Exogenous Estrogen Use Research Articles

RE: “CHARACTERISTICSRELATING TO OVARIAN CANCER RISK: COLLABORATIVE ANALYSIS OF 12 US CASE-CONTROL STUDIES. II. INVASIVE EPITHELIAL OVARIAN CANCERS IN WHITE WOMEN”

Data collected from 2,197 white ovarian cancer patients and 8,893 white controls in 12 US case-control studies conducted in the period 1956-1986 were used to evaluate the relation of invasive epithelial ovarian cancer to reproductive and menstrual characteristics, exogenous estrogen use, and prior pelvic surgeries. Clear trends of decreasing risk were evident with increasing number of pregnancies (regardless of outcome) and increasing duration of breast feeding and oral contraceptive use

Diet and endometrial cancer: a case-control study.

A case-control study of 168 cases with endometrial cancer and 334 controls was conducted in Birmingham, Alabama, between June 1985 and December 1988. Cases were identified at the University of Alabama Hospital and in a private practice; controls were selected from among women who attended the University optometry clinic. A food frequency questionnaire that evaluated the intake of 55 nutrients and 116 foods was obtained for 103 cases and 236 controls. Logistic regression was used to evaluate the effect of diet on endometrial cancer after adjustment for total calories, age, race, education, obesity, smoking status, age at menarche, number of pregnancies, age at menopause, diabetes, hypertension, and use of exogenous estrogens. High intake of certain micronutrients was associated with a decreased risk of endometrial cancer: the odds ratio for subjects in the upper tertile versus those in the lower tertile was 0.4 for both carotene and nitrate (95% confidence interval (CI) 0.2-0.8 and 0.2-0.9, respectively). There also was an inverse association between endometrial cancer and protein consumption (trend test; p = 0.002), and a moderate direct association with cholesterol intake (OR = 1.9, 95% CI 0.9-3.7) when terms for both these macronutrients were included in a logistic model. Total intake of animal and vegetable fat were not associated with endometrial cancer. More frequent consumption of several vegetables and certain dairy products was associated with a statistically significant decreased risk of endometrial cancer. These results suggest that diet plays an important role in the etiology of endometrial cancer.

Risk factors for neovascular age-related macular degeneration. The Eye Disease Case-Control Study Group.

Neovascular age-related macular degeneration (AMD) is one of five retinal disorders studied in the Eye Disease Case-Control Study. Data were obtained from 421 patients with neovascular AMD and 615 controls on a broad array of possible risk factors through interviews, clinical examinations, and laboratory analyses of blood samples. Decreased risk of neovascular AMD was associated with higher levels of carotenoids in the serum samples, higher horizontal cup-to-disc ratios, and use of postmenopausal exogenous estrogens in women. Increased risk of neovascular AMD was associated with cigarette smoking, higher levels of serum cholesterol, and parity greater than zero. No support was found for sunlight exposure, serum zinc levels, or iris color as risk factors for this disease. Although no association was found with a history of cardiovascular disease itself, the associations with postmenopausal exogenous estrogen use, cigarette smoking, and serum cholesterol level are consistent with a hypothesis linking risk factors for cardiovascular disease with neovascular AMD. The association noted between serum carotenoid levels and neovascular AMD supports the hypothesis that higher levels of micronutrients with antioxidant capabilities may decrease the risk of AMD.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group.

Data collected from 2,197 white ovarian cancer patients and 8,893 white controls in 12 US case-control studies conducted in the period 1956-1986 were used to evaluate the relation of invasive epithelial ovarian cancer to reproductive and menstrual characteristics, exogenous estrogen use, and prior pelvic surgeries. Clear trends of decreasing risk were evident with increasing number of pregnancies (regardless of outcome) and increasing duration of breast feeding and oral contraceptive use. Ovarian dysfunction leading to both infertility and malignancy is an unlikely explanation for these trends for several reasons: 1) The trends were evident even among the highly parous; 2) risk among nulliparous women did not vary by marital status or gravidity; and 3) risk among ever-married women showed little relation to length of longest pregnancy attempt or history of clinically diagnosed infertility. Risk was increased among women who had used fertility drugs and among women with long total duration of premenopausal sexual activity without birth control; these associations were particularly strong among the nulligravid. No consistent trends in risk were seen with age at menarche, age at menopause, or duration of estrogen replacement therapy. A history of tubal ligation or of hysterectomy with ovarian conservation was associated with reduced ovarian cancer risk. These observations suggest that pregnancy, breast feeding, and oral contraceptive use induce biological changes that protect against ovarian malignancy, that, at most, a small fraction of the excess ovarian cancer risk among nulliparous women is due to infertility, and that any increased risk associated with infertility may be due to the use of fertility drugs.

Estrogen Replacement Therapy and the Risk of Venous Thrombosis

Abstract purpose: Estrogen replacement therapy is believed by many physicians to cause thrombophlebitis and to be contraindicated in women at risk for this disease. However, clinical data supporting this assumption are scant, and further investigation is required. patients and methods: We tested the estrogen-thrombophlebitis association in a case-control study. Charts of all consecutive women aged 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism were reviewed; 121 cases and 236 controls matched for age, year of admission, admitting service, and socioeconomic status were obtained. Hormone use and nonuse were validated in a subset of randomly selected women. results: Cases and controls, whose average age was 65 years, did not differ significantly on matching variables or on current use of exogenous estrogen (5.1% of cases versus 6.3% of controls). Other analyses that variously excluded women with a past history of thrombosis, women less than 50 years of age, women with thrombosis occurring after admission, and women whose estrogen use was indeterminate also did not support an increased risk of thrombotic disease. Adjustment for the presence of independent thrombotic risk factors did not alter the odds ratio for estrogen use. conclusion: This case-control study of older women, unselected for other thrombotic risk factors, does not support the commonly held assumption that replacement estrogen increases the risk of venous thrombosis.

Urinary tract infections and estrogen use in older women.

To examine the relationship between exogenous estrogen use and risk of clinically diagnosed urinary tract infection (UTI) in older women. A case-control study. Two hundred seventy-six general practices. Cases (n = 3,616) were women, age 50-69 years, with a first recorded UTI in the calendar years 1989 or 1990. Controls (n = 19,162) were matched for age and practice. Clinical diagnosis of UTI. Women using estrogens for greater than or equal to 1 year had an increased risk of being diagnosed with a UTI compared to non-users, crude odds ratio (OR) 1.9 (95% CI 1.5-2.2). All of this excess risk was observed in women with intact uteri, OR 2.1 (CI 1.7-2.7). Hysterectomized women had no increased risk, OR 1.1 (CI 0.8-1.5). Controlling for diabetes, neurologic deficit, atrophic vaginitis, incontinence, and age did not affect the observed associations. Estrogen use is associated with an increased risk of UTI in older women with intact uteri but not in hysterectomized women. This observed differential effect on women with or without uteri may be explained by prescribing biases between these two groups of women, but we lack any evidence to support this conclusion over several alternative possibilities.

Estrogen replacement therapy and the risk of venous thrombosis

purpose: Estrogen replacement therapy is believed by many physicians to cause thrombophlebitis and to be contraindicated in women at risk for this disease. However, clinical data supporting this assumption are scant, and further investigation is required. patients and methods: We tested the estrogen-thrombophlebitis association in a case-control study. Charts of all consecutive women aged 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism were reviewed; 121 cases and 236 controls matched for age, year of admission, admitting service, and socioeconomic status were obtained. Hormone use and nonuse were validated in a subset of randomly selected women. results: Cases and controls, whose average age was 65 years, did not differ significantly on matching variables or on current use of exogenous estrogen (5.1% of cases versus 6.3% of controls). Other analyses that variously excluded women with a past history of thrombosis, women less than 50 years of age, women with thrombosis occurring after admission, and women whose estrogen use was indeterminate also did not support an increased risk of thrombotic disease. Adjustment for the presence of independent thrombotic risk factors did not alter the odds ratio for estrogen use. conclusion: This case-control study of older women, unselected for other thrombotic risk factors, does not support the commonly held assumption that replacement estrogen increases the risk of venous thrombosis.

A population‐based case‐control study of endometrial cancer in shanghai, china

A case-control study of 268 patients with endometrial cancer and 268 population controls was conducted during 1988-1990 in Shanghai, China, to evaluate etiologic factors in a population whose risk had not been substantially altered by the use of exogenous estrogens. In spite of this, the major risk factors resembled those found in other studies. The risk of endometrial cancer was significantly elevated among nulligravidas (OR = 5.4, 95% CI = 2.0-14.6) and decreased with number of pregnancies (p less than 0.01). Late age at menopause was associated with increased risk, while early age at menarche was unrelated. Use of oral contraceptives for more than 2 years was associated with a reduction in endometrial cancer risk (OR = 0.4, 95% CI = 0.1-1.2), while short-term use of oral contraceptives and other methods of contraception were unrelated. Obesity was a strong predictor of risk, with women in the highest quartile of weight having 2.5 times the risk of those in the lowest quartile. In contrast to many other studies, cigarette smokers were at elevated risk (OR = 1.7, 95% CI = 0.9-3.0). Risk was also elevated among women reporting a history of gall-bladder disease, polycystic ovaries, menstrual symptoms, and non-estrogen hormone use.

Clinical parameters predictive of malignancy of thyroid follicular neoplasms

Needle aspiration biopsy is commonly employed in the evaluation of thyroid nodules. Unfortunately, the cytologic finding of a “follicular neoplasm” does not distinguish between a thyroid adenoma and a follicular cancer. The purpose of this study was to identify clinical parameters that characterize patients with an increased risk of having a thyroid follicular cancer who preoperatively have a “follicular neoplasm” identified by needle aspiration biopsy. A total of 395 patients initially treated at Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1965 and 1985 were identified and their data were entered into a computer database. Patients with thyroid adenomas were compared to patients with follicular cancer using the chi-square test and Student's t-test. Statistically significant parameters that distinguished patients at risk of having a thyroid cancer (p <0.05) included age greater than 50 years, nodule size greater than 3 cm, and a history of neck irradiation. Sex, family history of goiter or neoplasm, alcohol and tobacco use, and use of exogenous estrogen were not significant parameters. Patients can be identified preoperatively to be at an increased risk of having a follicular cancer and accordingly appropriate surgical resection can be planned.

Recent time trends in uterine cancer.

Recent trends in corpus uterine cancer incidence rates were explored using 1979-86 data from the Surveillance and End Results Program (SEER); recent trends in hospitalizations for corpus uterine cancer were explored using 1979-86 data from National Hospital Discharge Surveys (NHDS); and recent trends in exogenous hormone use were delineated using data from the 1980, 1981, and 1985 National Ambulatory Medical Care Surveys (NAMCS). Uterine cancer incidence rates using SEER data have continued to decline since 1979. An acceleration in the decline since 1983-84 is suggested in all women and in women with intact uteri ages 45-64. Hospitalizations for uterine cancer have also declined since 1979, with a marked acceleration in the decline since 1983-84 for all women and for women ages 40-79 has increased 22 percent and use of unopposed exogenous estrogens in women of similar age has increased 7 percent, while use of exogenous progesterones have shown much more substantial increases of approximately 700 percent. Possible relationships between trends in exogenous hormone use and incidence rates of corpus uterine cancer are discussed.

Factors associated with obtaining nipple aspirate fluid: Analysis of 1428 women and literature review

Studies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid. New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed.

Cerebrovascular Disease and Stroke in Women

There are many special conditions which may predispose women to have a higher risk of stroke. These conditions include pregnancy and the puerperium, exogenous estrogen use, cerebral vasculitis, mitral valve prolapse and migraine. Recognition that certain stroke syndromes are more likely to affect women may aid the clinician in determining the optimal management of cerebrovascular disease and stroke in women.

Histologic and mammographic specificity of risk factors for benign breast disease.

This study evaluates the effects of potential risk factors for benign breast disease (BBD) with special attention to the histologic and mammographic specificity of the effects. Cases were 172 women with BBD that underwent biopsy; controls were 134 women free of breast signs or symptoms. All cases and controls had undergone mammography. For all types of BBD combined, parity, use of oral contraceptives, and use of exogenous estrogen after menopause were strongly protective, whereas obesity and early menarche were weakly protective. Family history of breast cancer was virtually unrelated to BBD. The protective effect of parity was stronger for BBD with intralobular or extralobular fibrosis, and with mammographic homogeneous density or large nodular densities, than it was for BBD without these characteristics. Similar relations with the histologic and mammographic features were observed for obesity. These findings suggest that some risk factors for BBD have effects that are related to specific features of its morphology.

Clinical stage I and II endometrial carcinoma treated with surgery and/or radiation therapy: Analysis of prognostic and treatment-related factors

This is an analysis of 266 patients with clinical stage I and II endometrial carcinoma treated with curative intent at the University of Florida between October 1964 and December 1980. There was a minimum 5-year follow-up. Thirty-nine patients who died of intercurrent disease less than 5 years from treatment were excluded from analysis of pelvic disease control and determinate disease-free survival. All patients were included in the analysis of complications. Pelvic disease control and determinate disease-free survival rates at 5 years were 91 and 88%, respectively, for stage I and 84 and 68% for stage II. There was no apparent difference in the rates of local control and survival or in the incidence of complications when comparing preoperative with postoperative radiation therapy. Tumor grade, stage, depth of myometrial invasion, and history of exogenous estrogen use or abnormal estrogen balance were of prognostic significance. Data on pelvic disease control, survival, and treatment complications are outlined, and management guidelines are discussed.

Epidemiology of endometrial cancer.

This review of endometrial cancer summarizes the demographic characteristics of patients with the disease, their hormonal risk factors related to endogenous and exogenous estrogens and medical history, and other risk factors. Endometrial cancer increased in incidence in the US in the early 1970s, but then declined again in the last 2 decades. Possible reasons are classification including estrogen- induced hyperplasia, but also increased use of exogenous estrogens primarily in post-menopausal women, who are the predominant victims. Postmenopausal estrogen usage decreased at the same time. The highest incidence occurs in Polynesian women, although US Caucasians have more endometrial cancer then Blacks or European women. Endometrial cancer is common in women with estrogen-secreting ovarian cancer. Women with polycystic ovaries, where the steroid androstenedione is secreted and converted to estrone in peripheral tissues, but progesterone is lacking, are higher risk for endometrial hyperplasia and cancer. Obese women are also at risk (estimated 20-fold), as they have low sex binding globulin and higher estrogen levels. Any exogenous estrogen, by any route, even if stopped for a week per month confers higher risk for endometrial cancer, as shown by virtually all case control studies. Very little data exists on the actual effect of taking progestins with postmenopausal estrogens. These tumors are less invasive, more differentiated, and often detected earlier than non-estrogen dependent endometrial cancers. Other putative risk factors, e.g., diabetes, hypertension, gall bladder disease, radiation exposure, and family history of breast cancer have no solid evidence for association. Smoking, however, is associated with a lower risk of endometrial cancer.

The influence of exogenous estrogen use on survival after diagnosis of endometrial cancer.

For examination of the effect of prior exogenous estrogen use on survival after diagnosis of endometrial cancer, 244 endometrial cancer cases newly diagnosed at North Carolina Memorial Hospital, Chapel Hill, North Carolina, between 1970 and 1976 were followed until 1982. Estrogen users (n = 46) were younger, had less advanced disease, and were more likely to be nonobese and white than were nonusers (n = 198). The estimated probability of surviving (Kaplan-Meier) five years after diagnosis was 0.89 for users and 0.53 for nonusers. When adjusted for age, grade, stage, obesity, race, and treatment (using the Cox proportional hazards regression model), the survival probabilities throughout the period of observation for estrogen users continued to be higher. The adjusted hazard rate for a nonuser was 2.05 (95% confidence interval (Cl) 0.96-4.39) times that for an estrogen user. The adjusted hazard rate from endometrial cancer only was 4.01 (95% Cl 1.22-13.21) times greater among estrogen nonusers. The more frequent occurrence of endometrial cancer in an earlier stage and grade among estrogen users may not be the sole cause of their lower hazard rate from this disease.

Disseminated Intravascular Coagulation in Prostatic Carcinoma Reversed by Ketoconazole

DISSEMINATED intravascular coagulation (DIC) is a well-recognized complication of malignant neoplasms. Between 13% and 25% of the patients with chronic DIC have underlying prostatic carcinoma. 1,2 The mechanism of DIC in these patients appears to be related to release of thromboplastins from prostatic tissue. 3 The treatment of DIC involves prompt identification, with control or eradication of the underlying disease process. Correction of circulatory volume, hemostatic elements, and possible sepsis is mandatory. The use of heparin sodium (Panheparin), e-aminocaproic acid, and exogenous estrogens in DIC related to prostatic carcinoma remains controversial. 4 The following report describes the use of ketoconazole in the treatment and reversal of DIC associated with prostatic carcinoma. Report of a Case An 82-year-old man with metastatic prostatic cancer was transferred to The Johns Hopkins Hospital, Baltimore, for evaluation of a coagulopathy and hematuria. Two years previously, the patient developed symptoms of urinary obstruction and underwent a

Effect of prolonged bed rest on lung volume in normal individuals.

Pulmonary function was assessed in supine subjects before, during, and after three separate bed-rest studies of 11 and 12 days duration. Forced vital capacity (FVC) increased during bed rest in each subject. Total lung capacity (TLC) was measured by helium dilution in one bed-rest study and increased in each subject, while residual volume and functional residual capacity of the respiratory system did not change. No change in FVC was found in an ambulatory control group using identical measurement techniques. Maintaining base-line plasma volume during one bed rest by the use of exogenous estrogen did not prevent an increase in FVC, and decreasing plasma volume with diuretics in ambulatory subjects to the same degree as seen in the bed rests did not cause an increase in FVC. We conclude that prolonged bed rest results in a small significant increase in TLC and that this change is not dependent on alterations in plasma volume.

Parameters related to 25-OH-D levels in a population-based study of women

We surveyed calcidiol levels (25-OH-D) in a geographically-defined population of 373 women, ages 20–80 yr to test for an association between occult osteomalacia and excess bone loss. Bone mass was measured by photon densitometry and an estimate of vitamin D was determined by measuring dietary and supplemental intake as well as sunlight exposure equivalent The relationship of smoking practices, alcohol use, exogenous estrogen use, and medications to calcidiol level was assessed. Calcidiol levels were not associated with bone mass levels observed at two different forearm sites. Low levels of calcidiol, indicative of generalized vitamin D deficiency, were not observed in this population though mean estimates of vitamin D intakes from food (119 ± 148 IU) or food and supplements (319 ± 463 IU) were less than the Recommended Dietary Allowance (400 IU). Calcidiol was significantly associated with estimates of vitamin D intake from food (r = 0.11), supplement use (r = 0.21), and sunlight equivalent exposure (r = 0.26). Calcidiol levels were negatively related to age (p = 0.0020) and positively related to exogenous estrogen use and premenopausal state independent of age.

Employment status and women's protection against coronary heart disease. Findings from the San Antonio Heart Study.

This study examined whether currently employed women are at increased risk of coronary heart disease relative to full-time homemakers. Subjects were 1,041 Mexican-American and non-Hispanic white women aged 25-64 years, residing in households randomly selected from three socioculturally distinct neighborhoods in San Antonio, Texas. No statistically significant differences between employed women and homemakers were found for obesity, total serum cholesterol, low density lipoprotein cholesterol, systolic and diastolic blood pressures, or cigarette smoking. Highly significant differences favoring employed women over homemakers were found for both Mexican Americans and non-Hispanic whites in high density lipoprotein (HDL) cholesterol, ratio of HDL cholesterol to total cholesterol, and triglycerides. These differences were not explained by obesity, exercise, cigarette smoking, alcohol consumption, use of exogenous estrogens, and use of oral contraceptives, or by the healthy worker effect, and were observed at all occupational levels. Employed women ate a less atherogenic diet than full-time homemakers, but it is not clear that this nutritional factor could explain the differences in HDL cholesterol and triglycerides found in this study. The magnitude of the employment status difference in HDL cholesterol for both ethnic groups was in a range (3-4 mg/100 ml) associated with protection against coronary heart disease.