Bone Mass,Serum Lipids,and Lipoproteins during Three Years of Opposed Estrogen Replacement

The effects of three years of low dose or moderate dose hormone replacement on bone mass and serum cardiovascular risk factor were measure in post-menopausal women. After six months of calcium supplementation, women chose to add hormone replacement therapy (HRT) or to remain on calcium. Those choosing hormones were randomized either to a law dose or moderate dose group. The low dose regimen was 0.3 mg/d equine estrogen and 2.5 mg/d medroxyprogesterone for three years. The moderate dose group rook 0.625 mg/d equine estrogen (days 1-25) and 5 mg/d medroxyprogesoerone (days 16-25) for the first two years, after which the cyclical regimen was replaced with a continuous regimen of 0.625 mg/d dequine estrogen and 2.5 mg/d medroxyprogesterone.Low dose HRT prevented the loss of radius bone mass observed in subjects taking calcium only. Moderate dose HRT also protected radius bone mass, increased lumbar spine bone mass, and improved the ratio of serum high density to low density lipoproteins.     

Bone density effects of continuous estrone sulfate and varying doses of medroxyprogesterone acetate. Ogen/Provera Study Group.

OBJECTIVE: To establish the optimum oral daily dose of medroxyprogesterone acetate with estrone sulfate for 2 years to maintain bone density. METHODS: A multicenter, double-blind study involved 568 postmenopausal women given estrone sulfate, 1.25 mg, and randomized to receive 2.5, 5, or 10 mg of medroxyprogesterone acetate. Bone density analyses of the lumbar spine and femoral neck were done at baseline and 12 and 24 months. RESULTS: There was a significant increase from baseline to 24 months in mean lumbar spine (4.0% +/- 0.27%) and femoral neck (3.2% +/- 0.28%) bone density, with no significant differences between the treatment groups. Factors most influencing bone density changes were baseline bone density and treatment duration. Significant increases were seen in the spine over 2 years; in the hip, those occurred in the first 12 months only. In both sites, lower baseline bone density resulted in greater increases. In the spine only, no previous hormone replacement therapy, higher body mass index, more than 2 years postmenopause, and nonsmoking resulted in greater gains. Once those covariates and center-to-center variations were corrected for, in the spine, the 10-mg group had smaller increases than the other groups. Changes were unrelated to age, parity, calcium, and alcohol intakes in either site. CONCLUSION: Daily estrone sulfate, 1.25 mg, with 2.5, 5, or 10 mg medroxyprogesterone acetate was effective for preventing bone loss in postmenopausal women.     

A study of combined continuous ethinyl estradiol and norethindrone acetate for postmenopausal hormone replacement

In a blinded, prospective, dose-response pilot study of continuous estrogen-progestin replacement therapy, 77 thin, nonsmoking, white women, who were 12 to 60 months postmenopausal and had normal medical histories, were randomly assigned to receive one of five dose combinations of daily ethinyl estradiol and norethindrone acetate (20 micrograms and 1.0 mg, 10 micrograms and 1.0 mg, 10 micrograms and 0.5 mg, 5 micrograms and 1.0 mg, and 5 micrograms and 0.5 mg) or conjugated estrogens 0.625 mg on days 1 to 25 and medroxyprogesterone acetate 10 mg on days 16 to 25. An additional 10 women meeting the same criteria served as a comparison group by taking calcium only. During 12 months of therapy, continuous users had significantly less vaginal bleeding and spotting than did sequential users. As compared with baseline values, bone metabolism and computerized tomographic measurements of vertebral trabecular bone density at month 12 indicated reduced bone turnover and increased density in hormone users. Endometrial biopsy specimens were negative for hyperplasia and neoplasia. The continuous ethinyl estradiol-norethindrone acetate tablet, even at the lowest doses studied, provided the same salutary effects on bone, endometrium, and postmenopausal symptoms as sequential therapy while minimizing annoying vaginal bleeding and spotting.     

A comparison of continuous combined hormone replacement therapy, HMG-CoA reductase inhibitor and combined treatment for the management of hypercholesterolemia in postmenopausal women.

OBJECTIVE: To compare the lipid-altering effects of hormone replacement therapy alone and in combination with HMG-CoA reductase inhibitor in postmenopausal women with hypercholesterolemia. METHODS: This was a prospective randomized controlled trial with 3 parallel groups. The patients (n = 35) were randomly assigned to receive pravastatin 20 mg/day (n = 12); continuous combined hormone replacement therapy (0.625 mg conjugated estrogen/day combined with medroxyprogesterone 5 mg/day) (n = 12); continuous combined hormone replacement therapy plus pravastatin (n = 11) for 16 weeks. RESULTS: Among patients treated with continuous combined hormone replacement therapy levels of total cholesterol (10.7%) and LDL cholesterol (12.6%) decreased significantly (p < 0.05), while levels of high density lipoprotein cholesterol (5%) and triglycerides (6.2%) increased insignificantly (p > 0.05). Patients in the pravastatin group achieved significant reductions of 18.8 and 21.4% in total cholesterol and low density lipoprotein cholesterol levels, respectively (p < 0.05). Among patients treated with a combination of continuous combined hormone replacement therapy plus pravastatin, levels of total cholesterol (20.5%) and low density lipoprotein cholesterol (23.8%) decreased the most, while levels of triglycerides (2.1%) decreased lower than the pravastatin-only group. The mean percentage of the differences between the baseline and treatment levels of the lipids and lipoproteins were not significant between the 3 study groups (p > 0.05). CONCLUSION: No significant difference between hormone replacement therapy alone and in combination with HMG-CoA reductase inhibitor in the treatment of postmenopausal women with hypercholesterolemia was noted in this study. The combination of hormone replacement therapy not only does not adversely affect the lipid-lowering effect of pravastatin alone, but hormone replacement therapy also offers additional benefits in the treatment of hypoestrogenic hypercholesterolemia 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.     

Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy

OBJECTIVE: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. STUDY DESIGN: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 microg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. RESULTS: At 3 months, 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P <.029) and bleeding and/or spotting (22% vs 44%; P <.001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P =.004 and P <.001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P <.05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. CONCLUSION: The 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study.     

Effects of low-dose hormone therapy on menopausal symptoms, bone mineral density, endometrium, and the cardiovascular system: a review of randomized clinical trials.

OBJECTIVES: First, to determine the extent of the effects of low-dose hormone therapy (HT) on menopausal symptoms, bone mineral density, endometrium, and the cardiovascular system, and, second, to determine the adverse effects of low-dose HT. METHODS: A literature review of electronic databases was conducted to identify all prospective, randomized trials comparing the effects of low-dose HT with placebo or standard-dose therapy, using key words such as: hormone replacement therapy (HRT), low-dose HRT/conjugated equine estrogens (CEE)/estradiol, lower-dose HRT/CEE/estradiol, ultra-low-dose HRT/CEE/estradiol, menopause, cardiovascular risk, bone metabolism. RESULTS: Low-dose HT has been shown to improve menopausal and vulvovaginal atrophic symptoms, compared to placebo, and is less likely to give rise to unacceptable side-effects, including irregular bleeding and/or breast tenderness. When compared to standard-dose HT, the low-dose HT has comparable effects on a range of menopausal symptoms and on bone density and has similar beneficial effects on surrogate end-points of coronary heart disease. CONCLUSIONS: A change to low-dose HT has been advocated following adverse findings in recent trials of standard-dose HT. Although a literature review has shown low-dose HT to alleviate menopausal symptoms and maintain or improve bone density with fewer side-effects than standard-dose therapy, further research is required to determine what effect the lower-dose therapy will have on fracture, cardiovascular and breast disease.     

Five years with continuous combined oestrogen/progestogen therapy. Effects on calcium metabolism, lipoproteins, and bleeding pattern

OBJECTIVE--To study the effect of long-term continuous combined oestrogen/progestogen therapy on calcium metabolism, lipoproteins, and bleeding pattern in early postmenopausal women. DESIGN--A prospective, open, controlled study. After initial examinations, control examinations were performed every three months for the first two years and every year for the following three (two) years, with determinations of bone mass, serum lipoproteins, and bleeding pattern. SETTING--Out-patient research clinic at The Department of Clinical Chemistry, Glostrup Hospital, Denmark. PARTICIPANTS--Eighteen healthy women between 6 months and 3 years after a natural menopause, entered in a trial of continuous long-term hormone replacement therapy and a comparison group of 19 age-matched untreated women. INTERVENTION--The treated group received 2 mg of 17 beta-oestradiol combined with 1 mg of norethisterone acetate orally each day continuously for 5 years with a 3 month therapy-free interval after the first 2 years. The women were investigated before treatment, then every 3 months for the first 2 years and every year for the next 3 years for determinations of bone mass, serum lipoproteins and bleeding patterns. The comparison group was followed-up in parallel for the first 4 years. Forearm bone mass was measured with single photon absorptiometry. Blood and urine samples were taken in the morning after an overnight fast and tobacco abstinence. MAIN OUTCOME MEASURES--The effects of hormone therapy on bone mineral content in the forearm, on serum and urine indices of calcium metabolism, on serum levels of total, high (HDL-C) and low (LDL-C) density lipoprotein cholesterol, and bleeding pattern. RESULTS--Bone mineral content in the forearm was stable during the 5 years of treatment, whereas it declined significantly averaging 10% after 4 years in the comparison group. The biochemical estimates of bone turnover decreased to premenopausal level in the hormone group, whereas they remained at a high level in the comparison group. In the hormone group total cholesterol and LDL-C decreased by 20% whereas HDL-C was virtually unchanged. The treatment was associated with minor irregular bleeding in nine women during the first 6 months of treatment, after which no bleeding was experienced. CONCLUSION--Continuous combined oestrogen/progestogen therapy can keep early postmenopausal women free of bleeding episodes for a period of 5 years, after the first 6 months in which spotting occurs in 25%. The therapy prevented bone loss completely. The changes in serum lipoproteins were concordant with a lipid profile associated with a decreased risk of coronary heart disease.     

Preventing postmenopausal bone loss with ossein-hydroxyapatite compounds. Results of a two-year, prospective trial.

OBJECTIVE: To evaluate, in postmenopausal women who refuse hormone replacement therapy (HRT), whether continuous administration of an osseinhydroxyapatite compound (OHC) reduces bone loss and protects from osteoporosis. STUDY DESIGN: Sixty postmenopausal women were included in an open study and were allocated to three groups. The first group (n = 19) received treatment consisting in 3.32 g/d of OHC per day, the second group (n = 21) received 2.5 g of calcium carbonate per day, and the third group (n = 20) was a treatment-free control group. Bone mineral density (BMD), assessed by dual x-ray absorptiometry, was measured prior to and at 12 and 24 months of treatment. RESULTS: Subjects on OHC therapy did not show significant changes related to baseline on bone mass across the study, whereas a significant decrease was detected in the calcium carbonate group during the second year (-3.7%, P < .05) and in the control group at the first and second BMD measurement (-3.5%, P < .05; -5.6%, P < .01). CONCLUSION: Continuous administration of OHC prevents bone loss in postmenopausal women, suggesting that this drug may be useful in the management of postmenopausal bone loss.     

Continuous Combined Piperazine Oestrone Sulphate and Medroxyprogesterone Acetate Hormone Replacement Therapy - A Study of Bleeding Pattern, Endometrial Response, Serum Lipid and Bone Density Changes

Summary: This pilot study was conducted to establish the optimum oral dosage of medroxyprogesterone acetate (Provera) given daily in combination with a fixed dose of piperazine oestrone sulphate (Ogen), as hormone replacement therapy. A group of 32 nonhysterectomized, symptomatic menopausal women were randomly allocated to receive piperazine oestrone sulphate 1.25 mg daily and medroxyprogesterone acetate 2.5 mg, 5 mg or 10 mg daily for a 2-year period. This was an open study and the patients were reviewed at 3-monthIy intervals for 2 years. Vaginal bleeding was reported by 58% of patients after the first 3 months of treatment. There was a gradual decline in the reported incidence of bleeding over the following 6 months particularly by women in the 5 mg and 10 mg Provera group. Only 10% of patients were still recording slight bleeding in the 10 mg group at 12 months. By 24 months all the women in the 5 mg and 10 mg Provera groups had ceased bleeding. There were 2 patients in the 2.5 mg Provera group with persistent proliferative endometrium at 24 months. All the remaining patients had atrophic endometrium. There was no significant difference in serum lipid changes between the 3 groups, but there was an overall reduction in total cholesterol, triglycerides and low density lipoprotein cholesterol in all women. There was no significant difference in bone mineral density changes between the groups over the 2-year period. Endometrial protection with increased incidence of amenorrhoea, without significant adverse effects, was seen with the use of 5 mg and 10 mg of provera.     

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The effect of hormone replacement therapy on postmenopausal bone loss.

Eighty-four postmenopausal women who were randomly allocated to one of four groups, completed a 1 year follow-up. The first group (n = 20) received 0.625 mg/day conjugated estrogens cyclically (CE; 25 days/month). The second (n = 23) received 0.625 mg/day of CE continuously, and the third (n = 17) received 50 micrograms/day of transdermal 17 beta-estradiol cyclically (24 days/month). All these groups also received 2.5 mg of medroxiprogesterone acetate sequentially for the last 12 days of hormone replacement therapy, while the fourth group (n = 24) constituted a treatment-free control group. Dual photon absorptiometry was carried out before therapy and was repeated after 1 year. Serum calcium, phosphate and osteocalcine levels, and the urinary calcium/creatinine and hydroxyproline/creatinine ratios, were measured prior to treatment and 6 and 12 months thereafter. All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous CE treatment group (4.4%, P less than 0.05) and in transdermal group (7.1%, P less than 0.01). Concomitant biochemical effects at 6 and 12 months, reduction in urine calcium and hydroxyproline, reduction in blood calcium, phosphate and osteocalcine, were compatible with the observed effects on bone mineral.     

Amenorrhea rate after switch from sequential hormone replacement therapy to continuous combined administration of low dose estradiol and norethisterone acetate

OBJECTIVE: Patient's wishes for a hormone replacement therapy (HRT) without withdrawal bleedings are decisive for a good compliance. Systematic experience concerning the bleeding profile when switching from a sequential hormone replacement therapy (s.c.HRT) to a continuous combined hormone replacement therapy (c.c.HRT) is sparse. This non-interfering study is designed to investigate the bleeding profile after such a switch. MATERIAL AND METHODS: 1 018 gynaecological centres recruited 3 917 patients pretreated with a s.c.HRT for this study. The switch from the s.c.HRT to the c.c.HRT was performed with a low-dose combination of 1 mg estradiol plus 0.5 mg norethisterone acetate (NETA). The bleeding profile was evaluated after 6 to 9 months of treatment according to the patient's diaries. RESULTS: Amenorrhoea was reached in 74.4 % of the enrolled patients after 3 months, in 90.6 % after 6 months, and in 92.1 % after 9 months of treatment. At the time of the switch to the c.c.HRT, already 32.4 % of the women were free of withdrawal bleedings. Parameters like age of the patients, body mass index (BMI), dosage of the estrogen during pretreatment did not influence the results considerably. 92.7 % of the physicians and 92.5 % of the women rated the combined treatment of 1 mg estradiol and 0.5 mg NETA (Activelle) as satisfactory. CONCLUSION: The switch from a s.c.HRT to a continuous combined treatment with 1 mg estradiol plus 0.5 mg NETA can be performed without problems, resulting in a high rate of amenorrhoea and a high acceptance of physicians as well as patients.     

Continuous combined hormone replacement therapy and risk of endometrial cancer

OBJECTIVE: Postmenopausal women who receive sequential hormone replacement therapy with estrogen combined with progestogen for 10 to 24 d/mo for a prolonged period may have an elevated endometrial cancer risk relative to those who have never received hormone replacement therapy. We investigated whether daily use of estrogen and progestogen (continuous combined hormone replacement therapy) could diminish any excess endometrial cancer risk.Study Design: A population-based study in Washington State obtained interview data from 969 women aged 45 to 74 years with endometrial cancer diagnosed during 1985 through 1991 or 1994 through 1995 and from 1325 age-matched control subjects selected primarily by random digit dialing. Women who had received only continuous combined hormone replacement therapy were compared with women who had only received another hormone replacement therapy regimen or who had never received hormone replacement therapy. RESULTS: The risk of endometrial cancer among users of continuous combined hormone replacement therapy (n = 9 case patients, n = 33 control subjects) relative to women who had never received hormone replacement therapy was 0.6 (95% confidence interval, 0.3-1.3); the risk relative to women who received hormone replacement that included progestogen for 10 to 24 d/mo was 0.4 (95% confidence interval, 0.2-1.1). Most continuous combined hormone replacement therapy use was short-term (<72 months) or recent (in the previous 24 months). CONCLUSION: Women who had received continuous combined hormone replacement therapy for several years did not appear to be at any increased risk for endometrial cancer relative to women who had never received hormone replacement therapy and may in fact be at decreased risk for endometrial cancer.     

Lipid changes after hormone replacement therapy for menopause

Three regimens of hormone replacement therapy were administered to 62 postmenopausal women for a period of 12 weeks and evaluated for their effect on blood lipids. Each group was given a continuous dose of 0.625 mg of conjugated estrogens combined with either a continuous dose of 2.5 mg of medroxyprogesterone acetate or 5.0 mg of medroxyprogesterone acetate, or a cyclic dose of 5.0 mg of medroxyprogesterone acetate on days 17-28 of the cycle. After treatment there was a significant decrease in the total cholesterol (P less than .0007) and low density lipoprotein cholesterol (P less than .0001) together with a significant increase in high density lipoprotein cholesterol (P less than .0029). There was no significant difference in the response of the blood lipids to the three hormone groups. Therefore, preference would depend on the combination that caused the least bleeding or amenorrhea.     

小剂量雌激素对绝经后骨质疏松症的治疗

目的:探讨减半剂量雌激素联合孕激素和钙剂对绝经后骨质疏松症的防治作用。方法:138例绝经2年以上因骨痛就诊的妇女。①测定用药前血性激素,血、尿骨代谢生化,并与20例未绝经的正常妇女相比较;②绝经者随机分为3组(每组46例),A组给予倍美力0.625mg+安宫黄体酮2mg+钙尔奇D1g/d,B组给予倍美力0.3mg+安宫黄体酮2mg+钙尔奇D1g/d,C组给予安慰剂+钙尔奇D1g/d,均连续用药2年。在用药前、用药后6个月、12个月、24个月分别测定血骨钙素(BGP)、碱性磷酸酶(BAP)、I型羧基末端终肽(CICP)、比林二酚(Pyd)、尿钙(Ca)、肌酐(Cr)、IL-6;行双光子(DEXA)测定骨密度(BMD),并超声测定子宫内膜及钼靶摄片了解乳房情况。结果:①与未绝经组比,绝经后血清E2、BGP、BMD值下降(P<0.05),血FSH、LH,尿Pyd/Cr、Ca/Cr比值增高(P<0.05)。②3组对象用药后3个月,骨痛均有不同程度改善;A组和B组用药后1年骨密度有明显提高,而C组在1年后骨密度呈下降趋势。3组对象治疗过程中均未发现子宫内膜的异常增厚。用药6个月时骨代谢生化指标及血清IL-6水平就有显著下降。结论:绝经后妇女中,小剂量雌、孕激素加钙剂能防治骨质疏松症的发生。     

Low-dose oral combination of 17beta-estradiol and norethisterone acetate in postmenopausal women decreases factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1.

OBJECTIVE: Controversies still persist concerning hormone replacement therapy (HRT) and its effects upon blood coagulation and fibrinolysis. This study was carried out to evaluate possible effects of continuously administered low-dose 17beta-estradiol (E2) and norethisterone acetate (NETA) on coagulation and fibrinolytic factors. METHODS: We conducted a randomized double-blind, placebo-controlled, 1-year study in 120 healthy postmenopausal women. The three groups consisted of a placebo group (n = 40), a group receiving oral continuous combined E2 1 mg and NETA 0.25 mg (n = 40) and a group receiving oral continuous combined E2 1 mg and NETA 0.5 mg (n = 40). RESULTS: The two low doses of E2-NETA induced significantly lower plasma levels of factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1 (PAI-1), compared with placebo treatmen CONCLUSIONS: Low-dose E2 (1 mg) in combination with NETA resulted in favorable changes of factor VII activity and fibrinogen, compared with placebo. The lower plasma levels of PAI-1 may lead to increased fibrinolytic activity. These findings suggest a decreased risk of developing coronary heart disease. Antithrombin activity was also reduced, which may increase the risk of developing venous thromboembolism. The clinical significance of the lower levels of these factors remains to be clarified.     

Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability

Objectives  The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E₂/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy.
Design  A randomised, double-blind, double-dummy, group comparative intervention trial.
Setting  Multicentre study executed in 32 centres in 7 European countries.
Sample  Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45–65 years.
Methods  Participants were randomised to receive 2.5 mg tibolone or 1 mg 17β estradiol plus 0.5 mg norethisterone acetate (E₂/NETA) daily for 48 weeks.
Main outcome measures  Prevalence of vaginal bleeding, hot flushes and adverse events.
Results  The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E₂/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7–9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E₂/NETA (3.2 versus 9.8%; P < 0.001).
Conclusion  Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.     

Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception

OBJECTIVE: The purpose of this study was to determine the rate of early postmenopausal bone loss in women who had used depot medroxyprogesterone acetate contraception through to menopause. STUDY DESIGN: Bone mineral density at the lumbar spine and femoral neck was assessed prospectively over 3 years in 15 women who reached a natural menopause and who did not undergo hormone replacement therapy and in 16 long-term users of depot medroxyprogesterone acetate who discontinued depot medroxyprogesterone acetate only on reaching menopause. Of the latter, 5 women subsequently underwent hormone replacement therapy. RESULTS: Early menopausal bone loss was rapid in the control group (6% from both sites over 3 years), but the users of depot medroxyprogesterone acetate (who did not take hormone replacement therapy) showed little change in bone mineral density. Between-group differences were statistically significant at years 2 and 3 at both sites (P <.03-<.002). In the users of depot medroxyprogesterone acetate who underwent hormone replacement therapy, bone mineral density increased significantly (P <.03) at the lumbar spine and was stable at the femoral neck. CONCLUSION: Women who use depot medroxyprogesterone acetate through to menopause have attenuated rates of bone loss from the lumbar spine and femoral neck, presumably because they have already lost the estrogen-sensitive component of bone.