Circulating hormone levels in menopausal women receiving different hormone replacement therapy regimens. A comparison

OBJECTIVE: To measure and compare plasma levels of sex hormones after the administration of different hormone replacement therapy (HRT) regimens. STUDY DESIGN: Ninety women with natural menopause were randomized into this comparative study. Eighty-five women completed one year of follow-up. Patients were randomly assigned to five groups. The first received 0.6 mg/d of conjugated equine estrogen (CEE) cyclically (n = 15). The second received 50 micrograms/d of transdermal estradiol (E2) cyclically (n = 17), and the third received 0.6 mg/d of CEE continuously (n = 17). All these groups also received 2.5 mg of medroxyprogesterone acetate (MPA) sequentially for the last 12 days of HRT, while the fourth therapy group received 0.625 mg/d of CEE and 2.5 mg/d of MPA continuously (n = 19). The fifth group constituted a treatment-free control group (n = 22). Levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, estrone (E1), prolactin (PRL), testosterone (T), androstenedione (A4), dehydroepiandrosterone sulfate (DHEA-S) and sex hormone binding globulin (SHBG) were determined prior to HRT and during the last week of the 6th and 12th months of HRT, between days 21 and 24 of estrogen administration. RESULTS: After HRT we found decreases in FSH, LH and PRL levels, increases in E2, E1 and SHBG, and no modifications in T, A4 and DHEA-S plasma levels. There were no significant differences between the treatment groups in FSH, LH, E2, PRL, T, A4 or DHEA-S. E1 and SHBG were significantly higher in the groups with oral HRT. CONCLUSION: All the observed changes in hormone levels are to be expected after HRT except for the decrease in PRL levels. Finally, although MPA dosage was not the focus of the present study, our results suggest that the dosage of 2.5 mg/d of MPA in sequential regimens is clearly inadequate to protect the endometrium from hyperplastic changes.     

Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy

BACKGROUND: Fluctuations in lipid and lipoprotein levels are encountered quite often in hyperlipidemic patients. We examined the possibility that lipid and lipoprotein levels fluctuate due to the different effects of estrogen and progestogen in postmenopausal hyperlipidemic women receiving combined hormonal replacement therapy. METHODS: In an open-label study conducted during 3 consecutive hormonal cycles (3 months), levels of fasting total cholesterol, triglycerides, and low (LDLC)- and high-density lipoprotein cholesterol (HDLC) were determined in 36 postmenopausal hyperlipidemic women on day 13 of conjugated equine estrogen (1.25 mg/d) therapy and on day 25 after 12 days of receiving estrogen plus medroxyprogesterone acetate (5 mg/d). RESULTS: While receiving estrogen and combined therapies, means +/- SD total cholesterol levels increased from 6.50 +/- 0.97 mmol/L (251 +/- 37 mg/dL) to 6.88 +/- 1.42 mmol/L (266 +/- 54 mg/dL) (P<.001); LDLC levels, from 4.05 +/- 1.14 mmol/L (156 +/- 44 mg/dL) to 4.62 +/- 1.36 mmol/L (178 +/- 52 mg/dL) (P<.001). Mean +/- SD HDLC cholesterol levels decreased from 1.44 +/- 0.32 mmol/L (55 +/- 12 mg/dL) to 1.29 +/- 0.28 mmol/L (50 +/- 10 mg/dL) (P<.001); triglyceride levels, from 2.23 +/- 1.03 mmol/L (197 +/- 91 mg/dL) to 2.06 +/- 1.04 mmol/L (182 +/- 92 mg/dL) (P<.001). CONCLUSIONS: Hyperlipidemic postmenopausal women receiving combined sequential estrogen and progestogen replacement therapy demonstrate very significant fluctuations in their lipid and lipoprotein levels. These fluctuations depend on the hormonal phase, ie, estrogen alone or combined with progestogen.     

Physical activity in urban white, African-American, and Mexican-American women

PURPOSE AND METHODS: The purpose of this study was to analyze physical activity in a large, diverse sample of urban women (N = 521; X = 40.5 +/- 10.5 yr) relative to race/ethnicity, income, age, and education, using a sex-specific physical activity questionnaire. We also examined demographic and behavioral predictors of high levels (> or = 2000 kcal.wk-1) of leisure-time physical activity (LTPA; exercise, sports, recreational activities) in this population. RESULTS: The majority of women were sedentary (0-666 kcal.wk-1 in LTPA), and only 8% of African-American women (N = 6), 11% of Mexican-American women (N = 4), and 13% of white women (N = 55) participated in the level of physical activity recommended by the surgeon general (i.e., moderate to vigorous physical activity most days of the week for at least 30 min). Women of color, women over 40, and women without a college education had the lowest levels of participation in LTPA. Logistic regression analysis indicated that education was the only significant predictor of high LTPA in white women (P < 0.01) and marital status was the only significant predictor of high LTPA in minority women (P < 0.001). Age, body mass index (BMI; kg.m-2), income, self-rated health, alcohol intake, and smoking were not significant predictors of high LTPA for any of the women. Because the majority of adult women from this sample do not participate in adequate amounts of physical activity as recommended by the surgeon general, they may be at increased risk for hypokinetic diseases. CONCLUSIONS: These results indicate that public health efforts to increase physical activity in women should be focused on women of color, women over 40, and women without a college degree. More attention to predictors of physical activity that are specific to race or ethnicity may improve intervention program design and implementation.     

Hormone replacement therapy: cardiovascular benefits for aging women

Observational studies suggest that hormone replacement therapy (HRT) reduces the risk of coronary artery disease by approximately 50%. This review focuses on possible mechanisms for this reduction in disease risk. HRT reverses many of the lipid and lipoprotein change associated with menopause, and the route of hormone delivery influences these changes. Oral HRT improves serum markers of clotting, although it may increase the risk of deep vein thrombosis. Endothelial function, particularly endothelium-dependent vasodilation, improves with estrogen. Central body fat appears to be reduced with oral HRT, possibly reducing the risk of coronary artery disease. Insulin sensitivity, which worsens after menopause, may be improved with HRT. Global systolic function, as measured by ejection fraction, may improve with oral HRT. Understanding how HRT regimens influence cardiovascular risk may allow physicians to make intelligent choices about HRT for particular patients.     

Contemporary views on estrogen replacement therapy. II. Hormonal therapy in women with imminent ischemic heart disease

The frequence of ischemic heart disease occurring increases 2-3 fold in postmenopausal period. It is a result of serum lipid profile changes. Estrogenotherapy restores correct lipid relations and protect coronary vessels in this way, preventing stenocardia and cardiac infarcts. Divergent opinions coexist with including progestogens to estrogen replacement therapy. However a view that well selected doses and kind of hormone effectively enhance serum HDL level, begins to prevail.     

Knowledge, beliefs, attitudes, and cancer screening among inner-city African-American women

Three hundred twenty-one inner-city African-American women were interviewed to determine their knowledge, attitudes, and beliefs regarding cancer and cancer screening, and their cancer screening histories. The women were recruited from a variety of sources in Atlanta and were interviewed in their homes by trained lay health workers. Half of the subjects had an annual household income of < $15,000. About half had received a Pap smear and clinical breast examination within the year preceding the interviews. For women > 35 years old, 35% had received a mammogram within the recommended interval. Younger women and women with higher incomes were more likely than older women and those with lower incomes to have received a Pap test and clinical breast examination within the preceding year, but income was not significantly associated with mammography histories. In general, women who were more knowledgeable about cancer and its prevention were more likely to have been appropriately screened. However, various attitudes and beliefs regarding cancer generally were not associated with screening histories. We conclude that cancer screening programs for inner-city minority women should focus on improving knowledge levels among older women rather than attempting to alter attitudes and beliefs.     

Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer

We sought to determine the strength of the evidence suggesting that estrogen and postmenopausal replacement hormones play a role in the development of breast cancer. We reviewed the existing English language literature in MEDLINE on hormones and breast cancer, including reports on cell proliferation and endogenous hormone levels, as well as epidemiologic studies of the relationship between the use of postmenopausal hormones and the risk of breast cancer in women. A factor that increases the probability that cancer will develop in an individual has been defined as a cancer cause. The Hill criteria for demonstrating a link between environmental factors and disease were used to review the evidence for a causal relationship between female hormones and breast cancer. We found evidence of a causal relationship between these hormones and breast cancer, based on the following criteria: consistency, dose-response pattern, biologic plausibility, temporality, strength of association, and coherence. The magnitude of the increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year. The positive relationship between endogenous hormone levels in postmenopausal women and risk of breast cancer supports a biologic mechanism for the relationship between use of hormones and increased risk of this disease. The finding that the increase in risk of breast cancer associated with increasing duration of hormone use does not vary substantially across studies offers further evidence for a causal relationship. We conclude that existing evidence supports a causal relationship between use of estrogens and progestins, levels of endogenous estrogens, and breast cancer incidence in postmenopausal women. Hormones may act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate the proliferation of malignant cells. Strategies that do not cause breast cancer are urgently needed for the relief of menopausal symptoms and the long-term prevention of osteoporosis and heart disease.     

Effects of hormone replacement therapy in bone resorption, in post-menopausal women

BACKGROUND: The effects of different therapies on bone loss rate can be measured using biochemical markers of bone resorption such as urinary hydroxyproline. AIM: To study the effects of hormone replacement therapy on urinary hydroxyproline in postmenopausal women. PATIENTS AND METHODS: Eighty three postmenopausal women without hormone replacement therapy, 54 postmenopausal women receiving hormone replacement therapy and 16 premenopausal women (considered as the control group) were studied. Hydroxyproline was measured in an early morning urine sample, after one day of diet without meat or gelatin. RESULTS: Urinary hydroxyproline in premenopausal women was 33.7 +/- 7.9 mg/g creatinine. The figure for postmenopausal women with hormonal replacement therapy was 33.7 +/- 5.9 mg/g creatinine. Postmenopausal women without replacement therapy had an urinary hydroxyproline of 47.4 +/- 8.5 mg/g creatinine, significantly higher than that of premenopausal and supplemented women. In 21 postmenopausal women, hydroxyproline was measured before and after three months of replacement therapy, values decreased 35.5 +/- 11% in this period and there was a direct correlation between initial values and the degree of reduction (r = 0.69, p < 0.001). CONCLUSIONS: Postmenopausal women receiving hormone replacement therapy have a urinary hydroxyproline excretion similar to that of premenopausal women.     

Compliance with hormone replacement therapy in postmenopausal women. A comparative study

OBJECTIVE: To assess compliance with hormone replacement therapy in postmenopausal women. METHOD: Two groups were compared prospectively: 100 women who sought treatment for menopausal symptoms, and 82 women who had undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy and were using estrogen replacement therapy. RESULTS: Compliance rates after 6 months were 81.0% and 84.1% in the two groups, respectively, and after 12 months, 73.0% and 80.5%. CONCLUSIONS: The high rates are attributed to our investment in patient education of the benefits of treatment and repeated and close follow-up.     

Hormonal replacement therapy and breast cancer]

Hormonal replacement therapy is prescribed more and more frequently to increase quality of life and decrease the symptomatic and organic consequences of the menopausal status. The different studies which analyzed the risk of breast cancer for women under hormonal replacement therapy show opposed conclusion. We reviewed articles published between 1980 and 1997 to try to conclude about the consequences of the action of this treatment in the risk of breast cancer from the characteristic of the hormonal replacement therapy and from known risk of breast cancer. Hormonal replacement therapy increases the incidence of breast cancer. Risk increase with the treatment duration and a low estrogen dose would be sufficient to palliate to the hormonal lack (< 0.625 mg/j). The risk of breast cancer becomes the same that this of women without hormonal replacement treatment when treatment interrupted. The association of estrogen and progestin should not be protective of breast cancer. But the hormonal treatment seems to be synergistic for the risk of breast cancer with late menopause, late age at the birth of first child. Hormonal treatment could increase the estrogenic period and should increased the risk of breast cancer in women with late age at menarche, late age at menopause and late age at first child. It should not increase the risk of breast cancer in women with benign breast disease, with family history of breast cancer and in nulliparous women. For women who undergone a bilateral oophorectomy before hormonal replacement treatment the risk would be the same than for women with natural menopause and without hormonal replacement treatment. However breast cancer should be diagnosed earlier in women with hormonal treatment because mammographies were made more frequently. Overall survival should not different between the women who were under hormonal therapy and theses were not.     

Endometrial cytology in normal postmenopausal women and during hormone replacement therapy

OBJECTIVE: To explore the possibility of endometrial cyopathologic examination as a method of monitoring endometrium during hormone replacement therapy (HRT) in postmenopausal women. METHODS: Endometrial cells were taken via tubal aspiration in 60 normal postmenopausal women (non-HRT group) and 41 with HRT for 3-18 months (HRT group). Their morphologic changes were observed and compared by cytopathologist. RESULTS: Atrophic endometrium was found in 51.7% of the non-HRT group. Its proportion increased with age and the time after menopause. Macrophages were seen in 68.3% of this group. However, in the HRT group the occurrence of atrophic type and macrophage (12.2%, 7.0% respectively) was significantly lower than that in the non HRT group (P < 0.05). Heterogeneity of endometrial cell type was shown both in non-HRT (38.3%) and HRT (65.8%) groups. CONCLUSIONS: Endometrial cells of postmenopausal women are not always atrophic in appearance. They change significantly during HRT. Endometrial cytological examination may be useful for monitoring during HRT.     

Patterns and correlates of hormone replacement therapy use among middle-aged Australian women

In this study, we examine the patterns of use of hormone replacement therapy (HRT) among women age 51 to 60 years and describe the characteristics of women who currently use HRT, previously used HRT, and have never used HRT. A brief postal survey of 800 women in this age range was used to determine HRT status. Telephone interviews were then conducted with 258 women (111 currently using HRT, 47 who previously used HRT, and 100 who had never used HRT) to determine characteristics of women who currently or previously used HRT or never used HRT, type of HRT used, duration of use, and reasons for use and nonuse. Nearly 40% of women were currently using HRT, 14% had previously used HRT, and 47% had never used HRT. Women currently using HRT were more likely than those not using HRT to have had a hysterectomy, attribute a greater number of symptoms to the climacteric, be in paid employment, and report a greater number of visits to the doctor over the past 12 months. HRT use among Australian women in their 50s is high and rising. Hysterectomy status, the attribution of symptoms to menopause, paid employment, and health care use were the most important correlates of HRT use. Few women specified long-term prevention of osteoporosis or heart disease as a reason for taking HRT.     

Incidence of ovulation in perimenopausal women before and during hormone replacement therapy

Once hormone replacement therapy (HRT) has been commenced, it becomes extremely difficult to advise women approaching the menopause on the need for contraception. In this study of twenty women, neither the regularity of their pre-existing menstrual cycle nor a random FSH concentration predicted the likelihood of subsequent ovulation whilst taking HRT. HRT is not reliably contraceptive and women commencing HRT whilst still menstruating spontaneously must be advised on the need for additional contraception.     

Re-framing the representation of women in advertisements for hormone replacement therapy

This review focuses on new developments in the pathophysiology and treatment of von Willebrand disease (vWd). New aspects of the cell biology, gene control, and structure-function correlates of von Willebrand factor (vWf) are reviewed. vWd is more prevalent than previously recognized, affecting up to 1% of the population; this is particularly evident in women's health. Blood group is an important determinant of von Willebrand factor levels; individuals of blood group O tend to have lower plasma levels of vWf than those in other blood groups. Currently available blood tests of vWf quantity and function are discussed, in addition to newer tests undergoing validation. Treatment of classical vWd with desmopressin acetate and plasma derivatives is discussed, as is the potential for intravenous immunoglobulin and corticosteroids in acquired vWd. Special situations, such as the management of vWd in pregnancy, are also discussed.     

Hormonal replacement therapy affects calcitonin gene-related peptide and atrial natriuretic peptide secretion in postmenopausal women

OBJECTIVE: Menopause is associated with critical changes in the cardiovascular system, and the possible effect of hormonal replacement therapy (HRT) on these changes is under investigation. The aim of our study was to evaluate in postmenopausal women the effects of HRT and clonidine on the response of plasma calcitonin gene-related peptide (CGRP) and plasma atrial natriuretic peptide (ANP) to the upright posture test and the saline infusion test respectively. METHODS: CGRP and ANP levels were measured with specific radioimmunological assays and expressed in pmol/l (means +/- S.E.M). DESIGN: Postmenopausal women (age 46-53 years) (n = 18) were studied before and after 3 months of HRT (n = 13) or clonidine treatment (n = 5). RESULTS: After HRT or clonidine treatment plasma CGRP levels (14.9 +/- 1.6 and 15.9 +/- 3.8 pmol/l) were significantly higher than before (9.8 +/- 0.6 and 10.5 +/- 1.6 pmol/l) (P < 0.01). The assumption of upright posture caused no change in plasma CGRP levels before treatment, while after HRT, but not after clonidine treatment, an increase in plasma CGRP levels was observed (P < 0.01 at 5 and 20 min). Basal plasma ANP levels significantly decreased after both HRT and clonidine treatment (P < 0.01). In untreated women the saline infusion test did not induce any change in plasma ANP levels; a significant response to the test was restored after HRT but not after clonidine treatment (P < 0.01 at 90 and 120 min). CONCLUSIONS: The results show that some of the adaptive responses modified by menopausal changes are restored by HRT but not clonidine treatment, suggesting a modulatory role for sex steroid hormones in cardiovascular function and salt and water balance.     

Menopause and hormone replacement therapy

Menopause is a normal part of life of most women and can be made easier with appropriate information about the events that occur. For those women who desire help for bothersome menopausal symptoms, effective therapy can be offered. The use of HRT for prevention is more complex. Several large randomized clinical trials, including the Women's Health Initiative (WHI) and the Heart and Estrogen Replacement Therapy Study (HERS) in the United States, are currently underway. These trials, which have as end points clinical events such as myocardial infarction, sudden death, fractures, and cancer, will provide answers to many of the questions raised in this discussion. Until the results of these trials are available, clinicians must be prudent in their recommendations and should keep their patients apprised of the relevant uncertainties of preventive HRT.     

Testing and treatment behaviour of HIV-infected women: white, African-American, Puerto Rican comparisons

Findings from a study of the testing and treatment behaviour and experiences of African-American (n = 31), Puerto Rican (n = 30) and non-Hispanic white (n = 23) HIV-infected women are reported. All women were 20-45 years of age and had not yet been diagnosed with AIDS. Data for the analyses presented were gathered through an interviewer-administered questionnaire completed before respondents participated in an unstructured interview. The analyses examine race/ethnic differences in women's delays in seeking testing and medical care, and in sources and types of HIV-treatment. Most significant for primary and secondary prevention efforts, the findings suggest that a significant proportion of women who suspect they are infected may delay being tested, and further, a substantial proportion who learn they are seropositive may delay seeking medical care. Thus important opportunities among HIV-infected women for secondary prevention through timely antiviral and prophylactic treatment, and for primary prevention through risk-reduction counselling may be being missed in many cases.     

Older women and hormone replacement therapy: factors influencing late life initiation

OBJECTIVE: To describe factors associated with initiation of hormone replacement therapy (HRT) by older women. DESIGN: A cross-sectional study of 671 randomly selected women aged 65 to 80 who participated in a larger telephone survey on preventive health behaviors. SETTING: A large health maintenance organization (HMO) in Seattle, Washington. PARTICIPANTS: Of the 521 women who responded (78%), 51 had begun taking HRT at age 60 or older and were identified as initiators. Women who had never used HRT or past users who had begun HRT before age 60 were classified as noninitiators (n = 362). Current users who started HRT before age 60 (n = 108) were excluded. MEASUREMENTS: Sources included the telephone survey, automated HMO pharmacy data, and HMO utilization and provider databases. RESULTS: Initiators were similar to noninitiators with respect to age, marital status, education, and health status. Initiators were more likely to have had a hysterectomy at age 60 or later than noninitiators. Sixty-two percent of the non-initiators said they had received no information about the benefits of HRT from their providers compared with 18% of initiators. HRT initiation was associated with belief in prevention benefits of HRT for fractures and cardiovascular disease and with reported encouragement from the physician to use HRT. CONCLUSIONS: Other than hysterectomy status, there were few sociodemographic or health characteristics that markedly distinguished older initiators from noninitiators. Our findings show the importance of physician counseling in an older woman's decision to initiate HRT.