Past oral contraceptive and hormone therapy use and endogenous hormone concentrations in postmenopausal women

OBJECTIVE: Exogenous sex hormone use is associated with many health effects. Current exogenous hormone use influences endogenous sex hormone levels, but little is known about longer term effects on endogenous hormones after cessation of use. The aim of this study was to examine the relationship between past hormone use and current endogenous hormone status. DESIGN: This was a cross-sectional study of 1,983 postmenopausal women aged 55 to 81 years from the general community. The women were not currently using exogenous hormones. Past use of oral contraceptives (OCs) and hormone therapy (HT) as well as circulating endogenous sex hormones and sex hormone-binding globulin concentrations were evaluated. RESULTS: Past OC users had significantly lower endogenous estradiol, estrone, androstenedione, testosterone, and sex hormone-binding globulin concentrations compared with never users independent of age, body mass index, smoking, physical activity, and reproductive factors. Past HT users had significantly lower testosterone and 17alpha-hydroxyprogesterone concentrations. Past OC use and HT use were both independently associated with lower testosterone concentrations: -9% (95% CI: -16% to -2%) for ever OC use compared with never OC use and -7% (95% CI: -17% to -2%) for ever HT use compared with never HT use. The magnitude of 5% to 10% differences in endogenous hormone concentrations was similar or greater for past OC use compared with past HT use, although OC use occurred earlier in the past. CONCLUSIONS: Past OC use and HT use seem to be related to long-term differences in endogenous sex hormones and sex hormone-binding globulin concentrations in postmenopausal women many years after cessation of use. These findings have implications for understanding the longer term effects of exogenous hormone exposures earlier in life with health and disease risk in later life.     

Rise and fall of hormone therapy in postmenopausal women with cardiovascular disease

Whereas observational data for postmenopausal women using hormone therapy (HT) have shown a protective effect against cardiovascular disease, prospective, randomized trials have demonstrated a harmful effect on the vascular system.This study describes the effects of HT on lipids, hemostatic parameters, inflammation, and the vascular wall. Reasons for the different results of observational and experimental studies of HT are postulated. The timing of hormonal supplementation seems crucial. Used chronically, HT has no harmful effects; however, first-time use of HT after a recent cardiovascular event results in an early increase in adverse cardiovascular events. In most observational studies, women started HT for postmenopausal symptoms, whereas in experimental studies, women started HT 10 to 20 years or longer after menopause. Cumulative evidence supports the hypothesis that HT has more effect in maintaining vascular health than in alleviating endothelial dysfunction. HT has not proven beneficial in the long term in women at risk of a cardiovascular event. The interval between menopause and the start of HT plays a crucial role in the effectiveness of HT in the vascular system.     

Early postmenopausal hormone therapy may prevent cognitive impairment later in life

OBJECTIVE: Estrogen deficiency has been implicated as a risk factor for cognitive impairment in elderly women, yet the role of hormone therapy (HT) to prevent this event remains controversial. The aim of this study was to investigate the impact of administration of HT for 2 to 3 years in the early postmenopausal years on the risk of cognitive impairment 5 to 15 years later. DESIGN: We followed a group of 343 women who had received HT in randomized, placebo-controlled trials and were reexamined 5, 11, or 15 years after completion of therapy. Of these women, 261 received either HT or placebo for 2 to 3 years during the trials with no further hormone treatment until follow-up, and the remaining 82 women reported either prolonged or current use of HT at reexamination. Outcome of the study was cognitive function assessed by the short Blessed test that includes tests of orientation, concentration, and memory function on a scale of 0 to 28 (score > or =6 indicates cognitive impairment). RESULTS: The mean age of participants at follow-up was 65 +/- 3 years. There was no difference in the mean cognitive scores between ever HT users and never users. For women who received 2 to 3 years of HT, the risk of cognitive impairment (cognitive score > or =6) was decreased by 64% (odds ratio [OR]: 0.36, 95% CI: 0.15-0.90; P = 0.03). A similar OR was found in long-term/current HT users. Adjustment for age, alcohol intake, current smoking, and education did not alter the results. CONCLUSION: The results of the present study suggest that previous short-term HT administered in the early phase of the menopause may provide a long-term protection against cognitive impairment.     

Association between hormonal changes at menopause and the risk of a coronary event: a longitudinal study

OBJECTIVE: To investigate the association of hormone levels at menopause, lifestyle variables, and body composition with the predicted 10-year risk of a coronary event, calculated using the PROCAM scoring system, in a population-based sample of Australian-born, middle-aged women. DESIGN: A 9-year prospective study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews, fasting blood, and physical measurements were taken annually. The risk of an acute coronary event was calculated using the PROCAM scoring system (includes: age, low-density lipoprotein cholesterol, smoking, high-density lipoprotein cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides). RESULTS: Retention rate after 8 years of follow-up was 88% (n = 387). In women not using hormone therapy (HT): higher than average body mass index (BMI) (P < 0.001), BMI that increased (P < 0.005), lower than average estradiol levels (P < 0.005), estradiol levels that decreased (P < 0.001), and high free testosterone levels (P < 0.05) were associated with increased risk of a coronary event. There was a trend for high exercise frequency to be associated with a decreased risk (P < 0.07). After BMI and lifestyle variables were taken into account, use of HT did not have a significant effect on risk of a coronary event. CONCLUSION: In this longitudinal observational study of middle-aged Australian-born women, high BMI, an increase in BMI, high free testosterone, low estradiol, and a decrease in estradiol levels were the main determinants of increased risk of an acute coronary event, based on the PROCAM scoring system calculation. More frequent exercise tended to lower the risk.     

Recent reversal of trends in hormone therapy use in a European population

OBJECTIVE: The impact of the Women's Health Initiative (WHI) randomized trial results published in July 2002 indicating that hormone therapy (HT) is potentially harmful for the heart and the mammary gland of naturally postmenopausal women was assessed for the first time in a European population. DESIGN: This study continuously monitored HT use from 1994 through 2003 in a population-based random sample of 5,758 women aged 35 to 74 years residing in Geneva (city and canton), Switzerland, yielding 1,938 naturally postmenopausal women with an intact uterus and 206 artificially postmenopausal women. Women in the former subgroup weighed substantially less than their WHI trial counterparts but were not otherwise at lower risk for cardiovascular disease. RESULTS: Among the naturally postmenopausal women with an intact uterus, current HT use increased from 29% to 46% (P < 0.0001) through July 2002 and then decreased abruptly to 31% in 2003. Current HT use remained stable (range, 38%-46%; trend P = 0.92) among the artificially postmenopausal women. CONCLUSIONS: Successive annual increases from 1994 through 2001 in the prevalence of current HT use by postmenopausal women living in Geneva were dramatically reversed to the level in 1994 just after the results of the WHI trial were published, but only for naturally postmenopausal women with an intact uterus. Approximately one in three of the latter women who stopped using HT may also have lost its beneficial effects on bone health.     

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

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

The effect of hormone therapy on the risk for age-related maculopathy in postmenopausal women

OBJECTIVE: To evaluate the effect of postmenopausal hormone therapy (HT) as well as the use of oral contraceptives and lifetime endogenous hormone exposure on the risk for age-related maculopathy (ARM) in postmenopausal women. DESIGN: This was a cross-sectional, controlled study. A total of 102 women from 60 to 80 years of age who were receiving HT and 100 controls underwent a detailed clinical funduscopic evaluation and stereoscopic fundus photography for the presence and grading of ARM. All participants completed a standardized questionnaire regarding vascular risk factors, HT, and lifetime exogenous and endogenous estrogen and progesterone exposure. Statistical analysis was performed using Student's t test, chi2 test, and a multivariate logistic regression model. RESULTS: The HT and the non-HT groups did not differ in terms of early (11% v 15%), late (6% v 6%), or wet (2% v 2%) ARM prevalence rates. Women with ARM were significantly older than controls (69 v 66 years; P = 0.001, 95% CI = 0.008 - 0.027) and were more likely to have ischemic heart disease (21% v 9%; OR = 2.86, P = 0.03, 95% CI = 0.020 - 0.360). Lifetime exogenous and endogenous hormone exposures and other cardiovascular risk factors were not significantly different among women with ARM as compared with controls. CONCLUSION: Postmenopausal HT may not affect the risk for either early or late ARM in women aged 60 to 80 years. The risk for both entities is not necessarily affected by either exogenous or endogenous lifetime hormone exposure. A history of ischemic heart disease may be associated with an increased risk for ARM.     

Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms

Objectives

We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS).

Study design

We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46–64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires.

Main outcome measures

CHD endpoints, obtained via registries.

Results

252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20–1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96–1.70]; P for interaction = 0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS.

Conclusions

In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies.     

The relationship between physical activity and lipoprotein subclasses in postmenopausal women: the influence of hormone therapy

OBJECTIVE: This study's objective was to determine if the association between physical activity and lipids and lipoprotein subclasses in postmenopausal women varies by hormone therapy (HT) use. DESIGN: The cross-sectional relationship between physical activity and lipid and lipoprotein subclass relationship was examined before group randomization in 485 postmenopausal (mean age 56.9 [2.9] y) white and African American women from the Woman On the Move through Activity and Nutrition study. This study is a randomized clinical trial designed to test whether a lifestyle intervention will reduce subclinical cardiovascular disease measures. RESULTS: Hormone therapy users (n = 286) were significantly (P < 0.05) younger, less likely to be African American, reported higher levels of physical activity, large very low-density lipoprotein particles (VLDL-P), and medium high-density lipoprotein particles (HDL-P), had a larger mean HDL-P size, and lower levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, small HDL-P, and small VLDL-P than nonusers (n = 196). Physical activity was significantly associated with favorable lipoprotein and lipid levels, regardless of HT use. Some relationships were found to vary significantly by HT use. In nonusers, mean HDL-P and LDL particles (LDL-P) size was significantly larger (P = 0.01 and 0.05, respectively) and total and small LDL-P were significantly lower (both P = 0.02) as activity increased. These relationship were not found in HT users. CONCLUSIONS: Physical activity was significantly related to some lipoprotein subclasses regardless of HT; however, several key lipoprotein subclasses were associated with higher levels of activity only among non-HT users.     

EMAS position statement: Managing obese postmenopausal women

Introduction

Obesity is a public health problem, with overweight individuals representing approximately 20% of the adult world population. Postmenopausal status is associated with higher prevalence of obesity, as 44% of postmenopausal women are overweight, among whom 23% are obese. Obesity often co-exists with other diseases, the most important being diabetes mellitus, dyslipidemia and hypertension. Furthermore, obesity increases the risk of gynecologic cancer, cardiovascular disease, venous thromboembolism, osteoarthritis and chronic back pain.

Aim

To formulate a position statement on the management of the menopause in obese women.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusions

Obese women seeking hormone therapy should be evaluated for their individual baseline risk of developing breast cancer, cardiovascular disease and venous thromboembolism. These risks should be weighed against expected benefit from symptom relief, improved quality of life and osteoporosis prevention. The lowest effective estrogen dose should be used (CEE 0.300–0.400 mg or estradiol 0.5–1 mg orally daily or 25–50 μg estradiol transdermally). With regard to progestogens, although no RCT data exist, there are observational studies showing that micronized progesterone or dydrogesterone may have a better risk profile with respect to breast cancer risk. There are no RCT data comparing various progestogens with regard to VTE risk. There are observational data, however, suggesting that micronized progesterone or pregnane derivatives may be associated with a lower VTE risk in postmenopausal women taking HT compared to nonpregnane derivatives. There is a rationale in suggesting the use of transdermal HT in obese women, since this route of administration has been associated with a lesser risk of venous thromboembolism than oral therapy.     

Hormone therapy and coronary artery calcification in asymptomatic postmenopausal women: the Rancho Bernardo Study

OBJECTIVE: To determine (1) whether past or current hormone therapy (HT) in postmenopausal women is associated with subclinical coronary artery plaque burden, (2) whether any association is independent of age, body size, blood pressure, lipids, fasting plasma glucose, cigarette smoking, leisure time physical activity, alcohol intake, use of lipid-lowering medications, and socioeconomic status, and (3) whether any association varies by duration of HT or by the use of combined versus unopposed HT. DESIGN: An observational study, with HT validated and coronary heart disease risk factors determined between 1997 and 1999 in a research clinic, and coronary artery calcium score (CACS) evaluated by electron beam computed tomography in 2001 through 2002. Participants were 204 community-dwelling postmenopausal women from the Rancho Bernardo cohort aged 55 to 78 years with no history of heart disease. RESULTS: The odds of severe CACS in current estrogen users (n = 127) was 0.40 (95% CI 0.19, 0.82), controlling for all covariates. Past users (n = 40) had intermediate odds (multiply adjusted OR = 0.66, 95% CI = 0.28, 1.58). In subgroup analyses, age-adjusted associations did not differ between the 68 women using unopposed estrogen versus the 59 using an estrogen-progestin regimen. Women who had used HT for at least 10 years (n = 86) had significantly less (P = 0.01) plaque burden than shorter term users (n = 41). CONCLUSIONS: Both the strong association and the duration of use effect independent of lifestyle and social class suggest an antiatherogenic effect of postmenopausal estrogen. Only a clinical trial can completely exclude confounding by social class, lifestyle, and unmeasured covariates.     

WHI risks: Any relevance to menopause management?

Two randomised controlled trials of hormone therapy (HT) were conducted within the US Women's Health Initiative. Both were chronic disease prevention trials, undertaken to determine whether HT reduced cardiovascular risk and increased breast cancer risk. Because the majority of subjects in both trials were asymptomatic and many years postmenopausal, and because substantial numbers had received HT prior to recruitment to the trials, care must be taken in drawing conclusions that the observed risks are applicable to women for whom HT is conventionally prescribed. Each of the reported risks must be examined critically to determine its likely applicability to symptomatic women treated for two to three years to relieve symptoms, but sometimes for substantially longer periods. Further, the risks reported in each of the two trials must be considered separately. Concerning cardiovascular disease, many subjects in the trials were at increased baseline risk because of their age, body mass index, smoking status, blood pressure and years since menopause, in contrast to the usual situation for symptomatic perimenopausal women. Therefore the reported overall cardiovascular risks in WHI, in both treatment arms, should be regarded as irrelevant to menopause management. In contrast, breast cancer risk is relevant, providing that proper note is taken of the fact that there was no increased risk after five years of combined hormone therapy in non-prior HT users and there was a tendency to a decreased risk in oestrogen only treated individuals. Other risks are analysed similarly.     

When is it appropriate to prescribe postmenopausal hormone therapy?

OBJECTIVE: To develop evidence and consensus-based recommendations for the use of hormone therapy (HT) in postmenopausal women. DESIGN: Using evidence from clinical trials and other publications, a multidisciplinary group of women's health experts developed consensus-based recommendations for HT use in more than 300 clinical scenarios. These panelists utilized the RAND Appropriateness Method and a quantitative scale to rate the appropriateness of treatment options for women with various risk factors and clinical scenarios. RESULTS: The panel judged it appropriate to prescribe all forms of HT to women with intolerable menopause symptoms and usual (age-expected) risks of cardiovascular disease (CVD), venous thromboembolism (VTE), or stroke. Use of HT was judged not appropriate for the clinical scenarios of bone preservation, cosmetic appearance, current memory loss, loss of libido, or CVD protection. For a woman still using HT after 5 or more years, it was considered appropriate to recommend the options of stopping or lowering the dose even if stopping was previously attempted. In treating intolerable symptoms in the presence of some elevated risk for diseases related to HT, route of administration may affect appropriateness but prior stroke or TIA# is a contraindication. CONCLUSIONS: Standard HT is appropriate for women with intolerable menopause symptoms in the absence of HT-related risk factors (eg, CVD, stroke, VTE, breast cancer). Panelists judged it appropriate to repeatedly present the option of stopping or reducing the dose. In most cases, presence of risk factors makes standard-dose oral HT not appropriate; however, some women may be candidates for a different dose or route of administration.     

Use of hormone replacement therapy among danish nurses at increased risk of osteoporosis

Observational studies and recent randomized trials have shown that postmenopausal hormone replacement therapy (HRT) may reduce the risk of osteoporotic fractures by about 30 to 40%. In this study we used a log linear graphical model to determine whether women with a known increased risk of osteoporosis were more likely to use HRT than other women and to examine whether women at increased risk modified this risk through their lifestyle. Cox regression analysis was used to analyze if women at risk of osteoporosis used HRT longer than women not at risk. Participants were Danish female nurses who, in 1993, were between 50 and 69 years of age (N=14,865). Data were collected from postal questionnaires. We concluded that nurses with a known family history of osteoporosis more often used HRT than nurses without this risk. No other direct associations were found between biological risk factors and ever use of HRT. The presence of biological risk factors of osteoporosis was not consistently modified by a healthier lifestyle. Nurses with a low body mass index (BMI) with a known family history of osteoporosis continued to use HRT longer than nurses without these risk factors.     

Health behaviors and other characteristics of women on hormone therapy: results from the Third National Health and Nutrition Examination Survey, 1988-1994

OBJECTIVE: To examine the prevalence of hormone therapy (HT) use and compare demographic characteristics, health behaviors, and health indicators between current HT users and never-users in a nationally representative sample of postmenopausal women. DESIGN: The Third National Health and Nutrition Examination Survey was a cross-sectional survey conducted between 1988 and 1994, including 3,673 postmenopausal women aged 40 years and older. RESULTS: Overall, 419 (11.4%) of the women reported current HT use, 857 (23.3%) reported past use, and 2,397 (65.3%) were never-users. Non-Hispanic black women and women aged 70 years or older were less likely to be current users. Higher socioeconomic status (education and income) and surgical menopause were associated with increased odds of current hormone use. After adjusting for the above variables, women who reported being inactive during leisure time and obese women (body mass index >or= 30) were less likely to be current users. Women who had 5 to 29 alcoholic drinks per month, perceived their health status as "good," took a multiple vitamin, were aware of having high blood cholesterol, and had a clinic for regular medical care were more likely to be current users. Smoking habits were not significantly different between the groups. CONCLUSIONS: Current HT users have different demographic profiles and may lead healthier lives than never-users. This is important to take into account when studying the effects of HT, and it may partly explain differences in findings regarding the health effects of HT use in observational studies compared with randomized clinical trials.     

Hormonal therapy is associated with a lower prevalence of breast arterial calcification on mammography

OBJECTIVE: To bring further understanding to the relationship between hormonal therapy (HT) and breast arterial calcification (BAC). METHODS: Of women arriving for breast cancer screening mammography, 1995 consented to complete a survey and have their mammograms analyzed for the presence of BAC. The survey assessed HT use and major risk factors for CAD. RESULTS: Of the 1919 women with complete data, there were 268 with BAC (14%). When categorized into three age groups, BAC was present in 40.7% of the women > or =65, 10.9% of those 55-64 and 3.0% of those <55. The > or =65 year-old group showed a nearly 50%-point lower prevalence of BAC among HT users compared with women who were not on HT (25.8% versus 74.2%, respectively, p=0.006). With age included as a continuous variable, past use of HT was significantly associated with a lower prevalence of BAC (p<0.03), while the presence of diabetes or a history of stroke were significantly associated with a higher prevalence of BAC (p<0.002). CONCLUSIONS: Well-established cardiovascular risk factors (diabetes, stroke, and age) appear to be associated with a significantly higher incidence of BAC, while HT during the menopausal years appears to be associated with a significantly lower prevalence of BAC.     

Do women using hormone replacement treatment have less pre-existing cardiovascular risk

Background: Several studies have suggested that women who choose to use hormone replacement therapy (HRT) already, before starting this therapy, have a better cardiovascular risk profile than those who do not use it. Some of these studies contain factors of confusion and biases, such as HRT users’ greater educational achievement or physical activity, which could have led to wrong conclusions. Aim: To study a cohort, without confounding factors in order to analyse whether the cardiovascular risk profile is different in women who choose to use HRT. Material and methods: Coronary risk factors of 387 women between 45 and 64 were studied. This study was carried out at the Unit for the Preventive Medical Examination of the South Metropolitan Health Service in Santiago (Chile) during the annual check-up. The first evaluation was in 1991–1992; with a second evaluation 5 years later. Of all the women, 174 (45%) never received hormones (Group A), 124 (32%) were HRT users at the time (Group B), and 89 (23%) were former-users (Group C). Results: No differences were found between the three groups for age, body mass index (BMI), educational background, alcohol consumption, smoking or physical activity. Blood pressure was similar in the three groups. No significant differences were found in total cholesterol (A, 221.7±42.2; B, 228.2±47.0; and C, 227.3±44.9 mg/dl); high density lipoprotein (HDL, A, 53.5±13.2; B, 51.8±12.8; and C, 54.0±12.4 mg/dl); low density lipoprotein (LDL, A, 141.7±38.9; B, 148.5±43.1 and C, 148.3±43.8 mg/dl); triglycerides (A, 134.5±67.9; B, 141.0±66.1; and C, 127.3±68.5 mg/dl) and glucose plasma levels (A, 90.5±32.2; B, 87.7±15.3; and C, 85.0±8.8 mg/dl). Conclusions: Our results suggest that women who choose to use HRT have a cardiovascular risk profile, before starting the therapy, similar to those who do not use it.     

The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy

Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether HT reduces this risk associated with early menopause. OBJECTIVE: To analyse whether early menopause based on various causes are independent risk factors for ischaemic heart disease, and to investigate whether the risks are modified by use of HT. METHODS: In a prospective cohort study questionnaires were mailed to Danish female nurses above 44 years of age in 1993. Information on menopause, use of HT and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the questionnaire, among them 10.533 were postmenopausal with definable menopausal age, free of previous ischaemic heart disease, stroke or cancer. Through individual linkage to national register incident cases of ischaemic heart disease were identified until end of 1998. RESULTS: Menopause below both age 40 and 45 was associated with an increased risk of ischaemic heart disease, seeming most pronounced for women who had an early ovariectomy but also among spontaneous menopausal women. Generally HT did not reduce the risk except for the early-ovariectomised women, where no increased risk of ischaemic heart disease for HT users was found. CONCLUSION: We found an increased risk of ischaemic heart disease associated with early removal of the ovaries that might be reduced with HT. The present study need confirmation from other studies but suggests that early ovariectomised women could benefit from HT.     

Hormone therapy initiation after the Women's Health Initiative

OBJECTIVES: To describe hormone therapy (HT) initiation after the 2002 publication of the Women's Health Initiative. DESIGN: Observational cohort (1999-2003) of women ages 40 to 79 years, five health plans, used HT in July 2002 and subsequently discontinued or never used before August 2002. RESULTS: Of discontinuers, 15.8% (3,203 of 20,205) reinitiated HT. Reinitiation was higher among estrogen users (23.8%) versus estrogen with progestin users (11.3%), and lower among those with diabetes (relative risk [RR]=0.68, 95% CI: 0.61-0.76), cardiovascular disease (RR=0.87, 95% CI: 0.83-0.92), and hyperlipidemia (RR=0.83, 95% CI: 0.79-0.88). Only 2.3% (2,072 of 90,261) of never users initiated (August 2002 to December 2003). First-time initiation was associated with cardiovascular disease (RR=1.17, 95% CI: 1.10-1.25) and hyperlipidemia (RR=1.24, 95% CI: 1.17-1.33) and was less common among those with diabetes (RR=0.70, 95% CI: 0.63-0.79). CONCLUSIONS: After the Women's Health Initiative, a minority of women reinitiated or became first-time initiators of HT. Women with cardiovascular disease, diabetes, and hyperlipidemia were less likely to reinitiate; women with cardiovascular disease and hyperlipidemia were more likely to be first-time initiators.