雷洛昔芬对绝经后妇女骨密度、骨代谢生化指标和血脂影响的随机对照研究

目的　确定盐酸雷洛昔芬 (RLX)对中国绝经后妇女骨密度、骨代谢生化指标及血脂的影响。方法　将来自 3所医院的 2 0 4例绝经后妇女 [平均年龄 (6 0± 5 )岁 ,平均体重 (6 3± 9)kg]随机分组 ,进行双盲安慰剂对照的临床研究 ,受试者每天接受RLX 6 0mg(n =10 2 ,RLX组 )或安慰剂 (n =10 2 ,安慰剂组 )治疗 12个月 ,并于服药前及服药 12个月后各进行一次骨密度、骨代谢生化指标及血脂的测定。结果　与安慰剂相比 ,RLX使腰椎和髋部骨密度显著升高 ,RLX组腰椎的骨密度增加2 30 % ,而安慰剂组降低 0 0 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1) ;RLX组髋部骨密度增加2 4 6 % ,安慰剂组增加 1 0 7% ,两组比较 ,差异有显著性 (P <0 0 5 )。RLX组骨代谢生化指标血清骨钙素和血清C端交联肽分别降低 2 7 6 %和 2 4 0 % ,而安慰剂组则分别降低 10 6 %和升高 15 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。RLX组总胆固醇和低密度脂蛋白胆固醇分别降低 6 4 %和34 6 % ,而安慰剂组则分别升高 1 4 %和降低 19 1% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。两组间高密度脂蛋白胆固醇和甘油三酯水平未见差异。仅有 5例因不良事件而提前退出研究 (RLX组 3例 ,安慰剂组 2例 )。结论　RLX能增加绝经后中国妇女     

Effect of combined oral estrogen/progestogen preparation (Kliogest) on bone mineral density,plasma lipids and postmenopausal symptoms in HRT-naïve Thai women

BACKGROUND: Kliogest is commonly prescribed for the relief of acute postmenopausal symptoms and prevention of postmenopausal bone loss. However, there have been few data on its effect in Asian women. METHODS: This 1-year, single-center, randomized, double-blind and placebo-controlled study evaluated the efficacy and safety of Kliogest in hormone replacement therapy (HRT)-na?ve Thai women. The subjects were 120 healthy Thai women aged between 45 and 65 years, with intact uterus, and who had been amenorrheic for at least 1 year. RESULTS: Kliogest increased spine (+ 6%, p < 0.01) and hip (+2%, p < 0.01) bone mineral density (BMD), and lowered plasma total cholesterol (TC) (-16%, p < 0.05) and low density lipoprotein cholesterol (LDL-C) (-16%, p < 0.05) concentrations. However, Kliogest also resulted in a decrease in high density lipoprotein cholesterol (HDL-C) concentration (-18%, p < 0.05). Compared to placebo, the reduction in menopausal symptoms by Kliogest was not statistically significant. The frequency and severity of treatment-related uterine bleeding decreased with the duration of Kliogest treatment. Furthermore, there was a fairly strong relationship between the change in serum estrone concentration and the average monthly weighted bleeding scores over the first 6 months (Spearman's correlation r = 0.54; p < 0.001), which became weaker over the entire treatment period (Spearman's correlation r = 0.27; p < 0.01). Although there was a small to moderate relationship between baseline estrone concentration and both lumbar (r = 0.23, p < 0.02) and hip (r = 0.20, p < 0.05) BMD, there was no significant relationship between Kliogest-induced change in estrone concentration and change in lumbar and hip BMD. CONCLUSIONS: Continuous treatment with Kliogest for 1 year reversed the potential postmenopausal bone loss in HRT-na?ve Thai postmenopausal women. However, its effect on cardiovascular risk is uncertain. Furthermore, Kliogest is safe but appears to have no significant effect on climacteric symptoms in the patients in the present study.     

Clinical efficacy of raloxifene in postmenopausal women.

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.     

Association of tibolone and fluoride displays a pronounced effect on bone mineral density in postmenopausal osteoporotic women.

A double-blind, placebo-controlled, randomized, prospective two-center study was carried out to assess the effects of tibolone + fluoride versus placebo + fluoride therapy on trabecular and cortical bone in postmenopausal osteoporotic women. Ninety-four subjects (mean age 61.1 years, postmenopausal 13.5 years on average) with low bone mineral density (BMD) at baseline were randomized to 2.5 mg of tibolone (Org OD 14, Livial) plus 26.4 mg of fluoride (Fluocalcic) or placebo plus 26.4 mg of fluoride daily over 2 years; 55 (58.5%) subjects completed the study, the main reason for discontinuation being untoward gastrointestinal effects. BMD at the lumbar spine was measured by both dual photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DXA), and at the hip by DXA at 6-month intervals. Baseline values (DXA, g/cm2) for tibolone + fluoride and placebo + fluoride groups were 0.733 and 0.744 for the lumbar spine, and 0.761 and 0.788 for the hip. Change from baseline and percentage change from baseline were calculated for the intent-to-treat and completers groups. An analysis of variance (ANOVA) model or Wilcoxon test was used for statistical evaluation. There was a mean increase in BMD at the lumbar spine measured by DPA of 25.3% and 12.3% in tibolone + fluoride and placebo + fluoride groups, respectively (p = 0.01); with DXA, respective changes were 32.6% and 14.0% (p = 0.013). Data on BMD at the hip showed mean increases of 7.9% and 2.6% for the tibolone + fluoride and placebo + fluoride groups, respectively. We conclude that combined tibolone + fluoride treatment induces a highly significant increase in BMD at the lumbar spine without simultaneous loss of the cortical bone allowing for a meaningful reduction of the fluoride dose when given in combination with tibolone.     

Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis.

OBJECTIVE: The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis. METHODS: Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months. RESULTS: After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (-53% and -47%, respectively) was significantly greater than for the raloxifene group (-23% and -27%, respectively; both p < 0.01). CONCLUSIONS: In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures.

A 2-year placebo-controlled, randomized, two-center prospective study was carried out to assess the effects of tibolone (Org OD14, Livial) on trabecular and cortical bone mass and bone biochemistry parameters in elderly postmenopausal women with and without previous fractures. In total, 107 subjects, 71 with fractures and 36 without fractures, were randomized to tibolone (n = 64) or placebo (n = 43). Their mean age was 63.1 years. Bone mineral density (BMD) (g/cm2) was assessed at baseline and every 6 months for 2 years by dual-energy X-ray absorptiometry (DXA). Mean baseline values were 0.79 and 0.80 for the lumbar spine in the tibolone and placebo groups, respectively, and for the femoral neck 0.64 in both groups. Serum and urinary bone biochemistry parameters were measured concurrently. An analysis of variance (ANOVA) model including center and group was applied. The completers' group was the primary subset for the analysis; the intention-to-treat (ITT) group was also analyzed. Results are expressed as the percentage change at 24 months and the annual rate of change percentage year. The tibolone group showed an overall mean increase (vs. placebo) in BMD at the lumbar spine of 7.2% (p < 0.001) and for the femoral neck 2.6% (p < 0.001). In subjects with previous fractures increases were 6.0% and 4.0% for the lumbar spine and femoral neck, while in those with no fractures, respective changes were 8.9% and 1.1%. Overall changes in the placebo group were 0.9% and -1.6% for the lumbar spine and femoral neck, respectively. A significant fall in bone biochemistry parameters showed that tibolone inhibits osteoclastic activity. In conclusion we have found that tibolone 2.5 mg induces significant increases of trabecular and cortical bone mass in elderly postmenopausal osteoporotic women with and without previous fractures.     

Low levels of endogenous estradiol protect bone mineral density in young postmenopausal women.

OBJECTIVE: Low levels of endogenous estrogens may play a role in the protection of bone mineral density (BMD) in healthy postmenopausal women. The aim of this study was to evaluate the effect of endogenous estradiol and testosterone on bone mass in young and older healthy postmenopausal women. METHODS: The study involved 99 postmenopausal women aged 55-75 years. The BMDs of the lumbar spine, proximal femur and total skeleton were determined. Measurements were taken of serum calcium, bone alkaline phosphatase, Crosslaps, estradiol, estrone, sex hormone binding globulin, testosterone, bioavailable testosterone and urine calcium. Estradiol was measured using a sensitive assay with a lower detection limit at 5 pg/ml. RESULTS: A multivariate analysis showed that the BMD of the lumbar spine was significantly predicted by estradiol (p < 0.05), and testosterone (p < 0.0001). Likewise, testosterone was found to be an independent predictor of the BMD of the total femur (p < 0.001) and the total skeleton (p < 0.001). The population was divided into two groups: < or = 65 (Group 1) and > 65 years (Group 2) of age and also stratified according to estradiol levels: > 10 and < or = 10 pg/ml. Significant differences in BMD were found in women in Group 1 in whom estradiol levels higher than 10 pg/ml were associated with a higher BMD of the lumbar spine (+ 14%, p < 0.01), proximal femur (+ 6%, p < 0.05) and total skeleton (+ 7%, p < 0.05) compared with women with estradiol levels below 10 pg/ml. Bone alkaline phosphatase levels (p < 0.05) and serum Crosslaps (not significant) were lower in women in Group 1 with a level of estradiol more than 10 pg/ ml. CONCLUSION: Endogenous estradiol levels higher than 10 pg/ml and testosterone protected bone mass in healthy postmenopausal women under 65 years of age. These results were not observed in the group of older women.     

Bone protection for early menopausal women in China: standard or half-dose estrogen with progestin? A one-year prospective randomized trail

The aim of the study is to compare the bone sparing effect of half-dose with standard-dose conjugated equine estrogen (CEE) combined with progestin. A total of 123 participants were administrated with 0.625?mg of CEE and 100?mg of micronized progesterone (MP) in group A, 0.3?mg of CEE and 100?mg of MP in group B, 0.625?mg of CEE and 10?mg of dydrogesterone (DDG) in group C for one year. Percent changes from baseline in BMD at lumbar spine and fracture rate were primary outcomes. Secondary endpoints included changes of BMD at femoral neck, total hip and arm, bone markers (alkaline phosphatase, calcium and phosphorus), serum alanine aminotransferase (ALT) and endometrial thickness. No fractures occurred during the treatment. Standard dose of CEE leads to significant changes in lumbar spine and arm. The 3.78% growth of BMD at femoral neck in group C marked a statistically difference. There was no statistically remarkable bone loss at hip in all three groups. Bone turnover markers and ALT significantly decreased from basic values. Endometrium thickened more with traditional dose of CEE. Both the half and standard dose CEE are effective in BMD preservation among early menopausal women with subtle side effects. Low-dose estrogen is less efficacious than traditional one.     

Statins have additive effects to vertebral bone mineral density in combination with risedronate in hypercholesterolemic postmenopausal women

BACKGROUND: Recent data suggest that statins used in the treatment of hypercholesterolaemia decrease fracture risk. In this study, we aimed to investigate prospectively whether statins have an additive effect to bisphosphonates (risedronate) according to the primary hypothesis that the addition of atorvastatin to risedronate would produce an increase, from baseline, in lumbar vertebrae and total hip BMD that was greater than that observed with risedronate alone. METHODS: A total of 120 hypercholesterolaemic postmenopausal women with osteoporosis or osteopenia were randomized to receive risedronate (5 mg/day) or risedronate (5 mg/day) plus atorvastatin (20 mg/day). Changes in bone mineral density in the lumbar spine and hip, and serum lipid and glucose metabolism changes were assessed. RESULTS: Compared with risedronate alone, at 6 months, risedronate plus atorvastatin produced significantly greater increases in the bone mineral density of the lumbar spine (1.58% versus 0.75%, p < 0.05). We found no difference after therapy in BMD of the total hip (1.2% versus 1.1%). Risedronate plus atorvastatin therapy had favorable effects on the serum lipid profile: LDL and total cholesterol. Serum fasting glucose and HbA1c levels were not affected during the treatments. CONCLUSION: Statins have modest additive effects to bisphosphonates in improving lumbar spine bone mineral density in hypercholesterolaemic postmenopausal women with established osteoporosis-osteopenia. A long-term study with adequate sample size is necessary to assess the effects of statins -- in combination or alone -- on the bones and prevention of fractures.     

1 and 2 mg 17beta-estradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women.

OBJECTIVES: The aim of this study was to assess the effects of 1 and 2 mg 17beta-estradiol on serum lipid profile. Beneficial effects have been clearly established in previous studies with a 2 mg dose; further evidence was required to confirm the beneficial effects of a 1 mg dose. METHODS: This double-blind, placebo-controlled study involved 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. RESULTS: High density lipoprotein (HDL) cholesterol levels were significantly (p<0.05) increased after 26 cycles in all active treatment groups compared with placebo. In addition, low density lipoprotein (LDL) cholesterol and lipoprotein(a) levels were significantly reduced, and apolipoprotein A1 and triglyceride levels were significantly increased, in all active treatment groups after 13 and 26 cycles. CONCLUSIONS: The results of this study clearly indicate that sequential combinations of either 1 or 2 mg 17beta-estradiol with dydrogesterone are associated with long-term, favorable changes in the serum lipid profile. There was no evidence that dydrogesterone compromised the 17beta-estradiol-induced improvements in lipid profile.     

Three-year follow-up of the use of transdermal 17beta-estradiol matrix patches for the prevention of bone loss in early postmenopausal women

OBJECTIVE: A total of 325 of 569 postmenopausal women who were initially recruited into two 2-year, double-blind, placebo-controlled, dose-ranging studies of a matrix transdermal formulation of 17beta-estradiol (Menorest) participated in open-label extensions for a third year. STUDY DESIGN: Those patients originally randomly assigned to receive 17beta-estradiol continued active treatment with dosages of 25, 50, 75, or 100 microg/d, whereas those originally randomly assigned to receive a placebo patch were switched to an active patch of identical size that delivered 17beta-estradiol at 25, 50, 75, or 100 microg/d. Follow-up was conducted, and bone density and other parameters were compared. RESULTS: Overall, gains in bone mass were maintained in patients who received 3 years of active treatment. In patients originally randomly assigned to receive placebo, initial losses in bone mass during the first 2 years were reversed and replaced with marked increases after the switch to active treatment. All patients who had initially received placebo showed significant, dose-related, clinically relevant increases (2.77% +/- 0.99%; P =.0048; to 7.36% +/- 0.74%; P =.0001) in lumbar spine bone mineral density relative to the end of the second year of the original study; smaller final-year increases were noted among the patients who had been actively treated for all 3 years. Similar trends were reported for femoral, trochanter, and total hip bone mineral densities. Mean total body bone mineral density either increased or remained unchanged in all dosage groups. These results were accompanied by parallel changes in levels of serum and urinary markers of bone turnover, with all markers approaching or returning to premenopausal levels by month 36. The high tolerability of this formulation during years 1 and 2 was maintained during year 3; 5.5% of patients withdrew from treatment because of adverse events in the final year. CONCLUSION: The Menorest formulation of transdermal 17beta-estradiol maintained bone mineral density gains in postmenopausal women and was well tolerated through a 3-year treatment period. It was also effective in reversing the initial bone loss associated with late commencement of therapy.     

The effects of short-term hormone replacement therapy on long-term bone mineral density.

INTRODUCTION: Short-term hormone replacement therapy (HRT) relieves menopausal symptoms and increases bone mineral density (BMD), but bone loss reoccurs upon discontinuation. This study assesses whether short-term HRT provides long-term BMD benefits. METHOD: This was a prospective study of women aged 50-54 years followed up for 9 years. Women were categorized into three groups according to the treatment they received: No-HRT (n = 340), Short-term HRT (2-4 years, n = 60), and Long-term HRT (9 years, n = 187). RESULTS: BMD increased significantly at the hip (2.4%, p < 0.001) and spine (8.0%, p < 0.001) over 9 years in the Long-term HRT group. Women without treatment lost BMD at the hip (-4.2%, p < 0.001) and spine (-3.5%, p < 0.001). Women in the Short-term HRT group had no significant loss of BMD at the hip (-1.6%, p = 0.08) or spine (-1.4%, p = 0.18) over 9 years. BMD in the Short-term HRT group was significantly higher at 9 years than in the No-HRT group at both spine (difference 0.023 g/cm(2), p = 0.048) and hip (difference 0.016 g/cm(2), p = 0.042). CONCLUSION: After 9 years, women who had taken short-term HRT had no significant loss of BMD and were better off in terms of BMD than those left untreated. Short-term HRT in the early postmenopausal period provides long-term BMD benefits.     

A randomized trial of oral contraceptive and hormone replacement therapy on bone mineral density and coronary heart disease risk factors in postmenopausal women

OBJECTIVE: To identify the effects of oral contraceptive (OC) and hormone replacement therapy (HRT) on bone mineral density and coronary heart disease risk factors in postmenopausal women. METHODS: Eighty healthy postmenopausal women were randomly assigned to a cyclic regimen of OC containing 30 microg of ethinyl estradiol and 150 microg of desogestrel or HRT containing 0.625 mg of conjugated equine estrogens 21 days per cycle and 5 mg of medrogestone 10 days per cycle for 12 months. Bone mineral density of lumbar spine and hip, biochemical markers of bone turnover, lipid-lipoprotein profiles, coagulation profiles, fasting plasma glucose, and blood pressure were evaluated. RESULTS: Both regimens caused significant increase in bone mineral density of lumbar spine, trochanter, intertrochanteric region, total hip, and Ward triangle. Only OC therapy was associated with a significant increase in femoral neck bone mineral density (mean score +/- standard error 2.5% +/- 0.7%, P < .01). Biochemical markers of bone turnover, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in both groups. Posttreatment levels of those bone markers and lipid-lipoprotein were significantly lower after OC therapy than HRT. Fasting plasma glucose and systolic blood pressure decreased significantly in both groups; however, only the OC group showed a significant decrease in diastolic blood pressure. CONCLUSION: Both OC and HRT increased bone mineral density of lumbar spine and hip, but OC suppressed bone turnover more than HRT. Both methods favorably affected lipid-lipoprotein metabolism, fasting plasma glucose, and blood pressure during the 12 months of treatment.     

Effects of smoking on serum lipoproteins and bone mineral content during postmenopausal hormone replacement therapy

We examined the effect of smoking on the treatment response in serum estrogens, serum lipids and lipoproteins, and bone mineral content in 110 postmenopausal women treated for 2 years with either percutaneous or orally administered combined hormones or placebo and followed up by examinations every 3 months. Serum estradiol and estrone levels during oral hormone administration were lower in smokers than in nonsmokers, whereas no differences related to smoking habits were observed during percutaneous hormone administration. Serum total and low-density lipoprotein cholesterol were significantly reduced in both smokers and nonsmokers receiving hormones, but the response in smokers was only half that observed in nonsmokers (not significant). When the impact of the route of hormone administration was examined in relation to smoking habits, the response in serum total and low-density lipoprotein cholesterol in smokers receiving oral hormones was significantly lower (p less than 0.05) than that observed in nonsmokers. No differences in serum lipids or lipoproteins were observed between smokers and nonsmokers receiving percutaneous hormones. The response in bone mineral content in smokers and nonsmokers receiving percutaneous hormones and placebo was not significantly different, although the overall response differed significantly in the two groups (p less than 0.001). In contrast, the response in smokers receiving oral hormones was significantly lower than that observed in the corresponding nonsmokers (p less than 0.01). We conclude that smoking greatly affects the response on circulating levels of estrogens in postmenopausal women treated with orally administered hormone replacement therapy and that the subsequent treatment response on serum lipids and lipoproteins and on bone mineral content is reduced accordingly. The study suggests that alternative routes of administration should be considered when postmenopausal estrogen therapy is instituted in women who smoke.     

A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Transdermal Estradiol Investigator Group.

OBJECTIVE: To determine the effects of four doses of a 7-day transdermal 17beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women. METHODS: This was a multicenter, double-masked, randomized, placebo-controlled study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, proximal femur, and total hip measured with dual-energy x-ray absorptiometry. Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured. RESULTS: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day resulted in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density of the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increases were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery system, effects of estrogen, and menopausal symptoms. CONCLUSION: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day effectively prevented bone loss in postmenopausal women.     

Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis

Objective. The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis.

Methods. Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months.

Results. After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (?53% and ?47%, respectively) was significantly greater than for the raloxifene group (?23% and ?27%, respectively; both p < 0.01).

Conclusions. In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

Long-term administration of tibolone plus gonadotropin-releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass, and lipid profiles

OBJECTIVE: To evaluate the effects of long-term administration of GnRH agonist (GnRH-a) plus tibolone for uterine leiomyomatosis. DESIGN: Prospective open clinical trial. SETTING: Department of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II", Naples, Italy. PATIENT(S): Twenty-five subjects with symptomatic uterine leiomyomas. INTERVENTION(S): Treatment for 2 years with leuprolide acetate (3.75 mg IM every 28 days) and tibolone (2.5 mg/d per os). MAIN OUTCOME MEASURE(S): Uterine and uterine leiomyoma sizes, endometrial thickness, lumbar spine bone mineral density (BMD), bone metabolism, lipid profile, myoma-related symptoms at baseline and every 6 months. Hot flashes and vaginal bleeding episodes recorded in a daily symptom diary. RESULT(S): After 6 months of treatment, a significant reduction was observed in uterine and leiomyoma volumes and myoma-related symptoms compared with baseline values. No significant change was observed in bone turnover, lumbar BMD, or serum total cholesterol, low-density lipoprotein cholesterol, or triglyceride levels. High-density lipoprotein cholesterol values were significantly lower than baseline values after 6 months of treatment but not after 18 months of therapy. A low mean number of hot flashes per day was observed. CONCLUSION(S): Long-term administration of GnRH-a plus tibolone reduces hot flashes and prevents bone loss without changing the lipid profile.     

Endometrial thickness and uterine diameter not affected by ultralow doses of 17beta-estradiol in elderly women

OBJECTIVE: Our purpose was to monitor changes in endometrial thickness and uterine diameter during treatment with ultralow doses of estradiol, which might improve the serum lipid profile in elderly women. STUDY DESIGN: Ultrasonographic changes were monitored in 60 women with an intact uterus in a group of 70 healthy women who were previously evaluated for changes in serum lipid levels. Subjects were 60 years and older and were randomly assigned to receive parenteral 17beta-estradiol (7.5 microg/24 h), delivered by a vaginal ring (Estring; Pharmacia-Upjohn, Malm?, Sweden), or no treatment for 12 months. RESULTS: Estring treatment yielded minor increases in serum estrone sulfate and 17beta-estradiol levels within the normal postmenopausal range. The maximal endometrial thickness was 2.8 mm at baseline and 2.6 mm at 12 months. No significant changes within or between the study groups were found in endometrial thickness or uterine diameter. There were no significant interactions between age and baseline serum estrone sulfate or 17beta-estradiol levels. CONCLUSIONS: Ultralow doses of 17beta-estradiol, which might improve serum lipid levels, did not significantly change endometrial thickness or uterine diameter. This might indicate that there is a "therapeutic window" for systemic effects of ultralow doses of estradiol in elderly women without any apparent increase in endometrial thickness.     

The value of skin densitometry in diagnosis of decreased bone mass in the spine of women during the period around and post-menopause]

OBJECTIVE: In peri- and postmenopausal women, the association of skin thickness with bone mass is well described, and a low skin thickness is a useful predictor of osteoporosis. In this study the association between skin thickness and bone mass of lumbar spine in peri- and postmenopausal women was assessed; and the potential for skin thickness as a screening test for osteoporosis evaluated. DESIGN/METHODS: Skin thickness was measured at the arm by ultrasonography (probe 22 MHz). Bone mass was measured at lumbar spine by dual-energy X-ray absorptiometry. One hundred and three peri- and postmenopausal women were studied. RESULT: Successive decrease of skin thickness going along with the loss of lumbar spine bone mass was found. There was a statistically significant difference (p < 0.05) in skin thickness between group of females with normal bone mass and group with osteoporosis. CONCLUSIONS: Ultrasound skin measurement is a very simple method which can be used in the diagnostics of osteoporosis of the lumbar spine in peri- and postmenopausal women.     

Alendronate for the prevention of bone mineral loss during gonadotropin-releasing hormone agonist therapy

OBJECTIVE: To evaluate alendronate as a prophylactic measure against bone mineral density (BMD) loss in reproductive-aged women receiving gonadotropin-releasing hormone agonist (GnRHa) therapy for 6 months. STUDY DESIGN: A randomized, double-blind, placebo-controlled, pilot trial at a university-affiliated community hospital. Subjects were 11 premenopausal women with indications for GnRHa therapy who were randomized to receive alendronate, 10 mg, or placebo, by mouth daily during 6 months of GnRHa use. Both groups received intramuscular depot leuprolide acetate, 3.75 mg every 28 days for a total of 24 weeks. BMD at the lumbar spine and femur was determined by dual energy x-ray absorptiometry at baseline and at the conclusion of treatment. Lipids and urinary N-telopeptide were measured before and during treatment. RESULTS: Alendronate-exposed subjects experienced a mean gain of 1.0% (P = .35) in lumbar BMD as compared to a significant mean loss in the control group 3.8% (P = .01). Subjects in the placebo group experienced a significant reduction in mean femur BMD of 3.4% (P = .02), while alendronate-exposed subjects had a loss of 0.4% (P = .65). Bone turnover, as evidenced by urinary N-telopeptide, increased over baseline for both groups. Neither group experienced significant changes in lipids during the study period. CONCLUSION: Alendronate appears to offer some degree of protection against BMD loss in young women during transient, induced hypoestrogenemia. Alendronate was associated with a gain in lumbar (trabecular) BMD but less than expected from studies of postmenopausal women. With the expectation that young women gain BMD, extending the safe and effective duration of GnRHa therapy in this population may require additional measures.