Oral 17beta-estradiol (1 mg) continuously combined with dydrogesterone improves the serum lipid profile of postmenopausal women

OBJECTIVE: To investigate the effects of 1 mg 17beta-estradiol continuously combined with 2.5, 5, 10, or 20 mg dydrogesterone on the serum lipid profile of postmenopausal women. DESIGN: Serum lipid profile was measured in two 1-year studies performed in healthy, nonhysterectomized, postmenopausal women. One study (n = 182) had an open design and investigated oral 17beta-estradiol 1 mg daily continuously combined with dydrogesterone 2.5 mg daily; the other study (n = 326) had a double-blind, randomized design and investigated oral 17beta-estradiol 1 mg daily continuously combined with dydrogesterone at doses of 5, 10, or 20 mg daily. RESULTS: With all four dosages of dydrogesterone, serum total and low-density lipoprotein cholesterol were significantly reduced (-4.6% to -7.6% and -6.3% to -11.6%, respectively), whereas high-density lipoprotein cholesterol was significantly increased (+4.3% to +7.4%). Serum apolipoprotein A1 and B also improved significantly, reflecting the favorable changes in high-density lipoprotein and low-density lipoprotein cholesterol, as did lipoprotein(a). CONCLUSION: Oral 17beta-estradiol 1 mg daily continuously combined with dydrogesterone 2.5 to 20 mg daily has beneficial effects on serum lipid profile in postmenopausal women.     

Soy protein and bone mineral density in older men and women: a randomized trial

OBJECTIVE: Test the hypothesis that soy isoflavone supplementation preserves bone mineral density (BMD) in men and women. METHODS: We conducted a controlled, parallel-arm, double-blinded trial with 145 participants, 50-80 years, with random assignment to soy beverage daily for 12 months. Active treatment (+ISO) received soy protein containing 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units; the comparison group (-ISO) received soy protein containing 3mg isoflavones. We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior-anterior spine (L1-L4) at baseline in 22 women and 123 men, and at 12 months in 13 women and 98 men. We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip. RESULTS: Among all participants, mean percent change in spine BMD (+/-S.E.) was 0.16+/-0.44 in -ISO (P=0.10) at 12 months. Treatment effects on spine BMD were significantly greater in women than men (P=0.01). At 12 months, in women, mean percent change was 0.58+/-0.70 in +ISO and -1.84+/-0.86 in -ISO (P=0.05); among men it was 1.32+/-0.53 in +ISO and 0.31+/-0.48 in -ISO (P=0.16). By comparison, percent change in hip BMD was similar in the treatment groups, and was not different between men and women. Mean percent change in hip BMD from baseline to 12 months was 0.54+/-0.38 in +ISO and -0.13+/-0.36 in -ISO (P=0.20) among all participants. CONCLUSIONS: Soy protein containing isoflavones showed a modest benefit in preserving spine, but not hip BMD in older women.     

Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the treatment of postmenopausal osteoporosis

OBJECTIVE: To compare the efficacy and tolerability of once-weekly (OW) alendronate (ALN) 70 mg and raloxifene (RLX) 60 mg daily in the treatment of postmenopausal osteoporosis. DESIGN: This 12-month, randomized, double-blind study enrolled 456 postmenopausal women with osteoporosis (223 ALN, 233 RLX) at 52 sites in the United States. Efficacy measurements included lumbar spine (LS), total hip, and trochanter bone mineral density (BMD) at 6 and 12 months, biochemical markers of bone turnover, and percent of women who maintained or gained BMD in response to treatment. The primary endpoint was percent change from baseline in LS BMD at 12 months. Adverse experiences were recorded to assess treatment safety and tolerability. RESULTS: Over 12 months, OW ALN produced a significantly greater increase in LS BMD (4.4%, P < 0.001) than RLX (1.9%). The percentage of women with > or = 0% increase in LS BMD (ALN, 94%; RLX, 75%; P < 0.001) and > or =3% increase in LS BMD (ALN, 66%; RLX, 38%; P < 0.001) were significantly greater with ALN than RLX. Total hip and trochanter BMD increases were also significantly greater (P < or =0.001) with ALN. Greater (P < 0.001) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months. No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen. CONCLUSION: ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover than RLX over 12 months. A greater percentage of women maintained or gained BMD on ALN than RLX. Both medications had similar safety and tolerability profiles.     

A prospective,randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women

OBJECTIVES: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. METHODS: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. RESULTS: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively). CONCLUSION: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.     

Dydrogesterone to oppose the 100 mg oestradiol implant.

Ten non-hysterectomised, post-menopausal women received the 100 mg oestradiol implant which was opposed by 20 mg dydrogesterone (nocte) for 14 days each 28-day cycle, for 6 cycles. Plasma oestradiol was measured at baseline and on three further occasions over 6 cycles. Endometrial biopsies were taken 5 weeks after implant, during the unopposed oestrogen and at week 24 during the progestogenic phase (sampling failed on both occasions in one patient). Secretory endometrium was seen in all women at the end of treatment. Cycle control was good and the mean day of onset of bleeding occurred on or after day 11 of the dydrogesterone dosage by the 5th cycle. Dydrogesterone 20 mg for 14 days every 28 days seemed to be sufficiently potent to counteract the proliferative effects of the high dose oestrogen implant.     

Endometrial safety of continuous combined hormone replacement therapy with 17β-oestradiol (1 or 2 mg) and dydrogesterone

Objectives: To determine the endometrial safety of oral 17β-oestradiol combined continuously with dydrogesterone in preventing endometrial proliferation. Methods: The low dose group comprised three 52-week (13 cycles of 28 days) studies (two of which were double blind) using a 17β-oestradiol dose of 1 mg daily combined with dydrogesterone 2.5, 5, 10 or 20 mg daily. The high dose group comprised two 24-week double-blind studies using a 17β-oestradiol dose of 2 mg daily combined with dydrogesterone 2.5, 5, 10 or 15 mg daily. Endometrial safety was verified by aspiration endometrial biopsies. Inadequate progestational response was defined as proliferative endometrium, endometrial polyp, hyperplasia and carcinoma. Results: Data was evaluable from 650 healthy postmenopausal women in the low dose group and 310 in the high dose group. Endometrial protection was achieved with dydrogesterone at doses of 5 mg or higher combined with 1 or 2 mg 17β-oestradiol. The success rate was 97%, 97% and 98% in women receiving 1/5, 1/10 and 1/20 mg, respectively, and 95%, 98% and 91% in women receiving 2/5, 2/10 and 2/15 mg, respectively. A lower success rate was achieved with the 2.5 mg dydrogesterone dosage (93% in the 1/2.5 mg group and 85% in the 2/2.5 mg group) due to more cases of proliferative endometrium. None of the women in the low dose group developed hyperplasia or carcinoma; five (0.7%) had endometrial polyps. In the high dose group, one woman given 2.5 mg dydrogesterone developed hyperplasia; there were no cases of carcinoma. Conclusion: 5 mg daily dydrogesterone appears to be the lowest effective dose to ensure endometrial safety in a continuous combined regimen with 1 or 2 mg 17β-oestradiol.     

Endometrial safety of continuous combined hormone replacement therapy with 17beta-oestradiol (1 or 2 mg) and dydrogesterone

Objectives: To determine the endometrial safety of oral 17β-oestradiol combined continuously with dydrogesterone in preventing endometrial proliferation. Methods: The low dose group comprised three 52-week (13 cycles of 28 days) studies (two of which were double blind) using a 17β-oestradiol dose of 1 mg daily combined with dydrogesterone 2.5, 5, 10 or 20 mg daily. The high dose group comprised two 24-week double-blind studies using a 17β-oestradiol dose of 2 mg daily combined with dydrogesterone 2.5, 5, 10 or 15 mg daily. Endometrial safety was verified by aspiration endometrial biopsies. Inadequate progestational response was defined as proliferative endometrium, endometrial polyp, hyperplasia and carcinoma. Results: Data was evaluable from 650 healthy postmenopausal women in the low dose group and 310 in the high dose group. Endometrial protection was achieved with dydrogesterone at doses of 5 mg or higher combined with 1 or 2 mg 17β-oestradiol. The success rate was 97%, 97% and 98% in women receiving 1/5, 1/10 and 1/20 mg, respectively, and 95%, 98% and 91% in women receiving 2/5, 2/10 and 2/15 mg, respectively. A lower success rate was achieved with the 2.5 mg dydrogesterone dosage (93% in the 1/2.5 mg group and 85% in the 2/2.5 mg group) due to more cases of proliferative endometrium. None of the women in the low dose group developed hyperplasia or carcinoma; five (0.7%) had endometrial polyps. In the high dose group, one woman given 2.5 mg dydrogesterone developed hyperplasia; there were no cases of carcinoma. Conclusion: 5 mg daily dydrogesterone appears to be the lowest effective dose to ensure endometrial safety in a continuous combined regimen with 1 or 2 mg 17β-oestradiol.     

The effect of low-dose conjugated equine estrogens and cyclic MPA on bone density

OBJECTIVE: to compare the effect of 0.3 and 0.625 mg conjugated equine estrogens on bone mineral density (BMD) in a private practice setting. METHODS: postmenopausal women interested in hormone replacement therapy were prescribed either 0.3 or 0.625 mg conjugated equine estrogens daily with 10 mg medroxyprogesterone acetate days 1-12 of the month. All women were given calcium citrate 1000 mg/day and vitamin D 400 IU/day. DEXA bone mineral density studies of the spine and hip were performed at baseline and 1 year. RESULTS: there was no significant difference in BMD at the spine, the trochanter or the femoral neck compared with baseline in either the 0.625 or 0.3 mg group. The mean percent increase in BMD for the 0.3 versus 0.625 mg group was: spine 2.6 versus 3.8%, femoral neck 1.8 versus 1.5%, and trochanter 0.5 versus 2.6%. CONCLUSION: both the 0.625 mg dose and the 0.3 mg dose of conjugated equine estrogens preserved BMD at the spine and hip over one year in early postmenopausal women who were also given cyclic medroxyprogesterone acetate, calcium citrate and vitamin D.     

Effect of low-dose transdermal E2/NETA on the reduction of postmenopausal bone loss in women

OBJECTIVE: To assess the efficacy of a continuous-combined transdermal patch (estradiol/ norethisterone acetate [E(2)/NETA] 25/125; Estragest TTS, Novartis, Basel, Switzerland) in the reduction of bone loss in postmenopausal women. DESIGN: In a 96-week, double-blind, randomized, multicenter, parallel study, 124 healthy women with an intact uterus more than 4 years after menopause received either transdermal continuous-combined E(2)/NETA (0.025/0.125 mg/day) or placebo patch for 24 treatment cycles; diet was normalized for calcium intake. Lumbar spine bone mineral density (BMD) ranged from 0.969 to 0.805 g/cm2 with a mean annual BMD decrement ranging from 3% to 8% within the last 24 months. BMD at lumbar spine L(2)-L(4) (postero-anterior) and femur were assessed by dual energy x-ray absorptiometry after 6, 12, and 24 cycles. Efficacy variables included measurement of biochemical markers of bone turnover (3, 6, 12, and 24 months). RESULTS: BMD at lumbar spine was significantly higher at all time points in the E(2)/NETA group than in the placebo group (P < 0.0001). Significant increases in BMD (P < 0.0008) from baseline were observed at all sites after 24 months in the E(2)/NETA group compared with placebo, which demonstrated a decrease from baseline. At endpoint, statistically significant decrements in the values of bone remodeling markers were observed (P < 0.05) with E(2)/NETA. CONCLUSIONS: E(2)/NETA 25/125 Estragest TTS was more effective than placebo in reducing the activation frequency of bone remodeling and in preventing bone loss at the spine and hip. Effects on the hip were similar to those observed for higher doses of estrogen.     

Continuous combined hormone replacement therapy with 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti): endometrial safety and bleeding profile

OBJECTIVES: The aim of the study was to confirm the endometrial safety and describe the bleeding profile of continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone in post-menopausal women. METHODS: An open, multicentre study was carried out in 290 healthy, non-hysterectomised post-menopausal women receiving oral continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti) for 1 year. Aspiration endometrial biopsies were performed at baseline and at the end of the study; those classified as hyperplasia or malignancy were considered treatment failures. RESULTS: Only one woman developed simple hyperplasia without atypia at the end of the study; the treatment failure rate was therefore 0.4%. Cross-sectional analysis showed that the percentage of women without bleeding increased from 71% during the first cycle to around 80% by the end of the study. Approximately 50% of the bleeding episodes occurred in the form of spotting; severe bleeding was rare and only seven women withdrew prematurely from the study due to uterine bleeding. Overall, 41% of the women were amenorrhoeic throughout the study. CONCLUSIONS: Continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone provides excellent endometrial safety and is associated with an acceptable bleeding profile.     

Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy

OBJECTIVES: Previous studies indicate that low-dose hormone replacement therapy (LD-HRT) can relieve vasomotor symptoms and prevent spine bone loss. METHODS: In the present study, we evaluated the effects of a low dose of conjugated equine estrogens (CEE; 0.3 mg) associated with different progestins in continuous combined scheme [2.5 mg of medroxyprogesterone acetate (n=25), 5 mg dydrogesterone (n=27), 2.5 mg nomegestrol (n=11)] as single group, on femur bone mineral density (BMD) and bone metabolism in young postmenopausal women (相似文献   

Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects

OBJECTIVE: A 2-year multicenter, double-blind, randomized, placebo-controlled study examined the efficacy and safety of different doses of 17beta-estradiol (E(2)) alone and continuous-combined oral formulations of E(2) and norethindrone acetate (NETA) versus placebo in the prevention of bone loss in newly menopausal women. DESIGN: Patients were randomized to one of seven groups: placebo, E(2) 0.25 mg, E2 0.5 mg, E(2) 1 mg, E(2) 1 mg/NETA 0.25 mg, E(2) 1 mg/NETA 0.5 mg, or E(2) 2 mg/NETA 1 mg. Treatment was a once-daily tablet taken for 26 months. The primary efficacy endpoint was the change in bone mineral density (BMD) at the lumbar spine, measured by dual-energy x-ray absorptiometry, at screening and at 13, 19, and 26 months. BMD changes at the femoral neck and trochanter were also assessed. Biochemical markers of bone metabolism were measured at baseline, and at 3, 6, 13, 19, and 26 months. Histological diagnoses of endometrial samples were tabulated for each treatment group. RESULTS: A total of 327 women were randomized and 189 women completed the 2-year trial. BMD at the lumbar spine decreased 2.3% in the placebo group. The lowest dose of unopposed E(2) prevented bone loss at the spine and hip. Significant increases in spine BMD compared with placebo occurred in all groups of treatment with E(2) and were more pronounced in the combination groups. Compared with placebo, women receiving active treatment experienced greater reductions in bone resorption markers. The effects were evident by 6 months and generally remained stable thereafter. Adverse events, primarily associated with the endometrium, were the most common reasons for discontinuation. CONCLUSIONS: There is a dose-dependent effect of E(2) on BMD. The addition of NETA seems to enhance the response in BMD observed with E(2). Low doses of E(2) (1 mg and lower) can be considered for the prevention of osteoporosis, while titrating the hormone dose to individual patient's needs.     

Association of serum complement (C3, C4) and immunoglobulin (IgG,IgM) levels with hormone replacement therapy in healthy post-menopausal women

BACKGROUND: Recently published data suggest that hormone replacement therapy (HRT) may increase cardiovascular risk during the early months of therapy. Activation of the immune system is known to be involved in several types of cardiovascular disease. In this cross-sectional study, serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving two different short-term HRT regimens, and in untreated women. METHODS: Serum C3, C4, IgM and IgG levels were assessed in 18 women receiving transdermal 17beta-estradiol (50 micro g/day) + continuous oral medroxyprogesterone acetate (MPA; 2.5 mg/day), in 56 women taking oral conjugated equine estrogen (CEE; 0.625 mg/day) + continuous MPA, and in 80 control women not receiving HRT. RESULTS: The mean serum C3 level was significantly higher in women using oral CEE + MPA than in women receiving transdermal 17beta-estradiol + MPA, and those not on HRT (P = 0.02 and P < 0.001 respectively). Furthermore, women taking oral CEE + MPA had significantly higher mean levels of C4 compared with untreated women (P < 0.01). IgG and IgM levels were similar among women either of the two HRT regimens and between women not on HRT. CONCLUSIONS: Oral HRT may be involved in the development of cardiovascular disease through inflammatory mechanisms, as suggested by increased serum levels of C3 and C4.     

Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.     

The effect of continuous oestradiol with intermittent norgestimate on bone mineral density and bone turnover in post-menopausal women

OBJECTIVE: To assess in post-menopausal women the efficacy and tolerability of a continuous oestradiol/intermittent norgestimate HRT regimen to prevent and to reverse post-menopausal loss of bone mineral density (BMD) and to determine the effects on serum bone turnover markers markers. METHODS: A 1-year, multicentre, international, placebo-controlled, randomised, double-blind clinical trial was conducted in 146 post-menopausal women with an intact uterus in order to assess the effect on bone loss of continuous oral 17beta-oestradiol (1 mg per day) combined with norgestimate (90 microg per day), for 3 consecutive days out of every 6-day treatment period (E2/iNGM). During a second year extension, all women agreeing to continue were on the E2/iNGM regimen. BMD was assessed prior to treatment and after 1 and 2 years or at the end of treatment in women stopping participation prematurely after at least 6 months of treatment. Serum bone turnover markers were determined prior to and at 1 year of treatment Adverse events were collected at three-monthly intervals during clinic visits over the treatment period. RESULTS: BMD in the lumbar spine, the primary endpoint, was evaluable in 117 subjects completing >6 months of treatment. BMD increased on average by 2.4% in women on the intermittent progestin regimen. It decreased by 1.4% in placebo treated women. The change from baseline and the difference between active and placebo treatment (Delta placebo) were highly significant (P < 0.0001). On E2/iNGM, also the BMD in the total hip increased (+1.49%, Delta placebo 3.73%, P < 0.0001). The serum markers for bone formation osteocalcin and type I collagen N-propeptide were significantly reduced compared to baseline by 31 and 44%, respectively and the bone resorption marker C-terminal crosslinked telopeptide of type I collagen by 59%. Minor increases (<10%) of markers in the placebo group were not significant. During a second year extension of the trial, all subjects were on active treatment. Subjects on placebo who lost (median+/-CI 95%) 0.66% (-2.3 to +0.5) of spine BMD during the first year now gained 4.41% (2.7-7.6). They also gained 1.6% (0.1-0.3.6) in the total hip. Subjects continuously on oestradiol/intermittent norgestimate (E2/iNGM) gained an additional 5.7% (2.3-13.5) in the lumbar spine and +0.1% (-0.6 to +2.2) at the total hip. Side effects reported by women on the intermittent progestin regimen significantly in excess over reports from the placebo group were uterine bleeding, abdominal and breast pain, but not headache. Back pain and weight gain was reported by significantly fewer women on active treatment compared to placebo. CONCLUSION: The continuous oestradiol/intermittent norgestimate HRT regimen is well tolerated, reduces bone turnover and prevents post-menopausal bone loss in healthy post-menopausal women.     

Safety analysis of high dose (>6 mg/kg/day) daptomycin in patients with concomitant statin therapy

There is a paucity of data regarding efficacy and safety of concomitant therapy of daptomycin and statins, so we reviewed patients that concomitantly received daptomycin and statins to identify any potential increase in toxicity in our cohort. This retrospective study included all patients that received >6 mg/kg/day of daptomycin along with statins and had efficacy and safety data. Patients on high dose (>6 mg/kg/day) daptomycin therapy that did not received statins served as controls. One hundred four patients were included. Median daptomycin dose was 7.8 mg/kg/day (range 6.5-10.8 mg/kg/day), for a mean duration of therapy of 17 days (range 10-51 days). Thirty-six patients received daptomycin and statins and 68 received only daptomycin. Muscular toxicity defined as CPK levels>1000 UI/L (2.5 times upper normal limit, range of determination 200-400 UI/L) was equally distributed between both groups (3/36, 8% vs 7/68, 10%; p=0.746). Despite biochemical toxicity, we did not find clinical toxicity and daptomycin treatment was completed in all cases. We did not find predictors of increased CPK during daptomycin therapy. Based on our data, concomitant administration of daptomycin and statins is safe and is not associated with an increased risk of rhabdomyolysis.     

Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene

OBJECTIVE: Osteoporosis is a significant health problem in postmenopausal women. Consequently, new and effective therapies are being sought to preserve bone mass and prevent osteoporosis in this population of women. The objective of this study was to compare the effects of lasofoxifene with raloxifene and placebo on indices of bone health in postmenopausal women. DESIGN: A randomized, double-blind, placebo- and active treatment-controlled study of 2 years duration was conducted. Women included 410 postmenopausal women aged 47 to 74 years. The four treatment groups were: lasofoxifene 0.25 mg/day, or 1.0 mg/day, raloxifene 60 mg/day, or placebo daily. All women received daily calcium and vitamin D supplements. The primary endpoint was percent change from baseline to 2 years in lumbar spine bone mineral density (BMD) in all women having baseline and at least one follow-up bone density measurement. Total hip BMD, biochemical markers of bone turnover, low-density lipoprotein cholesterol, and safety were also evaluated in all women. RESULTS: Both doses of lasofoxifene significantly increased lumbar spine BMD compared with raloxifene (P < or = 0.05) and with placebo treatment (P < or = 0.05). Least squares mean increases (95% CI) from baseline in lumbar spine BMD, compared with placebo, were 3.6% (1.9, 5.2) for lasofoxifene 0.25 mg/day, 3.9% (2.4, 5.5) for lasofoxifene 1.0 mg/day, and 1.7% (0.3, 3.0) for raloxifene. The two doses of lasofoxifene and raloxifene were equally effective at increasing total hip BMD. Lasofoxifene and raloxifene significantly reduced the levels of biochemical markers of bone turnover compared with placebo. In general, the effects of lasofoxifene were greater than the responses to raloxifene. At 2 years, lasofoxifene significantly (P < or = 0.05) reduced low-density lipoprotein cholesterol levels by 20.6% and 19.7% with 0.25 mg/day and 1 mg/day, respectively, compared with raloxifene (12.1%) and placebo (3.2%). Lasofoxifene and raloxifene had a similar adverse event profile with low rate of discontinuations due to adverse events. CONCLUSIONS: Lasofoxifene may be an effective and well-tolerated treatment option for the prevention of bone loss in postmenopausal women.     

不同治疗方法对绝经后乳腺癌患者骨密度的影响

目的 探讨不同治疗方法 对绝经后乳腺癌患者骨密度(BMD)的影响.方法 研究分为健康对照组(50例)、肿瘤组[48例,其中24例再行他莫昔芬(TAM)组治疗].采用双能X线骨密度仪(DEXA)测定所有研究对象的基线BMD.肿瘤组术后均进行辅助化疗,其中24例(TAM组)化疗后继续使用TAM行内分泌治疗.用DEXA测量腰椎和左髋部位的BMD,比较肿瘤组化疗前、后以及TAM组行内分泌治疗8个月后BMD变化.结果 肿瘤组化疗后腰椎部位BMD(0.87±0.15)g/cm2比化疗前(0.93±0.15)g/cm2明显降低(P<0.05);TAM组行内分泌治疗8个月后腰椎BMD(0.90±0.04)g/cm2和股骨颈(0.74±0.05)g/cm2等左髋部位的BMD均有明显增加(P<0.05).结论 化疗可能导致绝经后乳腺癌患者BMD的下降,而TAM治疗能缓解化疗引起的BMD降低.     

Prevention of postmenopausal bone loss with minimal uterine bleeding using low dose continuous estrogen/progestin therapy: a 2-year prospective study

Objective: To re-examine the minimal effective dose of conjugated estrogen (CEE)-progestin hormone replacement on postmenopausal bone loss. Design: A 2-year, prospective, open label, randomized study. Setting: Department of Obstetrics and Gynecology of a university hospital. Participants: Fifty-two postmenopausal or oophorectomized women. Intervention: One of the following regimens was continuously administered for 2 years: (1) CEE 0.625 mg/day, (2) CEE 0.625 mg + medroxyprogesterone (MPA) 2.5 mg/day, (3) CEE 0.31 mg + MPA 2.5 mg/day and (4) control. Measurements: Lumbar spine and femoral BMD by dual energy X-ray absorptiometry (DXA), a monthly based incidence of bleeding, serum lipids, PTH, calcitonin, Al-p, and osteocalcin. Results: Of the 52 patients enrolled in this study, 49 patients completed the 1 year of therapy and 36 completed the 2- year study. The control group showed a significant decrease in lumbar BMD over the 2 years (P < 0.05). The % changes in lumbar BMD at 2 years of CEE alone, CEE 0.625 + MPA and CEE 0.31 + MPA were 8.52% (95% confidence intervals; 4.61 ∼ 12.4%), 7.4% (0.60 ∼ 14.2%) and 3.20% (0.61 ∼ 5.84%), respectively, and were significantly higher than pretreatment values. The incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA. HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA. No significant changes in lipid profiles were seen in the control or in the group of women taking CEE 0.31 mg + MPA. Conclusions: Continuous hormone replacement therapy (HRT) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate option for women with a normal lipid profile or those women wishing to eliminate unscheduled bleeding.     

Determinants of one-year response of lumbar bone mineral density to alendronate treatment in elderly Japanese women with osteoporosis

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p < 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p < 0.05 and R2=0.103, p < 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p < 0.001), serum ALP level, and urinary NTX level (R2=0.074, p < 0.05 and R2=0.160, p < 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.