Insulin edema in diabetes mellitus associated with the 3243 mitochondrial tRNA(Leu(UUR)) mutation; case reports

OBJECTIVE: To determine the risk of breast cancer in relation to the use of combined estrogen and progestin hormone replacement therapy (HRT). DESIGN: A population-based case-control study. SETTING: The general female population of King County in western Washington State. PARTICIPANTS: Middle-aged (50 to 64 years) women, including 537 patients with incident primary breast cancer diagnosed between January 1, 1988, and June 30, 1990, who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry and 492 randomly selected control women without a history of breast cancer. MAIN OUTCOME MEASURE: Breast cancer risk in relation to use of menopausal hormones. RESULTS: Menopausal hormones of some type had been used by 57.6% of breast cancer cases and 61.0% of comparison women. The women who had ever taken combined estrogen-progestin HRT, representing 21.5% of cases and 21.3% of controls, were not at increased risk of breast cancer (relative odds [RO] = 0.9; 95% confidence interval [CI], 0.7 to 1.3). Compared with nonusers of menopausal hormones, those who used estrogen-progestin HRT for 8 or more years had, if anything, a reduced risk of breast cancer (RO = 0.4; 95% CI, 0.2 to 1.0). CONCLUSIONS: On the whole, the use of estrogen with progestin HRT does not appear to be associated with an increased risk of breast cancer in middle-aged women. Nonetheless, since the use of combined estrogen-progestin HRT has only recently become prevalent, future investigations must assess whether breast cancer incidence is altered many years after estrogen-progestin HRT has been initiated, particularly among long-term users.     

Are long-term hormone replacement therapy users different from short-term and never users?

The characteristics that differentiate long-term (> or = 10 years) hormone replacement therapy (HRT) users from short-term (<10 years) users and nonusers are not well documented. The epidemiology of long-term HRT use was investigated within a random sample survey of 703 women aged 50-80 years who were members of Group Health Cooperative (GHC) of Puget Sound. Women who had been menopausal for > or = 10 years comprised the study population. Long-term HRT users (29.4 percent) were compared with short-term (28.1 percent) and never users (42.5 percent). The authors examined the association between duration of HRT use and demographic characteristics, personal and family medical history, menopausal symptoms, information used in decision making, attitudes toward HRT, provider encouragement to use HRT, and GHC utilization. Compared with never users, the strongest correlates of long-term HRT use were having a hysterectomy before or after menopause, positive attitudes espousing the benefits of HRTs, and perceived provider encouragement to use HRT. Long-term HRT use was not associated with educational attainment, ethnicity, body mass index, health status, physical activity, or family medical history. Correlates commonly associated with HRT use, such as higher education, greater physical activity and functioning, and lower chronic disease comorbidity, did not significantly distinguish long-term from short-term users.     

Purification and characterisation of hepatic glutathione transferases from a herbivorous marsupial, the brushtail possum (Trichosurus vulpecula)

In 1994, as part of their participation in the University of North Carolina Alumni Heart Study, 1101 women aged 45-51 years answered questions about their menopausal status and current use of hormone replacement therapy (HRT). Little is known about the use of HRT in younger women. We were interested in determining both patterns of HRT use and patient characteristics associated with HRT use in this cohort of women approaching the average age of menopause. After excluding women with breast, endometrial, and ovarian cancer, we studied 1080 women. These women identified themselves as: "There is no indication that I am near menopause" (stage 1, n = 326), "I think I may be close to or in the beginning stages of menopause but am not sure" (stage 2, n = 410), "I have begun menopause" (stage 3, n = 202), and "I have been through menopause" (stage 4, n = 142). The overall rate of HRT use was 22% (0% in stage 1, 8% in stage 2, 52% in stage 3, and 76% in stage 4). Both patterns of HRT use and patient characteristics associated with HRT use differed based on the woman's perception of her menopausal stage. In logistic regression models, where HRT use was the outcome variable, independent predictors of HRT use included stage of menopause, having had a hysterectomy, having had a bilateral oophorectomy, no family history of breast cancer, having had a pelvic examination in the last year, being married, and not participating regularly in physical exercise. A woman's perception of her stage in the process of reproductive aging correlates with her use of HRT. Informed decision making about HRT use should be tailored to the individual's perception of her menopausal stage.     

Hormone replacement and menopausal symptoms following hysterectomy

Hormone replacement therapy (HRT) is recommended for most women who experience surgical menopause following hysterectomy/oophorectomy for noncancerous conditions; it is also commonly prescribed for postmenopausal women. Beginning in 1992, 1,299 women undergoing hysterectomy in 28 hospitals throughout Maryland were interviewed prior to hysterectomy and were subsequently followed over a 2-year period. Interviews included questions about HRT use and symptoms associated with menopause. The majority of the women (66 percent) were white, 55 percent had a high school education or better, 49 percent were obese (body mass index > or =27.3), and 11 percent were postmenopausal. Over 40 percent of premenopausal women underwent bilateral oophorectomy. At 3 months posthysterectomy, 89 percent of these women were on HRT; this figure dropped to 85 percent at 24 months. Among postmenopausal women, 50 percent were on HRT both at 3 months and at 24 months posthysterectomy. Among premenopausal women who had unilateral oophorectomy, 21 percent were on HRT at 3 months, increasing to 35 percent at 24 months. Among premenopausal women who had no ovaries removed, 5 percent were on HRT at 3 months, increasing to 13 percent at 24 months. There were few within-group differences between HRT users and nonusers, except that among postmenopausal women, HRT users were younger and more likely to be white and had higher income and educational levels. Women who were postmenopausal or who underwent bilateral oophorectomy were less likely to have hot flashes if they were on HRT, but women with 0-1 ovary removed who were on HRT were more likely to have hot flashes than those not on HRT. Black women were significantly more likely to experience hot flashes than were white women, independent of HRT status and weight. Obese women were on HRT at approximately the same rates as nonobese women but were significantly more likely to have hot flashes, even when analyses controlled for HRT and race.     

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.     

Women's health in midlife: the influence of the menopause, social factors and health in earlier life

OBJECTIVE: To describe the health symptoms of a large representative sample of British women at age 47 years, and to examine the influence of the menopause allowing for social factors and health in earlier adult life. DESIGN: A national prospective birth cohort study. Information on health problems, menstrual cycle, use of hormone replacement therapy and life stress at 47 years was collected using a postal questionnaire. Information on health, smoking behaviour and educational attainment earlier in life had been collected at previous home visits. SETTING: England, Scotland and Wales. POPULATION: A general population sample of 1498 women, 84% of those sent a questionnaire. MAIN OUTCOME MEASURE: Twenty self-reported health symptoms over the previous 12 months. RESULTS: Women who had experienced an early natural menopause had a strongly raised risk of vasomotor symptoms (hot flushes or night sweats), sexual difficulties (vaginal dryness or difficulties with intercourse) and trouble sleeping. However, there was little or no excess risk of other somatic or psychological symptoms. In contrast, all types of symptoms were more common among women who had had a hysterectomy or were users of hormone replacement therapy. Women with the least education, stressful lives, or a previous history of poor physical and psychological health at age 36 also reported more symptoms at 47 years compared with other women, but adjustment for these factors in a logistic regression model did not affect the relations between symptoms and current menopausal status. For vasomotor symptoms, postmenopausal women had an adjusted odds ratio of 4.7 (95% CI 2.6-8.5) and perimenopausal women had an adjusted odds ratio of 2.6 (95% CI 1.9-3.5) compared with premenopausal women. Corresponding adjusted odds ratios for sexual difficulties were 3.9 (95% CI 2.1-7.1) and 2.2 (95% CI 1.4-3.2), and for trouble sleeping were 3.4 (95% CI 1.9-6.2) and 1.5 (95% CI 1.1-2.0). CONCLUSIONS: Specific symptoms were clearly associated with the natural menopause. More general health concerns were common among women in middle life, particularly among those with stressful lives, or those who had had a hysterectomy or started taking hormone replacement therapy before they were postmenopausal. Appropriate advice and support needs to be easily accessible.     

Therapeutic approaches to primary and secondary brain tumours

INTRODUCTION: This study examined the long-term effects of hysterectomy, with and without bilateral oophorectomy, and treatment with estrogen replacement on bone mineral density in older hysterectomized women. METHODS: Subjects were 346 women 60-89 years of age, who were participants in the Rancho Bernardo Study and attended a follow-up clinic visit in 1988-1991. Bone density was measured at the ultradistal wrist, midshaft radius, lumbar spine and hip. RESULTS: Of these women, 182 had a hysterectomy with conservation of one or both ovaries and 164 had a hysterectomy with bilateral oophorectomy. Current estrogen users had the highest bone densities; those who never used estrogen replacement had the lowest. Only 9.1% of oophorectomized women, compared to 19.2% of those with ovarian conservation had never used estrogen (P < .01). After adjustment for covariates including estrogen replacement therapy, hysterectomized women with ovarian conservation had marginally higher bone densities at the wrist (P < .09) and spine (P < .06) than oophorectomized women. We found significant differences only among women currently using estrogen (P < .05 for wrist and P < .01 for spine densities, respectively). Bone density did not differ at any site by oophorectomy status among past or never users of estrogen. CONCLUSIONS: Hysterectomized women who use estrogen replacement therapy have better bone density, regardless of a bilateral oophorectomy. In addition, bilateral oophorectomy may not have a long-term negative effect on bone density; hysterectomized women who do not use estrogen appear to have equivalent bone density whether or not they had a bilateral oophorectomy.     

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.     

Recurrent pregnancies during oral contraception

The records of the Royal College of General Practitioners' Oral Contraception Study were examined for those women who had become pregnant while using combined oral contraceptive pills. Analysis reveals that these women are much more likely than average to have further failures if they resume taking the Pill (seven failures in 35 women-years, compared with one in 500 women-years for the whole study). This finding could occur through some factor in the patient's personality (patient failure) or through some factor in the patient's metabolism.     

Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes

OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.     

Role of endocrine factors in the development of stomach cancer

After the age of about 35, the natural cycle becomes less predictable. Oestrogen levels fluctuate, leading to some anovulatory cycles. Sometimes periods stop suddenly but more often become erratic and less frequent for a year or two before the final period (menopause). About 75% of women experience symptoms at the time of the menopause, which typically lasts 1-3 years and occurs at around the age of 50. Long-term effects of the menopause are a rapid decline in bone density and greater risk of heart disease. Useful life-style adjustments for menopausal women are to eat calcium-rich foods, stop smoking, restrict alcohol intake and exercise regularly, especially weight-bearing exercise such as walking, dancing or sports. Hormone replacement therapy (HRT) is effective in reducing menopausal symptoms and appears to reduce the long-term risks of osteoporosis and heart disease. Women may start taking HRT before periods cease if they have troublesome symptoms during the pre- and peri-menopausal stage. Women who have had a hysterectomy may use oestrogen on its own. Women who have a uterus need a combination of oestrogen and progestogen. Current evidence suggests that to take HRT for up to 5-8 years incurs no additional risk of breast cancer, although to take it for longer than 10 years seems to increase the risk slightly.     

Mood and symptom reporting among middle-aged women: The relationship between menopausal status, hormone replacement therapy, and exercise participation.

Vasomotor, somatic, and psychological symptoms associated with menopause are often treated with hormone replacement therapy (HRT), but the role of nonpharmacological interventions has received little attention. Two studies used the Profile of Mood States (POMS) and Women's Health Questionnaire (WHQ) to examine the effects of exercise among 4 groups of Australian women: premenopausal, perimenopausal, postmenopausal without HRT, and postmenopausal with HRT. Study 1, a comparison of exercisers and nonexercisers, showed that exercisers' moods were significantly more positive than sedentary women's moods, regardless of menopausal state. Exercising women also scored lower on somatic symptoms and memory-concentration difficulties. Study 2 examined the acute effects of aerobic exercise (premenopausal, postmenopausal without HRT, and postmenopausal with HRT) and found significant enhancements in mood and reductions in reported somatic and vasomotor symptoms immediately following an aerobic class. Exercise may assist in the alleviation of some menopausal symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term clinical follow-up after directional coronary atherectomy

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.     

Does hormone replacement therapy inhibit coronary artery calcification?

OBJECTIVE: To determine the association between the use of hormone replacement therapy (HRT) and coronary calcium, in postmenopausal women who had no history of coronary artery disease by double helical computed tomography (CT). METHODS: We used CT to compare the prevalence and extent of coronary calcium in 41 postmenopausal women who were on HRT from the first year of menopause and 37 age-matched controls who had never used HRT. RESULTS: Both groups had a similar rate of smoking, hypertension, a positive family history, and hypercholesterolemia. Coronary calcification was observed in 28.2% of the 78 women studied. The prevalence of coronary calcium was significantly lower among HRT users: six of the 47 (14.6%), compared with 16 of the 37 nonusers (43.2%) (P < .01). The recorded risk factors had no effect on the prevalence of coronary calcium. Stepwise logistic regression analysis, including age, coronary risk factors, and HRT use as independent variables, yielded HRT as the only variable determining the presence of coronary calcium (odds ratio = 0.2; 95% confidence interval 0.06, 0.63; P = .006). CONCLUSION: The lower incidence of coronary calcium in the HRT users suggests that HRT is associated with decreased prevalence of the coronary calcification.     

The influence of oral contraceptives on the risk of multiple sclerosis

OBJECTIVE: To examine the risk of multiple sclerosis in users of combined oral contraceptives. DESIGN: Cohort study conducted between 1968 and 1996 using diagnostic data supplied by general practitioners SETTING: General practices throughout the United Kingdom. POPULATION: Royal College of General Practitioners' Oral Contraception Study cohort of initially 46,000 women recruited during the late 1960s. METHODS: Directly standardised incidence rates of multiple sclerosis were calculated for current, former and never-users of oral contraceptives using first ever cases of multiple sclerosis reported by the general practitioners. The standardisation variables were age, parity, social class and smoking history. Five-year survival rates in the different contraceptive groups were calculated using standard life table techniques. RESULTS: One hundred and fourteen first ever cases of multiple sclerosis had been reported by November 1996 during 564,000 woman-years of observation. The incidence rate in both current and former users was not materially different to that in never-users. Although based on limited evidence there was no suggestion that the five-year survival was affected by a woman's use of combined oral contraceptives. CONCLUSIONS: These findings do not suggest a greatly elevated risk of multiple sclerosis during, or after, use of combined oral contraceptives.     

Neuropeptide Y potentiates norepinephrine-stimulated inositol phosphate production in the rat tail artery

In our cross-sectional study we investigated the separate influence of three main factors, namely menopausal and estrogen status, and chronological age, on ten neurovegetative climacteric complaints reported in the scale of Kupperman et al. A multivariate statistical analysis was performed by a multivariate statistical approach on 1161 untreated women seen at the Menopause Center of the Ferrara University Hospital. Ninety women (age range, 41-54 years) were premenopausal; 492 women (age range, 38-55 years) were perimenopausal with irregular periods or amenorrhea for less than 12 months; 468 women (age range, 41-69 years) had a spontaneous menopause (age range, 37-66 years); 111 had had hysterectomy with bilateral ovariectomy while still regularly menstruating. Serum estrone was used as the indicator of the patients' estrogen status. A clear positive trend was demonstrated between menopausal status and the prevalence of depression, hot flushes, insomnia and joint pain. However, only the prevalence of hot flushes amongst these four symptoms was significantly related with the climacteric estrogen decline (beta = -0.006, P = 0.001). Moreover, menopausal status appeared to influence the intensity of fatigue, hot flushes, insomnia and paresthesia. Age was found to significantly (P = 0.053) co-vary only with the intensity of the hot flushes, with a positive relation (beta = 0.092, r = 0.104, P = 0.003), whereas estrone values did not significantly co-vary with any symptom. Furthermore, while neurovegetative symptoms are largely present also in the absence of hot flushes, when these latter are present, they exacerbate both the intensity and the prevalence of all the other symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Socioeconomic status differences in hormone therapy

Socioeconomic status (SES) is a significant sociodemographic correlate of noncontraceptive hormone therapy, yet multiple dimensions of SES have not been examined systematically in previous studies of hormone therapy. This study examined the lifetime incidence of noncontraceptive hormone therapy, how usage varied by type of reproductive organ surgery, and the bivariate and net associations between a large array of SES indicators and the likelihood of ever using hormones by age 53-54 years in a population sample (n = 3,612) of non-Hispanic white female participants in the Wisconsin Longitudinal Study (1957-1993). Approximately half of the women had ever used noncontraceptive hormones; 38.5% were current users. In multivariate logistic regression analyses, the most robust SES predictor of hormone therapy was a woman's husband's occupational status (higher status associated with higher rates of use), after adjustment for all other measured sociologic and biomedical factors (e.g., other SES measures, other health behaviors, menopausal symptoms, age at menopause, health insurance). The association of hormone therapy with education differed between women who underwent hysterectomy and/or oophorectomy (higher odds for less educated women) and those with intact reproductive organs (lower odds for less educated women). Additionally, a woman's own earnings and household net worth were positive net correlates of noncontraceptive hormone therapy.