estrogens ( CEE ) plus medroxyprogesterone acetate ( MPA ) for relieving  vasomotor symptoms and vaginal atrophy .  DESIGN A r and omized , double-blind , placebo-controlled trial ( the Women 's Health , Osteoporosis , Progestin , Estrogen study ) . SETTING Study centers across the United States . PATIENT(S ) Two thous and , six hundred , seventy-three healthy , postmenopausal women with an intact uterus , including an efficacy-evaluable population ( n = 241 at baseline ) . INTERVENTION(S ) Patients received for 1 year ( 13 cycles ; in milligrams per day ) CEE , 0.625 ; CEE , 0.625 and MPA , 2.5 ; CEE , 0.45 ; CEE , 0.45 and MPA , 2.5 ; CEE , 0.45 and MPA , 1.5 ; CEE , 0.3 ; CEE , 0.3 and MPA , 1.5 ; or placebo . MAIN OUTCOME MEASURE(S ) Number and severity of hot flushes and Papanicolaou smear with vaginal maturation index ( VMI ) to assess vaginal atrophy . RESULT ( S ) In the efficacy-evaluable population , reduction in vasomotor symptoms was similar with CEE of 0.625 mg/d and MPA of 2.5 mg/d ( the most commonly prescribed doses ) and all lower combination doses . CEE of 0.625 mg/d alleviated hot flushes more effectively than the lower doses of CEE alone . VMI improved in all active treatment groups . CONCLUSION ( S ) Lower doses of CEE plus MPA relieve vasomotor symptoms and vaginal atrophy as effectively as commonly prescribed doses In this 3-yr , r and omized , double-blind , placebo- and active-controlled study , healthy postmenopausal women with osteoporosis ( 55 - 85 yr of age ) were treated with bazedoxifene 20 or 40 mg/d , raloxifene 60 mg/d , or placebo . The primary endpoint was incidence of new vertebral fractures after 36 mo ; secondary endpoints included nonvertebral fractures , BMD , and bone turnover markers . Among 6847 subjects in the intent-to-treat population , the incidence of new vertebral fractures was significantly lower ( p < 0.05 ) with bazedoxifene 20 mg ( 2.3 % ) , bazedoxifene 40 mg ( 2.5 % ) , and raloxifene 60 mg ( 2.3 % ) compared with placebo ( 4.1 % ) , with relative risk reductions of 42 % , 37 % , and 42 % , respectively . The treatment effect was similar among subjects with or without prevalent vertebral fracture ( p = 0.89 for treatment by baseline fracture status interaction ) . The incidence of nonvertebral fractures with bazedoxifene or raloxifene was not significantly different from placebo . In a posthoc analysis of a subgroup of women at higher fracture risk ( femoral neck T-score < or= -3.0 and /or > or=1 moderate or severe vertebral fracture or multiple mild vertebral fractures ; n = 1772 ) , bazedoxifene 20 mg showed a 50 % and 44 % reduction in nonvertebral fracture risk relative to placebo ( p = 0.02 ) and raloxifene 60 mg ( p = 0.05 ) , respectively . Bazedoxifene significantly improved BMD and reduced bone marker levels ( p < 0.001 versus placebo ) . The incidence of vasodilatation , leg cramps , and venous thromboembolic events was higher with bazedoxifene and raloxifene compared with placebo . In conclusion , bazedoxifene significantly reduced the risk of new vertebral fracture in postmenopausal women with osteoporosis and decreased the risk of nonvertebral fracture in subjects at higher fracture risk Summary In this 2-year extension of a 3-year study , bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women .  Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated . Introduction This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years . Methods A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year , r and omized , double-blind , placebo-controlled , phase 3 trial . In the core study ( N = 7,492 ) , subjects received bazedoxifene 20 or 40 mg/day , raloxifene 60 mg/day , or placebo . The raloxifene arm was discontinued after 3 years ; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years . Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo . Endpoints included incidence of new vertebral fractures ( primary ) and non-vertebral fractures , and changes in bone mineral density ( BMD ) and bone turnover markers . Results At 5 years , the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg ( 4.5 % ) and 40/20 mg ( 3.9 % ) versus placebo ( 6.8 % ; P < 0.05 ) , with relative risk reductions of 35 % and 40 % , respectively . Non-vertebral fracture incidence was similar among groups . In a subgroup of higher-risk women ( n = 1,324 ; femoral neck T-score ≤−3.0 and /or ≥1 moderate or severe or ≥2 mild vertebral fracture[s ] ) , bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo ( 37 % ; P = 0.06 ) ; combined data for bazedoxifene 20 and 40/20 mg reached statistical significance ( 34 % reduction ; P < 0.05 ) . Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo ( P < 0.05 ) and was generally safe and well tolerated . Conclusions The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women UNLABELLED Osteoporosis is an increasingly common health concern in postmenopausal women . In a 2-yr phase III study , bazedoxifene prevented bone loss , reduced bone turnover , and was well tolerated in early postmenopausal women with normal or low BMD . INTRODUCTION Bazedoxifene is a novel selective estrogen receptor modulator that has increased BMD and bone strength in experimental models , without stimulating breast or uterus . This 24-mo , r and omized , double-blind study assessed the efficacy and safety of three doses of bazedoxifene compared with placebo and raloxifene in the prevention of postmenopausal osteoporosis . MATERIAL S AND METHODS Healthy postmenopausal women with a BMD T-score at the lumbar spine or femoral neck between -1.0 and -2.5 or clinical risk factors for osteoporosis were r and omly assigned to one of five groups : bazedoxifene 10 , 20 , or 40 mg/d , placebo , or raloxifene 60 mg/d . All women received elemental calcium . Efficacy outcomes included changes from baseline through 24 mo in BMD of the lumbar spine , hip , femoral neck , and femoral trochanter and biomarkers of bone metabolism . RESULTS The intent-to-treat population included 1434 women ( mean age , 58 yr ; mean time from last menstrual period , 11 yr ) . All doses of bazedoxifene and raloxifene prevented bone loss , whereas in the placebo group , there was significant loss of BMD at all skeletal sites . Mean differences in percent change in lumbar spine BMD from baseline to 24 mo relative to placebo were 1.08 + /- 0.28 % , 1.41 + /- 0.28 % , 1.49 + /- 0.28 % , and 1.49 + /- 0.28 % for 10 , 20 , and 40 mg bazedoxifene and 60 mg raloxifene , respectively ( p < 0.001 for all comparisons ) . Comparable BMD responses were observed at other body sites . Significant and comparable decreases in serum osteocalcin and C-telopeptide levels from baseline and relative to placebo with active treatment were observed as early as 3 mo and were sustained through study conclusion ( p < 0.001 ) . Overall incidences of adverse events , serious adverse events , and discontinuations caused by adverse events were similar between groups . The most common adverse events included headache , infection , arthralgia , pain , hot flush , and back pain . CONCLUSIONS Treatment with bazedoxifene prevented bone loss and reduced bone turnover equally as well as raloxifene and was generally well tolerated in postmenopausal women with normal/low BMD OBJECTIVE To evaluate the effect of bazedoxifene/conjugated estrogens ( BZA/CE ) , a tissue selective estrogen complex , on  uterine bleeding in postmenopausal women . DESIGN International , multicenter , r and omized , double-blind , placebo- and active-controlled , phase III study ( Selective estrogen Menopause And Response to Therapy [SMART]-1 ) . SETTING Outpatient clinical . PATIENT(S ) Healthy , postmenopausal women ( N = 3,397 ) aged 40 to 75 years with an intact uterus . INTERVENTION(S ) Daily oral therapy with BZA 10 , 20 , or 40 mg , each with CE 0.625 or 0.45 mg , raloxifene 60 mg , or placebo . MAIN OUTCOME MEASURE(S ) Cumulative amenorrhea profiles and the incidence of bleeding or spotting over 2 years . RESULT ( S ) Treatment with BZA 20 or 40 mg with CE 0.625 or 0.45 mg was associated with rates of cumulative amenorrhea ( > 83 % during cycles 1 - 13 and > 93 % during cycles 10 - 13 ) and bleeding or spotting that were comparable to those with placebo . Subjects who received BZA 10 mg/CE 0.625 mg experienced slightly lower cumulative amenorrhea rates throughout the study compared with placebo-treated subjects . CONCLUSION ( S ) Postmenopausal women treated with BZA 20 or 40 mg with CE 0.625 or 0.45 mg had high rates of cumulative amenorrhea that were similar to those reported with placebo . This new menopausal therapy may offer a favorable bleeding and tolerability profile Abstract : For 285 subjects referred to a menopause clinic  data were prospect ively collected on the time elapsed since the onset of menopause ( menopausal age ) , sexual activity , dyspareunia , smoking , chronic cough and constipation . Prolapse and atrophy were sought on examination . FSH assay confirmed menopausal status . We found an anterior wall prolapse in 51 % of the subjects , of which 6 % were protruding beyond the introitus . Posterior wall prolapse was present in 27 % and apical prolapse in 20 % ; none was protruding beyond the introitus . No trend was noted between prolapse and menopausal age . Atrophy was evident in 34 % of the women , and this was related to menopausal age ( P<0.001 ) . Forty per cent of the sexually active women admitted to dyspareunia , of which 2/3 were superficial . This correlated with advancing menopausal age ( P<0.02 ) . In conclusion , genital prolapse was frequent in the population of postmenopausal women , predominantly cystocele , but the prevalence did not correlate with menopausal age CONTEXT Lower-than-commonly-prescribed doses of conjugated equine estrogens ( CEEs ) with medroxyprogesterone acetate ( MPA ) improve vasomotor symptoms and vaginal atrophy , provide acceptable bleeding and lipid profiles , and afford endometrial protection . This lower-dose therapy 's protection against loss of bone mineral density ( BMD ) associated with menopause has not been thoroughly investigated . OBJECTIVE To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD , total body bone mineral content ( BMC ) , and biochemical markers of bone turnover in postmenopausal women . DESIGN AND SETTING Two-year r and omized , double-blind , placebo-controlled sub study of the Women 's Health , Osteoporosis , Progestin , Estrogen trial , conducted at 19 US centers between August 1995 and October 2000 . PARTICIPANTS Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period . INTERVENTIONS Patients were r and omly assigned to receive CEEs , 0.625 ; CEEs , 0.625 and MPA , 2.5 ; CEEs , 0.45 ; CEEs , 0.45 and MPA , 2.5 ; CEEs , 0.45 and MPA , 1.5 ; CEEs , 0.3 ; CEEs 0.3 and MPA , 1.5 ( all doses in mg/d ) ; or placebo for 2 years . All participants also received elemental calcium at 600 mg/d . MAIN OUTCOME MEASURES Changes from baseline in spine and total hip BMD , total body BMC , and biochemical markers of bone turnover ( serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen ) , assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach . RESULTS At 24 months , women assigned to all of the active treatment groups had significant gains from baseline ( P<.001 ) in spine and hip BMD and total body BMC ( except total body BMC in the group receiving CEEs , 0.3 mg/d ) . These changes were significantly different from those in the placebo group , in which losses of bone mass in spine and total body were evident over the course of the study ( P<.001 ) . The loss in hip BMD from baseline in the placebo group was significant at 18 ( P = .02 ) but not at 24 months ( P = .06 ) . Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline ( P<.001 ) for all active treatment groups at all time points ; no changes were found for the placebo group . For women treated with CEEs alone , the gains in spine BMD for the group taking CEEs , 0.625 mg/d , were significantly higher than those of the group taking CEEs , 0.3 mg/d ( P = .02 ) , but not the group treated with CEEs , 0.45 mg/d ( P = .48 ) . CONCLUSIONS Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women Objective : Phase 3 studies of postmenopausal women with or at risk for osteoporosis reported that , compared with placebo , bazedoxifene increased the incidence of hot flushes . The current study evaluated the vasomotor effects of bazedoxifene in healthy nonflushing postmenopausal women . Methods : In this phase 2 study , nonflushing postmenopausal women ( n = 494 ) were r and omized to daily treatment with bazedoxifene 5 , 10 , or 20 mg ; raloxifene 60 mg ; or placebo for 12 weeks . The primary endpoint was the percentage of women reporting hot flushes at any time during the study ; secondary endpoints included the mean number and severity of hot flushes and the mean number of days with hot flushes . Effects on bone turnover markers and lipid parameters were also evaluated . Results : Over the 12-week study , 25.5 % of placebo-treated women reported hot flushes . The incidence of hot flushes with bazedoxifene 5 , 10 , and 20 mg and raloxifene 60 mg was 26.0 % , 33.7 % , 27.6 % , and 21.4 % , respectively , with no significant differences from that with placebo . The active treatment groups showed no significant differences from placebo in the mean number or severity of hot flushes during week 12 or any 4-week period . Bazedoxifene and raloxifene showed beneficial effects on lipid parameters and markers of bone turnover . All doses of bazedoxifene were generally well tolerated and did not increase endometrial thickness , vaginal bleeding , or breast pain compared with placebo over 12 weeks of therapy . Conclusions : Data from this phase 2 clinical trial suggest that bazedoxifene does not increase the incidence of hot flushes relative to placebo in nonflushing postmenopausal women CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women Objectives : The primary objective of the Selective estrogen Menopause And Response to Therapy 3 ( SMART-3 ) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens ( CE ) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy ( VVA ) associated with menopause . Methods : This was a phase 3 , multicenter , double-blind , r and omized , placebo-controlled , and active comparator-controlled study . Healthy postmenopausal women ( n = 664 ; aged 40 - 65 y ) were r and omized to BZA 20 mg/CE 0.625 mg , BZA 20 mg/CE 0.45 mg , BZA 20 mg , or placebo once daily for 12 weeks . Changes in vaginal maturation , vaginal pH , and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12 . Adverse events were recorded throughout the study . Results : BZA 20 mg/CE 0.625 or CE 0.45 mg significantly ( P < 0.01 ) increased superficial cells and decreased parabasal cells compared with placebo . Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo ( P < 0.05 ) . Improvements in vaginal dryness were also observed with both BZA/CE doses ( P < 0.05 ) . The incidence of treatment-related adverse events were similar across treatment groups . Conclusions : BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms . These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women OBJECTIVE To assess the effects of bazedoxifene/conjugated estrogens ( BZA/CE ) on sleep parameters and health-related quality of life ( HR-QOL ) . METHODS This was a 12-week , multicenter , double-blind , placebo-controlled phase 3 study . Postmenopausal women with an intact uterus and experiencing > or=7 moderate-to-severe hot flushes daily were r and omized to BZA  20 mg/CE 0.45 mg , BZA 20 mg/CE 0.625 mg , or placebo . In these secondary efficacy analyses , the Medical Outcomes Study ( MOS ) sleep scale and Menopause-Specific Quality of Life ( MENQOL ) question naires and the Menopause Symptoms Treatment Satisfaction Question naire ( MS-TSQ ) evaluated measures of sleep , menopausal symptoms , and satisfaction with treatment , respectively . RESULTS A total of 318 subjects ( mean age , 53.4 years ) received > or=1 dose of study drug . At Week 12 , BZA 20 mg/CE 0.45 and 0.625 mg showed significant improvements over placebo in the MOS sleep scale for time to fall asleep , sleep adequacy , sleep disturbance , and sleep problems indexes I and II ( P<0.001 ) . A reduction in hot flush frequency was significantly associated with improvement in sleep parameters ( P<0.05 ) based on linear regression and responder analyses . Both BZA/CE doses showed significantly greater improvements over placebo in vasomotor function and total MENQOL score ( P<0.001 ) . Results of the MS-TSQ showed that subjects treated with BZA/CE versus placebo reported significantly greater overall satisfaction with treatment ( P<0.05 ) , as well as greater satisfaction with sleep quality , ability to control hot flushes during the day and night , effect on mood/emotions , and tolerability . CONCLUSION Symptomatic postmenopausal women treated with BZA/CE experienced significant improvements in sleep parameters and overall HR-QOL OBJECTIVE To evaluate the efficacy of the tissue-selective estrogen complex , bazedoxifene/conjugated estrogens ( BZA/CE ) , for postmenopausal osteoporosis prevention . DESIGN Multicenter , r and omized , double-blind , placebo- and active-controlled , phase 3 trial ( Selective estrogen Menopause And Response to Therapy [SMART]-1 ) . SETTING Outpatient clinical study . PATIENT(S ) Women ( n = 3,397 ) more than 5 years and 1 - 5 years postmenopause were enrolled in the Osteoporosis Prevention I and II Sub studies , respectively . INTERVENTION(S ) Single tablets of BZA ( 10 , 20 , or 40 mg ) each with CE ( 0.625 or 0.45 mg ) , raloxifene ( 60 mg ) , or a placebo taken daily for 2 years . MAIN OUTCOME MEASURE(S ) The primary outcome for both sub studies was change in bone mineral density of the lumbar spine ; bone mineral density was also measured at the hip . RESULT ( S ) In both sub studies , bone mineral density increased significantly more with all BZA/CE doses compared with placebo at the lumbar spine and total hip , and for most BZA/CE doses compared with raloxifene at the lumbar spine . Osteocalcin and N-telopeptide significantly decreased with all BZA/CE doses vs. placebo and most BZA/CE doses vs. raloxifene . CONCLUSION ( S ) BZA/CE combinations decreased bone turnover and bone loss in postmenopausal women at increased risk for osteoporosis In this study we examine the influence of number of years since menopause on  spontaneous bone loss and response to  hormone replacement  therapy ( HRT ) in 274 women ( 56.1 + /- 4.2 years ) completing two placebo-controlled HRT studies of 2 or 3 year duration . Both cross sectionally and longitudinally , bone loss in untreated women was greatest closest to menopause and declined thereafter ( r = 0.34 , p < 0.01 for lumbar spine bone loss and r = 0.25 , p < 0.05 for femoral neck bone loss when correlated with number of years since menopause ) , such that the loss was eliminated in the femoral neck and bone mass increased in the spine in women > 10 years after menopause . In contrast , bone turnover was consistently elevated throughout postmenopause , both cross-sectionally and longitudinally . The association with number of years since menopause was counteracted by both 1 and 2 mg estradiol combined with gestodene , piperazine , estrone sulfate in combination with norethisterone , and a combination of 2 mg estradiol and 1 mg norethisterone acetate . In addition , the response to various HRT regimens was independent of baseline bone mass . Whereas bone loss was significantly related to number of years since menopause , all HRT regimens applied arrested bone loss in healthy postmenopausal women , regardless of number of years since menopause Objective : The aim of this study was to examine the endometrial , ovarian , and breast safety of bazedoxifene , a novel selective estrogen-receptor modulator , in postmenopausal women at risk for osteoporosis . Methods : Healthy postmenopausal women ( N = 1,583 ; mean age , 57.6 y ) with lumbar spine or femoral neck bone mineral density T scores between −1 and −2.5 and /or other clinical risk factors for osteoporosis were enrolled in a 24-month , phase 3 , r and omized , double-blind , placebo- and active-controlled trial . They received daily treatment with bazedoxifene 10 , 20 , or 40 mg ; placebo ; or raloxifene 60 mg . Reproductive safety assessment s included periodic transvaginal ultrasound measurements of endometrial thickness , ovarian volume , and presence of ovarian cysts ; periodic endometrial biopsies ; and adverse event reporting . Results : Bazedoxifene was not associated with a significant change from baseline in mean endometrial thickness at month 24 . The percentage of participants with a change from baseline in endometrial thickness or endometrial thickness greater than 5 mm at month 24 was similar among groups . There was no consensus diagnosis of endometrial hyperplasia or malignancy in the bazedoxifene or raloxifene groups ; the rates of other histologic findings , including endometrial polyps , were low ( < 5 % ) and similar among groups . No significant between-group differences were found in the change from baseline in ovarian volume , number or size of ovarian cysts , or incidence of ovarian cancer . Reports of breast pain ( < 4 % ) and breast cancer ( < 1 % ) were low and evenly distributed among groups . Conclusion : A favorable endometrial , ovarian , and breast safety profile was found after 2 years of treatment with bazedoxifene in healthy , recently postmenopausal women at risk for osteoporosis OBJECTIVES To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin ( E+P ) in the Women 's Health Initiative ( WHI ) r and omized trial . METHODS Subgroup analyses of prior hormone use on  invasive breast cancer incidence in 16,608 postmenopausal women in the WHI r and omized trial of E+P over an average 5.6 years of follow-up . RESULTS Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar . Duration of E+P use within the trial ( mean 4.4 years , S.D. 2.0 ) did not vary by prior use . Among 4311 prior users , the adjusted hazard ratio ( HR ) for E+P versus placebo was 1.96 ( 95 % confidence interval [ CI ] : 1.17 - 3.27 ) , significantly different ( p=0.03 ) from that among 12,297 never users ( HR 1.02 ; 95 % CI : 0.77 - 1.36 ) . The interaction between study arm and follow-up time was significant overall ( p=0.01 ) and among never users ( p=0.02 ) but not among prior users ( p=0.10 ) . The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users , and after about 5 years in women with no prior use . No interaction was found with duration ( p=0.08 ) or recency of prior use ( p=0.17 ) . Prior hormone use significantly increased the E+P hazard ratio for larger , more advanced tumors . CONCLUSION A safe interval for combined hormone use could not be reliably defined with these data . However , the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up , initially concentrated in women with prior hormone exposure , but with increasing risk over time in women without prior exposure , suggests that duration s only slightly longer than those in the WHI trial are associated with increased risk of breast cancer . Longer-term exposure and follow-up data are needed Objective : The aim of this study was to assess the safety and efficacy of bazedoxifene (BZA)/conjugated estrogens ( CE ) treating moderate to severe vasomotor symptoms in the Selective Estrogen Menopause and Response to Therapy 2 trial . Methods : This was an outpatient , multicenter , double-blind , r and omized , placebo-controlled , phase 3 study conducted in the United States . Healthy postmenopausal women ( N = 332 ; aged 40 - 65 y ) with moderate to severe hot flushes ( ≥7/d or 50/wk ) were r and omized to BZA 20 mg/CE 0.45 mg , BZA 20 mg/CE 0.625 mg , or placebo once daily for 12 weeks . Changes from baseline in the average daily number of moderate and severe hot flushes and daily severity score were assessed at weeks 4 and 12 ; adverse events were recorded . Results : BZA/CE significantly reduced the number and severity of hot flushes at weeks 4 and 12 ( P < 0.001 ) . At week 12 , BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg reduced hot flushes from baseline by 74 % ( 10.3 hot flushes [ baseline ] vs 2.8 [ week 12 ] ) and 80 % ( 10.4 vs 2.4 ) , respectively , compared with 51 % ( 10.5 vs 5.4 ) for placebo . More participants at week 12 had at least a 75 % decrease in hot flushes with BZA 20 mg/CE 0.45 mg ( 61 % ) and BZA 20 mg/CE 0.625 mg ( 73 % ) versus placebo ( 27 % ; P < 0.001 ) . The safety profile was similar between BZA/CE and placebo , and no unexpected safety findings were reported . Conclusions : BZA 20 mg paired with CE 0.45 or 0.625 mg is effective , with short-term safety , for treating vasomotor symptoms in postmenopausal women OBJECTIVE To evaluate the endometrial safety of a tissue selective estrogen complex ( TSEC ; pairing of a selective estrogen receptor modulator [ SERM ] with estrogens ) composed of bazedoxifene/conjugated estrogens ( BZA/CE ) in postmenopausal women . DESIGN R and omized , double-blind , multicenter , placebo- and active-controlled , phase 3 study ( Selective estrogen Menopause And Response to Therapy [SMART]-1 ) . SETTING Outpatient clinical . PATIENT(S ) Healthy , postmenopausal women ( n = 3,397 ) age 40 - 75 with an intact uterus . INTERVENTION(S ) Single tablets of BZA ( 10 , 20 , or 40 mg ) combined with CE ( 0.625 or 0.45 mg ) ; raloxifene ( 60 mg ) ; or placebo daily for 2 years . MAIN OUTCOME MEASURE(S ) Incidence of endometrial hyperplasia at 12 months in the efficacy evaluable population . RESULT ( S ) Treatment with BZA ( 20 or 40 mg)/CE ( 0.625 or 0.45 mg ) was associated with low rates ( < 1 % ) of endometrial hyperplasia that were not significantly different from those reported with placebo over 24 months . Endometrial thickness with BZA ( 20 or 40 mg)/CE ( 0.625 or 0.45 mg ) was not significantly different from that with placebo . CONCLUSION ( S ) When combined with CE ( 0.625 mg or 0.45 mg ) , BZA ( 20 mg ) was the lowest effective dose that prevented endometrial hyperplasia over 2 years of study , creating the possibility for a new , progestin-free menopausal therapy
target: Results of systematic review s and meta-analyses of r and omized controlled trials have shown that both systemic estrogen therapy or hormone therapy ( estrogen combined with a progestin ) are useful to prevent bone loss , and they are the most effective treatment for such climacteric symptoms as hot flushes , sweating , vaginal dryness , and dyspareunia .
  The combination of a SERM with estrogen as a tissue selective estrogen complex ( TSEC ) is a new strategy for the prevention of bone loss and the treatment of climacteric symptoms .
  This combination is particularly interesting from a clinical point of view , taking into account that estrogen alone did not increase breast cancer risk by the Women 's Health Initiative .
  TSEC is hypothesized to provide the benefits of estrogen-alone therapy , with an improved tolerability profile because the SERM component can make possible the elimination of progestin .
  The conclusion is that effectively , the combination of bazedoxifene and conjugated estrogens may be a promising alternative to hormone therapy for the prevention of osteoporosis and the treatment of postmenopausal symptoms in non-hysterectomized postmenopausal women
background: Decreasing levels of estrogens during menopause are associated with reduced bone density and an increased risk of osteoporosis .
  Many women also experience bothersome vasomotor and vaginal symptoms during the menopausal transition .
  Unfortunately , estrogen therapy and hormone therapy increase the risk of endometrial and breast cancer , respectively .
  The selective estrogen receptor modulators ( SERMs ) result in positive estrogenic effects on bone , with no negative effects on the endometrium and breast but do not provide relief from postmenopausal symptoms .
  The objective of this review was to critically evaluate the evidence from the reports published to date on the use of bazedoxifene ( a third-generation SERM ) in combination with conjugated estrogens in postmenopausal women .