Postmenopausal Women Receiving Estrogen Replacement Research Articles

Progestin enhances vasoconstrictor responses in postmenopausal women receiving estrogen replacement therapy.

Clinical and experimental evidence suggests that the cardioprotective effect of estrogen replacement is due to effects both on scrum lipids and on blood vessels. Current practice includes the use of a progestin in combination with estrogen if the patient still has her uterus: however, little is known about the effects of combination therapy on vascular reactivity. We therefore studied the effects of estrogen alone and with added progestin on forearm vascular resistance at rest, during reactive hyperemia, and after cold pressor stimulation using plethysmography in six healthy, postmenopausal women. Measurements were made before therapy: after giving conjugated estrogen i.v.; followed by a daily oral dose of 0.625 mg for 21 days; and sequentially after the addition of 10 mg of medroxyprogesterone acetate (MPA) for 10 days. Mean blood pressure did not change significantly. After 21 days of estrogen therapy, forearm blood flow, resting vascular resistance, and resistance after cold pressor stimulation did not change significantly. However, after addition of MPA, resting forearm vascular resistance rose significantly from baseline: 25.7 ± 2.7 U (SE) versus 38.3 ± 2.5 (p = 0.004). In addition, forearm vascular resistance rose to a higher level after cold pressor stimulus during combination therapy (32.3 ± 5.9 vs. 58.4 ± 5.7; p = 0.0057) than after estrogen replacement alone (32.3 ± 5.9 vs. 37.7 ± 5.3; p = NS). We conclude that combination hormone replacement therapy results in higher resting vascular resistance and increased pressor responsiveness than does estrogen replacement therapy alone.

Estrogen replacement therapy induces functional asymmetry on an odor memory/discrimination test

The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 post-menopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination test. Similar laterality effects were not observed for an odor detection threshold test employing phenyl ethyl alcohol. These results suggest that estrogen influences the lateralization of an odor memory/discrimination task and that hormone replacement therapy in the menopause may be an excellent paradigm for understanding lateralizing effects of hormones on some sensory processes.

Functional Impact of Relative Versus Absolute Sarcopenia in Healthy Older Women

To determine whether adjustment of muscle mass for height(2) or for body mass represents a more-relevant predictor of physical performance. Cross-sectional study, using baseline data from a trial comparing upper- and lower-body training. Women recruited from the community and gynecological practices in Connecticut. One hundred eighty-nine healthy older (aged 67.5 +/- 4.8), active women receiving estrogen for osteoporosis over 2 years. Total and appendicular skeletal muscle (ASM) and fat mass (AFM) were determined using dual x-ray absorptiometry. Physical performance, muscle strength, and fitness measures were obtained at baseline. Adjusting ASM for height(2) identifies lean women who are sarcopenic according to published standards yet fails to identify overweight and obese women whose ASM adjusted for body mass is low. ASM divided by body mass (ASM/body mass) is a stronger physical performance predictor, explaining 32.5%, 13.5%, 11.6%, 6.3%, and 6.8% of the variance in maximum time on treadmill, 6-minute walk, gait speed, 8-foot walk, and single leg stance, respectively, whereas ASM divided by height in m(2) (ASM/height(2)) explained only 2.9%, 0.2%, 2.0%, 0.04%, and 0.1%. Multivariate modeling demonstrated considerable overlap in aspects of ASM/body mass and AFM/body mass associated with performance, with ASM/body mass dominant. In contrast, ASM/height(2) is a much stronger predictor of leg press 1 repetition maximum and maximum power. The results suggest that relative sarcopenia with ASM adjusted for body mass is a better mobility predictor, with absolute sarcopenia a better indicator of isolated muscle group function in healthy postmenopausal women receiving estrogen replacement.

Emerging Risk Factors for Cerebrovascular Disease

Nontraditional risk factors for cerebrovascular disease are rapidly emerging. The categories are expanding, and include those related to infection, inflammation, sleep disorders, hemostasis, nutrition, endocrine, and one's individual genotype. Many of the promising factors lack large randomized prospective population studies confirming direct cause and effect. However there have been strong evidence supporting increased stroke risk factor for infection, obstructive sleep disorders, the metabolic syndrome and impaired glucose tolerance in particular. Unique drug targets have already been identified in some of these emerging risk factors. The complexity of the pathophysiology of this disease remains a challenge. For example despite repeated evidence of estrogen-related neuroprotection, large population-based studies in postmenopausal women receiving estrogen replacement did not demonstrate the expected neuroprotection. This suggests that aggressive research both at the basic science and transitional level needs to evolve, to ensure targeted successful stroke therapy. The advent of nanotechnology including the development of targeted therapeutic nanospheres, and of revolutionary molecular technology resulting in the synthesis of specific peptide mimetics, bodes well for the future development of cerebrovascular drug treatment.

Postmenopausal Hormone Replacement and Cardiovascular Disease: Incorporating Research Into Practice

The long-standing practice of prescribing hormones to postmenopausal women was based in part on the observation that following menopause, women's incidence of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cerebral vascular accident increased. Recent large-scale research has shown an increase in cardiovascular events for postmenopausal women receiving estrogen replacement in oral form. This article examines research on positive effects of hormone replacement therapy, discusses what is known about the development of cardiovascular disease in women, and evaluates recent research that has shown increased cardiovascular risk in women receiving hormone replacement. It concludes with recommendations for preventing cardiovascular disease in women. This is essential information for nurses, who need to be informed of ways to maintain their own health while serving as sources of health information for the public at large.

Catecholestrogens excretion in smoking and non-smoking postmenopausal women receiving estrogen replacement therapy

Estrogens are involved in the etiology of breast cancer. Their blastomogenic influence may be partly realized through their conversion into catecholestrogens, rate of which may be modified by smoking. The risk of having breast cancer diagnosed can increase in women using estrogen replacement therapy (ERT). The principal aim of this investigation was to compare the excretion of classical estrogens and catecholestrogens in smoking and non-smoking postmenopausal women receiving Progynova (estradiol valerate, 2 mg/day, 1 month). Total 16 women were studied before and after treatment. Urinary estrogen profile method based on isotope dilution capillary gas chromatography–mass spectrometry was used. Before ERT, significantly lower excretion of 16-epiestriol and 4-hydroxyestrone (4-OHE1) and lower ratio of 4-OHE1/E1 were revealed in smokers. After ERT, much higher excretion of 2-OHE1, and 4-hydroxyestradiol (4-OHE2), higher ratios of 2-OHE1/E1 and 4-OHE1/E1 and lower ratio of 2-methoxyestrone/2-OHE1 were discovered in smokers as compared to non-smoking women. In conclusion only combination of ERT + smoking and not smoking itself leads to the specific prevalence of catecholestrogens (2-OH- and carcinogenic and DNA-damaging 4-OH-metabolites) that may increase risk of genotoxic variant of hormone-induced breast carcinogenesis without influence on the total morbidity.

Vasodilator effects of estrogen are not diminished by androgen in postmenopausal women

Objective: To compare the effects of estrogen with estrogen-androgen treatment on vaginal blood flow velocity and fingertip postocclusive hyperemic blood flow response. Design: Prospective, randomized, parallel, double-blind study. Setting: Healthy human volunteers in an academic research environment. Patient(s): Postmenopausal women receiving estrogen replacement therapy for at least 12 months and treated with placebo before this investigation. Intervention(s): Esterified estrogens or esterified estrogen + methyltestosterone were administered orally; laser Doppler velocimetry was used to determine vaginal and fingertip blood flow responses at baseline and after 4 and 8 weeks of daily drug administration. Main Outcome Measure(s): Fingertip postocclusive area under curve (AUC); vaginal blood flow velocities. Result(s): The AUC for postocclusive fingertip blood flow and vaginal blood flow increased to a greater extent in the estrogen-androgen group, but changes were not statistically significant between groups. Conclusion(s): Estrogen-androgen treatment does not diminish the vasodilator effects of estrogen treatment in postmenopausal women.

Transvaginal ultrasonographic measurement of endometrial thickness in postmenopausal women receiving estrogen replacement therapy

OBJECTIVE: This study was undertaken to evaluate endometrial thickness by transvaginal ultrasonography in asymptomatic postmenopausal women receiving estrogen replacement therapy. The endometrial thickness in this study group was compared with endometrial thickness measurements in a group of women who had abnormal postmenopausal bleeding. The recent literature was reviewed. STUDY DESIGN: Asymptomatic postmenopausal women receiving estrogen replacement, seen for routine examination during the 1-year period from Jan. 1, 1994, to Dec. 31, 1995, had the endometrium evaluated by transvaginal ultrasonography. Women with abnormal postmenopausal bleeding were likewise evaluated and their measurements compared with those of the study group. RESULTS: Twenty-seven different estrogen and estrogen-progestin combinations in 327 asymptomatic women were studied. Additionally, 24 women who were bleeding, not receiving estrogen, and 46 women with abnormal bleeding on estrogen therapy underwent ultrasonography of the endometrium. Endometrial thickness ranged from 1 to 15 mm in women on a regimen of combined estrogen-progestin therapy, 1 to 14 mm in women using sequential estrogen-progestin, and 3 to 15 mm for women receiving unopposed estrogen in the study group. For women with abnormal bleeding not using estrogen, the endometrium measured an average of 12.3 mm (range 2 to 29 mm), with unopposed estrogen 8.3 mm (range 4 to 13 mm), and for estrogen with progestin 6.5 mm (range 2 to 15 mm). Significant pathologic features were found in those women who had bleeding and endometrial measurements between 5.0 and 29 mm. CONCLUSION: There was no significant difference between endometrial thickness measurements in women receiving various combinations of estrogen replacement. In general, expected endometrial measurements can range from 1 to 15 mm. In women with postmenopausal bleeding, however, significant pathologic features may exist with an endometrium measuring as little as 5 mm. (Am J Obstet Gynecol 1997;176:1334-9.)

Three-year follow-up of the use of a levonorgestrel-releasing intrauterine system in hormone replacement therapy.

The efficacy of a levonorgestrel-releasing intrauterine system in opposing endometrial proliferation and in preventing bleeding was studied in peri- and postmenopausal women receiving estrogen replacement therapy. This was an open, non-controlled follow-up study of the use of a levonorgestrel-releasing intrauterine system during continuous estrogen replacement therapy carried out by using oral, transdermal or subdermal estradiol. The efficacy of the progestin therapy was evaluated by transvaginal ultrasonography and by examination of endometrial biopsy samples taken 20 months (mean, range 17 - 22; first evaluation) and 34 months (mean, range 31 - 38 months; second evaluation) after insertion of the levonorgestrel-releasing intrauterine system, and by studying patterns of bleeding. Twenty-five women participated in the first evaluation, and 29 in the second. Seventy-six percent of the women were amenorrheic at the first evaluation, and 79% at the second evaluation. Others had spotting for 1-2 days monthly or less often. The mean time until amenorrhea was reached was 6 months (range 2-13 months) after insertion of the levonorgestrel-releasing intrauterine system. The median endometrial thickness assessed by ultrasound was 2 mm at both evaluations. No signs of proliferation were observed in any of the endometrial samples. Local progestin delivery via a levonorgestrel-releasing intrauterine system was effective in suppressing the endometrium and in eliminating bleeding in women receiving estrogen replacement therapy, and the intrauterine progestin therapy was also well accepted.

Association Between Increased Estrogen Status and Increased Fibrinolytic Potential in the Framingham Offspring Study

Although extensive evidence indicates that estrogen is responsible for the markedly decreased cardiovascular risk of premenopausal women, the mechanism through which estrogen might exert its protective effect has not been adequately explained. Since thrombosis is now recognized to play an important role in the onset of cardiovascular disease, we investigated the relation between estrogen status and fibrinolytic potential, a determinant of thrombotic risk. We determined levels of plasminogen activator inhibitor (PAI-1) antigen and tissue plasminogen activator (TPA) antigen in 1431 subjects from the Framingham Offspring Study. Fibrinolytic potential was compared between subjects with high estrogen status (premenopausal women and postmenopausal women receiving hormone replacement therapy) and low estrogen status (men and postmenopausal women not receiving hormone replacement therapy). In all comparisons, subjects with high estrogen status had greater fibrinolytic potential (lower PAI-1 levels) than subjects with low estrogen status. First, postmenopausal women receiving estrogen replacement therapy had lower levels of PAI-1 than those not receiving therapy (13.0 +/- 0.5 versus 19.5 +/- 1.0 ng/mL, P < .001). Second, premenopausal women had lower levels of PAI-1 than men of a similar age (14.8 +/- 0.6 versus 20.3 +/- 0.8 ng/mL, P < .001); this sex difference diminished when postmenopausal women not receiving hormone replacement therapy were compared with men of a similar age (19.6 +/- 0.7 versus 21.1 +/- 0.7 ng/mL, P = .089). Third, premenopausal women had markedly lower levels of PAI-1 antigen than postmenopausal women not receiving estrogen therapy (14.8 +/- 0.6 versus 19.5 +/- 1.0 ng/mL, P < .001). The between-group differences observed for TPA antigen were similar to those for PAI-1 antigen. Each of these comparisons indicates that the cardioprotective effect of estrogen may be mediated, in part, by an increase in fibrinolytic potential. These findings might provide at least a partial explanation for the protection against cardiovascular disease experienced by premenopausal women, and the loss of that protection following menopause.

Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages.

The chemotactic cytokine, monocyte chemoattractant protein-1 (MCP-1), and its murine homologue, JE, have been detected in atherosclerotic lesions but not in normal arteries, implicating that these proinflammatory cytokines may be involved in the pathogenesis of atherosclerosis. Epidemiologic studies reveal that postmenopausal women receiving estrogen replacement for treatment of osteoporosis have a greatly reduced risk of developing cardiovascular disease. Because JE/MCP-1 and estrogen play regulatory roles in the development of atherosclerotic lesions, we chose to examine the effect of estrogen treatment on JE/MCP-1 mRNA expression in macrophages. 17 beta-estradiol (E2) inhibited LPS-stimulated JE/MCP-1 mRNA expression in ANA-1 and J774A.1 murine macrophage cell lines and in thioglycolate-elicited murine peritoneal macrophages. Inhibition of JE/MCP-1 mRNA ranged from 50 to 90%, with a maximal effect occurring at a concentration of 300 pg/ml E2. Conversely, E2 had little effect on LPS-stimulated TNF-alpha mRNA production. Treatment of LPS-stimulated macrophages with moxestrol, an estrogen agonist, resulted in a similar inhibition, and the addition of the estrogen antagonist, tamoxifen, reversed E2 inhibition of JE/MCP-1 mRNA expression. Progesterone failed to inhibit LPS-induced JE/MCP-1 mRNA expression. Immunohistochemical analysis revealed the presence of estrogen receptors in ANA-1 cells, indicating that E2 inhibition of LPS-induced JE/MCP-1 mRNA expression in murine macrophages may be mediated through the estrogen receptor. Thus, another mechanism whereby estrogen exerts antiatherogenic effects may be through prevention of macrophage accumulation in the atherosclerotic lesion.

Progestin Enhances Vasoconstrictor Responses in Postmenopausal Women Receiving Estrogen Replacement Therapy

Clinical and experimental evidence suggests that the cardioprotective effect of estrogen replacement is due to effects both on serum lipids and on blood vessels. Current practice includes the use of a progestin in combination with estrogen if the patient still has her uterus: however, little is known about the effects of combination therapy on vascular reactivity. We therefore studied the effects of estrogen alone and with added progestin on forearm vascular resistance at rest, during reactive hyperemia, and after cold pressor stimulation using plethysmography in six healthy, postmenopausal women. Measurements were made before therapy: after giving conjugated estrogen i.v.; followed by a daily oral dose of 0.625 mg for 21 days: and sequentially after the addition of 10 mg of medroxyprogesterone acetate (MPA) for 10 days. Mean blood pressure did not change significantly. After 21 days of estrogen therapy, forearm blood flow, resting vascular resistance, and resistance after cold pressor stimulation did not change significantly. However, after addition of MPA, resting forearm vascular resistance rose significantly from baseline: 25.7 ± 2.7 U (SE) versus 38.3 ± 2.5 (p = 0.004). In addition, forearm vascular resistance rose to a higher level after cold pressor stimulus during combination therapy (32.3 ± 5.9 vs. 58.4 ± 5.7; (p = 0.0057) than after estrogen replacement alone (32.3 ± 5.9 vs. 37.7 ± 5.3; p = NS). We conclude that combination hormone replacement therapy results in higher resting vascular resistance and increased pressor responsiveness than does estrogen replacement therapy alone.

Effect of estrogen replacement therapy on the ST-segment response to postural and hyperventilation stimuli

It is widely recognized that exercise-induced ST-segment abnormalities often occur in women with normal coronary arteries. False-positive exercise responses from 14 to 67% have been reported. 1 The high frequency of ST-segment abnormalities at rest and in response to exercise in premenopausal women may be explained by their elevated plasma estrogen levels. Although direct testing of this hypothesis is difficult, the effect of estrogen on the ST-segment response to hyperventilation and postural shifts may provide insight into this question. These frequently used preexercise maneuvers are believed to provoke ST-segment shifts independent of myocardial ischemia. We designed this study to compare the frequency of abnormal ST-segment responses to sitting, hyperventilation and standing in postmenopausal women receiving estrogen replacement therapy versus those not receiving it.

Endometrial response following percutaneous estrogen replacement therapy. A morphometric investigation.

The endometrial response in 10 postmenopausal women receiving estrogen replacement therapy was evaluated morphologically and quantified by morphometric analysis. During 6 months of cyclic treatment with percutaneous estradiol-17 beta, 3 mg daily, the mean relative endometrial gland volume increased from 10% to 40%. In each individual woman this morphometric parameter was significantly correlated to the serum concentration of estradiol-17 beta. The decline in FSH level during treatment showed no significant correlation to the endometrial response or the estrogen level. In some endometrial samples from women during treatment, glands with incomplete epithelial lining and rows of glandular epithelial cells were observed. It is suggested that these phenomena represent early forms of glandular development.

Menopausal status associated with increased inhibition of blood coagulation

Postmenopausal women receiving estrogen replacement therapy (ERT) are not as prone to inappropriate venous and arterial thrombosis as are younger women taking oral contraceptives. To establish whether menopausal status per se has any effect on the coagulation-fibrinolytic system normal premenopausal women (mean age 29 years) were compared with younger (mean age 23) and older (mean age 51) surgically menopausal women and a group of naturally postmenopausal women (mean age 53). The results show that in postmenopausal women, irrespective of age or type, the shift is away from clot formatiuon and toward clot inhibition and fibrinolysis as determined by static in vitro analysis. This was characterized by statistically significant increases in antithrombin III antigen, alpha 1-antitrypsin antigen, and plasminogen activity. These changes may help to explain in part why ERT does not appear to cause increased thrombosis in older women.