A cross-sectional study of the effects of hormon replacement therapy on the cardiovascular disease risk profile in healthy postmenopausal women

OBJECTIVE: To assess risk factors for cardiovascular disease in healthy postmenopausal women who had been uninterruptedly on menopausal hormone replacement therapy (HRT) for at least 5 years or who had not received any HRT. DESIGN: Cross-sectional study. SETTING: The Royal Free Hospital and The Middlesex Hospital. PATIENT(S): A total of 256 healthy postmenopausal women were analyzed: 73 were taking tibolone, 60 were taking transdermal E(2), 58 were taking conjugated equine estrogens (E), and 65 were not taking any menopausal therapy. INTERVENTION(S): Cardiovascular disease risk factors measurement. MAIN OUTCOME MEASURE(S): Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein(a), insulin, glycated hemoglobin, high sensitivity C-reactive protein, fibrinogen, total antioxidants, and endothelin-1. RESULT(S): The different types of HRT induced disparate changes in the various markers of cardiovascular disease. Significantly higher high sensitivity C-reactive protein concentrations were found in women receiving conjugated equine E and tibolone than in women who were not taking any therapy. Glycated hemoglobin was significantly lower in women receiving transdermal E(2) and tibolone compared to women not on HRT. Women on tibolone had significantly higher systolic blood pressure. CONCLUSION(S): Because high sensitivity C-reactive protein has recently emerged as an important predictor of cardiovascular disease, the higher high sensitivity C-reactive protein levels observed in women on conjugated equine estrogens and on tibolone have potential important clinical implications.     

Transvaginal ultrasonographic assessment of the endometrium in asymptomatic, postmenopausal women using different HRT regimens containing tibolone or estrogen

OBJECTIVE: To assess the effects of hormone replacement therapy (HRT) on endometrial thickness as measured by transvaginal ultrasonography in asymptomatic, postmenopausal women. STUDY DESIGN: Between 1997 and 2001, 307 women who had no risk factors for endometrial cancer or abnormal vaginal bleeding were enrolled in a study. Patients received 1 of the following HRT modalities: (1) oral equine HRT modalities: (1) oral equine estrogen, (2) oral 17beta-estrogen, (3) transdermal 17beta-estrogen, or (4) oral tibolone. All women taking estrogens were also taking a progestin. Only the patients with endometrial thickness >7 mm underwent endometrial biopsy while taking HRT. RESULTS: Although we observed an increase in serum estrogen levels as compared to the levels before tibolone therapy, changes in endometrial thickness were not statistically significant in patients taking tibolone. CONCLUSION: Endometrial thickness with tibolone closely mimics the naturally atrophic postmenopausal state. Thus, tibolone is suggested for those postmenopausal women who have concerns about HRT.     

Effects of tibolone on plasma homocysteine levels in postmenopausal women

OBJECTIVE: To investigate the effects of tibolone on levels of plasma homocysteine, an independent risk factor for cardiovascular disorders, in postmenopausal women. DESIGN: Prospective, randomized clinical study. SETTING: University hospital. PATIENT(S): Postmenopausal healthy women. INTERVENTION(S): Tibolone (2.5 mg/d) or calcium (1250 mg/d) and conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (5 mg/d) were administered orally for 6 months. Blood samples were collected at the start and the end of therapy. MAIN OUTCOME MEASURE(S): Plasma homocysteine levels. RESULT(S): Administration of tibolone and calcium caused only a 4% decrease in plasma homocysteine levels compared with initial levels. In contrast, conjugated equine estrogens plus medroxyprogesterone acetate caused a 29% decrease in plasma homocysteine levels. CONCLUSION(S): Despite the reported beneficial effect of tibolone on the serum lipid profile, tibolone had no statistically significant effect on serum homocysteine levels in postmenopausal women. The possible cardiovascular protective role of tibolone might be unrelated to its effects on homocysteine levels.     

Effects of transdermal hormone replacement therapy on levels of soluble P- and E-selectin in postmenopausal healthy women

OBJECTIVE: To study the adhesion molecule pattern in postmenopausal women who were not receiving hormone replacement therapy (HRT), HRT users, and fertile women. DESIGN: Case-control study. SETTING: Second University of Naples, Naples, Italy. PATIENT(S): Fifty healthy naturally postmenopausal women and 20 fertile women. INTERVENTION(S): Twenty-six women received no HRT and 24 received continuous transdermal 17 beta-estradiol, 0.05 mg/d, plus oral acetate nomegestrol, 5 mg/d. MAIN OUTCOME MEASURE(S): Levels of the soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin. RESULT(S): Women who did not received HRT showed a trend toward higher levels of soluble E-selectin and had significantly higher levels of soluble P-selectin than did fertile women. Levels of soluble E-selectin and soluble P-selectin were significantly lower in HRT users than in nonusers. Levels of VCAM-1 levels were significantly higher in HRT users than in fertile women, but no significant differences in CAM concentrations were found between the other groups. CONCLUSION(S): Menopause may lead to increased levels of soluble E- and soluble P-selectin, whereas long-term HRT is associated with lower selectin concentrations. This suggests that HRT may have a beneficial effect on endothelial function.     

Conjugated estrogens and tibolone modify the gonadotrophin glycosylation pattern in postmenopausal women

OBJECTIVE: The purpose of this study was to evaluate the changes in the percentage of glycosylation of FSH and LH when using conjugated estrogens and tibolone as hormonal therapy (HT) in postmenopausal compared with regular menstrual cycles. DESIGN: The study had three groups, with 10 participants in each group. The control group consisted of 10 women with normal menstrual cycles, a second group with 10 postmenopausal patients who received conjugated estrogens (Premarin 0.625 mg), and a third group had 10 patients who received tibolone (Livial 2.5 mg). All patients had hormonal determinations before and 6 months after the use of HT. Concavalin-A was used to separate the different glycosylated species of gonadotrophins, defined as unbound (UB: triantennary and bisecting oligosaccharides), weakly bound (WB: biantennary and truncated oligosaccharides), and firmly bound isoforms (FB: hybrid- and high-mannose-type oligosaccharides) in patients serum. Elusions containing the fractions with the isoforms were concentrated using Centriprep membranes (Amicon, Beverly, Mass., USA) and the different gonadotrophins isoforms were quantified by chemiluminescence using an automated system Immulite. RESULTS: The pattern of distribution of gonadotrophins glycosylation in patients treated with conjugated estrogens and tibolone was similar to that observed in the control group with normal menstrual cycles, although with different glycosylation percentage. When the glycosylation percentages were compared for FSH, in the fraction UB the glycosylation did not have significant differences, but the fraction WB that has isoforms with high amounts of oligosaccharides showed a different percentage of glycosylation, where the recovery percentage was bigger with tibolone use (p < 0.05). The FB fraction had similar hormonal glycosylation with estrogens and tibolone use. When compared, LH glycosylation showed significant differences (p < 0.05) in the fraction UB with a bigger glycosylation degree, and in the fraction FB with a smaller glycosylation percentage, both in the tibolone group compared with conjugated estrogens use. CONCLUSIONS: Our results show that there are different percentages of glycosylation of gonadotrophins depending on type of HT (conjugated estrogens vs tibolone), and this could be of utility in young women with ovarian problem since to know the isoform that more favors to cellular activity could help a better therapeutic.     

The insulin-like growth factor-I system and hormone replacement therapy

OBJECTIVE: To determine the effects of hormone replacement therapy on plasma concentrations of free and total insulin-like growth factor (IGF)-I, IGF binding protein (BP)-1, and IGFBP-3. DESIGN: Clinical study. SETTING: Gynecologic clinic at a university hospital. PATIENT(S): Seventy-one postmenopausal women. INTERVENTION(S): Six cycles of four different hormonal replacement therapy regimens: oral conjugated estrogens, transdermal estradiol, oral conjugated estrogens and norethisterone, and transdermal estradiol and norethisterone acetate. MAIN OUTCOME MEASURE(S): Blood samples were collected before and after treatment for measurement of free and total IGF-I, IGFBP-1, and IGFBP-3. RESULT(S): Conjugated estrogen replacement therapy is associated with a decrease in plasma concentration of total IGF-I and increase in concentrations of free IGF-I and IGFBP-1. Transdermal estrogens have no effect on total and free IGF-I and IGFBP-1 concentrations. Oral norethisterone plus conjugated estrogens increased free IGF-I and IGFBP-1 concentrations but did not change IGF-I concentrations. Transdermal conjugated estrogens plus norethisterone acetate increased free IGF-I concentrations but not total IGF-I or IGFBP-1 concentrations. The plasma concentration of IGFBP-3 did not change in any group. CONCLUSION(S): Alterations in total IGF-I concentration can occur depending on the route of hormone replacement therapy administration. Free IGF-I concentrations were elevated in all study groups except that treated with transdermal estrogens.     

绝经后妇女激素补充治疗后同型半胱氨酸及超声心动图改变的初步观察

目的　观察绝经后妇女激素补充治疗 (HRT)后血浆总同型半胱氨酸 [H(e) ]及超声心动图的改变。方法　将受试者分为 4组。Ⅰ组、Ⅱ组为自然绝经妇女 ,各 30例 ,其中Ⅰ组给予HRT(结合雌激素 0 6 2 5mg d ,安宫黄体酮 2mg d ,或者每月后 14d加安宫黄体酮 4mg d) 3个月 ;Ⅱ组不给予HRT ,为对照 ;Ⅲ组 2 0例 ,为已接受HRT1 5年的绝经后妇女 ;Ⅳ组 2 0例 ,为从未应用HRT的绝经后妇女。Ⅰ组、Ⅱ组受试者于接受HRT前及接受HRT 3个月后测定H(e) ;Ⅲ组、Ⅳ组受试者测定H(e) ,并行超声心动图检查。结果　Ⅰ组、Ⅱ组接受HRT 3个月前后H(e)无明显变化 ,Ⅰ组接受HRT前为(9 3± 2 5 ) μmol L ,Ⅱ组为 (9 4± 2 9) μmol L ;Ⅰ组接受HRT后H(e)为 (9 1± 2 8) μmol L ,Ⅱ组为(9 8± 3 6 ) μmol L。两组比较 ,差异无显著性 (P >0 0 5 )。Ⅲ组H(e)明显低于Ⅳ组 ,分别为 (8 0±1 3) μmol L及 (10 3± 3 2 ) μmol L。两组比较 ,差异有显著性 (P <0 0 5 )。Ⅲ组、Ⅳ组的超声心动图检查结果无明显改变。结论　短期应用HRT对H(e)无明显改善 ,长期应用HRT可降低H(e)水平。绝经后妇女应用HRT 1 5年 ,未见超声心动图有明显变化。     

A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms

Patients whose postmenopausal symptoms were being satisfactorily controlled with conjugated equine estrogens, either 0.625 mg/day (n = 57) or 1.25 mg/day (n = 67), participated in a study that compared the efficacy of these oral regimens with that of 17 beta-estradiol, 0.1 mg/day, administered through intact skin. The study was a multicenter, double-blind, randomized, parallel-group trial during which two thirds of the patients who received each dosage of conjugated equine estrogens were changed to an estradiol transdermal system while the remainder continued with conjugated equine estrogens. A total of 124 patients was included in the analysis of efficacy. The analysis revealed no significant differences between the estradiol transdermal system and conjugated equine estrogens in control of hot flushes or other postmenopausal symptoms and no statistically significant differences between treatment groups in regard to estrogen-related side effects. Minor topical reactions to the transdermal systems were reported during only about 20% of study weeks. Thus, transdermal estradiol, 0.1 mg/day, appears to be equally effective as conjugated equine estrogens, 0.625 or 1.25 mg/day, for controlling postmenopausal symptoms and is well tolerated.     

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 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 17β-estradiol 0.05 mg/day, and 70 were given tibolone 2.5 mg/day. We compared the effects of tibolone and transdermal 17β-estradiol on lipids and climacteric 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 ? 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.     

The short-term effects of different regimens of hormone replacement therapy on left ventricular structure and performance in healthy postmenopausal women. A prospective,controlled echocardiographic study

OBJECTIVE: To compare the short-term effects of different hormone replacement therapy (HRT) regimens on left ventricular structure and function in healthy postmenopausal women. METHODS: Forty-two apparently healthy postmenopausal women were evaluated prospectively in this controlled study. Subjects were divided into 4 groups. Ten subjects, who did not accept HRT or any other treatments, formed the control group. The remaining subjects were assigned to receive oral estradiol (2 mg/day) + norethisterone acetate (1 mg/day) (n = 11), transdermal estradiol (0.05 mg) + norethisterone acetate (0.25 mg) (n = 11) or tibolone (2.5 mg/day) (n = 10) therapy during 12 weeks. Echocardiography and Doppler techniques were used to assess the cardiac effects of different HRT regimens. RESULTS: After 12 weeks of treatment, there were significant increases in left ventricular ejection fraction (transdermal group: p = 0.008, oral group: p = 0.003, tibolone group: p = 0.005) and cardiac output (transdermal group: p = 0.003, oral group: p = 0.003, tibolone group: p = 0.021) in all treatment groups. In addition, in the transdermal group, a slight increase in left ventricular end-diastolic volume was significant (p = 0.046). CONCLUSION: These data suggest that oral and transdermal HRT regimens and tibolone may contribute to the improvement in left ventricular systolic function without having an effect on left ventricular structure after short-term administration in healthy postmenopausal women.     

Differential effects of unopposed versus opposed hormone therapy,tibolone, and raloxifene on substance p levels

OBJECTIVE: To evaluate the effects of unopposed therapy (conjugated equine estrogens [CEE]) vs. opposed therapy (CEE and medroxyprogesterone acetate), tibolone, and raloxifene on serum substance p levels. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): One hundred eight postmenopausal women were assigned to four treatment groups: unopposed hormone therapy (HT) (n = 30), opposed HT (n = 48), tibolone (n = 18), and raloxifene (n = 12). INTERVENTION(S): Conjugated equine estrogens, CEE and medroxyprogesterone acetate, tibolone, and raloxifene were administered orally; blood samples were collected before therapy and 3 months after. MAIN OUTCOME MEASURE(S): Serum substance p levels were measured before and at the end of the third month of the treatment.The serum substance p levels were increased in the unopposed HT group after treatment. On the contrary, substance p levels were decreased in the opposed HT group, in the tibolone group, and in the raloxifene group. CONCLUSION(S): Addition of progesterone (P) to estrogen (E) treatment significantly decreases serum substance p levels. Tibolone and raloxifene exert the same effect.     

Effect of hormone replacement therapy and tibolone on serum total homocysteine levels in postmenopausal women

OBJECTIVE: To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. STUDY DESIGN: Ninety-five postmenopausal women aged 41-68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31) or tibolone 2.5 mg (n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. RESULTS: No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: -15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: -3.23%, NS). CONCLUSION: Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results.     

The effect of desogestrel for hormone replacement therapy on the blood lipid profiles of postmenopausal women.

OBJECTIVE: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT). METHOD: Eighty-nine healthy postmenopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests. RESULTS: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05). CONCLUSION: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.     

Long-term postmenopausal hormone replacement therapy effects on bone mass: differences between surgical and spontaneous patients.

BACKGROUND: Hormone Replacement Therapy (HRT) begun soon after spontaneous menopause or oophorectomy minimizes or even reverses the loss of bone that occurs normally during those years. The persistence of this HRT protective effect at long-term on bone density, however, is not well documented. AIM: to evaluate the effects of 5 years of HRT in postmenopausal women on bone mineral density of the lumbar spine. SUBJECTS AND METHODS: The 5-year prospective study enrolled 154 postmenopausal women, of them 136 completed the first year and were considered electible to continue the follow-up. These 136 postmenopausal women were allocated to two groups according their origin: surgical (n=68) and spontaneous (n=68). HRT was prescribed and bone mineral density (BMD) was measured at the lumbar spine prior to commencement of therapy, and then yearly for the duration of the study. All patients received a continuous therapy with standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or 50 microg/day of 17-beta-Estradiol in transdermal therapeutic systems (TTS). Subjects who experienced natural menopause also received 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Treated groups were compared with two non-treated control groups (surgical n=77; spontaneous n=53). RESULTS: Our data showed that HRT increased the BMD of women who had experienced spontaneous menopause. Comparison with a control group revealed that HRT also protected against bone loss in women who had undergone surgical menopause. CONCLUSION: Long term hormone replacement therapy increases bone mineral density in women who have experienced natural menopause, and protects against bone loss in surgically postmenopausal women.     

Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women

OBJECTIVE: To compare changes in mammographic density and the expression of markers of proliferation (Ki67) and apoptosis (Bcl-2) after 1 year of treatment with tibolone and continuous conjugated equine estrogens combined with medroxyprogesterone acetate (CEE-MPA). DESIGN: Comparative, randomized, evaluator-blinded study. SETTING: City research hospital. PATIENT(S): Thirty-seven postmenopausal women. INTERVENTION(S): Tibolone (2.5 mg; n = 18) or continuous conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (5 mg; n = 19) for 1 year. MAIN OUTCOME MEASURE(S): Mammographic density (BI-RADS density score), expression of immunohistochemical markers Ki67 and Bcl-2. RESULT(S): Mean breast density score decreased significantly from 2.22 to 1.67 in the tibolone group, compared with a significant increase in the CEE-MPA-treated group from 1.84 to 2.63. Ki67 expression decreased in 12 of 15, increased in 2 of 15, and remained unchanged in 1 of 15 subjects in the tibolone group, compared with 1 of 19, 15 of 19, and 3 of 19 subjects, respectively, in the CEE-MPA group. Bcl-2 expression decreased in 12 of 15, increased in 2 of 15, and remained unchanged in 1 of 15 subjects in the tibolone group, compared with 5 of 19, 9 of 19, and 5 of 19 subjects, respectively, in the CEE-MPA group. CONCLUSION(S): One-year treatment with tibolone induced a decrease in breast density, with a reduction in proliferation and a stimulation of apoptosis, whereas 1-year treatment with CEE-MPA induced an increase in breast density, with stimulation of proliferation and inhibition of apoptosis, indicating that tibolone effects on the breast are different from those of CEE-MPA.     

Short-term effects of three continuous hormone replacement therapy regimens on platelet tritiated imipramine binding and mood scores: a prospective randomized trial

OBJECTIVE: To evaluate the effects of continuous hormone replacement therapy (HRT) regimens on platelet-tritiated ((3)H-) imipramine binding (Bmax) and mood. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENT(S): Sixty postmenopausal patients. INTERVENTION(S): Randomization to 3 months of daily treatment with tibolone and conjugated equine estrogen (CEE).625 mg combined either with 2.5 or 5 mg of medroxyprogesterone acetate (MPA). The inclusion criteria-matched patients declined for HRT were prescribed daily alendronate. Pre- and posttreatment blood sampling for Bmax and mood evaluation with the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were done. MAIN OUTCOME MEASURE(S): Pre- and posttreatment Bmax and mood scores. RESULT(S): As compared with baseline, both CEE+MPA regimens and tibolone significantly increased Bmax. The comparisons of percent change from baseline Bmax for the CEE+MPA and tibolone groups were similar. All three HRT regimens improved the BDI significantly, while there were no significant changes in the STAI. In the alendronate group, there were no significant changes in both pre- and posttreatment Bmax and mood scores. CONCLUSION(S): Continuous treatment with CEE+MPA and tibolone increases platelet (3)H-imipramine binding and improves mood. Mood-enhancing effects of tibolone may occur through the serotonergic system, as is the case with estrogen.     

Effect of tibolone on markers of cardiovascular disease risk in postmenopausal women undergoing hemodialysis: a pilot study

OBJECTIVE: To assess the effect of tibolone on markers of vascular risk in postmenopausal women who were receiving hemodialysis. DESIGN: One-year open-label study. SETTING: "Zvezdara" University Medical Center, Belgrade, Serbia. PATIENT(S): Twenty-eight postmenopausal women undergoing chronic hemodialysis. INTERVENTION(S): Fifteen women received tibolone 2.5 mg three times per week; 13 other women served as controls. MAIN OUTCOME MEASURE(S): Mean arterial pressure and weight were measured at baseline and at 6 and 12 months, and blood was collected for insulin, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, lipoprotein(a), high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and markers of renal function. RESULT(S): Mean arterial pressure fell in the tibolone but not in the control group at 6 and 12 months versus baseline (mean [SD]: 93 [15] vs. 105 [11] mmHg and 94 [10] vs. 105 [11] mmHg, respectively). Weight, insulin, lipids, lipoprotein(a), hs-CRP, ET-1, VEGF, and renal function remained unchanged within each group, but high-density lipoprotein concentrations fell in the tibolone group after 12 months (1.2 [0.3] vs. 1.6 [0.6] mmol/L). CONCLUSION(S): The effects of tibolone on markers of vascular risk in postmenopausal women who are receiving hemodialysis and healthy women appear to differ. This should be taken into account when tailoring menopausal therapies to the specific requirements of each individual.     

A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes.

During a six-month randomized study involving 460 post-menopausal women, transdermal estradiol has proved to be as effective as oral conjugated equine estrogens in the control of menopausal symptoms and to produce similar estrogenic effects on the endometrium. The group of patients treated with transdermal estradiol showed better compliance and had fewer drop-outs. Moreover, the quality and duration of menstrual bleeding were considered more physiological in the transdermal estradiol group than in the orally treated patients. The trial was carried out with the co-operation of 17 Italian University Centres, under the supervision of Ciba-Geigy Italy S.p.A. Medical Department.