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.     

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.     

Effect of trimegestone alone or in combination with estradiol on bone mass and bone turnover in an adult rat model of osteopenia.

The effects of trimegestone (1 mg/kg/day orally), a novel norpregnane progestin, and 17 beta-estradiol (10 micrograms/kg/day subcutaneously), alone and in combination, on bone mass and turnover were investigated using an experimental model of osteoporosis involving ovariectomized rats. An equivalent dose (1 mg/kg/day orally) or norethisterone was used as a reference progestin. Six-month-old rats were ovariectomized and left untreated for 2 months to allow the development of osteopenia. Treatment with a progestin, alone or in combination with estradiol, was then started and continued for 2 months. Bone was assessed by a combination of static and dynamic histomorphometric measurements, by densitometry and by the use of biochemical markers of bone turnover. Ovariectomy induced a pronounced uterine atrophy, which was reversed by estradiol. Trimegestone effectively counteracted the uterotropic effect of estradiol, whilst norethisterone showed a less pronounced antagonistic effect. A severe osteopenia was established in the initial 2 months after ovariectomy, and further bone loss occurred during the 2-month treatment period in animals not receiving estradiol. This effect was associated with a marked increase in both biochemical and dynamic histomorphometric markers of bone turnover, reflecting in an imbalance between resorption and formation. 17 beta-estradiol given alone prevented further bone loss, but neither trimegestone nor norethisterone alone had a beneficial effect on bone mass and turnover. When given in combination with 17 beta-estradiol, however, trimegestone significantly improved its effect on bone mass and turnover. This effect was more potent than that induced by combined 17 beta-estradiol and norethisterone therapy. We conclude that trimegestone, when combined with 17 beta-estradiol, is a more effective progestin than norethisterone in preventing bone loss in adult ovariectomized rats.     

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.     

Evaluation of the effect of tibolone and transdermal estradiol on triglyceride level in hypertriglyceridemic and normotriglyceridemic postmenopausal women.

The objective of the present study was to quantify the magnitude of the association between the change in triglycerides and high-density lipoprotein (HDL) cholesterol levels with the use of tibolone and transdermal estrogen in postmenopausal women with hypertriglyceridemia and normotriglyceridemia. This prospective randomized study enrolled 140 postmenopausal women who had all been hysterectomized for almost a year or more. All subjects completed the 3-month follow-up. The 140 patients were divided into two groups: 70 were given transdermal 17beta-estradiol 0.05 mg/day, and 70 were given tibolone 2.5 mg/day. We compared the effects of tibolone and transdermal 17beta-estradiol on lipids and dimacteric symptoms of the patients. To evaluate the effects of tibolone and transdermal estrogens on triglycerides and HDL cholesterol in postmenopausal women with normotriglyceridemia and hypertriglyceridemia, the women were assigned to five groups according to triglyceride levels (0-100, 101-200, 201-300, 301-400 and > or = 401 mg/dl). We compared changes in the triglyceride and HDL cholesterol levels of each group after treatment. All 140 postmenopausal women completed the trial. No significant differences were found in baseline characteristics of the patients. The tibolone group showed a 22.6% decrease whereas the transdermal estrogen group had a 10.9% decrease in the mean triglyceride levels after 3 months of treatment. The mean decrease of triglyceride level with transdermal estradiol was approximately 11% in normotriglyceridemic and hypertriglyceridemic postmenopausal women. The mean decrease of triglyceride level was 17% in the normotriglyceridemic group and 22-30% in the hypertriglyceridemic groups with tibolone. While the mean HDL cholesterol level increased in the transdermal estrogen group (3.6%), it decreased in the tibolone group (9.3%). We found that tibolone decreased triglyceride levels much more than did transdermal estradiol. However, HDL cholesterol was decreased by tibolone and increased by transdermal estradiol. Tibolone had a more marked decreasing effect in postmenopausal women who had higher initial triglyceride levels. It is suggested that the beneficial effect of tibolone on the cardiovascular system might be greater in women with a high level of triglycerides.     

Evaluation of the hematochemical parameters and bone mineral density of women in physiological menopause treated with hormone replacement therapy with nomegestrol acetate and surgical menopause treated with estrogen replacement. Part II

AIM: The purpose of this paper was to estimate the effectiveness of the use of acetate nomegestrol in relation to indicator hematochemical parameters and bone mineral density (BMD) regarding patients in physiological menopause treated with hormone replacement therapy (HRT), compared to patients in surgical menopause treated with HRT by only administering transdermally hemi hydrate estradiol (estrogen replacement therapy, ERT). METHODS: Sixty women in menopause for at least 6 months ago, aged between 40 and 55 years, were recruited. Thirty of them were given HRT with acetate nomegestrol, and 30 were given only ERT, because they were subjected to general hysterectomy with bilateral adnexectomy. The standards for inclusion were: level of FSH >or= to 30 UI beta-estradiol 相似文献   

Ultrastructural aspects of the postmenopausal endometrium after oral or transdermal estrogen administration

In this report we examined the ultrastructural features of the postmenopausal endometrial cells of women treated with different doses of conjugated equine estrogen (CEE), or transdermal 17beta-estradiol. Eight women with uterine prolapse and at least 5 years of menopause were randomly divided into four groups and treated as follows: (I) no hormonal treatment; (II) 0.625mg/day of CEE orally; (III) 1.25mg/day of CEE orally; (IV) 50microg/day of 17beta-estradiol transdermally. Hormones were administered for 28 days followed by vaginal hysterectomy. Fragments of the endometrium were prepared for transmission electron microscopic analysis. We observed that the postmenopausal endometrium of the untreated group was atrophic with lined superficial epithelial cuboidal cells. The presence of gland and stroma cells with clear cytoplasm containing few organelles and heterochromatin nuclei were also observed. On the contrary, the endometrium of the group that received 0.625mg/day of CEE showed signs of proliferative cells such as the presence of numerous organelles in the cytoplasm and euchromatic nuclei. All of the proliferative effects on the endometrium were more pronounced in the groups that received 1.25mg/day of CEE and 50microg/day of transdermal 17beta-estradiol. We concluded that the ultrastructural proliferative changes of the postmenopausal endometrium induced by 1.25mg/day of CEE were similar to 50microg/day of transdermal 17beta-estradiol.     

Influence of exogenous estrogen administration on serum CA-125 originating from the endometrium.

OBJECTIVES: The purpose of the study is to assess the endometrial contribution of serum CA-125 using exogenous estrogen administration by ruling out ovarian activity. A randomized, controlled, prospective study was designed to assess the endometrial contribution of serum CA-125 and its influence from estrogen administration in menopausal women. METHODS: Twenty menopausal women with intact uterus and ovaries (study group) and 10 cases with previous total hysterectomy with intact ovaries (control group) were included in the study. The mean age of subjects in the study and control groups were similar at 53 +/- 1.9 (S.D.) and 51 +/- 2.7 years. The length of menopause in the study and control groups were also similar at 61.0 +/- 18 and 52.6 +/- 26.5 months, respectively. Group 1 consisted of 10 randomly selected cases and five controls who received 15 days of 50 microg/day transdermal 17beta-estradiol (TE). Group 2 consisted of the next randomly selected 10 cases and five controls who had 15 days of transdermal 100 microg/day 17beta-estradiol (Estraderm-Ciba) administration. Serum CA-125 and estradiol were measured at day 0, 15 by radioimmunoassay (RIA). RESULTS: Serum mean CA-125 levels increased significantly in endometrium intact menopausal women from day 0 to 15 of TE administration in group 2 and 1, 70% and 6%, respectively (P=0.03 and P=0.05, respectively). Interestingly, the increase in serum estradiol levels accompanied this change only in group 2. CONCLUSIONS: These results suggest that endometrial CA-125 secretion to serum is dependent on the dose of administered exogenous estrogen.     

The effects of transdermal estrogen therapy on bone mass and turnover in early postmenopausal smokers: a prospective, controlled study

OBJECTIVE: The purpose of this study was to investigate whether smoking reduces the effects of transdermal estrogen replacement therapy on bone. STUDY DESIGN: One hundred forty-eight women (0.5-5 years after menopause, aged 46-58 years) completed the study. Smokers were assigned randomly to receive either 1.0 mg (n=32 women) or 1.5 mg (n=31 women) of transdermal estradiol in gel daily, and nonsmokers (n=46 women) were assigned to receive 1.0 mg of transdermal estradiol for 2 years. The control group consisted of 17 smokers and 22 nonsmokers. Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover was assessed by measurements of urinary aminoterminal telopeptide of type I collagen and serum aminoterminal propeptide of type I procollagen. RESULTS: Lumbar spine bone mineral density increased similarly in smoking (+3.6%) and nonsmoking (+2.6%) estrogen users (P<.0001 to a decrease of 2.5% in the control group). Femoral neck bone mineral density increased 2.2% to 2.4% in smoking and nonsmoking estrogen users but decreased 0.2% in control subjects (P<.05). Urinary aminoterminal telopeptide of type I collagen decreased similarly in all estrogen-using groups (P<.05 to control group), but serum aminoterminal propeptide of type I procollagen decreased more in smoking than in nonsmoking estrogen users (P=.006). Serum 25-hydroxyvitamin D was 20% lower (P=.004) in smokers than in nonsmokers. CONCLUSION: Transdermal estrogen treatment protects smoking women as effectively as nonsmokers from osteoporosis. Smoking worsens the vitamin D state of postmenopausal women.     

Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic and endothelial effects

OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular beta2-adrenoceptor responsivity. METHODS: By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and beta-adrenoceptor responsivity. RESULTS: When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular beta2-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to pre-menopausal values in the group receiving transdermal estrogen compared with oral estrogen. CONCLUSION: Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/ benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease.     

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.     

Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy.

BACKGROUND: Despite biologically plausible mechanisms for cardiac protection from estrogen therapy, recent clinical trials have suggested possible cardiovascular risk rather than benefit. However, it has been speculated that cardioprotective benefits from hormone replacement therapy (HRT) may be more evident in the early postmenopausal period. We have previously reported early beneficial effects on biochemical markers of endothelial function in healthy women after short-term estradiol replacement therapy. In this study we aimed to evaluate the effect of long-term HRT on different vasoactive factors and oxidative stress in healthy recently postmenopausal women. METHODS: Fifteen women (age 50 +/- 1 years, time since menopause 1.6 +/- 0.1 years) were randomized to a sequential oral and transdermal estradiol regimen (2 mg oral micronized 17beta-estradiol/day or 1.5 mg 17beta-estradiol gel/day). Oral dydrogesterone (10 mg/day, 12 days/month) was then cyclically combined with either of the estrogen therapies for 1 year. Blood samples were collected at baseline and after 1, 2, 6 and 12 months of therapy to evaluate levels of follicle stimulating hormone (FSH), estradiol, 6-keto PGF1alpha (prostacyclin metabolite), nitrite/nitrate, epinephrine, norepinephrine, 8-isoprostane (8-epi PGF2alpha) and lipid profile values. RESULTS: FSH levels decreased (p < 0.001) while estradiol levels increased (p < 0.001) during HRT. Levels of epinephrine (p < 0.001), norepinephrine (p < 0.01), mean blood pressure (p < 0.01) and low density lipoprotein (LDL) cholesterol (p < 0.01) decreased, and nitrite/nitrate levels increased (p < 0.01) during HRT, which did not significantly affect 8-epi PGF2alpha levels. CONCLUSIONS: One-year HRT significantly reduced the levels of catecholamines, mean blood pressure and LDL cholesterol while it increased levels of nitrite/nitrate, indicating cardiovascular benefit in healthy recent postmenopausal women. Levels of 8-epi PGF2alpha did not change, suggesting no evident relationship between HRT and oxidative stress.     

Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women.

Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we studied the effects of ospemifene on bone turnover in postmenopausal women. This was a randomized, double-blind study in which 159 healthy postmenopausal women received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n = 39) for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring the levels of procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone-specific alkaline phosphatase (bone ALP) in serum. All markers were studied at baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo). CTX values decreased in the 90 mg ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3% (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9 and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo). These results show that ospemifene is effective in reducing bone turnover in postmenopausal women.     

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins.

OBJECTIVE: We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN: Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS: In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION: Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.     

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

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

Bone metabolism in postmenopausal women who were treated with a gonadotropin-releasing hormone agonist and tibolone

OBJECTIVE: To study the bone metabolism in postmenopausal women who have been treated with gonadotropin-releasing hormone agonist (GnRH-a) and tibolone. DESIGN: Prospective, open, controlled clinical trial. SETTING: Department of Gynecology and Obstetrics, University of Catanzaro, Catanzaro, Italy. PATIENT(S): One hundred twenty perimenopausal women with symptomatic uterine leiomyomas (groups A and B), and 40 healthy control women who underwent a normal spontaneous menopause (group C). INTERVENTION(S): Treatment for 12 months with leuprolide acetate plus tibolone (group A) or hysterectomy with bilateral oophorectomy (group B). MAIN OUTCOME MEASURE(S): Lumbar spine bone mineral density (BMD) and bone turnover markers at entry into the study, after medical treatment (only group A), and 12 months after discontinuation medical treatment (group A) or after surgery (group B). The same parameters were noted in healthy women before and 12 months after menopause (retrospective control group, group C). RESULT(S): At the women's entry into the study, no significant difference in BMD and bone turnover markers was detected between groups A and B. In group A, no significant variation in BMD or bone turnover markers was observed 12 months after medical treatment in comparison with baseline. At 12 months after discontinuation of treatment (in women who had achieved menopause) and after surgery, we observed a statistically significant decrease in BMD and in bone turnover markers in both groups in comparison with baseline. At 12 months after they became menopausal, we also observed a statistically significant reduction in BMD and in bone turnover markers in control group C. At the same 12-month follow-up visit, a statistically significant difference in BMD and in bone turnover markers was detected when comparing groups A and B with group C. CONCLUSION(S): Women previously treated with GnRH-a and tibolone similar to women who are menopausal as a result of surgery, have higher bone loss after menopause.     

Enriched post-discharge formula versus term formula for bone strength in very low birth weight infants: a longitudinal pilot study

AIM: To initiate a longitudinal pilot study comparing the effect of nutrient-enriched post-discharge formula (PDF) with standard term formula (TF) on bone strength of very low birth weight (VLBW) infants in the first six months post-term. METHODS: Two matched groups of VLBW infants were randomly assigned to enriched PDF (n=10) or TF (n=10) at corrected age of 40 weeks. Anthropometric measurements of growth and measurements of bone speed of sound (SOS) indicating bone strength and bone turnover markers (bone-specific alkaline phosphatase and cross-linked carboxy terminal telopeptide of type I collagen) were taken at term and at three and six months corrected age. RESULTS: The anthropometric measurements of infants fed PDF and TF were comparable at three and six months corrected age. Bone SOS of the PDF group increased from 2760+/-113 m/s at term to 2877+/-90 m/s and 3032+/-60 m/s at three and six months corrected age, respectively (P<0.001). Likewise, bone SOS of the TF group increased from 2695+/-116 m/s at term to 2846+/-72 and 2978+/-83 m/s at three and six months, respectively (P<0.001). No statistically significant difference was found between the groups in terms of growth and bone SOS measurements. The levels of both bone turnover markers decreased significantly during the study period (P<0.001 for both groups). CONCLUSION: Feeding with PDF after term had no short-term beneficial effect on bone strength and bone turn-over of VLBW infants.     

戊酸雌二醇对去卵巢大鼠骨质疏松的治疗作用

目的评价国产戊酸雌二醇对去卵巢大鼠骨质疏松的治疗作用.方法雌性健康未交配Wistar大鼠42只,于6月龄时分别行去卵巢和假手术,分组并行如下处理(1)治疗前对照组(8只)于去卵巢后6周处死;(2)治疗末对照组(8只);(3)假手术组(8只);(4)去卵巢17β雌二醇治疗(O+E)组(9只)去卵巢后6周予17β雌二醇20μg@kg-1@d-1皮下注射;(5)去卵巢戊酸雌二醇治疗(O+EV)组(9只)去卵巢后6周予戊酸雌二醇800μg/kg@d-1经胃肠道给药,后4组于去卵巢后14周处死,留取右侧胫骨、股骨及血标本,处死前收集24h尿标本,分别进行骨组织计量学、外周骨定量CT检查、股骨远端凹入实验,以及骨吸收指标脱氧吡啶啉等测定.结果去卵巢后,骨矿盐含量(骨量)减少,骨小梁结构稀疏,骨吸收和骨形成指标均增加.股骨远端松质骨骨量和骨矿盐密度(骨密度)显著降低,松质骨最大载荷和刚度均明显下降.与治疗末对照组相比,O+E和O+EV组骨吸收指标尿脱氧吡啶啉分别下降54.6%和77.4%(P均＜0.01),骨转换受抑制,胫骨近端次级骨小梁的体积比率分别增加122.3%和119.7%[(12.9±0.8)%和(12.8±0.9)%与(5.8±1.3)%比较,P＜0.01],骨小梁的结构得到改善.O+E和O+EV组股骨远端松质骨骨矿盐密度较治疗末对照组分别增加99.5%和128.4%,分别为(258.9±16.9)和(269.2土24.3)mg/cm2比(117.8±30.4)mg/cm3(P＜0.01).O+E组的股骨远端松质骨最大载荷和刚度均较治疗末对照组有显著增加(P均＜0.05),以上各指标在0+E和0+EV组之间差异无显著性.结论戊酸雌二醇能有效地抑制去卵巢大鼠过高的骨转换,使小梁骨骨量增加,结构改善,松质骨的力学特征得到改善.     

Effect of conjugated equine estrogen in combination with two different progestogens on the risk factors of coronary heart disease in postmenopausal Chinese women in Taiwan: a randomized one-year study

BACKGROUND: To compare the effect of hormone replacement therapy (HRT) using estrogen plus dydrogesterone or estrogen plus medroxyprogesterone acetate (MPA) on the risk factors for coronary heart disease (CHD) in postmenopausal women. METHODS: A randomized, prospective 1-year clinical trial was designed. All of the postmenopausal women (n = 279) received sequential conjugated equine estrogen (CEE) at a dose of 0.625 mg/day for 25 days (days 1-25) of each month. These women were also randomly assigned to receive either dydrogesterone 10 mg/day (E + D group, n = 140) or MPA 5 mg/day (E + P group, n = 139) for 14 days (days 12-25) of each month. Serum biochemical markers, lipoproteins, plasma prothrombin time (PT), partial prothrombin time (PPT) and antithrombin III-antigen (ATIII-Ag) were analyzed at baseline, and after 6 and 12 months of treatment. RESULTS: Liver function, renal function, PT and PPT did not change significantly during the 12-month trial. The E + D group had a more pronounced increase in high density lipoprotein cholesterol (HDL-C) than the E + P group (10.6% vs. 2.7%) after 12 months of treatment (p < 0.05). Both groups showed reduced concentrations of total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C) and ATIII, whereas triglyceride (TG) was increased at the end of the trial (without intergroup difference). CONCLUSIONS: Our study demonstrated a favorable effect on lipoprotein profiles with both hormone replacement therapy regimens. Dydrogesterone appears to be superior to medroxyprogesterone acetate from the perspective of modification of coronary heart disease risk factors.     

绝经后不同时期骨丢失的初步探讨

目的探讨妇女绝经后早期与晚期的骨丢失特点及骨转换规律,评价生化指标对预测骨丢失的意义。方法对３２例绝经１～３年（绝经早期组）妇女及３３例绝经１５～３０年（绝经晚期组）妇女,在试验初始（０个月）、６、１２个月分别测定骨密度、血总碱性磷酸酶、骨钙素、骨碱性磷酸酶、尿钙／尿肌酐、尿吡啶啉。结果绝经早期组妇女６、１２个月脊柱平均骨丢失率为１．３％、２．６％;股骨部位骨丢失不明显;腰椎骨丢失率＞３％（快速丢失）的１５例,＜３％（慢速丢失）的１７例。绝经晚期组６、１２个月股骨颈,Ｗａｒｄ＇ｓ三角骨丢失率分别为１．３％、１．９％,５．３％、４．６％,腰椎骨丢失不明显。两组尿吡啶啉随时间呈上升趋势,血骨钙素、骨碱性磷酸酶水平随时间变化趋势相似。生化指标与腰椎骨丢失率之间无相关性。结论绝经早期妇女骨丢失以腰椎部位敏感,快速与慢速骨丢失者约各占一半。绝经晚期妇女骨丢失以股骨颈、Ｗａｒｄ＇ｓ三角区显著,以慢速骨丢失者为主。两组妇女骨转换均增强