SEARCH · PubMed Health

Results for “Postmenopausal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed2003

The Erlangen Fitness Osteoporosis Prevention Study: a controlled exercise trial in early postmenopausal women with low bone density-first-year results.

OBJECTIVE: To investigate the effect of a 2-year vigorous, combined high-impact, strength, and endurance training program on bone mineral density (BMD) determined by dual-energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), and ultrasound in early postmenopausal women with osteopenia. DESIGN: Nonrandomized controlled trial, reporting 1-year data. SETTING: Community. PARTICIPANTS: Early postmenopausal (1-8y postmenopausal) osteopenic women (DXA T score at lumbar spine or total hip between -1 and -2.5 standard deviations). The exercise group (n=59; mean age, 55.1+/-3.4y) and control group (n=41; mean age, 55.9+/-3.1y) were recruited from community registers. INTERVENTION: Fourteen months of exercise training, with 2 joint sessions and 2 additional home training sessions. Exercise and control groups were supplemented individually with calcium and cholecalciferol up to 1500mg of calcium and 500IU of vitamin D per day. MAIN OUTCOMES MEASURES: BMD at the lumbar spine and total hip measured by DXA, isometric maximum strength, and maximal oxygen consumption (VO2max) during a stepwise running test to exhaustion. RESULTS: Bone density increased significantly at the lumbar spine for the exercise group (1.3%, P<.001) and decreased in the control group (-1.2%, P<.01). Differences at the total hip (-0.3%, not significant vs -0.8%, P<.05) and the femoral neck (-0.8%, P<.05 vs -1.8%, P<.001) were nonsignificant. Changes in isometric maximum strength were significant for each region (grip strength, trunk flexors and extensors, hip flexors, leg adductors and abductors, arm flexors and extensors) in the exercise group (11%-39%) compared with nonrelevant changes (-1.1% to 3.9%) in the control group. Between-group differences were significant (P<.01-.001) for all strength parameters. VO2max increased significantly by 11% (P<.001) in the exercise group but decreased in the control group by 4% (P<.05) while showing significant between-group differences. CONCLUSION: High-intensity exercise training can have a positive influence on bone density in early postmenopausal osteopenic women.

Absorptiometry, Photon↗

PubMed1999

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.

Cardiovascular Diseases↗

PubMed2002

Mood effect of raloxifene in postmenopausal women.

OBJECTIVE: Some experimental and observational data suggest a role of estrogen in depression. Raloxifene is a selective estrogen receptor modulator (SERM) approved for the prevention and treatment of postmenopausal osteoporosis. Its influence on mood in postmenopausal women has not been fully established. Thus, we investigated the effect of raloxifene on mood. METHODS: In a randomized double-blind osteoporosis prevention study, the action of raloxifene on mood was assessed in a subgroup of non-depressed postmenopausal women (mean age: 58.9 years) receiving raloxifene 60 mg/day (n=18) or placebo (n=18). The Hamilton Depression Rating Scale (HDRS) was applied to evaluate mood 3 and 12 months following treatment. RESULTS: Baseline HDRS scores were not different among treatment groups. Overall scores decreased from baseline at 3 and 12 months in the raloxifene group (P<or=0.006), but not in the placebo group. Depression and anxiety indexes decreased in the raloxifene group at 3 and 12 months (P<or=0.04); only anxiety index at 12 months decreased in the placebo group (P=0.045). CONCLUSIONS: These preliminary results suggest that raloxifene does not negatively influence mood in non-depressed, younger postmenopausal women. Larger, long-term studies are required to evaluate a possible mood improvement effect of raloxifene.

Administration, Oral↗

PubMed1997

A comparative study of an estradiol-releasing vaginal ring versus tibolone in postmenopausal women: a transvaginal color Doppler study.

OBJECTIVE: To evaluate endometrial blood flow characteristics in response to estrogen replacement therapy (ERT) and tibolone in postmenopausal women and to correlate the resistance index (RI) with plasma estradiol levels. MATERIALS AND METHODS: Transvaginal color Doppler ultrasound examinations were performed in 72 asymptomatic, postmenopausal women who demonstrated endometrial thickness < or = 5 mm. Thirty-six women receiving tibolone and 36 patients receiving ERT by a vaginal ring comprised the study groups. RESULTS: All postmenopausal women treated with tibolone or ERT showed continuous forward end-diastolic flow. The lowest RI was obtained in women with the vaginal ring inserted. The plasma concentrations of estradiol were found to be significantly higher in the vaginal ring group than those of tibolone. CONCLUSIONS: The data observed suggest that ERT and tibolone modify normal postmenopausal endometrial perfusion. Tibolone had a weaker estrogenic effect on endometrial blood flow resistance, and vaginal ring treatment enhanced endometrial blood perfusion through vasodilatation.

Anabolic Agents↗

PubMed2003

Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial.

Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32-0.88) for those with osteopenia and 0.31 (0.06-0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04-0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis.

Aged↗

PubMed2001

Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Aged↗

PubMed2000

[Basic principles of hormone replacement therapy in the postmenopause].

17 beta-estradiol, conjugated equine estrogens, esterified estrogens, and estriol constitute postmenopausal replacement therapy, all of which are in clinical use as oral preparations. Non-oral routes--matrix and reservoir patches, gel--were developed for estradiol, as was the intravaginal administration of estriol and estradiol. Daily doses of 1 mg estradiol(valerate) or 25 micrograms estradiol delivered via a patch or 0.5 mg gel or 0.3 mg conjugated equine estrogens are often sufficient to alleviate climacteric symptoms. Bone resorption may be effectively reduced and bone mineral density maintained by 1 mg estradiol or 25 micrograms transdermal estradiol. Maximal bone sparing dosages are 2 mg estradiol, 50 micrograms transdermal estradiol, 0.625 mg conjugated equine estrogens, and 1.25 mg estrone Estriol, predominantly used for the prevention and or treatment of urogenital symptoms, has no bone sparing effect at the doses in clinical use. Non-oral administration of estradiol may be superior in diabetic women and those with hypertriglyceridemia due to the different metabolism which does not mainly involve the hepatic first pass effect. Epidemiological data do not support any preference of oral versus non-oral routes of administration regarding side-effects such as venous thromboembolism. Progestogens--natural progesterone, derivatives structurally related to progesterone and testosterone, respectively--are necessary for endometrial protection. Sequential use of a progestogen for at least 10 days per month, preferably 12-14 days abolishes the increased incidence of endometrial hyperplasia which is likely to develop with unopposed use of estrogen. Observational studies do not suggest any superiority of a given progestogen regarding cardiovascular risk, prevention of osteoporosis, and cognitive function in postmenopausal women on estrogen replacement therapy. Tibolone, a derivative of norethindrone, is yet another option for replacement therapy. The recommended dose for treatment of climacteric symptoms and prevention of bone loss is 2.5 mg. Controlled clinical studies do not suggest that this compound is superior in achieving amenorrhea compared with continuous combined estrogen progestogen replacement therapy, as available data are inconsistent. In early postmenopause the sequential use of a progestogen in conjunction with an estrogen is the preferred treatment option. With advancing postmenopausal age either continuous combined replacement or tibolone may be choices in case withdrawal bleeding is no longer acceptable for women. However, there are no rigid age limit when to change treatments, the selection of which is largely influenced by the preference of the individual's acceptance of withdrawal bleeding.

Administration, Cutaneous↗

PubMedDate not supplied

Hormone replacement therapy in postmenopausal women with end-stage renal disease: a review of the issues.

Hormone replacement is an integral part of therapies to prevent osteoporosis in postmenopausal women and may be considered a component in the treatment of dyslipidemia, cardiovascular disease, and possibly cognitive function. The indications for, and efficacy and prescription of, hormone replacement therapy in postmenopausal women with ESRD have been infrequently studied and less than 10% of postmenopausal women on dialysis are receiving hormone replacement. Small studies suggest that hormone replacement therapy is valuable in treating the dyslipidemia of women on dialysis, but indicate that a reduction in the dosage of hormone replacement may be needed. A potential role for hormone replacement therapy in the treatment and/or prevention of osteoporosis and sexual dysfunction in postmenopausal women on dialysis exists as well.

Aged↗

PubMed2003

Permanent cessation of menses and postmenopausal hormone use in dialysis-dependent women: the HELP study.

BACKGROUND: Earlier onset of menopause is associated with an increased risk for cardiovascular disease, especially among women with surgical menopause. Information on age at or reasons for the permanent cessation of menses among women with end-stage renal disease (ESRD) remains limited, although cardiovascular disease accounts for more than half of all cardiovascular deaths in this population. METHODS: We used data from the Hemodialysis and Estrogen Levels in Postmenopausal Patients Study to examine the reported age when menses permanently ceased, reasons for the permanent cessation of menses, and prevalence of surgical menopause. We also investigated the frequency of current and past postmenopausal hormone (PMH) use among dialysis-dependent women and their views toward PMH therapy. RESULTS: Among 238 postmenopausal hemodialysis-dependent women, median age when menses permanently ceased was 48 years. Permanent cessation of menses was attributed to natural causes in 65%, surgical reasons in 30% (16%, hysterectomy without bilateral oophorectomy; 14%, hysterectomy with bilateral oophorectomy), kidney failure in 2%, radiation or chemotherapy in 1%, and other causes in 2%. Among women with a history of bilateral oophorectomy, 71% became menopausal before the age of 35 years. Current and past PMH use was reported by 6% and 17% of the women, respectively, whereas 77% were never administered hormones. Only 2% stated a kidney doctor ever recommended PMH therapy, and 54% said they would not take PMHs if prescribed by their kidney doctor. CONCLUSION: Many women with ESRD experience surgical menopause before the age of 35 years, which may contribute to the excess cardiovascular mortality among women with ESRD. PMH use remains low among dialysis-dependent women. However, two randomized controlled trials have noted a significantly increased risk for cardiovascular events in women administered estrogen in combination with progestin. Thus, risks associated with PMH use may outweigh the benefits in a population with a very high rate of cardiovascular disease, such as postmenopausal hemodialysis-dependent women.

Adult↗

PubMed2001

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis.

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline (Pyr), deoxy-pyridinoline (DPyr) and N-telopeptide of type 1 collagen (NTX) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGFbeta2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX) as well as bone resorptive cytokines (IL-11,TGFbeta2). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis.

Adult↗

PubMedDate not supplied

Discrimination ability of pyridinoline crosslinks related markers for bone resorption in postmenopause and osteoporosis.

We investigated the discrimination ability of pyridinolines crosslinks related bone resorption markers. Amino-terminal pyridinolines crosslinked telopeptides (NTx) and carboxy-terminal pyridinolines crosslinked telopeptides (ICTP), pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in 62 premenopausal (PRE), 30 early postmenopausal healthy subjects (POST) and 24 vertebral osteoporosis patients (VX). NTx, Pyr and Dpyr was significantly higher in POST than in PRE. ICTP was not changed in POST compared with PRE. NTx, ICTP, Pyr and Dpyr were significantly higher in VX than in PRE and POST. To evaluate discriminatory ability of four markers, we calculated t-scores, and generated receiver operating characteristic (ROC) curves. In POST, NTx, Pyr and Dpyr had a moderate t-score, 1.8, 1.4 and 1.3, respectively. In ICTP t-score was only -0.2. In VX compared with POST, ICTP, Pyr and Dpyr had a high t-score, 5.9, 7.9 and 7.5, respectively, but t-score of NTx was moderate, 3.6. The areas under ROC curves for NTx, ICTP, Pyr and Dpyr in POST were 75.8%, 33.8%, 78.1% and 79.5%, respectively. In VX, compared with POST, those for NTx, ICTP, Pyr and Dpyr were 94.0%, 86.0%, 97.4% and 95.1%, respectively. In conclusion, NTx performed well in early postmenopausal status, but did not in osteoporosis. ICTP did not have discrimination power in postmenopause but performed well in osteoporosis. Pyr, Dpyr performed moderately well in postmenopause and performed well in osteoporosis.

Adult↗

PubMed2006

Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women.

OBJECTIVE: We examined the serum level of undercarboxylated osteocalcin (uc OC), which is a sensitive marker of vitamin K status, and levels of bone turnover markers in early postmenopausal women receiving vitamin K2 treatment with or without vitamin D3. METHODS: Thirty-four postmenopausal women with a mean age of 53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia and osteoporosis) were treated with vitamin K2 or with a combination of vitamin K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2 plus 0.75 microg 1alpha-hydroxyvitamin D3. Serum levels of uc OC, intact osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2 years after the start of treatment. RESULTS: Serum uc OC levels in women treated with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with vitamin K2 did not show significant changes, while those in women who received the combined treatment decreased significantly (p < 0.05). On the other hand, urinary DPD level in women treated with vitamin K2 did not change, while that in women who received the combined treatment tended to decrease (p < 0.1). CONCLUSION: Serum uc OC levels in early postmenopausal women who received vitamin K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2 and vitamin D3 may be effective for sustaining BMD in early postmenopausal women whose bone turnovers are highly activated.

Alkaline Phosphatase↗

PubMed2006

Effects of raloxifene on platelet functions in patients with postmenopausal osteoporosis.

Many studies have addressed the effects of estrogenic compounds on platelet function. Raloxifene is a selective estrogen receptor modulator (SERM), which is currently used for the treatment of postmenopausal osteoporosis. At present, there are no clinical data about the effects of raloxifene on platelet function. The purpose of this study was to determine if raloxifene at therapeutic doses affects platelet function in patients with postmenopausal osteoporosis. The effects of raloxifene on platelet function were investigated using a commercial platelet function analyzer (PFA-100) with collagen epinephrine and collagen adenosine 5'-diphosphate (ADP) cartridges. We studied platelet function of 30 patients with postmenopausal osteoporosis before and 15 days after initiation of raloxifene 60 mg/daily. Closure times did not differ significantly between samples obtained before (117.8 +/- 20.5 s) and after raloxifene therapy (106.5 +/- 25.4 s) in collagen/epinephrine cartridges (P > 0.05). There was also no statistically significant difference in mean closure times with collagen/ADP cartridges at baseline (86.2 +/- 18.5 s) and after raloxifene therapy (84.4 +/- 13.8 s) (P > 0.05). Platelet counts (278.3 +/- 72.9 vs. 262.4 +/- 56.7 109/L, P > 0.05) and mean platelet volumes (8.9 +/- 1 vs. 9.1 +/- 1 fL, P > 0.05) were not different before and after raloxifene therapy. Although estrogen related compounds do affect platelet function, there is suggestive data in our study that raloxifene in therapeutic dose exhibit no effect on platelet function in patients with postmenopausal osteoporosis.

Aged↗

PubMed1998

Hormone and nonhormone therapy for the maintenance of postmenopausal health: the need for randomized controlled trials of estrogen and raloxifene.

Multiple health benefits have been postulated for the long-term use of hormone therapy in postmenopausal women, most notably for prevention of osteoporotic fractures and coronary heart disease, as well as several risks, including cancer of the breast and uterus and venous thromboembolism. Cardiovascular disease is the most common cause of death among postmenopausal women. If real, the reduction in risk of coronary heart disease by hormone use suggested by observational studies would likely outweigh the risks. The decision to initiate and maintain hormone therapy is complicated by uncertainties about estrogen's true benefits and risks. Raloxifene, a selective estrogen receptor modulator (SERM), appears to have many of the benefits of estrogen without the cancer risks. It is not known if SERMs can provide significant cardiovascular protection. This article reviews the relation of use of postmenopausal hormones and raloxifene to women's health and addresses the need for large randomized trials to quantify the effect of both postmenopausal estrogen and raloxifene on cardiovascular health.

Cardiovascular Diseases↗

PubMedDate not supplied

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years.

OBJECTIVE: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known. Therefore, the main objectives of these analyses are (1) to compare the effect of 5 years of treatment with raloxifene (60 mg/day) with placebo in terms of the likelihood of developing osteoporosis and (2) to evaluate the effect of 5 years of raloxifene treatment on the endometrium and incidence of vaginal bleeding. DESIGN: The current analyses include integrated data from two identically designed, prospective, double-blinded trials including postmenopausal women (mean age, 55 years) randomly assigned to either placebo (n = 143) or raloxifene (60 mg/day; n = 185). Osteoporosis and osteopenia were diagnosed according to World Health Organization criteria, using the manufacturer's database for the lumbar spine and the National Health and Nutrition Examination Survey's 1998 reference base for the hip. Endometrial thickness was determined using transvaginal ultrasonography. Clinical diagnoses of endometrial hyperplasia or endometrial cancer were confirmed by blinded review of histopathology reports. RESULTS: Compared with the case of placebo, raloxifene treatment for 5 years reduced bone turnover markers (osteocalcin: -10.9%, P < 0.001; bone-specific alkaline phosphatase: -7.2%, P = 0.042; urinary C-telopeptide: -11.1%, P = 0.034) and was associated with increased BMD in the lumbar spine (2.8%; P < 0.001) and total hip BMD (2.6%; P < 0.001). Women taking raloxifene were less likely to develop osteoporosis (relative risk [RR] for raloxifene v placebo: 0.13; 95% CI: 0.00, 0.37; P = 0.001) or osteopenia (RR: 0.23; 95% CI: 0.00, 0.81; P = 0.038) at the lumbar spine and were more likely to convert to normal BMD status at the lumbar spine (RR: 4.01; 95% CI: 1.34, 11.23; P = 0.043) and total hip (RR: 3.92; 95% CI: 1.12,14.27; P = 0.011) at 5 years, compared with the case of placebo. Raloxifene also significantly reduced total cholesterol (-5.5%; P < 0.001) and low-density lipoprotein cholesterol (-8.7%; P < 0.001), compared with the case of placebo. No significant changes in high-density lipoprotein cholesterol (P = 0.257) or triglycerides (P = 0.620) were detected. Incidence of hot flashes was higher among women taking raloxifene compared with those taking placebo [raloxifene, 47 (28.8%); placebo, 21 (16.8%); P = 0.017]. Women taking placebo or raloxifene reported a similar incidence of vaginal bleeding (P = 0.999) or of mean endometrial thickness of more than 5 mm at baseline and at each visit, up to the 5-year endpoint (P >/= 0.349). No diagnoses of endometrial hyperplasia or endometrial cancer were made in either treatment group. CONCLUSIONS: Five years of raloxifene treatment in healthy postmenopausal women preserves BMD, significantly reduces the likelihood of development of osteoporosis, and was not associated with an increased rate of vaginal bleeding, endometrial hyperplasia, or endometrial carcinoma, compared with the case of placebo.

Bone Density↗

PubMedDate not supplied

A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women.

OBJECTIVE: Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. DESIGN: Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. RESULTS: Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. CONCLUSIONS: These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.

Double-Blind Method↗

PubMed2001

Clinical features affecting the results of estrogen replacement therapy on bone density in Japanese postmenopausal women.

Although estrogen replacement therapy (ERT) has been established as an effective treatment for postmenopausal bone loss, the clinical features which predict the effects of ERT have not been well investigated in Japanese postmenopausal women. We analyzed the role of physical factors influencing the effect of ERT on vertebral bone mineral density (BMD) in 94 Japanese postmenopausal women treated for 2 years or longer. The increase in BMD with ERT is 17.6 +/- 27.6 mg/cm(2)/year (mean +/- SD) during the first 2 years. Rates of BMD change were negatively correlated with the estimated initial BMD, and positively correlated with age and years since menopause, while no correlation was noted with the body mass index by a simple correlation analysis. The relationships between BMD change and estimated initial BMD or age also held in a multiple regression analysis. The estimated initial BMD and age together accounted for 34.4% of the BMD change during ERT. Furthermore, there were very few (2.4%) nonresponders with a negative linear regression slope of BMD in the osteoporosis and osteopenia group, although 32.7% of the normal initial BMD group were nonresponders. These results suggest that the initial BMD and age are potent predictive factors of the ERT effect on BMD change in Japanese postmenopausal women.

Adult↗

PubMed2006

Identification of an aromatase haplotype that is associated with gene expression and postmenopausal osteoporosis.

CONTEXT: Osteoporosis has a significant genetic component. The aromatase-dependent conversion of androgenic precursors is the main source of estrogens in postmenopausal women. OBJECTIVE: The objective of the investigation was to study the relationship of a set of single nucleotide polymorphisms (SNPs) of the aromatase gene with osteoporosis and determine their functional influence on gene transcription. DESIGN, PARTICIPANTS, AND METHODS: This was a case-control study including 135 women with vertebral fractures due to postmenopausal osteoporosis and 312 controls. Alleles at four SNPs situated between exons I.2 and 3 were determined by Taqman assays. Total aromatase RNA and differential allelic-specific expression were studied by RT-real time PCR in adipose tissue samples taken from 50 individuals. RESULTS: The SNPs studied were in strong linkage disequilibrium. A common haplotype, present in about half of the population, was identified as being associated with an increased risk of fractures (odds ratio 1.8, 95% confidence interval 1.2-2.8, P = 0.006). There was evidence of differential allelic expression. In heterozygous individuals, transcripts bearing T alleles at rs700518 SNP (which were included in the risk haplotype) were less abundant than those with the alternative C alleles (P < 0.001). Total aromatase expression was four times lower in fat samples from individuals who were homozygotes for the unfavorable alleles than in the opposite homozygotes (P = 0.007). CONCLUSIONS: A common haplotype of aromatase associated with gene expression is also associated with the risk of osteoporotic vertebral fractures in postmenopausal women. These data are in line with the hypothesis that the aromatase-dependent synthesis of estrogens plays an important role in bone homeostasis in postmenopausal women.

Adult↗