Hormone Replacement Therapy In Women Research Articles

Postmenopausal hormone therapy and the risk of cardiovascular disease

Sex hormones exert significant effects on the cardiovascular system. Ovarian hormone deficiency associated with menopause plays an important role in the development of cardiovascular disease in women. The reduced risk of cardiovascular diseases associated with hormone replacement therapy (HRT), reported in observational studies, has not been subsequently confirmed in randomized clinical trials. Therefore, at the present time, HRT is not recommended for postmenopausal women for the prevention of cardiovascular diseases. However, the possible role and safety of HRT in women who experience menopausal symptoms that significantly affect their quality of life is still under debate. The increased risk of cardiovascular disease in the larger randomized trial was found in the oldest women and in those who started HRT late after menopause began. Further basic and clinical studies are necessary to evaluate the mechanisms underlying the possible detrimental or protective effects of HRT and to assess benefits and risks of different dosages, route of administration, and duration of HRT. In the absence of clear evidence on the safest hormone regimen, the prescription of HRT in order to reduce menopausal symptoms should be limited to younger postmenopausal women at low risk for cardiovascular diseases, starting in the period close to the beginning of menopause. The benefit of HRT in relieving menopausal symptoms and reducing the occurrence of hip fractures should be weighted against the increased risk of cardiovascular disease and breast cancer. For this purpose, it is crucial to identify the presence of cardiovascular risk factors in perimenopausal and postmenopausal women. The cardiovascular effects of sex hormones, the increased risk of cardiovascular disease after menopause, and the effects of HRT on cardiovascular risk are critically reviewed, as well as their impact on the recommendations for clinical practice.

Association of Serum C-Reactive Protein Level with Sex-Specific Type 2 Diabetes Risk: A Prospective Finnish Study

Our objective was to assess whether the association of serum C-reactive protein (CRP) with type 2 diabetes risk is modified by sex. We prospectively followed 12,861 Finnish men and women who were 35-74 yr of age, and free of diabetes, coronary heart disease, stroke, and cancer at baseline. Hazard ratios of type 2 diabetes were estimated for different levels of serum CRP. During the follow-up, 208 men and 113 women developed diabetes. The multivariable-adjusted (age, physical activity, education, smoking, alcohol and coffee drinking, family history of diabetes, use of antihypertensive drugs, cholesterol-lowering agents, and hormone replacement therapy in women, systolic blood pressure, serum high-density lipoprotein cholesterol, serum triglycerides, and body mass index) hazard ratios of diabetes at three different levels of CRP (0.05-0.99, 1.0-2.99, and > or =3.0 mg/liter) based on the recommendation by Centers for Disease Control and the American Heart Association were 1.00, 1.46, and 1.85 (P for trend = 0.006) in men, and 1.00, 3.83, and 8.37 (P for trend <0.001) in women, respectively. CRP had a stronger association with diabetes risk in women than men (P for interaction: chi2 = 6.42; 1 df; P < 0.025). This positive association between CRP and diabetes risk did not change when participants were stratified by age group, smoking status, level of obesity, alcohol drinking habit, or family history of diabetes. High baseline level of serum CRP was associated with an increased risk of diabetes among both men and women, but this association was stronger in women than men.

Hormone replacement therapy in women with systemic lupus erythematosus and risk of cardiovascular disease

We sought to determine the impact of hormone replacement therapy (HRT) on the occurrence of coronary artery disease (CAD) in women with systemic lupus erythematosus (SLE). Women in the University of Toronto lupus database who had taken HRT with no history of CAD were compared with all post-menopausal female patients with no history of HRT or CAD. Chi-squared and t-tests were used to compare the risk factors of CAD and Kaplan-Meier curve, log rank test and proportional hazard model with time-dependent covariates were used to compare the time from entry into the clinic to occurrence of CAD. A total of 114 HRT-user patients with no history of CAD were compared with 227 post-menopausal non-HRT user SLE controls. The groups were similar with respect to lupus anticoagulant, antiphospholipid antibody, cumulative steroid dose and classic cardiac risk factors. A similar percentage of patients developed CAD in the control (13.7%) and HRT (11.4%) groups. There was no difference in the time to development of CAD. In the multivariate analysis, HRT was not a risk factor for CAD. Only age (P = 0.0001, HR = 1.11, 95% CI = 1.05, 1.17) and SLEDAI-2K (P = 0.0001, HR = 1.10, 95% CI = 1.05, 1.16) were significantly associated with the risk of CAD. In this small group of patients with SLE, HRT alone did not appear to predispose to CAD.

Cost-effectiveness of hormone replacement therapy for menopausal symptoms in the UK

To estimate the cost-effectiveness of five-year treatment of hormone replacement therapy (HRT) compared with no treatment for women with menopausal symptoms in the UK. A Markov cohort simulation model with tunnel techniques was used to assess the cost-effectiveness of HRT in women aged 50 years. For the clinical effects of HRT we used, where possible, results taken from the Women's Health Initiative (WHI). The model had a life-time horizon with cycle lengths of one year and contained the following disease states: hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary heart disease, stroke and venous thromboembolic events. An intervention was modelled by its impact on the disease risks during and after stopping treatment. The model was populated with UK-specific data on risks, mortality rates, quality-of-life weights and costs. The main outcome of the model was cost per quality-adjusted life year (QALY) gained of HRT compared with no treatment. The results indicated that it was cost-effective to treat women with menopausal symptoms with HRT in the UK. The severity of menopausal symptoms was the single most important determinant of cost-effectiveness, but HRT remained cost-effective even where symptoms were mild or effects on symptom relief were small. Treatment of women with menopausal symptoms with HRT is cost-effective.

Inflammatory biomarkers, physical activity, waist circumference, and risk of future coronary heart disease in healthy men and women

The aim of this study was to determine the contribution of physical activity and abdominal obesity to the variation in inflammatory biomarkers and incident coronary heart disease (CHD) in a European population. In a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, we examined the associations between circulating levels or activity of C-reactive protein, myeloperoxidase (MPO), secretory phospholipase A2 (sPLA2), lipoprotein-associated phospholipase A2 (Lp-PLA2), fibrinogen, adiponectin, waist circumference, physical activity, and CHD risk over a 10-year period among healthy men and women (45-79 years of age). A total of 1002 cases who developed fatal or non-fatal CHD were matched to 1859 controls on the basis of age, sex, and enrolment period. Circulating levels of C-reactive protein, sPLA2 (women only), fibrinogen, and adiponectin were linearly associated with increasing waist circumference and decreasing physical activity levels. After adjusting for waist circumference, physical activity, smoking, diabetes, systolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, and further adjusted for hormone replacement therapy in women, C-reactive protein, MPO (men only), sPLA2, fibrinogen, but not Lp-PLA2 and adiponectin were associated with an increased CHD risk. Inactive participants with an elevated waist circumference were characterized by deteriorated levels of inflammatory markers. However, several inflammatory markers were associated with an increased CHD risk, independent of underlying CHD risk factors such as waist circumference and physical activity levels.

The antitumorgenic actions of estrogen receptor beta in breast cancer cells.

Abstract Abstract #3056 Recent studies have suggested that ERβ may oppose actions of ERα in breast cancer cells and clinical studies indicate that loss of ERβ expression in ERα positive tumors is associated with a poor prognosis and perhaps resistance to tamoxifen therapy. Clinical evidence indicates that in post menopausal women hormone replacement therapy significantly decreased incidence of colon cancer, suggesting that estrogens have a protective role . We have recently found that in SW 480 colon cancer cells, (ER negative) stable expression of ERβ decreased SKP2, c-myc but not p27kip1 mRNA measured by real time PCR. These results were confirmed for c-myc and SKP2 at the protein level. However, ERβ expression increased only p27 protein levels. Addition of E2 did not regulate effects of ERβ expression.&amp;#x2028; Similar results have been observed with T47D (ER positive breast cancer cells) stably over expressing ERβ. In the latter cells and MCF7 (ER alpha positive) cells over expressing ERβ, E2 induced β catenin protein expression was blocked by ERβ. The latter also blocked AKT and ERK activation by E2 and induced apoptosis, in an E2 independent fashion. ERβ expression also blocked E2 induced growth in MCF 7 cells. Antibody array analysis showed that ERβ regulated &amp;gt;100 proteins at or above the 2 fold level in T47D breast cancer cells,where as 2D PAGE/MS showed that over 60 proteins changed significantly, both types of analysis and Western blots indicate that ERβ regulates Sp1,HSP70,β catenin, c-Jun, JNK,c-Jun ,BAD among other proteins. Antibody arrays and MS have therefore revealed unsuspected targets of ERβ action. Thus, ERβ appears to oppose several actions of ERα in breast cancer cells and block colon cancer cell growth, independently of E2. Design of selective ERβ activating agents or delivery of ERβ using gene therapy may be of substantial utility in the treatment of breast and colon cancer. Category27. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3056.

Coronary heart disease and hormone replacement therapy after the menopause

The discordance in coronary heart disease (CHD) outcome between randomized, controlled trials and observational studies of hormone replacement therapy (HRT) is likely the result of the dissimilar cohorts studied. This observation led to the formation of the timing hypothesis that benefits and risks of HRT depend upon age of HRT initiation and/or time of HRT initiation in relation to menopause. This hypothesis has been supported with data from large, randomized, controlled trials that have studied HRT and selective estrogen receptor modulators (SERMs) in the prevention of CHD. Initiation of HRT in women <60 years of age and/or within 10 years of menopause reduces both CHD and total mortality; SERMs have been shown to reduce CHD in women <60 years. What has become clear from the cumulated literature is that in young postmenopausal women who initiate HRT in close proximity to menopause, the adverse effects of HRT are rare and no greater than those of other commonly used pharmacological agents and that the primary prevention benefits for CHD are at least equivalent to those of other commonly used therapies. Additionally, the literature indicates that the duration of HRT confers greater CHD benefit especially in women <60 years who initiate therapy. The cumulated literature dispels misperceptions concerning HRT and CHD.

Use of total abdominal hysterectomy and hormone replacement therapy in BRCA1 and BRCA2 mutation carriers undergoing risk-reducing salpingo-oophorectomy

Risk-reducing salpingo-oophorectomy (RRSO) reduces the risk of developing ovarian and breast cancer in BRCA 1 and BRCA 2 (BRCA1/2) mutation carriers. The short-term use of hormone replacement therapy (HRT) after RRSO may relieve menopausal symptoms and does not appear to affect the breast cancer risk reduction gained by RRSO. Multiple factors may influence decisions regarding whether or not total abdominal hysterectomy (TAH) is done at the time of RRSO, whether HRT is elected after surgery, and if so, which type of HRT is selected. Our investigation has been to examine factors associated with TAH and HRT use and to determine if the choice of TAH at the time of RRSO and the type of HRT that was chosen has changed since the report of data from the Women's Health Initiative (WHI) in 2002, which showed that the relative risk for breast cancer is higher in subjects who used combined estrogen-progestin HRT compared with those who used estrogen alone. We identified 73 female BRCA1/2 mutation carriers who were known to have undergone RRSO between 1/1972 and 11/2005 who had no history of breast or ovarian cancer at the time of the surgery. Information regarding whether or not TAH was done in addition to RRSO, the type of HRT, and the subsequent diagnosis of breast cancer was collected. Of 73 unaffected BRCA1/2 carriers known to have had RRSO, 40 (40/73, 55%) also underwent TAH. Thirty-three of 73 (33/73, 45%) began HRT following RRSO. Of 33 HRT users, 17 (17/33, 52%) used estrogen only and 14 (14/33, 42%) used combined hormonal therapy. There was no difference in use of HRT in women with TAH (17/40, 43%) vs. those without (16/33, 48%) (P = 0.6). There was no difference in the proportion of women who underwent TAH before and after the WHI report in 2002. Use of HRT, most notably combined estrogen-progestin HRT, appears to have declined since 2002, although this result did not reach statistical significance. In this single institution study, the majority of BRCA1/2 mutation carriers undergoing RRSO also underwent TAH, and a substantial number took HRT. TAH did not increase the likelihood of taking HRT compared to RRSO alone.

Treatment strategies for reducing the burden of menopause-associated vasomotor symptoms.

Vasomotor symptoms (VMS), such as hot flashes and night sweats, are the most bothersome symptoms of menopause and affect an estimated 75% of women aged over 50 years. To discuss the burden, pathophysiology, and management of menopause-associated VMS and to evaluate pharmacologic options available for the treatment of VMS, including herbal remedies, hormone replacement therapy (HRT), and nonhormonal therapies. Lifestyle changes, including regulation of core body temperature, relaxation techniques, regular physical activity, weight loss, and smoking cessation may help reduce the risk of VMS and should be implemented by all women with menopause-associated VMS. The role of herbal remedies in the treatment of VMS remains unclear, as clinical trial efficacy data are inconsistent and inconclusive. Nevertheless, soy isoflavones, red clover isoflavones, black cohosh, and vitamin E are commonly used to treat VMS and may be considered in women with mild symptoms that are not controlled by lifestyle changes alone. These herbal remedies appear to be safe when used for short durations (d 6 months). HRT, consisting of estrogen (in women without a uterus) or estrogen plus progestin (in women with a uterus) is the most widely studied and most effective treatment option for relief of menopause-associated VMS and is considered the standard of care for women with moderate-to-severe VMS. HRT should be used at the lowest effective dose and for the shortest duration possible (preferably d 5 years) in women in whom the potential benefits outweigh the potential risks. Nonhormonal therapies, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, and clonidine, may be appropriate alternatives in women who cannot or will not use HRT for VMS relief, such as those with a history of or at risk for breast cancer. The physical and financial burden imposed by menopauseassociated VMS is immense. Optimum management of VMS includes lifestyle changes in all women and HRT in women with moderate-tosevere symptoms. Less effective herbal remedies or nonhormonal therapies may be appropriate in certain women, such as those with mild symptoms or those who cannot or will not take HRT.

Treatment Strategies for Reducing the Burden of Menopause-Associated Vasomotor Symptoms

BACKGROUND: Vasomotor symptoms (VMS), such as hot flashes and night sweats, are the most bothersome symptoms of menopause and affect an estimated 75% of women aged over 50 years. OBJECTIVE: To discuss the burden, pathophysiology, and management of menopause-associated VMS and to evaluate pharmacologic options available for the treatment of VMS, including herbal remedies, hormone replacement therapy (HRT), and nonhormonal therapies. SUMMARY: Lifestyle changes, including regulation of core body temperature, relaxation techniques, regular physical activity, weight loss, and smoking cessation may help reduce the risk of VMS and should be implemented by all women with menopause-associated VMS. The role of herbal remedies in the treatment of VMS remains unclear, as clinical trial efficacy data are inconsistent and inconclusive. Nevertheless, soy isoflavones, red clover isoflavones, black cohosh, and vitamin E are commonly used to treat VMS and may be considered in women with mild symptoms that are not controlled by lifestyle changes alone. These herbal remedies appear to be safe when used for short durations (d 6 months). HRT, consisting of estrogen (in women without a uterus) or estrogen plus progestin (in women with a uterus) is the most widely studied and most effective treatment option for relief of menopause-associated VMS and is considered the standard of care for women with moderate-to-severe VMS. HRT should be used at the lowest effective dose and for the shortest duration possible (preferably d 5 years) in women in whom the potential benefits outweigh the potential risks. Nonhormonal therapies, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, and clonidine, may be appropriate alternatives in women who cannot or will not use HRT for VMS relief, such as those with a history of or at risk for breast cancer. CONCLUSION: The physical and financial burden imposed by menopause associated VMS is immense. Optimum management of VMS includes lifestyle changes in all women and HRT in women with moderate to severe symptoms. Less effective herbal remedies or nonhormonal therapies may be appropriate in certain women, such as those with mild symptoms or those who cannot or will not take HRT.

The role of hormone replacement therapy in the management of premature ovarian failure

Premature ovarian failure (POF) generally occurs before 40 years of age and is characterized by amenorrhea and follicle-stimulating hormone levels within the menopausal range. Variations in the endogenous estradiol levels can also occur. The potential risks and benefits of hormone replacement therapy for women with POF are discussed in this Viewpoint.

PAI-1 Antagonists: Predictable Indications and Unconventional Applications

At present, thrombolytic agents represent the only direct way of augmenting fibrinolytic activity in humans. While these agents are proven to be efficacious in the treatment of acute thrombotic events, they are not a viable option for long-term administration. There are numerous drugs available that indirectly to increase fibrinolytic activity by reducing plasma levels of plasminogen activator inhibitor-1 (PAI-1), including ACE inhibitors, insulin-sensitizing agents, and hormone replacement therapy in women. At present, efforts are underway to develop and test synthetic, selective PAI-1 antagonists. The potential applications of PAI-1 antagonists include thrombotic disorders (arterial and venous), amyloidosis, obesity, polycystic ovarian syndrome, and perhaps even type 2 diabetes mellitus. The availability of specific PAI-1 antagonists promises to expand the limits of understanding the role the fibrinolytic system plays in human disease and break through the current confines of therapeutic options that can effectively restore and augment the activity of the fibrinolytic system.

Hormonal Replacement Therapy in Women With Parkinson Disease and Levodopa-Induced Dyskinesia

Eleven postmenopausal women with Parkinson disease and levodopa-induced peak-dose dyskinesias underwent a double-blind, placebo-controlled, crossover study. The active treatment consisted of estrogen replacement therapy for 12 weeks, followed by medroxyprogesterone acetate for 2 weeks. Estrogen replacement therapy-medroxyprogesterone acetate administration significantly improved peak-dose dyskinesia without worsening motor disability, thus suggesting a possible benefit on dyskinesias in postmenopausal women with Parkinson disease.

Past use of oral contraceptives and hormone replacement therapy in women with angiographic coronary artery disease: a case-control study

To evaluate the relationship between past use of hormone replacement therapy (HRT)/ oral contraceptives (OC) and angiographic coronary artery disease (CAD). A case-control study. All women who were submitted to coronary angiography from January to December 2004 at the University Hospital, Ribeirão Preto School of Medicine (Brazil), were enrolled in this study and divided into two groups: with and without CAD. For the purposes of these analyses, coronary artery disease was defined as equal or greater than 70% luminal diameter stenosis in at least one epicardial coronary artery. The reproductive status was obtained from the medical records with a detailed questionnaire. We used unpaired t test, Fisher exact test or Qui-Square to compare the variables. Data were available for 203 of 383 patients who were submitted to angiocoronariography. Compared to patients without CAD (n = 119), patients with CAD (n = 84) were older (CAD: 62.8 ± 11.1 years vs. no-CAD 53.1 ± 12.1 years; P<0.0001), had a higher frequency of multiparity (CAD: 84% vs. no-CAD: 68%; P=0.03) and a higher proportion of them was menopausal (CAD:97% vs. no-CAD:79%; P=0.0009). The frequency of HRT use was higher among patients without CAD (CAD:28% vs. no-CAD:56%), with the use of HRT being associated with a lower risk for CAD [odds-ratio: 3.2 (1.2–8.3)]. The use of OC was not associated with a significant reduction of risk for CAD and the frequency of OC use did not differ between groups. There was no difference in the time of use of HRT or OC between CAD and no-CAD patients (HRT use: CAD = 4.9 ± 4.2 years vs. no-CAD = 2.7 ± 2.1 years; P=0.07; time of OC use: CAD = 8.8 ± 6.7 years vs. no-CAD = 6.1 ± 4.1 years; P=0.08). HRT but not OC use is associated with a reduced risk for CAD.

Effect of Hormone Replacement Therapy in Women on Ocular Refractive Status and Aberrations

To evaluate the effects of hormone replacement therapy (HRT) on refractive status, corneal topography, and aberrations of the eye in postmenopausal women. Thirty-six healthy postmenopausal women (72 eyes) were included in the study. All patients received HRT that consisted of 0.625 mg/day conjugated estrogen and 5 mg/day medroxyprogesterone acetate in a continuous combined regimen. Schirmer II test and tear film break-up time (BUT) were performed on all patients at the time of enrollment and 6 months after initiation of HRT. Refractive status, corneal topography, and wavefront aberrations were evaluated with the NIDEK Optical Path Difference-Scan before and 6 months after HRT was initiated. Mean patient age was 50.8 +/- 2.6 years (range: 47 to 57 years). The mean duration of menopause was 2.7 +/- 0.8 years (range: 1.4 to 3.5 years). The Schirmer II test and tear film BUT measurements were significantly lower after HRT (P < .05). Before HRT, the mean spherical equivalent refraction was -0.19 +/- 1.79 diopters (D) (range: -4.38 to +3.00 D). After HRT, the mean spherical equivalent refraction was -0.22 +/- 1.81 D (range: -4.63 to +/- 2.63 D). No significant differences were noted between refractive status, corneal topography, and wavefront aberrations of eyes of patients before and 6 months after HRT (P > .05). Hormone replacement therapy in postmenopausal women does not significantly affect refractive status, corneal topography, and wavefront aberrations of the eye at 6-month follow-up.

Hormone Replacement Therapy in Women with Epilepsy

To the Editors: Changes in reproductive hormone levels may influence seizure activity (Scharfman and MacLusky, 2006). A previous survey suggested that hormone replacement therapy (HRT) may adversely affect seizure control in women with epilepsy (Harden et al., 1999). Although this trial was terminated prematurely, resulting in greatly reduced statistical power, the results provide evidence that intake of estrogen/medroxyprogesterone acetate HRT in postmenopausal women with epilepsy is associated with some worsening in seizure control. A more recent study by Harden and colleagues (Harden et al., 2006) confirms the results of their previous survey (Harden et al., 1999), and raises a number of interesting points for discussion: Although HRT was widely used at the time the trial was initiated, intriguing ethical issues exist in conducting a placebo-controlled study to test the hypothesis that active treatment could cause seizure aggravation. One may argue, however, that based on evidence available at the time, HRT might have been a safe option in the enrolled population. Because an adverse influence on seizure control was confirmed, the question arises, what HRT component was responsible for the effect? The bulk of the evidence points to estrogens, which can have a facilitating effect on seizure activity (Logothetis et al., 1959; Logothetis and Harner, 1960; Hom and Buterbaugh, 1986; McEwen, 2002), although evidence on this is not univocal (Scharfman and MacLusky, 2006). Whether medroxyprogesterone acetate contributed to seizure deterioration is unknown. The authors elected to test the HRT preparation most widely prescribed in the United States. However, it might have been preferable in this population to combine estrogens with natural progesterone. Natural progesterone is converted to neuroactive metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006). Preliminary evidence suggests a positive effect of progesterone in catamenial epilepsy (Herzog, 1995, 1999). Whether use of natural progesterone instead of MPA would be a safer option for HRT is unknown. From a practical point of view, the relevance of this study has been reduced by the drastic decline in the use of HRT in postmenopausal women, after publication of the WHI results (Rossouw et al., 2002). Today, HRT is no longer recommended as preventive treatment in asymptomatic women, because the increased risks of breast cancer, coronary heart disease, stroke, and pulmonary embolism clearly outweigh any benefits. The authors are correct in pointing out that their results should not be interpreted as contraindicating the use of HRT for short-term control of postmenopausal symptoms in women with epilepsy. Their results do suggest, however, that the HRT regimen tested may not be the optimal one to use in these women. An interesting ancillary observation was that serum lamotrigine (LTG) levels decreased after initiation of HRT in both women who were treated with this drug. Although exclusion of these women from the analysis did not alter the results, these findings confirm previous reports that serum LTG levels can be reduced to a clinically significant extent by estrogen-containing preparations, including oral contraceptives (Sabers, 2003; Reimers et al., 2005; Sidhu et al., 2006). Careful clinical observation and, if possible, monitoring of serum LTG levels are recommended whenever estrogen-containing preparations are started or discontinued in women taking LTG.

More is Not Better: Hormones for Menopausal Women with Epilepsy?

Hormone Replacement Therapy in Women with Epilepsy: A Randomized, Double-Blind, Placebo-Controlled Study. Harden CL, Herzog AG, Nikolov BG, Koppel BS, Christos PJ, Fowler K, Labar DR, Hauser WA. Epilepsia 2006;47(9):1447–1451. PURPOSE: Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. METHODS: This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. RESULTS: Twenty-one subjects were randomized after completing baseline. The subjects’ ages ranged from 45 to 62 years (mean, 53 years; SD, μ5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25–30% while taking CEE/MPA. CONCLUSIONS: CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.

Body Mass and Colorectal Cancer Risk in the NIH-AARP Cohort

In most studies, body mass index (BMI) has been associated with increased risk of colorectal or colon cancer in men, but the relation is weaker and less consistent for women, possibly because of interactions with age or hormone replacement therapy. The authors examined the relation between BMI and colorectal cancer incidence in a large, prospective US cohort of 307,708 men and 209,436 women from the NIH-AARP Diet and Health Study. During follow-up of the cohort from 1995 to 2000, 2,314 cases of colorectal cancer were observed in men and 1,029 in women. BMI was related to increased risk of incident colon cancer, but not rectal cancer, for both men and women. For men, relative risks of colon cancer for a BMI of 18.5-<23, 23-<25, 25-<27.5, 27.5-<30, 30-<32.5, 32.5-<35, 35-<40, and > or = 40 kg/m(2) were 1.0 (referent), 1.11, 1.22, 1.44, 1.53, 1.57, 1.71, and 2.39, respectively (95% confidence interval: 1.59, 3.58; p-trend < 0.0005). Corresponding relative risks for women were 1.0, 1.20, 1.29, 1.31, 1.28, 1.13, 1.46, and 1.49 (95% confidence interval: 0.98, 2.25; p-trend = 0.02). BMI was related to colon cancer risk for younger (aged 50-66 years) but not older (aged 67-71 years) women. The association was not modified by hormone replacement therapy in women or physical activity in men or women.

Life prevalence and determinants of hormone replacement therapy in women living in Porto, Portugal

Objective To survey the life prevalence and determinants of hormone replacement therapy (HRT) in Portugal. Methods We evaluated 908 women with mean age (standard deviation) 62.3 (9.6) years, as part of the assembling of a cohort of adults, representative of Porto inhabitants. Extensive data collection was conducted and included socio-demographic, lifestyle and clinical characterisation. The latter comprised gynecologic and obstetric history, as well as lifetime use and duration of HRT. Results Life prevalence of hormone replacement therapy was 26.8% (95% confidence interval: 23.9–29.8). Prevalence of lifetime HRT was higher in younger (born after 1949: 37.1%) and more educated women (over 12 schooling years: 48.7%), as in white-collar workers (36.8%), and women using private healthcare (39.4%). HRT use was also more frequent among ever smokers (43.1%), and in women reporting regular sports practice (35.6%). Ever users of oral contraceptives underwent HRT more frequently (33.3%) and women who experienced menopause more recently were more likely to use HRT (after 1994: 40.5%). No differences were found in the prevalence of HRT according to whether women had been hysterectomised or oophorectomised. Education, regular sports practice and menopause year were independent determinants of HRT. Median duration of therapy was 2 years. Short-term HRT users were more educated, and had more recent menopause. Long-term HRT users were more educated, engaged in sports more frequently, and were more frequently oophorectomised. Conclusions Prevalence of hormone replacement therapy increased until 2001 and was mainly determined by high socioeconomic status, regardless of important therapeutic indications, such as oophorectomy and hysterectomy.

Update on the Cardiovascular Risks of Hormone Replacement Therapy

Systematic reviews of randomized, controlled trials have shown that use of hormone replacement therapy in women increases the risk of total cardiovascular disease (venous thromboembolism, stroke and coronary heart disease; there may also be an increased risk of peripheral arterial disease). The relative increase in risk is similar to that for use of combined oral contraceptives, but the absolute increase in risk is higher owing to the higher age of hormone replacement therapy users. The increased risk appears confined to current users, increases with age and obesity, and may differ with type of preparation. Transdermal hormone replacement therapy may carry a lower risk of venous thromboembolism compared with oral hormone replacement therapy. The mechanism for the increased risk is probably activated blood coagulation. The risk of venous thromboembolism is higher in women with thrombophilias; however, the value of screening for thrombophilias is not established. Further research is required to establish the risks of cardiovascular (and other) diseases in different groups of women for different types of hormone replacement therapy, including an individual participant meta-analysis of reported randomized, controlled trials.