Estrogen Users Research Articles

Postmenopausal Hormone Use and Symptoms of Gastroesophageal Reflux

Previous studies suggest that elevated levels of estrogen and progesterone, either through endogenous or exogenous sources, increase gastroesophageal reflux. To evaluate the relationship between symptoms of gastroesophageal reflux disease (GERD) and postmenopausal hormone (PMH) therapy, including the use of selective estrogen receptor modulators and over-the-counter (OTC) hormone preparations, we performed a prospective cohort study of 51,637 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PMH therapy biennially since 1976, and information about symptoms of GERD in 2002. Among eligible participants, 12 018 women (23%) reported GERD symptoms. Compared with women who never used PMHs, the multivariate odds ratio (OR) for the risk of GERD symptoms was 1.46 (95% confidence interval [CI], 1.36-1.56) for past hormone users, 1.66 (95% CI, 1.54-1.79) for current users of estrogen only, and 1.41 (95% CI, 1.29-1.54) for current users of combined estrogen and progesterone. The risk of GERD symptoms increased significantly with increasing estrogen dosage (P < .001) and increasing duration of estrogen use (P < .001). Moreover, current selective estrogen receptor modulator users experienced an OR of 1.39 (95% CI, 1.22-1.59) for GERD symptoms, and women currently using OTC hormone preparations had an OR of 1.37 (95% CI, 1.16-1.62). Postmenopausal use of estrogens, selective estrogen receptor modulators, or OTC hormone preparations is associated with a greater likelihood of symptoms of GERD. This suggests a hormonal component to the pathophysiologic characteristics of GERD in women.

Synergism between Oral Estrogen Therapy and Cytochrome P450 3A5*1 Allele on the Risk of Venous Thromboembolism among Postmenopausal Women

Hormone therapy increases the risk of venous thromboembolism (VTE) among postmenopausal women. This effect may be modulated by the expression of cytochromes P450 3A5 (CYP3A5) and 1A2 (CYP1A2) which are involved in the hepatic metabolism of estrogens. The objective was to investigate the impact of CYP3A5 and CYP1A2 genetic polymorphisms on the association of VTE with hormone therapy. We conducted a case-control study. This study was conducted in eight French hospital centers and in the general population. CYP3A5 and CYP1A2 genotypes were evaluated among 195 cases with a first documented episode of idiopathic VTE and 533 controls matched for center, age, and admission date. The outcome measure was hormone therapy by route of estrogen administration. Overall, oral but not transdermal estrogen increased VTE risk [odds ratio (OR) = 4.5, 95% confidence interval (CI) = 2.6-7.6, and OR = 1.2, 95% CI = 0.8-1.8, respectively]. The allele frequency of CYP3A5*1 was 9 and 10% among cases and controls (OR = 1.0; 95% CI = 0.6-1.5) and that of CYP1A2*1F was 72 and 71% among cases and controls (OR = 1.5; 95% CI = 0.8-2.8). Compared with nonusers, OR for VTE in users of oral estrogen was 3.8 (95% CI = 2.1-6.7) among patients without CYP3A5*1 allele and 30.0 (95% CI = 4.4-202.9) among patients with this allele (test for interaction P = 0.04). By contrast, there was no significant interaction between CYP3A5*1 allele and transdermal estrogen on VTE risk. There is no interaction between CYP1A2 genetic polymorphism and hormone therapy on VTE risk. Women with CYP3A5*1 allele using oral estrogen can define a subgroup at high VTE risk. Additional data are needed to assess the relevance of this genetic biomarker in the medical management of menopause.

Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis

Objective To assess the risk of venous thromboembolism in women using hormone replacement therapy by study design, characteristics of the therapy and venous thromboembolism, and clinical background.Design Systematic review and...

Hormone therapy initiation after the Women's Health Initiative

To describe hormone therapy (HT) initiation after the 2002 publication of the Women's Health Initiative. 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. 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). 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.

Body Mass and Endometrial Cancer Risk by Hormone Replacement Therapy and Cancer Subtype

Epidemiologic studies unequivocally show that greater body mass increases the risk of endometrial cancer, but whether risk varies by use of postmenopausal hormone therapy (HT), location of fat deposition, or cancer subtype is still unclear. We examined these associations among 33,436 postmenopausal women in the Cancer Prevention Study II Nutrition Cohort, who completed questionnaires on diet, lifestyle, and medical history at baseline in 1992. A total of 318 cases were eligible through June 2003. Cox-proportional hazards analyses were used to estimate multivariate-adjusted rate ratios (RR). As expected, adult body mass index (BMI) was a strong predictor of risk [RR, 4.70; 95% confidence interval (CI), 3.12-7.07 for BMI 35+ versus 22.5-25.0, P trend < 0.0001]. Use of estrogen plus progestin postmenopausal HT modified the association. Among never-users, risk was significantly linear across the entire range of BMI examined (RR, 0.51; 95% CI, 0.29-0.92 for <22.5 versus 22.5-25.0; RR, 4.41; 95% CI, 2.70-7.20 for > or =35 versus 22.5-25.0, P trend < 0.0001), but among ever estrogen plus progestin users, the association was not significant (P trend = 1.0; P interaction < 0.0001). We observed no difference in risk according to tendency for central versus peripheral fat deposition. Greater BMI (> or =30 versus <25.0) increased risk of both "type I" (classic estrogen pathway, RR, 4.22; 95% CI, 3.07-5.81) and "type II" (serous, clear cell, and all other high grade) cancers (RR, 2.87; 95% CI, 1.59-5.16). The increased risk of endometrial cancer across the range of BMI in women who never used postmenopausal HT stresses the need to prevent both overweight and obesity in women.

Incidence of Dementia in Long-term Hormone Users

Results from epidemiologic studies of postmenopausal hormone use and dementia have been conflicting. Investigators from the Women's Health Initiative Memory Study reported that the incidence of dementia in women aged >/=65 years assigned to hormone use was increased. Here the authors report results from a prospective cohort study of 2,906 dementia-free women (1,519 hormone users and 1,387 hormone nonusers) aged > or =75 years who were recruited from a Southern California health plan in 1999 and followed through 2003. Cognitive status was assessed annually using the Telephone Interview of Cognitive Status-modified, supplemented by the Telephone Dementia Questionnaire and medical record review. The mean self-reported age at initiation of hormone use was 48.3 years for users of estrogen alone (n = 1,072) and 54.9 years for users of estrogen plus progestin (n = 447); self-reported mean durations of hormone use were 30.5 years and 23.2 years, respectively. There were 283 incident dementia cases identified during follow-up. After adjustment for age, education, and medical history, hazard ratios for incident dementia were 1.34 (95% confidence interval: 0.95, 1.89) in estrogen/progestin users and 1.23 (95% confidence interval: 0.94, 1.59) in estrogen users. These findings do not provide support for an effect of estrogen or estrogen/progestin use in preventing dementia.

Hormone replacement therapy use and variations in the risk of breast cancer

To determine the effect of different types and formulations of hormone replacement therapy (HRT) on the risk of breast cancer in postmenopausal women. Population-based case-control study. UK, 1988-2004. Women 50-75 years between 1998 and 2004. Breast cancer incidence to estimate the rate ratio (RR) associated with use of various HRTs over a 30-year period. We identified 6347 incident cases of breast cancer that were matched with 31,516 controls. Cases were on average 61 years at diagnosis and 22% had undergone a hysterectomy. The rate of breast cancer was increased with the use of opposed estrogens in oral form (adjusted RR 1.38; 95% CI 1.27-1.49) in contrast to patch form (RR 1.08; 95% CI 0.81-1.43). This rate was similarly elevated with both continuous (RR 1.29; 95% CI 1.07-1.56) and sequential (RR 1.33; 95% CI 1.21-1.46) forms of opposed estrogen. The rate of breast cancer was not increased among exclusive users of unopposed estrogens (RR 0.97; 95% CI 0.86-1.09) or of tibolone (RR 0.86; 95% CI 0.65-1.13). Users of tibolone who had switched from opposed estrogens, however, had an elevated rate (RR 1.29; 95% CI 1.09-1.52). The rate of breast cancer increased by 25% (95% CI 20-30%) with every ten prescriptions of orally administered opposed estrogen. The risk of breast cancer varies with the formulation and preparation of HRT. Opposed estrogens (progesterone-estrogen) in oral form are associated with an increased risk of breast cancer, which increases with use. Transdermal opposed estrogens, unopposed estrogens and tibolone do not increase this risk. However, this study is an observational study that carries risks of various biases, and thus the findings need to be interpreted with caution.

Menopausal Hormone Therapy and Risk of Epithelial Ovarian Cancer

Substantial increase in the use of menopausal hormone therapy (HT) throughout the 1990s, followed by widespread discontinuation after the 2002 publication of the Women's Health Initiative findings, has resulted in large numbers of former HT users among U.S. women. However, few studies have examined whether ovarian cancer risk varies according to recency and duration of specific HT regimens. We assessed risk of epithelial ovarian cancer among users of unopposed estrogen (ET) and combined estrogen/progestogen (EPT). In a population-based study in Washington state, 812 women with ovarian cancer diagnosed in 2002 to 2005 and 1,313 controls were interviewed in person about the use of HT and other characteristics. Women who used a single form of therapy (ET or EPT) were compared with women who never used HT using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). Risk was increased among current or recent (within the last 3 years) users of ET with > or = 5 years of use (ORs, 95% CIs: 1.6, 1.1-2.5 and 1.8, 0.8-3.7, respectively). Little increase in risk was noted among long-term ET users who discontinued use in the more distant past (OR, 1.2; 95% CI, 0.6-2.6). No increase in risk was noted among women who used only EPT, regardless of duration. Compared with women who never used HT, current users of EPT had an OR of 1.1 (95% CI, 0.8-1.5), and risk declined with increasing time since stopping; the OR was 0.7 (95% CI, 0.4-1.0) among women who had discontinued EPT within the last 3 years and 0.5 (95% CI, 0.3-0.7) among women who stopped at an earlier point. Long-term ET may be associated with an increased ovarian cancer risk that wanes after use ceases. We did not observe an increased risk with EPT, and with increasing time after stopping, a reduction in risk became increasingly evident. The progestogen component of HT may confer a risk reduction that is masked by an opposing effect of estrogen until, among former users, estrogenic influences have diminished. These findings, if replicated, may have implications both for public health and development of chemoprevention strategies.

The oestrogen paradox: an hypothesis

As shown in Figure ​Figure1,1, a wide range of epidemiologic and observational data suggest that oestrogens are associated with the development of breast cancer [1,2]. With these data as a background, it was quite surprising that recently published data suggested that women taking postmenopausal hormone therapy (MHT) with oestrogen alone for 5 to 9 years unexpectedly experienced a decrease in the risk for breast cancer [3,4]. However, when taken for more than 20 years, the risk appeared to increase [5,6]. We call this the 'oestrogen paradox' to highlight the fact that short-term oestrogen use decreases the risk for breast cancer whereas long-term use increases it. A second component of the oestrogen paradox is that high-dose oestrogen therapy in postmenopausal women with breast cancer causes tumour regression, whereas the anti-oestrogen tamoxifen is equally effective in causing remissions in similar patient groups [7-9]. It is paradoxical then that both oestrogens and anti-oestrogens cause tumour regressions. Figure 1 Hormonal risk factors associated with an increased risk of breast cancer and related to oestrogen exposure. For references supporting the validity of this figure, see Santen [1]. E, oestrogen; E2, oestradiol; HRT, hormone replacement therapy; OOX, oophorectomy; ... Short-term oestrogen use and breast cancer risk The initial publication of the Women's Health Initiative (WHI) [3] reported a 23% decrease in invasive breast cancer incidence in patients taking oestrogen alone compared with placebo, a finding which narrowly fell short of statistical significance (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.59 to 1.01). A recent exploratory analysis of updated data from this study examined subgroups to determine whether oestrogens might reduce the incidence of breast cancer significantly in women falling into certain categories [4]. Notably, this analysis reported a statistically significant 33% reduction in invasive breast cancer incidence in patients who strictly adhered to their oestrogen therapy (HR 0.67, 95% CI 0.47 to 0.97). In addition, a 31% lower incidence of localized breast cancer (HR 0.69, 95% CI 0.51 to 0.95) and a 29% reduction in ductal cancers (HR 0.71, 95% CI 0.52 to 0.99) were reported in oestrogen users. The decreases in breast cancer risk were limited to women who had not previously used MHT [4]. In a concurrent report from the Nurses Health Study [2], a significant 26% decrease in risk for breast cancer was observed in obese women, and a nonsignificant 10% decrease in all study participants, taking oestrogen alone for 5 to 9 years. Other observational studies reported a reduction in risk with oestrogen alone but of lesser magnitude and not statistically significant. For example, Schairer and colleagues [5] reported a 7% reduction in breast cancer risk at 6 years in women receiving oestrogen alone, and Lyytinen and coworkers [10] identified a similar 7% reduction. These combined results, although not conclusive, are highly suggestive of a beneficial effect of oestrogen in reducing breast cancer risk. However, this conclusion must be considered provisional until rigorous confirmation in additional studies is reported.

Response to Letter Regarding Article, “Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women: Impact of the Route of Estrogen Administration and Progestogens: The ESTHER Study”

We thank Drs Micheletti and Chevallier for their interest in our report.1 First, we believe that odds ratios (ORs) and 95% confidence intervals (CIs) estimated from logistic regressions provide adequate information about significance and the size and direction of the effect of norpregnane derivatives. Because elevation in venous thromboembolism (VTE) risk is substantial (OR: 4) and significantly different from 1 (with the 95% CI not crossing 1), our results suggest a thrombogenic effect of norpregnanes, and the probability value ( P <0.006) indicates that the probability of the result being due to chance is very small. Second, only the main effects …

Hormones and Breast Cancer: What's the Story?

It has now been 30 years since the first epidemiologic report linked menopausal estrogen therapy—the exogenous estrogens that, along with progestins, came to be known as “hormone replacement therapy”—with an increased risk of breast cancer ([1][1]). Today, the body of evidence on this

Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer

The purpose of this study was to assess whether endometrial cancer risk among long-term users of (1) sequential estrogen plus progestin 10-24 days per month exceeds that of nonusers and (2) daily estrogen plus progestin (continuous combined hormone therapy) is below that of nonusers. In this population-based case-control study with 1038 endometrial cancer cases diagnosed in 1985-1999 and 1453 control subjects, exclusive users of a single form of hormone therapy were compared with never users of hormone therapy. For sequential therapy, only long-term use (> or = 6 years) was associated with increased risk (odds ratio, 2.0; 95% CI, 1.2-3.5). Continuous combined therapy was associated with decreased risk (odds ratio, 0.59; 95% CI, 0.40-0.88), with no increased risk among long-term users (odds ratio, 0.77; 95% CI, 0.45-1.3). These results support the hypotheses that continuous combined therapy does not increase (and may decrease) endometrial cancer risk and that long-term sequential therapy can lead to a modest increased risk. However, the collective results of all studies of these questions and their clinical implications remain unclear.

Endometrial cancer risk in estrogen users after switching to estrogen–progestin therapy

It is unknown whether postmenopausal unopposed estrogen users are better off, in terms of endometrial cancer risk, switching to a combined estrogen-progestin regimen or stopping hormone use altogether. We analyzed data from a series of three population-based case-control studies in western Washington state during 1985-1999, comparing proportions of "switchers" and "stoppers" in cases and controls. We also assessed whether the risk of endometrial cancer in either group of former unopposed estrogen users returned to that of never users. After multivariate adjustment using unconditional logistic regression, women who switched to a combined regimen with a progestin added for at least ten days/month (37 cases, 47 controls) had half the risk of endometrial cancer of women who stopped hormone use altogether (86 cases, 78 controls) (adjusted odds ratio = 0.5, 95% confidence interval: 0.3-1.1). Most subgroups of former users, whether they switched or stopped, had some increased risk of endometrial cancer compared to never users. Results from this study suggest that unopposed estrogen users may reduce their risk of endometrial cancer more by switching to a combined regimen with progestin added for at least ten days/month than by stopping hormone use altogether.

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.

Relationship between Reproductive Exposures and Age-Related Cataract in Women

The objective of this study is to evaluate the relationship between reproductive exposures and age-related cataract among women. This was a hospital based case-control study. The study population included female patients, aged 50 years and above who attended the Eye clinic at the University of Malaya Medical Centre. The outcome measurement was based on ophthalmologic examination by an ophthalmologist. The data on exposure was obtained from face to face interview using a structured questionnaire. In order to reduce the recall bias, patients' medical records were used to substantiate the exposure status. Multiple logistic regression was used to assess the association of age-related cataract with exogenous estrogen usage (HRT and OCP) and duration of menses. Important confounders such as age, history of diabetes, cigarette smoking and steroids usage were controlled for in the analysis. Females with 29 years or less of endogenous estrogen exposure of, have almost three times the risk of developing age related cataract (adjusted OR 3.42: 95% CI: 1.28, 9.16), similarly among those with exposure of 30-32 years (adjusted OR 3.64: 95% CI: 1.08, 12.26). Hormone Replacement Therapy used for more than three years was found to be a protective factor of age-related cataract. There is evidence that reproductive exposure may play a role in reducing the occurrence of age-related cataract among Malaysian women.

Association of Estrogen and Progestin Potency of Oral Contraceptives With Ovarian Carcinoma Risk

To estimate the association of the estrogen and progestin potency of combined oral contraceptive pills (OCPs) with epithelial ovarian carcinoma risk. This population-based case-control study included 745 women with incident, histologically confirmed epithelial ovarian carcinoma and 943 controls, matched on age and ethnicity. Data were collected using a standard questionnaire, picture albums, and calendars. The association of OCP potency with epithelial ovarian carcinoma risk was modeled using unconditional logistic regression. When compared with women who never used hormonal contraception, users of OCPs with low estrogen (equal to or less than 0.035 mg ethinyl estradiol) and low progestin (less than 0.3 mg norgestrel) were at significantly reduced risk of ovarian carcinoma (odds ratio 0.19; 95% confidence interval 0.05-0.75). The risk among these women was lower than among users of estrogen or progestin of high potency, but the difference was not statistically significant. However, in a subset of 205 women who reported exclusive use of norethindrone, users of 0.5 mg or less, had a significantly reduced risk of ovarian cancer compared with women using 10 mg of this progestin. Increased norethindrone dose resulted in a significant increase in ovarian carcinoma risk, indicating a dose-response association. Combined OCPs were effective at decreasing the risk of epithelial ovarian carcinoma, with the strongest risk reduction associated with low-potency formulations. II.

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen. We performed a multicenter case-control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0). Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.

Are Some Types of Hormone Therapy Safer Than Others?

Despite great strides in hormone therapy (HT) research, clinical trial data on the benefit-to-risk profile of different formulations, doses, and routes administration of HT remain lacking. Most of the large-scale clinical trials1–3 have tested oral conjugated equine estrogens with or without medroxyprogesterone acetate, and data on nonoral routes and different types and doses of estrogens and progestogens have been limited. The evidence is mounting that route of delivery and possibly type and dose of HT are important factors, particularly for venous thromboembolism (VTE). Results of clinical trials4,5 and observational studies6 have been concordant in demonstrating an increased risk of VTE with oral exogenous HT. Recent studies suggest that VTE risk may be lower with transdermal than oral estrogen7 and with estrogen alone than with combined therapy.4 However, in the absence of rigorous evidence from large-scale clinical trials on differential effects by hormone formulation or route of delivery, should these findings influence clinical practice? Article p 840 The Estrogen and Thromboembolism Risk (ESTHER) study,7 published in the current issue of Circulation , adds important, relevant data to bolster the case that HT type and route of delivery do indeed make a difference. This well-designed, French, multicenter case-control study of VTE enrolled 271 consecutive cases of VTE in women (age, 45 to 70 years) and matched them to hospital and community controls. Current HT use was present in 46% of the VTE cases compared with 37% of controls. Oral HT users had 4-fold-increased odds of VTE; however, there was no increased risk among transdermal hormone users (odds ratio, 0.9). Previous randomized trials have suggested that the risk of VTE may …

Postmenopausal Hormone Replacement Therapy and Risk of Acute Pancreatitis: A Population-Based Case-Control Study

To examine whether acute pancreatitis is associated with the use of postmenopausal hormonal replacement therapy in Danish women over 45 yr of age. We based this population-based case-control study on data from three Danish counties for the years 1991-2003. We identified all women (>45 yr of age) with a first hospital discharge diagnosis of acute pancreatitis in the county hospital discharge registries (N = 1,054). Using the Danish Civil Registration System, we selected 10 age-matched population controls for each case, using risk set sampling (N = 10,540). Data on all prescriptions for estrogens or combined estrogen/progestins redeemed within 90 days before the hospitalization (current users) and 91-365 days before (former users) were collected from the prescription databases. Conditional logistic regression was used to estimate the relative risk of acute pancreatitis after exposure to estrogen or combined estrogen/progestin, adjusted for other risk factors for acute pancreatitis. The adjusted relative risk for acute pancreatitis in current users of menopausal estrogens was 1.1 (95% confidence interval [CI] 0.8-1.4), and 1.1 (95% CI 0.8-1.5) in former users. For current users of combined estrogen/progestins, the adjusted relative risk was 1.2 (95% CI 0.9-1.6), and for former users, 1.6 (95% CI 1.0-2.5). Our data did not support a substantial association between acute pancreatitis and the use of postmenopausal hormone therapy.

Effects of estrogen and estrogen–progestogen therapy on homocysteine levels and their correlation with carotid vascular resistance

Objective. To evaluate the correlation between homocysteine levels and carotid vascular resistance in menopausal women submitted to estrogen and estrogen–progestogen therapy.Methods. Eighty-six women with a mean age of 52 years were enrolled in a prospective, randomized, double-blind, 6-month study. Patients were allocated to use one of three oral therapies: placebo (n = 26), micronized estradiol 2 mg/day (n = 30) or micronized estradiol 2 mg/day plus norethisterone acetate 1 mg/day (n = 30). Evaluation of homocysteine levels and Doppler sonography of the common carotid artery, used to calculate pulsatility index (PI), were carried out prior to initiating therapy and at the end of the study. The correlation between these two parameters was evaluated using Pearson's coefficient of correlation.Results. There was a significant reduction in homocysteine levels in the groups treated with estrogen alone or estrogen combined with norethisterone. PI was significantly lower only in users of estrogen alone; however, no significant correlation was found between homocysteine measurements and PI.Conclusion. No significant correlation was found between homocysteine levels and carotid vascular resistance following hormone therapy.