Hormone replacement therapy and cognition in an Australian representative sample aged 60-64 years

OBJECTIVE: To investigate the relationship between hormone replacement therapy (HRT) and level of cognitive performance intra-individual variability, and interactions with statin use, progesterone therapy and type of menopause. METHODS: A representative sample of 60-64 year olds was recruited from the Canberra and Queanbeyan regions in Australia. They were administered tests of verbal memory, working memory, speed of information processing, simple and complex reaction time, verbal intelligence and the Mini-Mental State Exam. Intra-individual variation (consistency) on performance on simple and complex reaction time tasks was calculated. Women provided information on HRT use and demographic, health and lifestyle variables. RESULTS: Four hundred and four (35.0%) current postmenopausal HRT users, 316 (27.4%) previous HRT users and 434 (37.6%) women who had never used HRT, were included in this study. There were significant overall differences between HRT current and previous users on age, prevalence of diabetes, alcohol use, body mass index, level of anxiety and lung function. After controlling for potentially confounding health and demographic variables, there were no significant main effects detected between HRT groups on any cognitive measure. Significant interactions were detected between HRT group and statin use on intra-individual variability on simple reaction time, and between HRT group and menopause type on intra-individual variability on choice reaction time. All other interactions were non-significant. CONCLUSIONS: HRT use had no effect on level of cognitive performance. Two interactions were detected between HRT use and statin use, and type of menopause on intra-individual variability. Given the large number of comparisons, little weight can be placed on these significant results.     

A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life

The results of several observational studies suggest that the use of estrogen replacement is associated with better mood, cognitive function and quality of life. Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting, enhances cholinergic activity in the brain, decreases brain and plasma levels of beta-amyloid, increases serotonin postsynaptic responsivity and the turnover of noradrenaline, and inhibits monoamine oxidase activity. However, the findings from the Women's Health Initiative controlled trial showed that hormone replacement (estrogen plus progestin) not only failed to improve mood, cognition and quality of life but also increased the risk of dementia. At present, there is limited information about the effect of unopposed estradiol replacement therapy (ERT) on the mental health outcomes of women at increased risk of cognitive decline (aged 70 years and over). We designed the present randomized, double-blind, placebo-controlled trial to clarify this issue. One hundred and fifteen women were randomized to treatment with estradiol (n=58; 2mg per day) or placebo for a total period of 20 weeks. The outcomes of interest in this study included changes in the Beck Depression Inventory (BDI) scores between baseline and week 20, as well as changes in quality of life scores (as measured by the SF-36) and cognitive function (CAMCOG, Block Design, Memory for Faces, California Verbal Learning Test (CVLT) and verbal fluency (VF)). Nineteen women treated with estradiol and 10 of those treated with placebo discontinued the use of the medication during trial, most frequently due to adverse reactions (OR=4.11, 95% CI=1.29-15.37). Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures (p>0.05). A separate analysis restricted to women who completed the 20-week-trial produced similar negative results. The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function, mood and quality of life. Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women.     

Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study.

OBJECTIVE: The incidence of sleep apnea syndrome (SAS) in women increases after menopause. Progestins alone do not alleviate SAS in menopausal women. However, progestins may require concomitant estrogen administration and estrogen alone may stimulate breathing during sleep. To test these hypotheses, we studied the effects of estrogen alone and estrogen combined with progestin on SAS in menopausal women, using a prospective, cross-over, inception cohort study. DESIGN: In this pilot study, five women who developed SAS after menopause underwent 2 nights of polysomnography to obtain a baseline, then returned for polysomnography after 3-4 weeks of taking micronized 17 beta-estradiol (E2) and after 10-12 days of taking E2 combined with medroxyprogesterone acetate (E2 + P). Sleep stages were scored according to Rechtshaffen and Kales, frequency and length of apneas were recorded for each subject each night, and the data were analyzed by Student's t test. RESULTS: E2 and E2 + P both reduced the Respiratory Distress Index. E2 also raised the lowest oxygen desaturation associated with apneic episodes. Total minutes of rapid eye movement sleep increased, and the number of waking episodes decreased when the women were taking E2 and E2 + P, as previously reported. CONCLUSIONS: Within 1 month after initiating E2 or E2 + P, SAS was reduced in all patients. The Respiratory Distress Index decreased by 25%, and the addition of progestin brought the SAS reduction to 50% in this pilot study. A randomized study in a large group of patients is justified by the findings of this study. Because SAS increases the risk of cardiovascular disease and fatal accidents, the amelioration of SAS by sex steroid hormones could have significant implications for the health of menopausal women.     

Hormone replacement therapy awareness in a biracial cohort of women aged 50-54 years.

OBJECTIVES: Previous studies of hormone replacement therapy (HRT) among women have focused on factors associated with the use of such therapy. Most of the studies involved populations of white women. Consequently, little is known about HRT awareness among the general population of women, and particularly among black women. The present study focused on factors associated with HRT awareness among a cohort of black and white women aged 50-54 years. DESIGN: Of more than 2,700 women, aged 50-54 years, who were members of a health maintenance organization, 700 were randomly selected and mailed a questionnaire addressing their awareness of HRT, as well as their menopausal status, medical history, and sources of information on HRT. RESULTS: Of the 700 women, 479 (68.4%) responded to the questionnaire. After exclusions, 421 (88%) were analyzed. On adjusted analysis, the factors most strongly associated with HRT awareness were a higher educational level, the perception of going or having gone through menopause, the presence of menopausal symptoms, and having undergone a bilateral oophorectomy. Black race (independent of educational level) was associated with a lower likelihood of HRT awareness. The most common source of information on HRT for women in this cohort was the physician, followed by the media. CONCLUSIONS: HRT awareness among women is strongly influenced by race, educational level, and the perception of going or having gone through menopause. Public health efforts to encourage wider use of HRT among older women should focus on increasing HRT awareness among black women and women with a lower educational level.     

Vitamin E status in men and women aged 60-90 years

The vitamin E status in men and women aged 60-90 years (62 men and 124 women) was examined. Plasma free vitamin E was analysed according to a modified version of the Hansen and Warwich method--a fluorometric micromethod for serum tocopherol. Serum cholesterol, triglycerides and HDL-cholesterol were quantified by the enzymatic methods on a Computer Directed Analyzer. Anthropometric data included the measurement of 13 skinfold thickness dimensions and Quetelet's index of obesity computed from weight (in g) and height (in cm2). The distribution of plasma free tocopherol level ranged from 10 mumol/1 to 69.9 mumol/1 for men and from 20 mumol/1 to 64.9 mumol/1 for women (median: 40-44.9 mumol/1 for both groups). Using the range of 12-46 mumol/1 free tocopherol of the plasma as the criterion, 78.5% of the subjects were classified as having the optimal vitamin E status. With the total free tocopherol levels above 49.9 mumol/1 of plasma, 21.5% of the subjects had an over average vitamin E status. It has also been found that there were correlations between the total free plasma tocopherol and plasma lipids (plasma triglycerides, plasma cholesterol, in men and women) and HDL-cholesterol in the male population.     

Routine screening mammography in women older than 74 years: a review of the available data

OBJECTIVE: The efficacy of population screening mammography for the age group of 50-74 years has been demonstrated. However, only limited data are available regarding women aged 75 and over, and recommendations for breast cancer screening in this age group vary in different countries. The aim of the current study is to review the evidence of the efficacy of breast cancer screening in women over the age of 74 years. METHODS: Studies published in English were retrieved by systematically searching MEDLINE (for papers published until August 2006), and by manually examining the references of the original articles and reviews retrieved. All studies that dealt with screening mammography over age 74 years were included. The studies were reviewed according to their outcomes and study design, focusing on breast cancer mortality and stage of breast cancer at diagnosis. RESULTS: Three studies focused on the relationship between breast cancer screening and mortality; in the 75-84 years age group, the risk of disease-specific mortality was approximately two-fold higher among women who did not perform screening mammography compared to women who did. Another four studies showed that women who underwent screening mammography had significantly smaller tumors and earlier disease stage at diagnosis. CONCLUSIONS: Regular mammography screening in older women may be associated with an earlier-stage disease and lower breast cancer mortality. These data support the use of screening mammography above age 75 years based on individual evaluations, rather than setting an upper age limit for breast cancer screening.     

Continuous renal replacement therapy in children with severe sepsis and multiorgan dysfunction - A pilot study on timing of initiation

Objective:Scanty literature is available regarding continuous renal replacement therapy (CRRT) utility in severe sepsis with multiorgan dysfunction syndrome (MODS) from developing countries. Author unit''s experience in pediatric CRRT is described and outcome of early initiation of CRRT with sepsis and MODS is assessed.Results:Twenty-seven children required CRRT (male - 16). The median age was 11 years (range 1.1–16). Twenty-one had severe sepsis with MODS. Eighteen patients were given CRRT within 48 h of admission to Intensive Care Unit (ICU). Statistically significant improvement in the P/F ratio, decrement in plateau pressure and vasoactive-inotropic score were noted in survivor group compared to nonsurvivor group (P = 0.022, 0.00, and 0.03, respectively). There was no statistically significant difference in duration of ICU stay, fluid overload, CRRT duration, PRISM score at 12 and 24 h, percentage of decrease in inotrope score, plateau pressure, and percentage of increase in P/F ratio in relation to timing of CRRT initiation. However, the survival rate was 61.1% (11/18) who received CRRT within 48 h of ICU admission compared to 33.3% (3/9) who received after 48 h (P = 0.0001).Conclusion:Our study emphasizes the CRRT role in improving the oxygenation status and hemodynamics. Survival benefit may be expected in those children who receive CRRT early in the course of sepsis. However, multicenter RCTs are required to prove mortality benefit.     

Fine needle aspiration cytology of breast cancer in women aged 70 years and older

Aims: Elderly breast cancers are associated with a more favourable biological marker profile and higher proportion of specific subtypes, some of which are of low histological grade. We reviewed the fine needle aspiration cytology (FNAC) to assess the cytological characteristics and any clues to assist in the diagnosis. Methods: The aspirates of 140 cancers of various histological types and grades and 39 benign lesions were evaluated for 13 cytological parameters including cellularity of the direct and cytospin smears, epithelial cell clusters, cellular atypism, cytoplasmic features, vacuoles, mitotic figures, presence of myoepithelial cells, single background epithelial cells, the presence of naked nuclei, stromal fragments and necrosis. Results: We found that the presence of background single epithelial cells, atypism of such cells, absence of benign appearing epithelial fragments, nuclear atypism of the epithelial cells within the fragments, presence of moderate amount of cytoplasm of these cells, absence of myoepithelial cells within the cluster, and absence of bipolar nuclei in the background have a strong association with malignancy. Scoring only the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei in a scoring system can differentiate between benign and malignant aspirates with high (>90%) sensitivity and specificity. Conclusions: Assessing the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei facilitates identification of malignancy in the aspiration of breast lesions from elderly patients.     

Climacteric symptoms and knowledge about hormone replacement therapy among Hong Kong Chinese women aged 40-60 years

OBJECTIVES: To evaluate the use of hormone replacement therapy (HRT), the prevalence of climacteric symptoms, and the knowledge about HRT. METHODS: A prospective study was conducted by telephone interview among a randomly selected population-based sample of 978 Hong Kong Chinese women aged 40-60 years. RESULTS: Of 414 women with a history of either natural or surgical menopause, 22 (5.3%) and 17 (4.1%), respectively, were either past or current users of HRT. The climacteric symptom scores of premenopausal women were significantly lower than those of perimenopausal women, but were comparable with those of postmenopausal women. The commonest climacteric symptom was 'muscle and joint pains' which was reported in 553 (56.6%) women, while only 228 (23.3%) and 151 (15.4%) women reported hot flushes and night sweating, respectively. Moreover, only 230 (23.5%) women realized that HRT could relieve menopausal symptoms and only 33 (3.4%) women were aware that HRT was protective against osteoporosis. In general, women with more climacteric symptoms, who had ever used HRT, and those with higher education level and higher family income, had better knowledge about HRT. CONCLUSIONS: Postmenopausal Hong Kong Chinese women have a low HRT usage rate and the majority of them are lacking of the knowledge about HRT.     

The response to ovarian hyperstimulation and in-vitro fertilization in women older than 35 years

There are conflicting reports concerning the effect of femaleage and potential reproductive function. We assessed the responseto ovarian hyperstimulation in two consecutive FVF cycles in25 women >35 years of age and compared their response toa control group of 48 women <35 years of age who conceivedin our IVF programme. In the older women, the maximal oestradiolresponse was proportional to the number of vials of HMG usedand did not differ from the response of the younger women. Similarly,the number of follicles of diameter >1.0 cm, the number ofoocytes recovered and the number of embryos which cleaved didnot differ between the older and the younger women. However,conception rates were markedly lower in the older women thanthe overall pregnancy rate in the FVF programme during the sametime period. We conclude that the older women in this studyhave a normal response to ovarian stimulation but may have adecreased receptivity of the endometrium or increased numbersof embryos with chromosomal abnormalities, leading to a reducedrate of implantation.     

Postmenopausal hormone therapy, timing of initiation, APOE and cognitive decline

Associations between postmenopausal hormone therapy (HT) and cognitive decline may depend on apolipoprotein E (APOE) status or timing of initiation. We included 16,514 Nurses' Health Study participants aged 70-81 years who were followed since 1976 and completed up to 3 telephone cognitive assessments (2 years apart), between 1995 and 2006. The tests assessed general cognition (Telephone Interview of Cognitive Status; TICS), verbal memory, and category fluency. We used longitudinal analyses to estimate differences in cognitive decline across hormone groups. APOE genotype was available in 3697 participants. Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was -0.04 (95% confidence interval, -0.07 to -0.004); for current estrogen + progestin users, the mean difference was -0.05 (95% confidence interval, -0.10 to -0.002). These differences were equivalent to those observed in women who are 1-2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p interaction, 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users. Regardless of timing of initiation, HT may be associated with worse rates of decline in general cognition, especially among those with an APOE e4 allele.     

Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years

OBJECTIVE: To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years. DESIGN: This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial, a randomized, placebo-controlled, double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol. Four hundred seventeen postmenopausal women, aged 60 to 80 years, were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a standardized questionnaire. RESULTS: At baseline, 16% of women reported hot flashes, 32% reported vaginal dryness, and 35% reported trouble sleeping. Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes, vaginal dryness, or sleep difficulties than those who received placebo. Treatment with ultralow-dose estradiol did not cause breast tenderness, uterine bleeding, or other symptoms often attributed to estrogen, but vaginal discharge was more common in women who received estradiol compared with those who received placebo. CONCLUSION: In this population of older, largely asymptomatic women, ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge. Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger, more symptomatic women.     

Use of hormone replacement therapy in Italian women aged 50-70 years

OBJECTIVES: The aim of the present cross-sectional analysis was to describe patterns and determinants of use of hormone replacement therapy (HRT) in a large sample of women attending mammographic screening. METHODS: Between 1999 and 2001, 8533 women aged 50-70 years were recruited by 11 screening centres, and structured interviews were made collecting information on socio-demographic characteristics, lifestyle habits, medical and reproductive history (overall response rate 87%). RESULTS: Current HRT use was reported by 6.9% of women (n=585), the average duration of use being 3.5 years; 13.2% were ever HRT users. Binomial and multinomial logistic regression (MLR) analyses showed that younger age, higher educational level, past mammographic examination and history of bilateral oophorectomy were the major predictors of current and ever HRT use. Current use was also more frequently reported by women who were thinner, nulliparae, had had induced menopause, had a later onset of menopause, with history of oral contraceptive use and hysterectomy without bilateral oophorectomy. By contrast, those who were diabetics or had positive history of cardiovascular disease were less likely to be current HRT users. No differences were found in HRT use according to marital status, type of occupation, menopausal status, smoking, history of breast cancer, hypercholesterolemia, hypertension and phlebitis. CONCLUSIONS: Our results support previous findings indicating that HRT use in Italian women is uncommon and of short duration. Current HRT users were less likely than non-users to report several characteristics associated with higher mortality and morbidity, in accordance with the healthy-user phenomenon described in other countries.     

Predictors and persistence of foot problems in women aged 70 years and over: a prospective study

Objective

To examine the prevalence and correlates of foot problems in older women over a 6-year period.

Study design

Women aged 70–75 years who participated in the Australian Longitudinal Study on Women's Health completed a postal questionnaire incorporating questions relating to demographics, major medical conditions and health status in 1999 (n = 8059) and 2005 (n = 4745).

Main outcome measures

Self-reported foot problems at baseline and at 6 years follow-up, major medical conditions, body mass index (BMI).

Results

At baseline, 26% of the sample reported foot problems. At follow-up, 37% remained free of foot problems, 36% had developed a new foot problem, 13% experienced resolution of their foot problems and 14% experienced persistent foot problems. Increase in BMI was significantly associated with the development of new foot problems and the persistence of existing foot problems.

Conclusions

Foot problems are common in older women and are associated with increased BMI. Maintaining a healthy bodyweight may therefore play a role in the prevention of foot disorders in older women.