Comparison of soft tissue body composition in postmenopausal women with or without hormone replacement therapy considering the influence of reproductive history and lifestyle

OBJECTIVES: To examine long-term effects of at least 5 years' conventional hormone replacement therapy (HRT), reproductive history and lifestyle on fat mass and muscle mass in postmenopausal women. RESEARCH DESIGN AND METHODS: A cross-sectional retrospective approach was used, including 64 healthy women (56-69 years, mean age 63.4 years). Hormone users were compared with age-matched non-users with respect to (a) type of HRT used (oestrogen vs oestrogen plus gestagen vs no hormones), (b) categories of oestrogens used (oestradiol-based oestrogens vs conjugated equine oestrogens vs no oestrogens) and (c) categories of gestagens used (testosterone derivatives vs progesterone derivatives vs no gestagens). Data on hormone use, reproductive history (age at menarche, age at menopause, number of years postmenopausal, number of children) and lifestyle (physical activity level, alcohol consumption, smoking habits) were collected by questionnaires. Body composition was analysed by multiple-frequency bioelectrical impedance analysis, estimating fat mass, fat-free mass and body cell mass as absolute values (FM, FFM, BCM, respectively) and percentages of body weight (% FM, % FFM, % BCM). RESULTS: Analysis of covariance, adjusting body composition variables for body mass index, showed that (a) unopposed oestrogen users, oestrogen plus gestagen users and non-users did not differ significantly in body composition variables, (b) users of oestradiol-based oestrogens had significantly more BCM than oestrogen abstainers (p < 0.05), (c) users of testosterone-based gestagens had more BCM than gestagen abstainers (p = 0.05). Stepwise multiple regression analyses, including HRT-related, reproductive and lifestyle variables, indicated that the duration of HRT (p < 0.05) and physical activity level (p = 0.01) were significant positive predictors of % BCM, whereas the number of children significantly positively predicted FM and % FM (each p < 0.05). No significant associations between fat-free mass and HRT were found. CONCLUSIONS: The results suggest that conventional doses of oestrogens and gestagens used in HRT might be a factor in preserving muscle mass after long-term administration. It is recommended that BCM is used instead of FFM as an indicator of muscle mass. Studies relating muscle mass to HRT in postmenopausal women should consider physical activity as a possible confounding variable.     

Plasma adiponectin levels in postmenopausal women with or without long-term hormone therapy

OBJECTIVE: Recent large, prospective, randomized studies show that hormone therapy (HT) does not confer a protective effect against cardiovascular disease (CVD) but may in fact increase cardiovascular events. Low plasma adiponectin levels are considered to be related to the development of atherosclerosis and CVD. The purpose of this study was to determine the effect of long-term hormone therapy on plasma adiponectin levels in postmenopausal women. METHODS: We recruited a total of 88 postmenopausal women aged 55-69 years old. Our sample consisted of 44 women who had undergone estrogen plus progestogen therapy (EPT) for more than 5 years and 44 age-matched women who had not received HT. We measured plasma adiponectin levels, the serum levels of their lipid profiles, high-sensitivity C-reactive protein (hs-CRP), fasting glucose levels, fasting insulin levels and estradiol levels. Their medical histories including their age at menopause, vitamin use, exercise, alcohol ingestion and cigarette smoking were also assessed by a questionnaire. RESULTS: The mean duration (mean+/-S.D.) of HT was 8.4+/-2.4 years. The mean serum estradiol level (mean+/-S.D.) of the HT group was 47.9+/-36.8 pg/L, significantly higher than that of the non-HT group (p<0.01). Plasma adiponectin levels were significantly lower in the HT group than in the non-HT group (p<0.05). Plasma adiponectin levels were inversely correlated to cholesterol, triglycerides and HOMA-IR (r=-0.33, p<0.05; r=-0.40, p<0.01 and r=-0.30, p<0.05, respectively) in the non-HRT group, but such correlations were not seen in the HT group. In the multivariate analysis, hormone therapy and serum estradiol levels were the independent factors associated with plasma adiponectin levels after adjustments were made for potential confounders. CONCLUSION: Plasma adiponectin levels were significantly lower in postmenopausal women with long-term HT than in those without HT, suggesting that long-term HT may modulate plasma adiponectin level in postmenopausal women.     

Selective sparing of brain tissue in postmenopausal women receiving hormone replacement therapy

Determining the benefits and/or drawbacks of hormone replacement therapy (HRT) on women's health is an imperative public health goal. Research in rodents suggests benefits of estrogen on neuronal growth and function. However, little research has investigated the effects of HRT on brain tissue in humans. We used high-resolution magnetic resonance imaging and an optimized voxel-based morphometric technique to examine the effects of HRT on brain volume in postmenopausal women. We report two main results: (a) HRT is associated with the sparing of grey matter in prefrontal, parietal, and temporal brain regions and white matter in medial temporal lobe regions, and (b) longer durations of therapy are associated with greater sparing of grey matter tissue. HRT should be considered a possible mediator of age-related neural decline in both grey and white matter tissues.     

Effect of percutaneous androgen replacement therapy on body composition and body weight in postmenopausal women

Objectives: This study was carried out to assess the effect of topical androgen replacement therapy on body weight, body composition and fat distribution in postmenopausal women. Methods: 39 healthy postmenopausal women (51.4±2.24 years), with increasing body weight, were prospectively studied for 6 months. Body composition (fat mass, kg, %) was measured by means of dual-energy X-ray absorptiometry (DXA). Hormonal and lipid parameters were also measured. Subjects were divided into two groups. An androgen gel (group A) or placebo gel (group P) was topically administered to the abdominal and gluteo-femoral regions. DXA was performed before commencement of topical treatment and after 6 months. Results: A highly significant total body weight reduction was found in group A (68.0±13.1 to 65.4±11.8 kg). Abdominal fat (37.3±11.2 to 35.1±9.7%), gluteo-femoral fat (46.3±6.6 to 45.4±7.7%), total body fat (38.2±7.9 to 36.1±8.6%) and BMI (24.8±4.3 to 23.7±3.8) were also found to have decreased significantly in this group. No significant reduction in body weight (kg) and body fat (%) could be measured in the placebo group. No influence on lipid parameters was found although total testosterone increased significantly in group A (0.29±0.24 to 0.72±0.17 ng/ml). Conclusions: Topically applied androgen is capable of reducing abdominal fat accumulations as well as total body weight in postmenopausal women with unexplained weight gain. In contrast to systemic androgen application, topical administration has no effect on the lipid profile. Gluteal fat, however, is less effectively influenced by androgens.     

Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy

AIMS: In order to assess the effects of menopause and hormonal replacement therapy (HRT) on body weight and body fat distribution (determined by dual energy X-ray), early postmenopausal women were given either oral calcium (500 mg/day, control group, n=13) or HRT, a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n=18; Climen, Schering). RESULTS: There were no differences in basal body weight and body fat distribution in the two groups before the study. In control group, a significant (P<0.05) increase in body weight (from 63.5+/-2.0 to 68.7+/-2.0 kg after 36 months) paralleled a shift to a prevalent central, android fat distribution with a slight but significant (P<0.05) increase in total body fat mass (from 23.4+/-2.1 to 29.1+/-2.1 kg), an increase in trunk (from 10.1+/-0.4 to 12.7+/-0.4 kg, P<0.05), arms (from 2.4+/-0.2 to 2.9+/-0.2 kg, P<0.05) and legs (from 6.5+/-0.4 to 7.8+/-0.4 kg, P<0.05) fat. In the HRT group total body bone mineral showed a significant increase (from 1086+/-21 to 1128+/-19 mg/cm(2), P<0.05) increase after 36 months, with no significant increase in body weight (from 62.6+/-1.8 to 65.0+/-1.9 kg), and no modifications in trunk (from 10.0+/-0.2 to 10.1+/-0.2 kg) and arms (from 2.4+/-0.1 to 2.6+/-0.1 kg) fat, but a significant increase in legs fat (from 6.9+/-0.3 to 9.9+/-0.4 kg, P<0.05). CONCLUSION: Present results demonstrate that menopause is associated with an accelerated increase in body weight and body fat, with a prevalent central, android fat distribution, that can be counteracted at least in part by oral HRT.     

Serum leptin levels and body composition in postmenopausal women: effects of hormone therapy

OBJECTIVE: To confirm the effect of postmenopausal hypoestrogenism and hormone therapy (HT) on body composition and serum leptin levels. DESIGN: Prospective, longitudinal study evaluating body composition (body mass index, and total and percent fat mass and lean mass measured at the arms, legs and trunk) with dual-energy x-ray absorptiometry and serum leptin levels by radioimmunoassay in 44 healthy postmenopausal women randomized to receive either no treatment (n = 22) or transdermal 17beta-estradiol (50 microg/day) in continuous regimen and nomegestrol (5 mg/day for 12 days/month) in a sequential regimen (n = 22). RESULTS: One year after the beginning of the study, in untreated women, total and trunk fat mass and percent fat were significantly increased, whereas trunk lean mass was significantly decreased. On the contrary, women treated with HT did not show any significant difference in body composition parameters. In untreated women, serum leptin levels were significantly increased at the end of the study in comparison with baseline values. Serum leptin levels at the other times evaluated were not significantly different from baseline values. In women treated with HT, serum leptin levels did not show significant changes throughout the study. CONCLUSIONS: Untreated postmenopausal women show an increase in total and percent fat mass and a centralization of fat distribution. Serum leptin levels parallel this increase, resulting in significantly higher levels 1 year after the study. Women treated with HT are protected against these changes. This may represent a protective mechanism against cardiovascular diseases.     

Vaginal microflora in postmenopausal women on hormone replacement therapy

To study the spectrum of vaginal microflora in postmenopausal women on hormone replacement therapy (HRT) and to compare the efficacy of Papanicolaou (Pap) smears with other methods for their detection. Eighty postmenopausal women were recruited for the study. These included 40 women who had attained spontaneous and were on HRT (User 1); 20 hysterectomised women on only estrogen therapy (User 2) and 20 controls (Non users). Their clinical data was recorded and specimens were collected for vaginal cultures (for aerobic bacteria and fungi), vaginal pH, Gram stain and Pap stain on cervical-vaginal smears and toluidine blue on wet smears. Vaginal pH was significantly lower in Users as compared to Non users. Lactobacilli and Gardnerella were more frequently isolated from Users while Bacteroides and E. coli were more common in Non users. Cultures were significantly more sensitive than Gram stained direct vaginal smears in detection of aerobic bacteria; however, Candida could be detected on Gram stain alone in all the cases. Frequency of detection of organisms significantly improved by application of Gram stain to the cervico-vaginal smears. However, clinically relevant organisms like Candida, Gardnerella and Mobiluncus could be identified on Pap smears alone in >50% cases. Lactobacilli could be readily identified in Pap smears in 98% cases. Wet mounts could detect cocci more easily as compared to Pap smears. Altered vaginal microbial profile in post menopausal women receiving HRT may cause bacterial and fungal vaginitis. Although culture studies remain the gold standard to detect these microorganisms, Pap and Gram stains and wet smears provide useful supplements and may be used as alternative procedures especially in resource limited settings lacking adequate culture facilities.     

Effects of hormone replacement therapy on cardiovascular responses in postmenopausal women with and without type 2 diabetes

OBJECTIVE: To determine whether blood pressure (BP) responses to pressor stimuli during hormone replacement therapy are reduced by oral conjugated equine estrogens 0.625 mg/day (ERT) and ERT in combination with 5 mg/day continuous medroxyprogesterone (HRT) in women with and without type 2 diabetes. METHODS: Twenty type 2 diabetic and 20 non-diabetic women completed a three period, randomised, double bind crossover studying the effects of 1 month of therapy of ERT, HRT and placebo on BP responses to mental arithmetic and isometric stress and to intravenous infusions of noradrenaline and angiotensin II. RESULTS: Significant differences were found between the effects of ERT, HRT and placebo therapy on BP responses to mental arithmetic in the women with type 2 diabetes apparently due to a smaller response during ERT therapy. BP responses to mental arithmetic were not affected in non-diabetic women. BP responses to isometric exercise and to intravenous infusions of noradrenaline and angiotensin II were similar in the type 2 diabetic and non-diabetic women and were not affected by ERT or HRT therapy. Plasma renin activity differed significantly between ERT, HRT and placebo therapies in type 2 diabetic women, apparently because of lower levels during ERT and HRT therapy. CONCLUSIONS: ERT and HRT may produce beneficial effects on BP responses to psychological stress and on plasma renin activity in women with type 2 diabetes. BP responses to isometric exercise and to intravenous infusions of noradrenaline and angiotensin II are not altered by ERT or HRT in type 2 diabetic or non-diabetic women.     

Endometrial bleeding in postmenopausal women: with and without hormone therapy

The aim of this study was to present a review of the potential mechanisms involved in the occurrence of endometrial bleeding in postmenopausal women using hormone therapy. Selected literature on the incidence of bleeding in postmenopausal women using estrogen progestogen therapy was reviewed. The incidence of spotting and bleeding in women using continuous-combined hormone therapy was presented. Relevant articles related to the role of angiogenic factors and vasculogenesis in the endometrium, endometrial leukocytes, and endometrial metalloproteinases were used for the review. The cause or etiology of endometrial bleeding with hormone therapy is unknown. Several options are known to alter angiogenesis or be involved in tissue remodeling during normal menstruation. Vascular endothelial growth factor and thrombospondin-1 are proangiogenic and antiangiogenic factors that could cause dysfunction in vasculogenesis that could result in blood vessel fragility and bleeding. The role of pericytes in maintaining vessel morphology and integrity is discussed. Endometrial leukocytes and metalloproteinases are involved in normal menstruation, but their role in postmenopausal bleeding is not clear suggesting involvement of mechanisms in the bleeding. There is limited information on clinical investigation into the etiology of postmenopausal bleeding associated with hormone therapy. The major cause of hormone therapy-related bleeding is unknown. Alterations in angiogenic factors that could result in vascular dysfunction and vessel breakdown provide a working hypothesis as to the potential cause of vessel breakdown.     

Six months of hormone replacement therapy does not influence muscle strength in postmenopausal women

OBJECTIVES: Postmenopausal hormone replacement therapy (HRT) has positive effects on fracture incidence before any effects on bone mineral density can be demonstrated. This has been attributed to increased muscle strength by HRT. This study was designed to evaluate the effect of 6 months of HRT on muscle strength in postmenopausal women. METHODS: Forty postmenopausal women, aged 60-78 were included in the study. They were randomly divided in two groups with 20 women in each group. One group received Menorest 50 microg/24 h (estradiol 4.3 mg) and Gestapuran 2.5 mg (medroxyprogesteron) daily and the other group received placebo treatment. The study was conducted as a double blinded, prospective and placebo controlled trial. Hand grip strength, isokinetic knee flexion and extention, and physical activity were measured before treatment, after 3 and 6 months. Physical activity was estimated using a classification system of physical activity. A JAMAR hydraulic hand dynamometer and a Cybex II dynamometer were used to evaluate muscle strength. RESULTS: Hand grip strength in the right hand, increased significantly in both groups (HRT P<0.001 and placebo P<0.01) and in the left hand in the HRT group (P<0.01). However, there were no differences in muscle strength between the two groups. There was no significant change in isokinetic knee flexion or extension after 6 months in either of the groups. The estimated physical activity increased slightly in the placebo group, but there was no significant difference compared to the treatment group. CONCLUSIONS: Our data suggest that 6 months of HRT does not influence muscle strength in postmenopausal women.     

Ascorbic acid status in postmenopausal women with hormone replacement therapy.

OBJECTIVES: Hormone oral contraceptives affected ascorbic acid status adversely in young women. In vitro, estrogens and progesterone inhibited ascorbic acid accumulation in intestinal cells. This is a pilot study to examine the relation between hormone replacement therapy (HRT) and plasma ascorbic acid levels among a group of healthy non-smoking postmenopausal women. METHODS: Healthy non-smoking postmenopausal women aged 48-72 years, 34 with HRT and 21 without HRT, were recruited in summer, 1997. Their fasting plasma ascorbic acid levels were measured and information on ascorbic acid intakes (diet and supplements) was collected through questionnaires. RESULTS: Women taking HRT in this study did not have significantly lower plasma ascorbic acid levels compared with non-HRT users. When subjects were further divided into groups based on ascorbic acid supplementation, HRT users without supplement had a lower mean plasma ascorbic acid level (54+/-16 microM, n=10) compared with non-HRT users (66+/-14 microM, n=12) (P=0.08 for the effect of therapy). HRT users and non-users taking ascorbic acid supplement had similar plasma levels (66+/-10 microM, n=24; 66+/-12 microM, n=9, respectively). CONCLUSION: HRT does not affect ascorbic acid status of healthy well-nourished non-smoking postmenopausal women that are using ascorbic acid supplement. Future larger case-control or supplement intervention study is needed.     

The effect of hormone replacement therapy on appendicular lean tissue mass in early postmenopausal women

OBJECTIVE: The impact of hormone replacement therapy (HRT) on skeletal muscle mass is still a controversial issue in women's health. Some authors hypothesize anabolic effects, others catabolic. These hypotheses, however, await confirmation by longitudinal observations based on more direct measurements of muscle mass. The aim of the present preliminary study was to evaluate the effect of a 3-year HRT program on appendicular lean tissue mass (LTM(A)) in early postmenopausal women aged 45-54 years. DESIGN: This was a randomized, double-blind and placebo-controlled trial. Women received HRT with 2 mg estradiol valerate combined either continuously with 1 mg cyproterone acetate (days 1-28; n = 15) or sequentially with 75 mug levonorgestrel (days 17-28; n = 15), or placebo (n = 18). Serum estradiol was measured by radioimmunoassay. LTM(A) was measured by dual photon absorptiometry (baseline) and dual energy X-ray absorptiometry (years 2 and 3). RESULTS: Baseline serum estradiol did not show significant correlation with the respective LTM(A) (r = 0.018, p = 0.88, n = 75). Cross-sectional analysis found no significant differences between the intervention groups at any time points. The longitudinal changes between years 2 and 3 showed a trend toward decreasing LTM(A) in those receiving HRT (-0.08 +/- 0.12 kg, n = 30) compared to those receiving placebo (0.12 +/- 0.25 kg, n = 18, p = 0.44). CONCLUSIONS: The present preliminary study did not find significant effects on LTM(A) caused by HRT. The trends toward decreasing LTM(A) in the HRT groups might suggest catabolic rather than anabolic effects. These trends, however, await confirmation by larger clinical trials.     

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.     

Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.     

Fatty acid composition of serum phospholipid of premenopausal women and postmenopausal women receiving and not receiving hormone replacement therapy

OBJECTIVE: To compare the fatty acid composition of serum phospholipid of premenopausal women with that of postmenopausal women receiving and not receiving hormone replacement therapy (HRT). DESIGN: Women between the ages of 43 and 70 were recruited for two separate case-comparison studies. Participants were grouped as either premenopausal, postmenopausal receiving HRT, or postmenopausal not receiving HRT. All participants were required to complete a 3-day dietary record before providing a 12-h fasting blood sample. Fatty acid composition of phospholipids and lipid concentrations was determined from serum samples. RESULTS: The postmenopausal women receiving HRT had significantly higher concentrations of palmitic acid (16:0), palmitoleic acid (16:1), and di-homo-gamma-linolenic (20:3n-6) and significantly lower levels of docosapentaenoic acid (22:5n-3) than the other groups in both studies. In addition, the postmenopausal women receiving HRT had lower levels of behenic (22:0), lignoceric (24:0), and nervonic acid (24:1) in comparison with the postmenopausal women not receiving HRT. CONCLUSION: The results of this study indicate that the fatty acid composition of serum phospholipids in women is influenced by menopausal status and hormone use. These results are of interest because high levels of 20:3n-6 and low levels of docosapentaenoic acid have been associated with increased myocardial infarction plus stroke mortality from cardiovascular disease.     

Determinants of hormone replacement therapy duration among postmenopausal women with intact uteri

OBJECTIVE: To investigate factors associated with hormone replacement therapy (HRT) duration among postmenopausal women with intact uteri. DESIGN: A Cox proportional hazard model on time to HRT discontinuation is estimated for 2,632 postmenopausal HRT users with intact uteri who began a new episode of treatment between January 1990 and December 1994 in Saskatchewan, Canada. RESULTS: Major contraindicating medical events were highly associated with HRT discontinuation among postmenopausal women. Women who were diagnosed with uterine cancer while taking HRT were almost four times as likely to discontinue HRT, and women who were diagnosed with breast cancer while taking HRT were nearly five times as likely to discontinue HRT. Other statistically significant factors associated with the duration of HRT episodes include administration mode and the ability to try different types and strengths of HRT. Women initiating HRT with a transdermal patch were 50% more likely to discontinue it. Women who were willing and able to experiment with different HRT reduced their likelihood of discontinuing by one-half to three-fourths. CONCLUSIONS: Although some of the factors associated with the hazard of HRT discontinuation among postmenopausal women who are taking the treatment for preventive benefits are immutable, clinicians may influence HRT continuation rates through initial drug choice or modifications in drug type or regimen over the course of therapy.     

Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women

OBJECTIVE: The objective of this study was to determine the relationships of serum estrogen levels after hormone replacement therapy (HRT) every other day and every day with body mass index (BMI) in postmenopausal and bilaterally ovariectomized women. METHODS: Eighty-six postmenopausal and 51 bilaterally ovariectomized women who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly treated with HRT every other day or every day. Seventy-four patients received oral administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) every other day, and 63 patients received oral administration of 0.625 mg CEE and 2.5 mg MPA every day as conventional HRT. RESULTS: Eighty-four postmenopausal and 50 bilaterally ovariectomized women completed this study. Serum estradiol levels after HRT every day in postmenopausal and bilaterally ovariectomized women were significantly (P <0.05 and <0.01, respectively) correlated with BMI, while those after HRT every other day were not correlated with BMI. The differences between estradiol levels after 12 months of treatment and initial estradiol levels were also significantly (P <0.01) correlated with BMI in both postmenopausal and bilaterally ovariectomized women who received HRT every day but not in women who received HRT every other day. Serum estrone level after HRT every day and the difference between estrone level after 12 months of treatment and initial estrone level were significantly (P <0.05 and <0.01, respectively) correlated with BMI only in bilaterally ovariectomized women. CONCLUSION: Serum estradiol levels after HRT every day increase more in overweight women than in non-overweight postmenopausal and bilaterally ovariectomized women. The results of the present study regarding the relationship between serum estradiol levels after HRT and BMI should be useful for selecting dosages of drugs to be used in HRT.     

Assessment of DNA damage in postmenopausal women under hormone replacement therapy

OBJECTIVE: To evaluate the possible DNA damage in peripheral blood leukocytes of postmenopausal women under different hormone replacement therapies (HRT), comet assay, a standard method for assessing genotoxicity has been used. METHOD: 46 women were categorized in three groups-Group A: 15 surgical menopausal women who underwent surgery for benign conditions, receiving conjugated equine estrogen, 0.625 mg/day (CEE) for 2.3 +/- 1.5 years, Group B: 16 spontaneous menopausal women receiving conjugated equine estrogen, 0.625 mg/day plus medroxyprogesteron acetate, 5mg/day (CEE + MPA) for 2.4 +/- 1.0 years and Group C: 15 spontaneous menopausal women receiving tibolone, 2.5mg/day for 2.4 +/- 1.3 years. Control group consisted of 15 spontaneous menopausal women who never had HRT. RESULTS: Significant differences in terms of DNA damage were observed between Group A and B with controls as mean total comet scores 23.93 +/- 5.84, 19.44 +/- 6.19 and 10.07 +/- 2.40, but no significance (P > 0.05) were detected between Group C and controls as mean total comet scores 12.07 +/- 3.65 and 10.07 +/- 2.40, respectively. CONCLUSION: Reduced DNA damage were observed with tibolone compared to CEE or CEE + MPA therapy. Studies of this approach are needed.     

B cell subsets in postmenopausal women and the effect of hormone replacement therapy

Objectives: In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5⁺ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. Methods: Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5⁺) and conventional CD5⁻ B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1 were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. Results: In late postmenopausal women (≥30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. Conclusion: HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.