经皮用雌二醇凝胶预防绝经早期骨丢失的三年探索性观察

目的 探索经皮用雌二醇（E2）凝胶在中国妇女中预防绝经早期骨丢失的用法。方法 将60例身体健康、绝经1－5年的妇女,开放随机分为4组,每组15例,采用周期联合方法分别予含0．75或1．5mgE2的经皮17β-E2凝胶（E2凝胶）与100mg微粉化天然黄体酮（MP）或2mg醋甲羟孕酮（MPA）口服,每日睡前应用,每月连用25d,停药5d。用单光子吸收法测前臂皮质骨骨密度;定量CT法测腰椎松质骨骨密度;双能X线吸收法测腰椎与髋部骨密度。在治疗0、6、12、18、24与36个月时分别测量骨密度、骨代谢生化指标,行绝经症状评分。结果 59例（98％）完成1年;56例（93％）完成2年,51例（85％）完成3年。治疗6个月时,4个组症状缓解率平均约80％;2年时腰椎松质骨骨密度升高平均为4．3％－7．5％;3年时第2－4腰椎骨密度升高4．2％－6．2％;股骨颈骨密度升高1．6％－3．8％。与治疗前相比,差异均有显著性（P＜0．05）;4组间比较,骨密度的改善差异无显著性（P＞0．05）。阴道出血率1．5mgE2凝胶＋2mgMPA治疗者、0．75mgE2凝胶＋2mgMPA治疗者较高,其他两组较低。结论 每日0．75mg与1．5mgE2凝胶可有效缓解绝经相关症状,预防绝经早期骨丢失。雌孕激素补充治疗3年,可连续增加腰椎骨密度,增加并维持股骨上端骨密度。     

A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles

OBJECTIVE: To compare the effects of two doses of conjugated equine estrogen (CEE) and two of esterified estrogen plus methyltestosterone (E + A) in surgically menopausal women. STUDY DESIGN: A two-year, parallel-group, double-blind study of 311 women who were randomly assigned to one of four regimens: (1) CEE, 0.625 mg/d; (2) CEE, 1.25 mg/d; (3) esterified estrogens, 0.625 mg, + methyltestosterone, 1.25 mg/d; or (4) esterified estrogens, 1.25, + methyltestosterone, 2.5 mg/d. Study parameters were symptoms, lipids, bone mineral density, side effects and safety. RESULTS: All treatments prevented loss of bone in the spine and hip. The higher E + A dose increased spine and hip BMD more than other treatments (P < .002). All treatments improved menopausal symptoms, with non-significantly greater improvements in well-being and sexual interest in the E + A groups. Similar and significant decreases in low-density lipoprotein were observed in all groups, but high-density lipoprotein and triglycerides were increased only in the unopposed estrogen groups (P < .05). Hirsutism was uncommon and similar in all groups at two years. Discontinuation rates and reasons for withdrawal from the study were similar in both groups. No clinically significant side effects or laboratory test abnormalities were seen. CONCLUSION: As compared to estrogen alone, E + A significantly improved BMD and was well tolerated in surgically menopausal women.     

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.     

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.     

Different cerebrovascular effects of medroxyprogesterone acetate and norethisterone acetate in the New Zealand White rabbit.

OBJECTIVE: The lack of a cardioprotective effect of hormone replacement therapy (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI) may in part be explained by the progestin used. The aim of this study was to elucidate the effect of different progestins on cerebrovascular reactivity in an animal model. METHODS: Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens (CEE) (1.25 mg/day); 17beta-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day + 1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the basilar and posterior cerebral arteries were mounted in myographs for tension recordings. Concentration-response curves to potassium, acetylcholine, sodium nitroprusside, L-NAME (N(omega)-nitro-L-arginine methyl ester), calcium and endothelin-1 were established. RESULTS: Treatment with MPA caused a significant increase in vasoconstriction, expressed as E(max) (mN/mm, mean +/- SEM; p < 0.05), in response to potassium (3.18 +/- 0.19 vs. 2.47 +/- 0.19) and calcium (4.00 +/- 0.22 vs. 3.34 +/- 0.14) in the posterior cerebral artery, and to endothelin-1 (6.88 +/- 0.69 vs. 5.22 +/- 0.30) in the basilar artery, when compared with NETA. This difference was neutralized in the groups receiving the combined treatment of MPA + CEE and NETA + E2. No overall differences were seen between CEE and E2. CONCLUSIONS: In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens, as in the case of HRT, this difference is eliminated.     

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.     

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.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.     

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.     

Evaluation of the effects of various gestagens on insulin sensitivity, using homeostatic model assessment, in postmenopausal women on hormone replacement therapy.

The objective of the present study was to compare the effects of various gestagens on insulin sensitivity in postmenopausal women on hormone replacement therapy (HRT). This prospective study enrolled 156 postmenopausal women who had menopausal status for at least 6 months. Group 1 was treated with 17 beta-estradiol (E2; 2 mg) plus norethisterone acetate (NETA; 1 mg); Group 2 was given E2 (2 mg) plus medroxyprogesterone acetate (MPA; 2.5 mg); Group 3 was given E2 (2 mg) plus dydrogesterone (DG; 10 mg); and Group 4 was given E2 (2 mg) plus micronized progesterone (MP; 100 mg). Group 5 was the surgical menopausal group and was given only E2 (2 mg) continuously. All 156 subjects completed the 3-month follow-up on the trial. The patients were analyzed by using homeostatic model assessment (HOMA) for insulin sensitivity before treatment and 3 months after treatment, comparing the effects of various HRT regimens on insulin sensitivity. No significant differences were found in the baseline characteristics of the patients (p > 0.05). There were no significant differences in mean values of HOMA before HRT among the five groups (p > 0.05). There were statistically significant differences in mean values of HOMA only in Group 1 (E2 + NETA) and Group 3 (E2 + DG) after HRT (p > 0.05). E2 + NETA and E2 + DG were found to improve insulin sensitivity in postmenopausal women after 3 months of treatment, whereas E2 + MPA, E2 + MP and E2 only did not show such an effect in postmenopausal women.     

半水合雌二醇贴剂治疗绝经期症状的临床观察

目的:评价半水合雌二醇贴荆(松奇)治疗绝经期症状的安全性、有效性和药物不良反应.方法:60例绝经期妇女,血清FSH>30 U/L,E_2<109.8 pmol/L,随机分为实验组和对照组.实验组30例,连续使用半水合雌二醇贴剂,每7日更换1次,并每日口服甲羟孕酮2 mg;对照组30例,每日口服戊酸雌二醇1.5 mg,甲羟孕酮2 mg;两组连续治疗12周.用药前及用药12周观察绝经症候群,测血清E_2、FSH、脂蛋白、凝血功能,并观察安全性指标及药物不良反应.结果:两组绝经相关症状评分Kupperman指数有明显降低,绝经症候群有极显著改善,两组E_2均值有明显升高.肝、肾功能,凝血功能及血糖无明显变化;实验组用药后脂蛋白a[Lp(a)]值明显下降,血脂谱其余各项均无明显变化.两组其他安全性指标差异无统计学意义.结论:半水合雌二醇贴剂治疗绝经期症状是安全、有效的,尤其适用于不适宜选择口服途径用药的妇女.     

Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period.

OBJECTIVE: To compare the effects of a 12-week treatment with 17ss-estradiol given alone and in sequential combination with 3.75 mg of nomegestrol acetate (Naemis), or a placebo on biochemical markers of bone turnover in menopausal women. PATIENTS AND METHODS: A double-blind, randomized, placebo and estradiol-controlled multicenter study was conducted. A total of 176 patients who had been menopausal for 1-10 years, hysterectomized or not, having no contraindications to hormone replacement therapy, without any risks factors for osteoporosis, received one of these treatments during 12 weeks: placebo, 1.5 mg estradiol (E(2)) or 1.5 mg E(2)/3.75 mg nomegestrol acetate (E(2)/NOMAC). The primary efficacy variables were the change in bone markers (total alkaline phosphatase, bone alkaline phosphatase and osteocalcin; urinary type-I collagen peptides). RESULTS: The four biochemical markers decreased only in the E(2)/NOMAC group. Bone alkaline phosphatase, osteocalcin and urinary type-I collagen peptides decreased in the E(2) group. For both active treatment groups compared to the placebo group, the changes were statistically significant after a 12-week treatment. There were no statistically significant differences between the E(2) and the E(2)/NOMAC groups except for total serum alkaline phosphatase, whose mean value decreased in the E(2)/NOMAC group but increased slightly in the E(2) group (p < 0.001). Furthermore, after a 6-week treatment, the changes in biochemical markers of bone turnover were similar to those found after 12 weeks. Safety data were satisfactory with regard to estradiol given alone or in combination with nomegestrol acetate. CONCLUSION: These results demonstrated that 1.5 mg E(2) is effective in reducing bone turnover in postmenopausal women and proved that the combination of 1.5 mg E(2) and 3.75 mg nomegestrol acetate has no deleterious effect on bone remodelling.     

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     

Long-term use of gonadotropin-releasing hormone analogs and hormone replacement therapy in the management of endometriosis: a randomized trial with a 6-year follow-up

OBJECTIVE: To identify the effects of long-term GnRH agonist use (6-24 months), with and without add-back therapy, and spontaneous reversibility of bone mass density (BMD) up to 6 years after treatment. DESIGN: A prospective, randomized, long-term follow-up study. SETTING: Obstetrics and gynecology department in a university hospital in the United Kingdom. PATIENT(S): Forty-nine symptomatic women with a laparoscopic diagnosis of endometriosis who had been identified for treatment with long-acting GnRH agonist and volunteered to participate in the study. INTERVENTION(S): Women were randomly allocated to receive hormone replacement therapy (HRT) as a daily oral dose of estradiol, 2 mg, and norethisterone acetate, 1 mg, or no treatment in addition to monthly subcutaneous implants of goserelin acetate for up to 2 years, until cessation of symptoms. Bone mineral density (BMD) at the lumbar spine (C2-C4) and hip (Ward triangle) was measured every 6 months. MAIN OUTCOME MEASURE(S): BMD changes in both groups. RESULT(S): 45 women were followed up for 6 years, at the end of which the groups did not differ significantly in the reduction in mean BMD at the lumbar spine or hip. CONCLUSION(S): BMD reduction occurs during long-term GnRH agonist use and is not fully recovered by up to 6 years after treatment. Use of HRT does not affect this process.     

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.     

The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa

INTRODUCTION: Osteopenia is a serious complication of anorexia nervosa (AN). Although in other states of estrogen deficiency, estrogen replacement therapy increases bone mass, its role in AN remains unresolved. STUDY OBJECTIVE: To study the effect of estrogen-progestin administration on bone mass in AN. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study of 50 adolescents with AN (mean age 16.8 +/- 2.3 yrs) was conducted in a tertiary referral center. MAIN OUTCOME MEASURES: Bone mineral density (BMD) of the lumbar spine and left hip were prospectively measured using dual-energy x-ray absorptiometry at baseline and annually. INTERVENTIONS: Twenty-two subjects received estrogen-progestin and 28 standard treatment (Rx) alone. Estrogen-progestin was administered daily as an oral contraceptive containing 20-35 mcg ethinyl estradiol. All subjects received calcium supplementation and the same medical, psychological, and nutritional intervention (standard Rx). Mean length of follow-up was 23.1 +/- 11.4 months. RESULTS: At presentation, patients were malnourished (79.5% +/- 7.6% IBW), hypoestrogenemic (estradiol 24.7 +/- 10.7 pg/mL), and had reduced bone mass (lumbar spine BMD -2.01 +/- 0.69 SD below the young adult reference mean). Ninety-two percent of subjects were osteopenic and 26% met WHO criteria for osteoporosis. Body weight, and no treatment group, was the major determinant of BMD. At one-year follow-up, there were no significant differences in absolute values or in net change of lumbar spine or femoral neck BMD between those who received estrogen-progestin and those who received standard Rx (80% power of finding a 3% difference in BMD at 1 yr). In those followed for 2-3 yrs, osteopenia was persistent and in some cases progressive. CONCLUSION: In our study population, estrogen-progestin did not significantly increase BMD compared with standard Rx. These results question the common practice of prescribing hormone replacement therapy to increase bone mass in AN.     

Inhibition of ovulation with oral progestins--effectiveness in premenstrual syndrome

Forty-eight women with premenstrual problems were recruited for therapy with either medroxyprogesterone (MPA) or norethisterone (NET), both compared with placebo, in a double-blind cross-over study. Thirty-five (73%) completed the study. At an oral dose of 15 mg daily for 21 days each cycle, both MPA and NET suppressed ovulation, although reduction of urinary total oestrogen excretion was significantly greater with NET. Breakthrough bleeding occurred in 74% of the cycles treated with MPA but only in 22% of those with NET. Symptoms were monitored daily by visual analogue scales. Both progestins significantly reduced breast discomfort, compared with placebo. While MPA significantly improved individual psychological symptom scores by the second active treatment cycle and pooled psychological symptom scores in both active cycles, NET was no more effective than the placebo. Similar numbers from both groups withdrew because of adverse effects. Among the women treated with MPA, the response to active and placebo therapy was related to the pretreatment psychological symptom profile. The results suggest that the beneficial effect of therapy with MPA in women with premenstrual problems was a consequence of disruption of menstrual cyclicity rather than a result of ovulation suppression.     

Initial 17beta-estradiol dose for treating vasomotor symptoms

OBJECTIVE: To compare the efficacy of different doses of 17beta-estradiol (E2) for relief of vasomotor symptoms in menopausal women. METHODS: This was a randomized, double-masked, placebo-controlled, 12-week study in which 333 menopausal women with moderate or severe hot flushes were assigned to treatment with 0.25 mg, 0.5 mg, 1 mg, or 2 mg oral micronized 17beta-E2, or placebo. The number and severity of hot flushes were recorded daily. RESULTS: There was a significant linear correlation between increased dosage of 17beta-E2 and decreased moderate to severe hot flushes per week (P <.001). Rapid reduction in moderate to severe hot flushes was only achieved with 1 and 2 mg, showing a significant difference from placebo at week 4 (P <.05). At week 4, half the women on placebo had reduced moderate to severe hot flushes of at least 52%; the corresponding figures were 56%, 69%, 86%, and 91% for 0.25, 0.5, 1, and 2 mg, respectively. At week 12, all doses except 0.25 mg were significantly better than placebo for reducing moderate to severe hot flushes (P <.001). Although there were no significant differences, twice as many women in the 2-mg group discontinued treatment due to adverse events, compared with the placebo group. CONCLUSION: Oral micronized 17beta-E2 showed a dose-response effect for reducing moderate and severe hot flushes in menopausal women. 17beta-E2 1 mg appeared to be the most useful initial dose.     

Bone remodeling and bone mineral density during pregnancy

INTRODUCTION. The effect of pregnancy upon the maternal skeleton is not fully understood. The information that has been gathered by recent studies is conflicting with regard to overall loss or gain of bone during pregnancy. The aim of the present longitudinal, controlled study, therefore, was to investigate the effect of pregnancy on lumbar spine, wrist, and hip bone mineral density, and to describe bone remodeling during pregnancy as indicated by biochemical markers of both bone resorption and formation. MATERIALS AND METHODS. Thirty healthy women (15 subjects seeking pregnancy and 15 non-pregnant controls) were studied. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry before conception and within 2 weeks after parturition. Markers of bone resorption (urinary cross-linked type I collagen N-telopeptides, serum type I collagen C-telopeptides) and bone formation (total and bone specific alkaline phosphatase, osteocalcin), and total serum calcium were analyzed before, during (once in each trimester), and after pregnancy. RESULTS. During pregnancy, BMD decreased significantly by 3.4+/-4.1% at the lumbar spine and 4.3+/-3.9% at the trochanter, while there was a slight but significant increase in BMD at the proximal 1/3 of the forearm (1.3+/-1.9%). Total hip and femoral neck BMD did not change significantly, nor did total and ultradistal forearm BMD. Bone resorption increased during pregnancy with peak levels in the third trimester (N-telopeptides) or post partum (C-telopeptides), respectively. The increase in bone resorption was accompanied by a significant decrease in serum calcium in the third trimester. Markers of bone formation showed a biphasic pattern with decreases from baseline to the first (total and bone specific alkaline phosphatase) or second trimester (osteocalcin), respectively, followed by a significant increase in the third trimester and post partum. There was no change in any parameter in the control group throughout the study. CONCLUSION. In conclusion, pregnancy is characterized by high bone turnover with resorption preceding formation. During the first and second trimester bone remodeling is uncoupled. Serum calcium decreases as bone resorption peaks in late pregnancy. There are significant decreases in bone mineral density at sites rich in trabecular bone, such as the lumbar spine and the trochanter.     

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.