Anticardiolipin antibodies during hormone replacement therapy in healthy postmenopausal women

Objective: The aim of the study was to investigate IgG and IgM anticardiolipin (aCL) antibodies in the course of hormone replacement therapy (HRT).

Subjects and methods: Thirty clinically healthy postmenopausal women with no history of previous thrombotic events or autoimmune disease were divided in two groups: control group (n=12, mean age 52.9±4.5 years, and 6.2±3.6 years duration of amenorrhea) and a second group (n=18, mean age 53.6±3.5 years, and 5.7±4.5 years of amenorrhea) who were allocated to HRT, containing 2 mg 17-beta estradiol plus 1 mg norethisterone acetate daily for 6 months. ACL antibodies of IgG and IgM isotype were assessed using ELISA and the Kupperman menopausal index (KI) was calculated at baseline and after 3 and 6 months of treatment. Results: HRT had a beneficial effect on climacteric symptoms, evaluated by KI (baseline versus 3rd month and 3rd month versus 6th month, P<0.001). The KI did not change in the control group. The values of IgG at the three studied periods did not change significantly and were 14.1±4.2, 13.1±4.9 and 13.4±3.7 in the HRT group and 12.7±3.1, 13.7±1.8 and 13.1±3.8 GPL, respectively, in the control group. IgM aCL antibodies increased during HRT and were as follows: 7.7±4.8 at baseline, 12.9±5.6 at 3rd month and 9.3±3.2 MPL at 6th month. In the control group, IgM were 8.0±2.8; 7.9±2.3 and 7.1±2.3 MPL, respectively. The differences between the two groups were significant at the third and the 6th month (P<0.01 and P<0.05). Conclusion: These data suggest that HRT is associated with elevation of IgM ACA in healthy postmenopausal women. As IgG aACA are considered more pathogenic, it seems unlikely that the early prothrombogenic effects of HRT can be assigned to ACA.     

Carotid and uterine vascular resistance in short-term hormone replacement therapy postmenopausal users

Objective: To compare the short-term effects of oral hormone replacement therapy (HRT) and placebo on carotid and uterine vascular impedance. Methods: 80 postmenopausal women selected from the outpatient clinic of the Hospital Leonor Mendes de Barros in São Paulo, Brazil, were randomized to oral HRT (estradiol 2 mg/norethisterone acetate 1mg—Kliogest^r) or placebo. Carotid and uterine arteries pulsatility indices (PIs) were assessed by color Doppler at baseline, after 4 and 12 weeks of treatment. Seventy-six women completed the trial, 38 in each group. Results: The carotid PI did not decrease significantly in either group. In the uterine arteries, the drop in PI was steeper and greater for HRT women. Drops occurred despite the supposed counteracting effect of norethisterone acetate. In placebo group, there was no significant difference between 4 and 12 weeks of treatment compared with the baseline. The results did not change when analyzed in a real treatment approach. Conclusion: Oral continuous HRT are effective at 12 weeks in reducing impedance to flow in uterine, but not in carotid circulation. These results suggest that the effects of HRT vary by vascular site, and do not have a detectable short-term vascular effect in the carotid area.     

Tibolone, oral or transdermal hormone replacement and colour Doppler analysis: a prospective, randomised pilot study

Objective: To compare the plasma thromboxane, the plasma viscosity and the Doppler flow modifications induced by tibolone and by oral or transdermal continuous combined hormone replacement therapy. Methods: Forty-two post-menopausal patients underwent either on: oral daily treatment with tibolone (2.5 mg) (Group I; n=14); or continuous oral administration of 0.625 mg conjugated equine estrogens + medroxyprogesterone 5 mg per day (Group II; n=14); or continuous estradiol transdermal supplementation, at a dose of 50 μg per day, + medroxyprogesterone 5 mg per day (Group III; n=14). The duration of the study was 6 months and the patients were submitted to transvaginal ultrasonographic evaluation of pelvic organs; Doppler analysis of the uterine, internal carotid and ophthalmic arteries; thromboxane and plasma viscosity assays in basal condition, and at 1, 3 and 6 months from the beginning of the study. Results: Although the endometrial thickness increased significantly, there were no cases in which it exceeded the normal range (≤5 mm). In all the three groups, the pulsatility index of the uterine, internal carotid and ophthalmic arteries significantly decreased during the therapy showing a reduced impedance since the first month of treatment. Similar variations were observed for the peak systolic blood flow velocity of the internal carotid and ophthalmic arteries. Hormone replacement therapy and tibolone induced a deep, significant and rapid decrease in plasma thromboxane and plasma viscosity levels. Conclusions: Hormone replacement therapy and tibolone seem to have beneficial effects on vascular and hemorrheological parameters.     

Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy

Objective: To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy (HRT). Methods: This prospective, double-blind and placebo-controlled study included 50 postmenopausal women randomly divided into two groups: 25 women on soy germ isoflavones (60 mg per day, capsules) and 25 women on placebo. Inclusion criteria included: non-vegetarian, non-asian women whose last menstruation dated at least 12 months prior to the beginning of the study, with FSH>40 mIU/ml, hot flushes and contraindication for HRT, not using tamoxifen or antibiotic and no disease of the gastrointestinal tract. For 6 months, the Kupperman menopausal index (KMI), the vaginal cytological maturation value (MV) and both hormonal and lipid profiles were assessed. The t-test and analysis of variance (ANOVA) were employed to compare the two groups. Results: In both groups, a decreased KI rate was observed. However, isoflavone was significantly superior to placebo in reducing hot flushes (44% versus 10%, respectively) (P<0.05). After 6 months, the isoflavone group showed increased estradiol levels with unchanged FSH, LH, and vaginal cytology, and a reduction of 11.8% in LDL and an increase of 27.3% in HDL (P<0.05). In the placebo group, just a reduction in MV was observed after 6 months (P<0.05). Conclusions: Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile, showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT.     

Transvaginal color Doppler and CA125 as tools in the differential diagnosis of postmenopausal ovarian masses

Objective: To evaluate whether transvaginal color Doppler and CA125 are valid in differentiating malignant from benign postmenopausal ovarian masses. Methods: Sixty-two women with ovarian masses were studied with transvaginal color Doppler ultrasound before surgery. Serum CA125 levels were also measured. Resistance index (RI) and pulsatility index (PI) were calculated from the waveforms generated from blood flow within the ovary. Results: Benign tumors had a significantly higher pulsatility index (mean 1.23 ± 1.02; range 0.65–2.99) and resistive index (mean 0.78 ± 0.22; range 0.5–1.1) than did malignant tumors. However some overlap in individual values for benign and malignant lesions was found. RI and PI sensitivity were significantly higher than those with CA125 (P < 0.05). Blood flow was detectable by color Doppler imaging in 95% of cases with malignant masses. Conclusion: Doppler sonographic evaluation of resistance and pulsatility indexes in the vessels of ovarian masses together with CA125 increased the sensitivity of prediction of malignancy for pelvic masses, but further work is needed before the validity of these factors is proved.     

Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: A randomized comparative dose-ranging study

Objectives: We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E₂V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E₂) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study. Methods: 440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E₂V+2.5 mg MPA; 1 mg E₂V+5 mg MPA; or 2 mg of E₂+1 mg NETA. After the first 6 months, the E₂V dose was increased to 2 mg in both E₂V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits. Results: Significantly fewer bleeding days were experienced in the first 3 months by women taking E₂V/MPA compared with women taking E₂/NETA. When the dose of E₂V was increased in the E₂V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E₂/NETA group compared with either of the E₂V/MPA groups. The overall continuation rates ranged from 70 to 86%. Conclusions: These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E₂V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT.     

Modification of serum IGF-I,IGFBPs and SHBG levels by different HRT regimens

During the menopause, levels of SHBG, IGF-I and IGFBPs are significantly modified by the use of different HRT regimens. Objective: The aim of this study is to evaluate the influence of three different HRT regimens on serum levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in postmenopausal women. Methods: 41 postmenopausal women requesting HRT were enrolled in the study. Subjects were divided in three groups according to the therapy assigned; Group A: estradiol 2 mg/day+cyproterone acetate 1 mg/day in a cyclic sequential regimen; Group B: estradiol hemihydrate 2 mg/day plus norethisterone acetate (NETA) 1 mg/day in a continuous combined regimen; Group C: estradiol hemihydrate 1 mg/day plus NETA 0.5 mg/day in a continuous combined regimen. Blood samples were drawn before the start of hormonal treatment and after 6 months of HRT. Levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in the serum were measured by means of a specific immunoassay. Results: In group A, a significant increase of SHBG, no change of IGFBPs and a significant decrease of IGF-I were observed; in group B and in group C, no significant variations for any of the parameters were recorded. Conclusions: The association of cyproterone acetate to oral estradiol determines a significant reduction of IGF-I levels and an increase of SHBG; nevertheless, it does not seem to influence the serum levels of the IGF-I binding proteins. The treatment with oral continuous combined estrogens plus androgenic progestins, at low doses, produces minor, not significant, changes in the circulating levels of IGF-I, SHBG and IGFBPs.     

Can climacteric women self-adjust therapeutic estrogen doses using symptoms as markers ?

Objectives: To investigate if disappearance of climacteric symptoms during hormone replacement therapy (HRT) also means good therapeutic level of serum estradiol. The study group comprised of 32 postmenopausal women who had frequent climacteric symptoms. Methods: The women increased the daily treatment doses of percutaneous estradiol every 2 weeks until they felt comfortable with it. Each woman continued at that treatment dose for up to 3 months. Blood samples for estradiol assay were drawn at baseline, every time before the estradiol dosage was increased and at the end of the study. Climacteric symptoms were scored according to the Kupperman menopausal index. Results: Despite the relief of climacteric symptoms, serum estradiol concentration was at a menopausal level (<50 pg/ml) in 22% of the women. In all, 45% of the subjects showed serum estradiol remaining under 60 pg/ml, 29% of the women showed levels of 60–100 pg/ml and 26% showed serum estradiol concentration more than 100 pg/ml. Conclusions: The disappearence of climacteric symptoms during HRT does not quarantee that estrogen levels are sufficiently high for obtaining long term benefits of HRT.     

老年大鼠模型视网膜血管改变及视网膜中央动脉血流变化的高分辨率超声图像检测

背景：视网膜对缺血非常敏感,所以眼部血流动力学的改变可直接影响眼的功能,目前评估眼部血液循环可借助多种仪器设备。 目的：应用高分辨率小动物超声影像系统检测视网膜中央动脉的血流动力学变化,结合视网膜血管消化铺片技术检测视网膜血管结构变化,以明确老年大鼠视网膜中央动脉血流动力学的变化规律。 方法：使用高分辨率小动物超声影像系统测量老年大鼠和青年大鼠及视网膜中央动脉的血流参数,包括收缩期峰值血流速度、舒张末期血流速度,计算搏动指数、阻力指数和收缩期舒张期血流速度比值。同时使用视网膜血管消化铺片技术检测视网膜血管形态学改变。 结果与结论：与青年大鼠组相比,老年组大鼠视网膜血管内皮细胞增生,排列紊乱,管径增粗,血管壁不光滑;视网膜中央动脉血流速度、舒张末期血流速度均降低(P < 0.01),计算搏动指数、阻力指数及收缩期峰值与舒张末期血流速度比值则升高(P < 0.01)。说明使用高分辨率小动物超声影像系统检测视网膜中央动脉收缩期和舒张期峰值速度及阻力指数能较敏感地反映血管的老化过程。     

The effect of HRT on cerebral haemodynamics and cerebral vasomotor reactivity in post-menopausal women

BACKGROUND: Cerebral vasomotor reactivity (CVR) is an index of cerebrovascular dilatory capacity which can readily be assessed using trans-cranial Doppler ultrasound. Impaired CVR is associated with elevated risk of stroke. We performed a randomized, double-blind placebo-controlled trial to investigate the effect of two HRT preparations upon CVR. METHODS: We examined middle cerebral artery mean flow velocity (MFV), internal carotid artery pulsatility index (PI) and CVR to an i.v. acetazolamide bolus using ultrasound in three groups of post-menopausal women randomized to oral estradiol 1 mg+norethisterone 0.5 mg (group N), estradiol 1 mg+dydrogesterone 5 mg (group D) or placebo (group P). The MFV, PI and CVR were measured before and after 3 months treatment. RESULTS: Thirty-eight post-menopausal women were recruited (N=12, D=14, P=12); mean (SE) age was 56.7 (4) years. Neither HRT preparation affected CVR [% (SE) change from baseline N +4.2 (11); D +3.8 (5.5); P +4.0 (3.8); all comparisons P = NS]. PI was significantly reduced in recipients of dydrogesterone [% (SE) change from baseline D -5.4% (4.6); N +12.3 (6.9); P +11.6 (6.9). P=0.025]. Middle cerebral artery velocity was significantly increased following dydrogesterone treatment compared with placebo [% (SE) change from baseline D +6.8 (3.4) N +3.9 (4.2) P -4.6% (3.4) P=0.03 for D versus P]. CONCLUSION: HRT did not alter CVR. The reduced PI and increased MFV suggest HRT-induced intracranial vasodilatation, which is more apparent in dydrogesterone recipients. Differences may exist between progestogens with regard to changes in intracranial haemodynamics.     

The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy

Objective: To determine the changes in levels of urinary NTx at the end of the 6th month of oral and transdermal hormone replacement therapy (HRT) and the effects of additional alendronate therapy for osteoporotic women. Method: Of 66 postmenopausal women 23 were treated with oral estradiol+norethisterone acetate (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The third group consisted of 21 women with osteoporosis (bone mineral density<100 mg/cm³) and treated with oral E+P plus alendronate 10 mg/day. Result: Significant decreases of urinary NTx levels were seen after HRT in all study groups (P<0.05). But the decline of NTx levels was not different between the oral and transdermal HRT groups (P>0.05). There was no additional decrease in the levels of NTx with alendronate therapy (P>0.05) but NTx excretion diminished more in patients with high baseline levels. Conclusion: The decline of NTx at the end of the 6th month of HRT reflects the decrease of bone resorption and it is not related to the route of administration.     

National differences in lipid response to postmenopausal hormone replacement therapy

Objective: To compare the response of serum lipids and lipoproteins to the transdermal hormone replacement therapy (HRT) in five European countries. Methods: Five-hundred and sixty-seven healthy postmenopausal women from Belgium, Finland, the Netherlands, Sweden, and the UK received transdermal estradiol 50 μg daily for 12 months. In addition, two groups received transdermally norethisterone acetate (NETA) continuously, two groups sequentially (170 or 350 μg/day); one group received sequentially oral NETA (1 mg/day), and one group dydrogestrone (20 mg/day). Serum total cholesterol, HDL-, HDL2-, LDL-cholesterol, lipoprotein(a) (Lp(a)), and triglycerides were assessed before and at the end of treatment. Results: No significant national differences existed in the pretreatment levels of lipids and lipoproteins. Mean cholesterol, LDL, Lp(a), and triglycerides decreased during HRT, and HDL and HDL2 increased. Individual changes in responses to HRT were strongly dependent on pretreatment values. In this regard, British women differed from the others: their cholesterol, HDL, HDL2, and Lp(a) responses, when related to the pretreatment levels, were smaller than those of the others. Conclusion: A national difference discovered in response of serum lipids to HRT calls for caution in generalization of lipid data from one nation to another during HRT.     

Vascular reactivity and atheromatous plaques in post-menopausal women on tibolone treatment. Open prospective study with Doppler ultrasonography in internal carotid artery

Background: Arteriosclerosis is the main cause of ischaemic ictus. The middle cerebral and anterior cerebral arteries, which irrigate over 70% of the entire cerebral tissue, spring from the internal carotid. Additionally, it is in the extracraneal vessels that embolism, thrombosis and stenosis originate more frequently. Aim: To evaluate the variations in blood flow (pulsatility index: PI) and to assess the evolution of atherogenic lesions (thickening of the vascular intima and the presence of atheromatous plaques) in the internal carotid artery after tibolone therapy. Subjects and methods: A total of 116 healthy menopausal women were included in this open, prospective and comparative study. Of them, 101 subjects completed the 48 weeks follow-up. Subjects were allocated in two groups: group T (n = 55) received 2.5 mg/day of tibolone daily and group C (n = 61) was a free-treatment control group. To evaluate both resistance to blood flow and the existence and evolution of atheromatous plaques in the internal carotid, an ultrasonograph with a pulsed Doppler was used. The PI was used as the parameter of vascular tone. To study atherosclerotic lesions in the internal carotid artery, we used morphological criteria. Measurements were done before entering in the study, and at 12, 24, 36 and 48 weeks of treatment. Results: After tibolone treatment the PI in the internal carotid artery was observed markedly diminished. Moreover, tibolone reduces both the thickness and length of atheromatous plaque and the degree of vascular stenosis. Conclusion: tibolone administration reduced the carotid atheromatous plaque in thickness and length and improved cerebral perfusion.     

Intrauterine administration of levonorgestrel in two low doses in HRT. A randomized clinical trial during one year: effects on lipid and lipoprotein metabolism

Objective: To investigate the effects on lipid and lipoprotein metabolism of two doses (5- or 10 μg/24 h) of levonorgestrel released from an intrauterine device (IUD) in combination with orally administered estradiol (2 mg estradiol valerate) in perimenopausal women. Design: A 1-year prospective randomized single blind clinical trial. setting: Department of Obstetrics and Gynaecology, Östra Hospital, Göteborg, Sweden. Subjects: Fifty-one perimenopausal women with climacteric symptoms. Outcome measures: Cholesterol in serum and in lipoprotein fractions; high-density lipoprotein 9HDL), low-density lipoprotein (LDL). Triglycerides in serum and in very low-density lipoprotein. Results: In both treatment groups significant elevations in HDL-cholesterol of similar magnitude were observed after 1 month and these changes were maintained during the 12 month observation period. In both treatment groups an initial significant decrease of LDL-cholesterol was observed and the decrement was maintained after 12 months. Serum levels of cholesterol decreased significantly in both groups after 1 month and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5 μg group. However, the initial reduction of serum cholesterol in the LNG-IUD 10 μg group did not differ from baseline after 12 months. Serum triglyceride levels fluctuated during the observation period. No significant changes occurred. Conclusion: continuous combined HRT with intrauterine administration of levonorgestrel, 5- or 10 μg/24 h, in perimenopausal women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol compared with pretreatment values. the low doses of levonorgestrel did not reverse the beneficial effects on lipid metabolism usually seen after estradiol administration.     

Long-term treatment with vaginal estradiol tablets--an impact on uterine artery blood flow

OBJECTIVE: We investigated, using color Doppler ultrasound, possible detectable blood changes of prolonged treatment with 17-beta-estradiol tablets on uterine artery blood flow, in a cohort of low risk postmenopausal women. METHODS: 39 postmenopausal women, who were taking local estrogen therapy for at least 6 months, were examined in the study group. Forty-two women who never used hormone replacement therapy consisted a control group. They were examined with color Doppler ultrasound and the pulsatility index of the uterine artery was measured. The groups were divided into three subgroups (the age, the duration of the postmenopause, and the duration of the treatment) and the data were compared among groups and within subgroups. RESULTS: The overall mean age of the patients was 66 years, the mean duration of the postmenopause was 15 years, the overall mean PI was 1.96 +/- 0.90, and the mean duration of taking vaginal estradiol tablets was 1.97 years for the study group; and 64 years, 13 years and 2.88 +/- 0.96 for the control group, respectively. There was a difference in the mean PI among groups. No significant differences in pulsatility index values in the subgroups were found. CONCLUSION: Long-term treatments with vaginal estradiol tablets in low risk women causes lowering of the uterine artery PI values compared to the women who are not receiving hormone replacement therapy.     

Comparison of the effects of tibolone and estrogen replacement therapy on echocardiographic basic cardiac functions in post-menopausal women: a randomized placebo controlled study

Objectives: This study is designed to investigate and compare the effects of synthetic steroid tibolone and HRT on systolic and diastolic heart functions in post-menopausal women. Methods: This prospective, randomized placebo controlled double blind study was conducted in a university clinic. Fifty-eight non-smoking, otherwise healthy post-menopausal women who did not receive any kind of HRT at least for 3 years within the onset of menopause were included in the study. The patients were randomly allocated to either 2.5 mg per day tibolone (OD, n=18), daily combined 0.625 mg of conjugated estrogens 2.5 mg⁻¹ of medroxy progesterone acetate pill (EP, n=20) or a vitamin pill (n=20) in a double blinded fashion. Their basic systolic and diastolic functions were investigated with HP Sonos-1000 echocardiography using standard positions and windows before and 6 months after the initiation of HRT. Results: Mean age, weight, length of post-menopausal period, heart rate, systolic and diastolic pressures were similar between the groups. At the initiation of the study all groups had similar echocardiographic measurements. However, at the end of 6 months, left ventricular end-systolic and -diastolic volumes were decreased significantly compared to pretreatment and placebo in both EP and OD treated groups. (55.5±18.4 and 53.7±19.1.8 ml; 109.9±19.9 and 110.7±20.8 ml versus 74.5±14.9 and 142.7±19.1 ml, respectively; P<0.05). Improvement in diastolic functions was significant in EP/OD groups compared to pre-treatment period and the placebo groups (E/A 1.34±0.1 and 1.38±0.1 versus 1.18±0.09, deceleration time 204±11.1 and 202.8±27.1 ms versus 237.6±26.9 ms, respectively). Besides increase in left ventricular mass adjusted for height, decrease in left ventricular relative wall thickness, and systemic vascular resistance were significant in EP and OD treated groups than placebo and the pre-treatment measurements. Although improved in both OD and EP groups, the changes in systolic and diastolic functions were significantly higher in the OD treated group. Based on our preliminary results, we may conclude that both EP and OD regimens may improve cardiac performance and age related dysfunctions. Conclusion: The present results may further support that both OD and EP exert many direct effects on cardiovascular system other than metabolic changes regarding lipoproteins. The greater improvement in the OD group may be explained by its weak androgenic activity which is consistent with the in vitro data that androgens are potent relaxing agents on coronary arteries and restores cardiac myosin isoenzyme and ATPase patterns which mandates further clinical studies.     

Longterm effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease

Objectives: The aim of the present study was to evaluate the effects of HRT on symptoms of angina pectoris, quality of life and factors of importance for compliance in women with ischemic heart disease. Methods: Sixty postmenopausal women with coronary artery disease were randomized into three groups: one group received transdermal 17β-estradiol at a dose 50 μg per 24 h alone for 18 days followed by 10 days of combined treatment with medroxyprogesterone acetate (MPA) 5 mg orally; the second group received placebo and the third group received conjugated estrogens orally for 18 days followed by a combined treatment with MPA for 10 days. Clinical evaluations were performed at baseline, after 3, 6 and 12 months. The investigations included gynecological history, occurrence of climacteric symptoms, quality of life evaluation, cardiac history and symptoms of angina pectoris. Results: Forty-six women (77%) completed the study during 1 year. The following cardiac events occurred in the women who completed the study: one patient was hospitalized because of congestive heart failure (patch), two patients because of angina pectoris, one patient because of coronary bypass operation (CEE) and three patients underwent balloon dilatation (placebo), all three on CEE. Among the 14 women who discontinued, two patients had TIA (patch), one experienced palpitations (CEE) and one woman died from myocardial infarction (placebo). Overall improvement in mood and cognitive functions were reported in all three treatment groups. Conclusions: HRT does not seem to have negative effects on symptoms of angina pectoris and seems to increase quality of life in older women with coronary heart disease. It also seems safe from the cardiovascular point of view.     

Influence of hormonal replacement therapy on the regional cerebral blood flow in postmenopausal women

Objectives: The aim of this study was evaluation of the influence of hormonal replacement therapy (HRT) on the regional cerebral blood flow in postmenopausal women. Methods: The study group were 20 postmenopausal women, mean age 48.7 years (S.D. ±4.9 years). The control group were ten regularly menstruating women, mean age 32.6 years (S.D. ±13.2 years). In the studied group we measured the severity of climacteric syndrome with the use of Kupperman index and serum FSH and 17β-estradiol level with the use of radioimmunological method. Cerebral blood flow was measured at rest using Single Photon Emission Computed Tomography (SPECT). Tracer accumulation evaluation was performed in three slices defined as: cerebellar slice, thalamic slice and ventricular slice, the reference region was delineated in the cerebellum. In ten women with an impairment in the cerebral blood flow at the beginning of the study all the tests were repeated after 12 months of HRT. Results: Before HRT mean value of the Kupperman index in the study group was 29.8 points (S.D. ±7.1 points); 17β-estradiol 27 pg/ml (S.D. ±2 pg/ml); FSH 56 IU/l (S.D. ±49.5 IU/l); SPECT study revealed cerebral blood flow impairment in ten women. In all the studied slices cerebral blood flow was lower in the study group than in the controls. After 12 months of HRT the mean value of the Kupperman index in the study group was 13.2 points (S.D. ±2.1 points) (P<0.05); 17β-estradiol 44 pg/ml (S.D. ±25 pg/ml); FSH 36.4 IU/l (S.D. ±57.3 ng/ml); we found cerebral blood flow increase in all studied slices: right cerebellar slice: 5.2%; left cerebellar slice: 4.1%; right thalamic slice: 3.8%; left thalamic slice: 3.3%; right ventricular slice: 7.5%*; left ventricular slice: 6.7%* (* P<0.05). Conclusions: Cerebral blood flow is lower in the postmenopausal women than in regularly menstruating women. HRT increases regional cerebral blood flow and this improvement coexists with an increase of serum 17β-estradiol level.     

Hormone replacement therapy, C-reactive protein, and fibrinogen in healthy postmenopausal women

Objective: To investigate short-term and long-term effects of combined hormone replacement therapy (HRT) on C-reactive protein (CRP) and fibrinogen plasma concentrations in healthy postmenopausal women. Methods: In this cross-sectional study 241 healthy postmenopausal women were enrolled. A total of 81 women were receiving the following treatments for 3 months; transdermal 17β-estradiol (17β-E₂)+medroxyprogesterone acetate (MPA) (n=21), oral 17β-E₂+norethisterone acetate (NETA) (n=27), and conjugated equine estrogens (CEE)+MPA (n=33). The same combined therapies were implemented in another 58 women for 12 months; transdermal 17β-E₂+MPA (n=10), oral 17β-E₂+NETA (n=16), and CEE+MPA (n=32). Control group included 102 healthy postmenopausal women not receiving HRT. The effect of the type and the duration of HRT regimens on plasma levels of CRP, fibrinogen and lipids were investigated. Results: Median CRP concentrations were significantly higher in women receiving oral 17β-E₂+NETA (P=0.037) and CEE+MPA (P=0.0001) for 3 months than in women taking the same types of HRT for 12 months and of those were not on HRT. Median CRP levels were similar in women taking transdermal 17β-E₂+MPA for 3 and 12 months, compared with controls. Fibrinogen levels were not different between nonusers and any group of HRT users. Conclusions: These elevated levels of CRP, which appears very recently as a crucial marker for cardiovascular disease, may be responsible for the early increased cardiovascular risk after starting oral combined HRT. But this increased risk in the early period seems to decrease with long-term use. Transdermal 17β-E₂+MPA had insignificant effect on CRP both in short-term or in long-term use.