Past Use Of Hormone Replacement Therapy Research Articles

Menopausal symptoms and attitudes toward hormone replacement therapy among Israeli women

Menopause occurs around midlife and is an inevitable component of women’s aging. The study aimed to investigate the associations between the lifetime prevalence of menopausal symptoms and health-related characteristics among Israeli postmenopausal women aged 55–75 years. Additionally, this study aimed to estimate the use of hormone replacement therapy (HRT) and women’s attitudes toward this treatment. Data for this study were extracted from a cross-sectional national telephone survey conducted in Israel between 2018 and 2020. For the current study, only postmenopausal women aged 55–75 years were included. Multivariate analyses were used to identify demographic and health-related characteristics associated with menopausal symptoms. The study included 688 participants. Most (68.8%) reported one or more menopausal symptoms, specifically vasomotor symptoms (50.4%). According to the multivariate logistic regression analysis, menopausal symptoms were associated with moderate-high anxiety and/or depression symptoms (OR = 2.01, 95% CI 1.12–3.58) and with osteoporosis (OR = 1.78, 95% CI 1.08–2.92). Although most (78.3%) symptomatic women were bothered by their symptoms, 29.1% received any treatment for symptom relief and only 12.6% reported current or past use of HRT. The findings show that menopausal symptoms were associated with a higher prevalence of anxiety and/or depression symptoms and osteoporosis in the years following menopause. Most symptomatic women did not receive any treatment and the majority were against HRT. Knowledge and awareness about menopause and treatment options should be increased among Israeli women. Additionally, the promotion of positive attitudes toward menopause and HRT use among women and healthcare providers is strongly recommended.

Is There an Association Between Meningioma and Hormone Replacement Therapy?

Molecular and clinical observations suggest a role of sex steroid hormones in the occurrence of meningioma. However, there is limited and often conflicting data on the use of hormone replacement therapy (HRT) as a possible risk factor for meningioma. The goal of this study was to investigate whether there is an association between a diagnosis of meningioma and either current or past HRT use in women. We retrospectively reviewed records in the Mayo Clinic Jacksonville electronic patient database between 1993 and 2003 to identify women with a diagnosis of either symptomatic or incidentally discovered, clinically silent meningioma. Records were also searched to identify women with a documented history of either current or past HRT use. Of the 355,318 women, ages 26 to 86, evaluated for any medical issue, 18,037 (5%) were documented as current or past HRT users. A total of 1,390 women with a history of symptomatic or incidentally discovered meningiomas were identified, 156 (11%) of whom were either current or past HRT users. A logistic regression analysis, adjusted for age, demonstrated a positive association between a diagnosis of meningioma and HRT use, with an odds ratio of 2.2 (95% CI, 1.9 to 2.6; P < .0001). The frequency of meningioma in women with either current or past HRT use was 865 in 100,000, whereas the frequency of meningioma in women without the history of HRT use was 366 in 100,000. The study provides evidence of a positive association between HRT use and diagnosis of meningioma, and therefore, HRT use may be a risk factor for meningioma.

Past use of hormone replacement therapy and risk of invasive breast cancer

10518 Background: Although current use of hormone replacement therapy (HRT) is associated with a greater risk of breast cancer than past use, the effects of longer term past use of HRT are not well quantified. Methods: We examined the relationship between past HRT use and invasive breast cancer risk within the Nurses’ Health Study, a prospective cohort of 121,700 registered nurses aged 30–55 in 1976 who update information on cancer risk factors and outcomes through biennial questionnaires. For this analysis, the follow-up period was 1980 through 2004 and only included person-time for postmenopausal women. Status of HRT use (never, past, or current), type of HRT (oral unopposed estrogen (E alone) or combination oral estrogen + progesterone (E+P)), and duration of HRT use were assessed every 2 years and defined prospectively. Proportional hazards models controlled for age, body mass index, parity, age at first birth, family history of breast cancer, benign breast disease, alcohol consumption, type of menopause, and ages at menarche and menopause. Results: During 1,388,368 person-years of follow-up among postmenopausal women, invasive breast cancer was diagnosed among 1,554 women who had never used HRT, 459 past users of E+P and 527 past users of E alone. Regardless of duration of use, past use of E alone was not associated with breast cancer risk. Although past use of E+P for less than 10 years was not associated with breast cancer risk (RR (95% CI) 1.01 (0.88–1.17) for &lt; 5 years and 0.95 (0.74–1.21) for 5–9.9 years), past use of E+P for greater than 10 years was associated with an increased risk of breast cancer (RR 1.53 (1.09–2.16) for 10–14.9 years and 1.48 (0.87–2.51) for 15 or more years). Results were similar regardless of time since last use, although power was limited for this subgroup analysis. Conclusions: Past use of E+P for greater than 10 years was associated with a persistent elevation in breast cancer risk. The relationship between duration of past use and breast cancer risk did not appear linear, but suggested a possible threshold effect. No significant financial relationships to disclose.

Breast cancer risk associated with different HRT formulations: a register-based case-control study

BackgroundPrevious epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations – particularly concerning different progestins.MethodsA case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations.ResultsA total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC) associated with current or past use of HRT was 1.2 (1.1–1.3), and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI), and never having used oral contraceptives (OCs) during lifetime.Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations) were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe.ConclusionThe BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for residual confounding and bias in this observational study do not permit causal conclusions. Apparently, there is not much variation of the BC risk across HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of some of the subgroups suggest cautious interpretation.

P3-144: Association of hormone replacement therapy and cognitive impairment: Evidence of confounding by demographics and serum α-tocopherol status

Studies of hormone replacement therapy (HRT) and cognitive function in older women have varied from beneficial to possibly detrimental. Some studies have suggested that cognitive effects of HRT may differ by age at HRT initiation, or interact with other cognitive risk factors. Cognitive testing methodology has differed between studies, and observational studies have not always had data on relevant potential confounders. This analysis of data from an observational ancillary study to the Women's Health Initiative (WHI) examines whether HRT use is associated with cognitive impairments of memory or mixed–domain type, determined by a neuropsychological test battery. Study subjects were 523 women age 60 years and over at time of cognitive testing. Estrogen use history (“never” (N=243), “past” (N=140) or “current” (N=140)) was determined from previous WHI data and updated at cognitive test visit. Memory impairment was considered present if women scored at least 2 sd below age and education–specific norms for one or more tests of memory. Mixed domain impairment was defined as scoring below norms on one or more tests in two or more domains (memory, executive function, language, attention, and visual function). In unadjusted analyses, neither current (OR 1.1 95% CI 0.7–1.7) nor past (0.6 95% CI 0.3–1.0) HRT use was associated with memory impairment. Reduced odds of mixed–domain impairment were seen for past HRT users (0.3; 0.1–0.7) but not current users (0.7; 0.4–1.3). Among ever–users, no association was seen between mixed domain impairment and age at first use (p=.58) or use of progestins (p=.23). Adjusting for previously–identified covariates (age, education, race/ethnicity, and lowest quartile serum α–tocopherol), the association of past HRT use with mixed impairment was no longer statistically significant (OR 0.5; 0.2–1.1). Adjusting additionally for Apo e4 or cardiovascular disease did not affect these results. No evidence of interactive effects was seen between HRT use and age, serum α–tocopherol, or e4. No association was seen between current HRT use and memory or mixed–domain impairments. Confounding by age, education, race/ethnicity, and serum tocopherol status appeared to account for the bivariate association between past HRT use and mixed domain cognitive impairment.

Case control study of hormone replacement therapy (HRT) and breast cancer in Japanese women

10012 Background: Some prospective studies in US and UK (represented by Women’s Health Initiative and Million Women Study) show that HRT use may increase the risk of breast cancer. However, it is unclear whether or not this perspective is applicable to Japanese women, due to several factors such as the difference in incidence of breast cancer, difference in HRT prevalence, which are to be concerned in this study. To investigate the relationship between HRT use and breast cancer, a case-control study was conducted in Japan. Methods: We sent self-administered questionnaire to 4,500 cases who have a previous history of confirmed histological breast cancer and 4,500 controls who were selected according to the inclusion criteria. All the subjects were between age 45 and 69 at the time of enrollment. Among these subjects, 3,434 in case group and 2,427 in control group sent back their questionnaire (total 5,861). The datacenter was run in Kitasato Univ. and the statistical analysis was performed using SAS (version 9.1). Control was selected by considering the screening record for GI disease and respiratory disorders, with no previous history of breast cancer, gynecological and hormonal disease at the time of screening. We asked about past history of exposure to the factors supposed to be breast cancer-causing; previous or current use of HRT, age at diagnosis, academic background, BMI, lifestyle habits, age of menarche, birth history, history of breast feeding, family history, use of contraceptive agents and menopausal status. Results: As the main analysis result, 164 (5.0%) out of 3,316 cases and 253 (7.4%) out of 2355 controls had used HRT (Odds ratio 0.432 [95% CI 0.352–0.530]. Conclusions: The result of this study shows that HRT users were less likely to develop breast cancer than never users. However, in this study, there was a difference in the observation period for the past use of HRT between cases and controls. Considering the transition of HRT prevalence in Japan, there may be a possibility that this difference can be a cause of a serious bias for the main analysis result. Further sensitivity analyses are needed to evaluate the robustness of the findings and this point is under consideration. No significant financial relationships to disclose.

Hormonal exposures and the risk of intracranial meningioma in women: a population-based case-control study

BackgroundThe role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women.MethodsThe association between oral contraception (OC) or hormone replacement therapy (HRT) and intracranial meningioma in women was investigated using a population-based, matched case-control study. Exposures for 143 cases and 286 controls matched on age within five years were obtained by interview. Diagnoses were confirmed histopathologically and estrogen and progesterone receptor assays conducted.ResultsAlthough risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 – 2.7), and in current users (OR = 2.5, 95% CI 0.5 – 12.6), the confidence intervals were wide. No significant association between meningioma risk and duration of OC use was found. Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 – 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 – 2.2). Of 142 available specimens, 2 (1%) expressed estrogen receptors, whereas 130 (92%) expressed progesterone receptors (PR). OC use was associated with increased risk of a meningioma expressing less rather than more PR (OR = 3.2, 95% CI 1.3 – 8.0). Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas.ConclusionThis study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma.

Myocardial infarction risk and hormone replacement: Differences between products

Objectives To establish the risk of myocardial infarction (MI) in users of hormone replacement therapy (HRT) compared with non-users and to compare the risk between different HRT regimens. Methods A population-based cohort and case-control study, and a case-control study nested within a cohort of HRT users, using the UK General Practice Research Database. Differences between HRT regimen, mode of administration and duration and recency of use were examined whilst adjusting for confounding. Results In the cohort and case-control study, 4537 cases of MI were identified in 2.62 million observed women years, cases were age-matched to 27,220 controls. In both studies, current and past HRT use were associated with reduced risk estimates for MI compared with no prior use. MIs were less likely to be fatal amongst women who had used HRT than amongst never users (OR adj 0.58; 95% CI 0.45–0.75). No difference in risk was seen between current and past use, oral and transdermal HRT or between different regimens ( p > 0.44). In the nested study, no difference was found in the association with MI risk between different oestrogen–progestogen combinations or between different combinations and tibolone. Unopposed oestrogen use was not associated with a decrease in risk compared with combined HRT. Conclusions These results are consistent with previous observational studies in supporting the hypothesis that use of postmenopausal HRT is associated with a decrease in risk of acute myocardial infarction (AMI). Case fatality differed between HRT users and non-users, suggesting a protective effect of HRT. This study does not demonstrate a difference between regimens.

Looking Farther Afield

Looking Farther Afield

Hormone replacement therapy and risk for foot, distal forearm, proximal humerus, and pelvis fractures.

This case-control epidemiologic study examines the relationship between hormone replacement therapy (HRT) and risk for fractures of four sites among women 45 years of age and older. From October 1996 to May 2001, incident patients with distal forearm ( n=744), foot ( n=618), proximal humerus ( n=331), and pelvis ( n=109) fractures were recruited from five Kaiser Permanente Medical Centers in northern California. Controls ( n=1617) were selected at random from the same five medical centers over the same time period within strata defined by 5-year age group, gender, and white versus nonwhite or unknown recorded race/ethnicity. Trained interviewers collected information using a standardized questionnaire. Compared with postmenopausal women who never used HRT, postmenopausal women currently using HRT for at least 3 months had a decreased risk of fracture at the distal forearm (adjusted OR=0.55, 95% CI: 0.43, 0.72), proximal humerus (adjusted OR=0.51, 95% CI: 0.36, 0.74), and pelvis (adjusted OR=0.51, 95% CI: 0.27, 0.95), but not the foot (adjusted OR=1.05, 95% CI: 0.81, 1.35). Past use of HRT for more than 7 years also appeared to be associated with a reduced risk of fracture at the distal forearm and proximal humerus. The longer a woman went without HRT after her last menstrual period, the greater her risk of fracture in the distal forearm, proximal humerus, and pelvis. The findings of this study support long-term, current use of HRT for the prevention of osteoporotic fractures, but other risks and benefits also need to be considered.

Influence of Hormone Replacement Therapy on C-Reactive Protein: Population-Based Data

Observational data, possibly resulting from confounding due to self-selection, show that use of hormone replacement therapy (HRT) is associated with reduced coronary risk, while randomized trial data do not. One possible explanation for the trial findings is that adverse effects of HRT-- such as an elevation of C-reactive protein (CRP)--might counterbalance other benefits of HRT.Women aged 40-74 years were identified from a cross-sectional, annual nationally representative study of the English population, the Health Survey for England 1998. Valid data were available from 4,112 of the 4,319 women in this age group. Of these, 710 (17%) were current, 465 (11%) past and 2,937 (71%) never users of HRT.To study the association between current and past use of HRT and CRP levels. CRP was expressed as a continuous variable (logged) and in percentiles.Current, past and never users of HRT did not differ in terms of age, body mass index or smoking status. However, compared with past and never users of HRT, current users tended to take more vigorous physical activity and were more likely to drink more alcohol than is currently recommended. Excluding potentially confounding conditions, median CRP levels were significantly higher in current (2.5 mg/l) and in past (1.9 mg/l) than never HRT users (1.4 mg/l). Controlling for age, smoking and body mass index logged CRP remained significantly raised only among current users.HRT use was significantly and independently associated with raised CRP levels in an English nationally representative sample. Increases in CRP may represent one plausible mechanism by which HRT may adversely affect risk of coronary heart disease.

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study.

Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. Cases and controls did not differ with regard to menstrual and reproductive history except in age at birth of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role for HRT on risk of SAH in postmenopausal women.

Understanding Attitudes of Older Women toward Hormone Replacement Therapy

Background. Counseling women facing the decision to initiate, continue, or discontinue hormone replace ment therapy represents a major challenge for provid ers. Women's attitudes deserve careful consideration in this context, because attitudes may influence hormone replacement therapy use and patients' satisfaction with decision-making. Little is known about factors that may explain different attitudes.Methods. To evaluate the association between char acteristics of peri- and postmenopausal women and their attitudes toward hormone replacement therapy, we conducted a population-based, computer-assisted telephone survey of 1,076 randomly selected women, ages 50–80, at a staff-model health maintenance organization. Women with a positive or neutral attitude were compared to those with a negative attitude. We exam ined associations between attitudes and demographic and clinical characteristics, self-rated health status, physical function, personal and family history of condi tions affected by hormone replacement therapy, gyne cologic visits, provider characteristics, interactions with provider, and sources of information about hor mone replacement therapy.Results. The perception of being adequately informed about the benefits of hormone replacement therapy by one's provider was associated with a tripling of the likelihood of having a positive attitude toward hormone replacement therapy. Additional fac tors associated with positive attitudes included past hormone replacement therapy use, younger age, a higher level of physical functioning, and personal history of heart disease. Relationships between these vari ables and attitudes varied among current hormone replacement therapy users and nonusers.Conclusions. The study findings reinforce the critical role of provider counseling in shaping women's atti tudes about hormone replacement therapy.

Hormone replacement therapy use in urban older women attending meal sites: associations with sociodemographic and health characteristics and use of preventive services.

To examine sociodemographic, health and preventive health practices associated with hormone replacement therapy (HRT) use in urban community-dwelling older women. Survey. Community-based meal sites throughout the city of Los Angeles. A convenience sample of 705 community-dwelling women older than age 60 who completed questionnaires for the Prevention for Elderly Persons Program. Demographic and life style characteristics, functional status, preventive practices, and current and past use of HRT. Among the 705 women surveyed, 13% reported current use and 17% reported past use of HRT. Current users were more likely to be younger and more likely to report a history of osteoporosis, hysterectomy, and calcium use than never users. White women were more likely to be current users than black women. Only a small proportion of the older urban women studied are currently using HRT. In particular, efforts to increase the use of these preventive services need to focus on black women and women who do not have a prior history of osteoporosis.

Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa Women's Health Study.

Long-term, postmenopausal use of hormone replacement therapy (HRT) appears to increase breast cancer risk. Whether the effect of HRT use on risk of breast cancer varies among histological types of invasive carcinoma is unknown. To determine associations between HRT use and risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma. Prospective cohort study whose participants were followed up continuously for 11 years from January 1986 to December 1996. Iowa Women's Health Study, a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 incident breast cancer cases occurred in the at-risk cohort of 37 105 women. Multivariate-adjusted relative risk (RR) of tumor-specific breast cancers associated with duration of ever, current, or past HRT use. Duration of ever HRT use was associated with risk of invasive carcinoma with a favorable histology, with an RR of 1.81 (95% confidence interval [CI], 1.07-3.07) for those who used HRT 5 or fewer years vs an RR of 2.65 (95% CI, 1.34-5.23) for those who used HRT for more than 5 years (P for trend = .005) after adjustment for age and other breast cancer risk factors. There was no association between ever HRT use and the incidence of DCIS or invasive ductal or lobular carcinoma. Among current hormone users, after adjusting for age and other breast cancer risk factors, the RRs (95% CIs) of invasive carcinoma with a favorable histology were 4.42 (2.00-9.76) and 2.63 (1.18-5.89) for 5 or fewer years of use and for more than 5 years of use, respectively. Risk of invasive ductal or lobular carcinoma was associated with current use (< or =5 years) of HRT with an RR of 1.38 (95% CI, 1.03-1.85). Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use.

Influence of current and past hormone replacement therapy on bone mineral density: a study of discordant postmenopausal twins.

There is controversy about the ideal timing of hormone replacement therapy (HRT) and duration of treatment. In this study we have examined intrapair differences in bone mineral density (BMD) in twins who were discordant for HRT use. Twin pairs in which only one co-twin had been exposed to HRT for more than 12 months continuously were selected from 365 postmenopausal monozygotic (MZ) and dizygotic (DZ) pairs recruited as part of the St Thomas' Adult UK Twin Registry of normal volunteers. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. Intrapair differences in BMD between HRT users and non-users were compared. A total of 65 HRT-discordant pairs were identified, of which 36 were discordant for current HRT use (mean age: 55.3 years, median duration of HRT use: 36 months) and 29 were discordant for past HRT use (mean age: 60.4 years, median HRT duration: 30 months). Among current users BMD was consistently and significantly higher than in non-users at both sites (lumbar spine mean intrapair difference (IPD%): 12.3%, 95% confidence interval (CI): 7.1%, 17.5%; femoral neck IPD%: 8.6%, 95% CI: 3.4%, 13.7%). The intrapair differences were substantially smaller when past users and non-users were compared (lumbar spine IPD%: 2.4%, 95% CI: -3.7%, 8.6%; femoral neck IPD%: 0.4%, 95% CI: -5.3%, 6.0%). These differences remained little changed after adjusting for the potential confounding effects of the duration of HRT use, and intrapair differences in alcohol and tobacco consumption and physical exercise. The results confirm, in a closely matched design, the findings of other observational research that current use of HRT has a major effect on BMD at the lumbar spine and femoral neck. Past users of HRT do not, however, show the same benefits. The clinical implications of these findings are that HRT needs to be used continuously to influence BMD and that alternative treatments need to be considered in those who discontinue HRT.

Assessment of the risk for venous thromboembolism among users of hormone replacement therapy.

Although hormone replacement therapy (HRT) provides health benefits, concerns about harmful effects have been raised, including an increased risk of venous thromboembolism. The purpose of this review is to assess the risk for venous thromboembolism associated with HRT. Data searches involved the MEDLINE database from January 1982 to December 1997, and bibliographies of retrieved articles. Seven case-control studies and 1 prospective cohort study considering venous thromboembolism as the outcome of interest were selected and rated according to methodological criteria. Results of case-controls studies were pooled to determine an overall estimate. The pooled risk ratio (95% confidence interval) for venous thromboembolism among current users of HRT compared with non-users (never-users and past-users combined) was 2.1 (1.4 to 3.0) in the case-control studies (n = 7). Based on one prospective cohort study, the risk of primary pulmonary embolism associated with HRT was 2.1 (1.2 to 3.8). No association was found with past use of HRT. The risk of venous thromboembolism was higher within the first year of treatment. There was no strong evidence for a dose-response relationship with estrogen. No striking difference in risk of venous thromboembolism was observed between unopposed and opposed regimens. The small number of women using transdermal estrogen therapy precluded any firm conclusions about the impact of the route of estrogen administration. Current use of oral estrogen as HRT is associated with a 2- to 3-fold increased risk of venous thromboembolism. However, the absolute risk remains low, and these findings need to be weighed against the potential benefits of treatment. Whether transdermal estrogen therapy is safe with respect to venous thromboembolism has yet to be adequately investigated.

Effect of replacement estrogen on insulin-like growth factor-I in postmenopausal women: the Rancho Bernardo Study.

Insulin-like growth factor-I (IGF-I) is associated with protein, carbohydrate, and bone metabolism. Results of previous studies examining the effect of exogenous estrogen on levels of IGF-I have been inconsistent. We examined the cross-sectional association between serum IGF-I levels and hormone replacement therapy (HRT) use in 672 postmenopausal women aged 50 yr and older. The mean age-adjusted IGF-I level was highest in the 415 women who reported never or past HRT use (126.8 micrograms/L), lowest in the 128 women who reported using estrogen alone (99.3 micrograms/L), and intermediate in the 115 women who reported using combination estrogen and progesterone (112.4 micrograms/L). A significant linear decline in mean age-adjusted IGF-I levels by duration of HRT use among all current users was seen. The decrease in serum IGF-I with current use of HRT is not consistent with the fact that both HRT and increased levels of IGF-I have been associated with improved glucose and bone metabolism and lipid profile. Further research is needed to evaluate the effect of the addition of a progestin to oral HRT on IGF-I-induced changes in GH levels.