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PubMed1989

Diet and urinary estrogen profile in premenopausal omnivorous and vegetarian women and in premenopausal women with breast cancer.

The urinary estrogen profile was studied in the midfollicular phase twice, and diet four times during 1 yr in 10 premenopausal breast cancer (BC) patients consuming an omnivorous normal Finnish diet and in two control groups, one consuming an omnivorous (n = 12) and the other a lactovegetarian (n = 11) diet. Total fat intake in relation to caloric intake was almost identical in all three groups. Only with regard to grain fiber intake did the BC patients differ significantly from both other groups. No differences were found between the groups with regard to urinary excretion of 13 individual estrogens and total estrogens, with the exception of 4-hydroxyestrone (4-OH-E1), which was significantly lower (P less than 0.05) in the BC group than in the vegetarians. A high carbohydrate to protein ratio in the diet had a negative correlation with the excretion of 2-hydroxyestrogens and 2-hydroxyesterone (2-OH-E1) to 4-OH-E1 ratio. The BC group had significantly higher urinary 2-OH-E1 to E1 ratio (P less than 0.05) compared to the vegetarians. The 2-OH-E1 to 4-OH-E1 ratio was highest in the BC group (= 7.1) and differed significantly from that of the omnivores (= 4.3; P less than 0.02) and vegetarians (= 3.6; P less than 0.005). This ratio showed a negative correlation with intake of carbohydrates, starch, total and grain fiber. Urinary excretion of 4-OH-E1 correlated positively with total and grain fiber intake and plasma SHBG. Protein intake correlated positively with urinary 2-methoxy-E1 excretion, and retinol intake positively with catechol estrogen, E1 and E2 excretion. It is concluded that estrogen production and urinary estrogen profile in premenopausal breast cancer patients is normal with the exception of a low 4-OH-E1 excretion and high urinary 2-OH-E1 to 4-OH-E1 ratio. This ratio, which seems to depend on diet, is the only urinary estrogen parameter separating premenopausal BC patients from the control omnivorous and lactovegetarian women.

Adult↗
PubMed1983

Nutrient intake and hormonal status of premenopausal vegetarian Seventh-day Adventists and premenopausal nonvegetarians.

The relationship between dietary nutrients and plasma estrone, estradiol-17 beta, estriol, dehydroepiandrosterone sulfate, and prolactin levels was investigated in 14 premenopausal Seventh-day Adventist vegetarian (SV) women and 9 premenopausal non-Seventh-day Adventist nonvegetarian (NV) women. The SV subjects consumed less fat, especially saturated fat, and used significantly less fried food than the NV subjects. Plasma levels of estrone and estradiol-17 beta in the SV subjects were significantly lower than in the NV subjects. SV estradiol-17 beta and estriol levels were positively correlated with linoleic acid and protein intake, while NV prolactin levels were significantly correlated with intakes of oleic and linoleic acids and total fat. The data suggest that specific dietary nutrients were related to the hormonal milieu of these SV and NV subjects.

Adult↗
PubMed1997

Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Virgilio-Menopause-Health Group.

In women, sex hormone-binding globulin (SHBG) concentrations are the result of a balanced effect of stimulatory and inhibitory factors. Estrogens represent the principal stimulatory hormones, whereas androgens, insulin, excess body fat, and the pattern of body fat distribution have inhibitory effects. Menopause is characterized by major changes in blood sex steroid concentrations, notably a marked reduction of estradiol levels. In this study, we therefore investigated the relationship between hormonal and nonhormonal regulatory factors of SHBG and its blood levels in two groups of premenopausal and postmenopausal women characterized by normal-high or reduced estrogen concentrations. The data were obtained from an analysis of the cross-sectional database obtained during the first survey of the Virgilio-Menopause-Health Project, an epidemiologic longitudinal study aimed at investigating the impact of menopause on body weight, fat distribution, and related major metabolic, hormonal, and cardiovascular risk factors. A total of 329 women, 133 in premenopause and 196 in postmenopause without diabetes, thyroid diseases, or relevant cardiovascular, renal, and hepatic dysfunction, were included in the study. A clinical history (including dietary and physical-activity habits), anthropometry (body mass index [BMI], waist to hip ratio [WHR], and bioelectrical impedance analysis [BIA]), and morning blood samples in the fasting state for sex hormones, insulin, and biochemistry were available for all the women. Premenopausal and postmenopausal women showed no significant difference in SHBG concentrations (38.7 +/- 17.9 v 36.6 +/- 17.5 nmol/L, respectively). On the contrary, postmenopausal women were characterized by a marked reduction of estradiol levels and significantly lower levels of testosterone. After adjusting for age, insulin was lower and the glucose to insulin ratio was higher in postmenopause than in premenopause. Age-adjusted values for all anthropometric parameters were not significantly different in the two groups. In simple correlation models, SHBG was significantly and negatively correlated with BMI, WHR, and insulin and testosterone levels in both premenopausal and postmenopausal women, whereas estradiol levels correlated positively and significantly with SHBG only in the premenopausal group. A significant positive correlation between the glucose to insulin ratio and SHBG was present in both groups. Using multiple regression models, in the premenopausal group, SHBG levels were correlated positively with estradiol and negatively with testosterone and insulin, but not with the WHR. On the contrary, in the postmenopausal group, SHBG values had a significant negative correlation with the WHR, whereas the relationship with estradiol was not significant; moreover, the relationship with testosterone and insulin, although significant, became less marked. In conclusion, this study indicates that (1) there is no significant difference in SHBG blood concentrations between premenopause and postmenopause; (2) SHBG values are correlated positively with estradiol and negatively with insulin and testosterone concentrations, but the predictive value of these variabiles on SHBG appears to be different in premenopause and postmenopause; and (3) SHBG levels decrease with increasing WHRs, particularly in the postmenopausal group. Therefore, determinants of SHBG blood concentrations are likely to change on passing from premenopausal to postmenopausal status. In particular, there seems to be a threshold level for which estradiol is an important determinant of SHBG blood concentrations.

Adult↗
PubMed1995

Early adult body weight, body mass index, and premenopausal bilateral breast cancer: data from a case-control study.

Previous studies using current or recent adult body weight and body mass index are inconclusive as to a possible effect of increased body mass on premenopausal breast cancer incidence. Only five studies have presented data on early adult body mass, and no study has reported these data for premenopausal bilateral breast cancer. Because premenopausal bilateral breast cancer is assumed to be partly genetic and partly environmental in origin, it is crucial to identify possible modifiable risk factors for this cancer. We present data on early adult body weight and body mass (Quetelet Index, QI) from a case-control study of 142 premenopausal bilateral breast cancer cases from Los Angeles County, California, Connecticut, and Quebec, Canada, and 229 sister controls. The odds ratio (and 95% confidence interval) of premenopausal breast cancer adjusted for age, education, alcohol consumption, and oral contraceptive use was 0.7 (0.3-1.4) for women in the highest tertile of QI at age 18. The results do not suggest that elevated body mass index at a young age increases the risk of premenopausal bilateral breast cancer, but lend only weak support to the hypothesis of an inverse association between body mass index and premenopausal breast cancer.

Adolescent↗
PubMed1997

The growth pattern of ovarian dermoid cysts: a prospective study in premenopausal and postmenopausal women.

OBJECTIVE: To evaluate prospectively the evolution of ovarian dermoid cysts and the safety of nonsurgical management in premenopausal women. DESIGN: A prospective study. SETTING: Tertiary hospital-based ultrasonographic unit. PATIENT(S): Between 1985 and 1994, 72 premenopausal and 14 postmenopausal women had ovarian dermoid cysts < 6 cm in diameter diagnosed by ultrasound and were followed up at Kaplan Medical Center in Israel. INTERVENTION(S): Ultrasound examination was scheduled at 3 and 9 months after the initial diagnosis and then annually. Every cyst was measured in three planes. The growth rate of the cysts was calculated from the data gathered. MAIN OUTCOME MEASURE(S): Prospective evaluation of the evolution of dermoid cysts and the safety of nonsurgical management in premenopausal women by an ultrasonographic follow-up. RESULT(S): For the premenopausal and postmenopausal women, the mean age (+/-SD) at diagnosis was 32.3 +/- 8.2 and 61.1 +/- 6.9 years, the mean duration of follow-up was 34.5 +/- 21.6 and 35.3 +/- 26.8 months, the mean cyst size at diagnosis was 3.7 +/- 1.2 and 4.1 +/- 1.5 cm, and the calculated mean growth rate was 1.77 +/- 3.86 and -1.59 +/- 2.48 mm/y, respectively. The difference in the mean growth rate of the cysts between the two groups was statistically significant. The mean growth rate was significantly different from zero in the premenopausal group but not in the postmenopausal group. Twenty-eight women were delivered of 35 healthy infants without complications attributable to the dermoid cysts. The cysts were removed surgically in 24 of the 86 women (27.9%), and benign cystic teratomas were confirmed by histologic examination in all cases. CONCLUSION(S): Premenopausal women with ovarian dermoid cysts of < 6 cm in diameter can be safely managed expectantly, especially if pregnancy is desired. The mean growth rate of dermoid cysts in premenopausal women is 1.8 mm/y.

Adolescent↗
PubMed1999

A prospective, multidisciplinary evaluation of premenopausal women with iron-deficiency anemia.

OBJECTIVE: The cause of iron deficiency anemia (IDA) in premenopausal women is often presumed to be menstrual blood loss. The purpose of this study was to determine the diagnostic value of a comprehensive gynecological and gastrointestinal evaluation in premenopausal women with IDA. METHODS: Nineteen premenopausal, nonpregnant women older than 18 yr of age with IDA defined by a hemoglobin < 12 gm/dl with serum ferritin < 10 ng/ml participated in the study. Evaluations included directed history and physical examination by a specialist in gynecology and a subspecialist in gastroenterology, esophagogastroduodenoscopy, colonoscopy, upper gastrointestinal radiography with small bowel follow-through, antiendomysial antibody, and fecal occult blood tests. RESULTS: Seven of 19 (37%) premenopausal women with IDA were diagnosed to have a gynecological cause of anemia by a specialist in that field. Although only four of these seven patients had digestive complaints, all but one (86%) were discovered to have gastrointestinal disease by upper endoscopy; findings were duodenal ulcer and Helicobacter pylori (H. pylori) gastritis (one), esophagitis and H. pylori gastritis (one), erosive esophagitis (one), gastric arteriovenous malformations (one), and nodular/erosive H. pylori gastritis (two). Fecal occult blood testing was positive in only two (29%) subjects; upper endoscopy revealed erosive esophagitis and gastric arteriovenous malformations. Twelve of the 19 (63%) premenopausal women with IDA were not diagnosed to have a gynecological source of anemia by a specialist in that field. Fecal occult blood testing was negative among all women tested and the only digestive complaint was heartburn (pyrosis) in seven. Each was identified to have esophagitis, duodenal ulcer, or gastritis by upper endoscopy. Colonoscopic examination of the 12 subjects without gynecologic etiology for IDA revealed pan colitis (one), diverticulosis (one), diverticulosis and melanosis coli (one), hyperplastic polyps (one), and nodular lymphoid aggregates (one). CONCLUSIONS: Significant upper gastrointestinal disease is identifiable among most premenopausal women with IDA (18 of 19 or 95%), even when careful evaluation by a specialist in gynecology suggests a gynecological source. Upper endoscopy should be considered in the evaluation of all premenopausal women with IDA expressing digestive complaints or in those with IDA refractory to iron supplementation. Lower endoscopic examination may be reserved for those women with symptoms or signs suggestive of colorectal disorders.

Adult↗
PubMed1997

Comparison of endometrial changes among symptomatic tamoxifen-treated and nontreated premenopausal and postmenopausal breast cancer patients.

Breast cancer patients who received tamoxifen as adjuvant therapy have been reported to have more endometrial lesions such as polyps, hyperplasia, or carcinoma. We conducted a prospective study to elucidate the endometrial changes of premenopausal and postmenopausal breast cancer patients with tamoxifen. Sixty-seven symptomatic breast cancer patients who had been on tamoxifen treatment, including 34 premenopausal and 33 postmenopausal patients, and another group of 48 patients who had not been on tamoxifen, including 25 premenopausal and 23 postmenopausal patients, were recruited. Symptomatic patients were defined as having hypermenorrhea or abnormal vaginal bleeding among premenopausal patients or postmenopausal bleeding among postmenopausal patients. Endometrial thickness and uterine size determined by vaginal ultrasonography, histologic findings, and risk factors for endometrial cancer were compared. The mean endometrial thickness and uterine size showed no statistically significant difference in premenopausal patients with (n = 34) or without (n = 25) tamoxifen treatment, whereas there was a significant difference in the postmenopausal patients with (n = 33) or without (n = 23) tamoxifen treatment (12.11 +/- 12.38 mm vs 5.41 +/- 2.70 mm, P = 0.025; 234.71 +/- 76.36 cm3 vs 108.81 +/- 81.27 cm3, P = 0.0018, respectively). The frequency of endometrial histopathologic findings was 23.5% (8/34) in tamoxifen-treated women compared with 12.0% (3/25) in nontreated women (P = 0.269) in the premenopausal groups. In contrast, it was remarkably high with 66.7% (22/33) in tamoxifen-treated women compared with 30.4% (7/23) in the nontreated women in the postmenopausal groups (P = 0.025). There were four postmenopausal patients with tamoxifen, including three with atypical endometrial hyperplasia and one endometrial carcinoma, in contrast to no postmenopausal nontreated patients, although this difference did not reach statistical significance in this study (P = 0.096). There was a remarkably high prevalence of endometrial histopathologic findings in symptomatic tamoxifen-treated breast cancer patients, especially postmenopausal women. Tamoxifen might be associated with premalignant or malignant changes in postmenopausal endometrium. Thus timely, aggressive histologic assessment such as curettage or hysteroscope should be performed to detect the endometrial lesions when symptoms occur. Vaginal ultrasonography could be a useful tool to detect the endometrial lesions.

Aged↗
PubMed1998

Carotid atherosclerosis in premenopausal and postmenopausal women and its association with risk factors measured after menopause.

BACKGROUND AND PURPOSE: In women, symptoms of coronary artery disease are delayed by 10 to 15 years in comparison with men, most likely because of the protective effect of ovarian hormones. This report compares the prevalence and degree of carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8 years after menopause. METHODS: Scans were performed in the same laboratory over the same time period for both groups. Intima-media thickness (IMT) was averaged across the common, bulb, and internal carotids. The plaque index summarized degree of focal plaque based on the size and number of plaques throughout both carotid systems. RESULTS: Mean IMT was 0.69 mm for premenopausal women and 0.77 mm for postmenopausal women (P < 0.001). Prevalence of plaque was 25% among premenopausal women and 54% among postmenopausal women (P < 0.001). In both premenopausal and postmenopausal women, risk factors measured before menopause were associated with carotid atherosclerosis. Premenopausal risk factors independently associated with IMT were higher pulse pressure (P < 0.001), triglycerides (P = 0.002), body mass index (P < 0.001), and study group (a surrogate for both age and menopausal status; P < 0.001). Premenopausal risk factors independently associated with focal plaque were ever smoking (P = 0.002), higher pulse pressure (P = 0.028), higher LDL (P = 0.003), age at baseline (P = 0.050), and study group (P < 0.001). CONCLUSIONS: Subclinical carotid atherosclerosis can be observed in middle-aged women. Risk factors measured before menopause are clearly associated with subclinical disease measured both concurrently and at 5 to 8 years after menopause.

Adult↗
PubMed1995

[The significance of bone mineral density measurement of premenopausal women].

We examined the starting age for measuring bone mineral density (BMD) in premenopausal women to detect osteopenia as soon as possible. BMD of the second to fourth lumbar spine vertebrae was measured by dual-energy X-ray absorptiometry to determine normal values for 500 healthy premenopausal women (aged from 17 to 55). We found the rate for low BMD premenopausal women, whose BMD was under the peak bone mass-2SD. And we compared normal BMD women with low BMD women with reference to menstrual history, obstetrical history, and life style, by means of a questionnaire. The peak bone mass of premenopausal women was reached between 35 and 39 years of age (1.059 +/- 0.097g/cm2). The low BMD rate was 7% in all premenopausal women, and increased to 13.5% at from 45 to 49 years. On the other hand, it was only from 5.7 to 7.4% even at from 20 to 29 years. There was the positive correlation between BMD and the body mass index (BMI). There was no statistically significant difference between the low BMD women and the normal BMD women in menstrual history, obstetrical history or life style (parity was 1.7 +/- 1.6 and 1.1 +/- 1.2, respectively, p < 0.05). We concluded that premenopausal women should have their BMD measured after aged 45, and be measured once from 20 to 40 years of age if possible.

Absorptiometry, Photon↗
PubMed1994

Histopathologic adequacy of office endometrial biopsies taken with the Z-sampler and Novak curette in premenopausal and postmenopausal women.

This study compared the adequacy of office endometrial biopsies taken with the Novak curette and a disposable, flexible polypropylene biopsy device, the Z-sampler, in premenopausal and postmenopausal women. Between September 1988 and November 1991, 407 women had paired office endometrial biopsies with the Z-sampler followed by the Novak curette. Overall, 83.0% of endometrial biopsies obtained with the Z-sampler were adequate for histopathologic diagnosis as compared to 84.5% obtained with the Novak curette (P = .53). In 181 (44.5%) premenopausal women, 94.5% of Z-sampler biopsies were adequate as compared to 95.6% of Novak curette biopsies (P = .80). In 226 (55.6%) post-menopausal women, 73.9% of Z-sampler biopsies were adequate as compared to 75.7% of Novak curette biopsies (P = .66). The Z-sampler biopsies were adequate in 94.5% of premenopausal women as compared to 73.9% of postmenopausal women (P < .0001). The Novak curette biopsies were adequate in 95.6% of premenopausal women as compared to 75.7% of post-menopausal women (P < .001). While we did not demonstrate a significant difference in the adequacy of endometrial samples taken with the Z-sampler and Novak curette in premenopausal and postmenopausal women, postmenopausal women had a significantly lower rate of adequate samples obtained with either device as compared to premenopausal women.

Adult↗
PubMedDate not supplied

Estradiol concentrations in premenopausal women with coronary heart disease.

BACKGROUND: Because of the beneficial effects of estrogen, premenopausal women are normally protected against coronary heart disease (CHD) and are at lower risk for myocardial infarction; consequently, CHD occurs very rarely in menstrually active women. Given this background, the aim of the present study was to test the hypothesis that decreased concentrations of estrogen are associated with CHD in premenopausal women. METHODS: Fourteen premenopausal women with CHD were investigated and compared with a healthy control group comparable for age and cardiovascular risk factors. Relevant characteristics of patients and controls were assessed: age, blood pressure, body mass index, total cholesterol and high-density lipoprotein cholesterol, triglycerides, former pregnancies, ovariectomy and related surgical interventions, smoking history and former use of oral contraceptives. To ensure the premenopausal status of the participants, the regularity of the menstrual cycle and the follicle-stimulating hormone concentrations were also assessed. Plasma estradiol and progesterone and urine estrone concentrations (24 h urine collection) were measured at day 6 after estimated ovulation to assess the relative increase in plasma estradiol and progesterone during the second half of the menstrual cycle. RESULTS: Compared with the control group, premenopausal women with CHD had significantly lower concentrations of plasma estradiol (408.9 +/- 141 pmol/l and 287.8 +/- 109 pmol/l respectively; P = 0.0228) and total estrogen (2061 +/- 693 pg/mumol creatinine and 1607 +/- 448 pg/mumol creatinine respectively; P = 0.025) in the urine. However, the progesterone concentrations were not significantly different between the groups. These findings might be explained by a partial ovarian dysfunction, as the patient group had a significantly higher number of tubal sterilizations (eight compared with one). CONCLUSION: Our data provide support for the hypothesis that decreased concentrations of estradiol might be an additional pathogenetic factor for the development of CHD in menstrually active premenopausal women.

Adult↗
PubMed1984

A case-control study of risk indicators among women with premenopausal and early postmenopausal breast cancer.

Among 714 premenopausal and 130 postmenopausal breast cancer cases matched with 8440 controls for age in years and menopausal status, risk indicators for breast cancer were similar, although most associations were stronger in the premenopausal women. Compared with nulliparous women, the relative risk (RR) for those with first birth before age 25 years was 0.7 (95% confidence limits [CL] from 0.5 to 0.9) among premenopausal women, and 0.7 (0.4-1.4) for postmenopausal women. In the premenopausal cases, a history of breast cancer in a sister gave a RR of 3.0 (2.1-4.1) and in a mother 1.9 (1.4-2.5), whereas for the postmenopausal women the RRs were 1.4 (0.6-3.1) and 1.3 (0.6-2.6), respectively. Fibrocystic breast disease was also a significant predictor of subsequent breast cancer in the premenopausal and postmenopausal women. In relation to women having a single birth, premenopausal women with six or more births had a risk of breast cancer of 0.6 (0.4-1.0), which was present even after adjustment for age at first birth.

Age Factors↗
PubMed1978

Effect of premenopausal castration and incremental dosages of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone, and estradiol.

Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured serially in 11 premenopausal patients before and after hysterectomy with bilateral salpingo-oophorectomy. One week after operation an incremental dosage regimen of conjugated estrogens (CEE) in tablet form was commenced on a basis of two weeks with therapy (0.3, 0.625, 1.25, and finally 2.5 mg.), with each dose interspersed by two weeks without therapy. FSH, LH and E2 levels were measured at the end of each period with and without therapy. E2 levels fell within 24 hours of operation while FSH and LH levels rose gradually. CEE therapy produced an elevation of E2, but circulating concentrations comparable to the premenopausal values were only maintained during the dosage periods of 0.625 and 1.25 mg. of CEE. In only one instance did CEE succeed in reducing FSH to premenopausal levels, and that was at a dosage of 2.5 mg., in which instance the E2 level was higher than the premenopausal value. LH was never reduced to a premenopausal level. Thus, the data indicate that CEE alone in dosages up to 2.5 mg. per day was unable to reproduce in postmenopausal women the gonadotropin and E2 blood serum levels shown to exist prior to oophorectomy. Usual CEE treatment after menopause, therefore, in itself does not represent physiologic "hormone replacement therapy," if defined as the dosage required to maintain premenopausal circulating concentrations of reproductive hormones.

Castration↗
PubMed1983

Unique efficiency of methionine metabolism in premenopausal women may protect against vascular disease in the reproductive years.

Premenopausal women develop occlusive artery disease less frequently than postmenopausal women. In coronary heart disease, higher blood levels of homocysteine-cysteine mixed disulphide have been reported. Therefore, in healthy subjects, we studied the role of menopausal status in the transsulphuration of methionine in 10 premenopausal and 10 postmenopausal women. To exclude the role of aging, we compared these results with those in 10 younger and 10 older men of comparable age groups. An oral methionine load (0.1 g/kg of body weight) was administered after overnight fasting. Before and during 8 h, thereafter, serum levels of methionine, homocystine, and homocysteine-cysteine mixed disulphide were measured. In the fasting state, serum methionine levels were similar in the premenopausal women and both groups of men. Postmenopausal women had significantly lower fasting levels. Peak levels and clearances of methionine after loading did not differ between the groups. In the fasting state, homocystine was never detectable; yet, after methionine loading, slight homocystinemia was present in 12 out of 20 men, and was more pronounced in all postmenopausal women. However, homocystinemia did not occur in any of the premenopausal women after loading. Fasting serum homocysteine-cysteine mixed disulphide levels did not differ between both groups of men and postmenopausal women. In premenopausal women, both fasting and postloading disulphide levels were significantly lower than in any other group. We conclude that premenopausal women have a unique efficiency of methionine handling, and thereby are preserved against the accumulation of homocysteine after methionine loading. We speculate that this phenomenon might account for the lower incidence of vascular disease in women in the reproductive life cycle.

Adult↗
PubMed1991

Tamoxifen in premenopausal patients with metastatic breast cancer: a review.

The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration.

Breast Neoplasms↗
PubMed1989

Sex steroids and bone density in premenopausal and perimenopausal women.

Bone density begins to decline in women before menopause, and the degree of bone loss is variable. We performed a cross-sectional analysis on the entry data of a 5-yr prospective study of risk factors for osteoporosis to determine the correlation of bone density with serum sex steroid concentrations and body weight. We studied 292 healthy white women, aged 35-50 yr, who were menstruating regularly or had had menses in the past 12 months. Blood samples were drawn in the early follicular phase for estradiol (E2), testosterone (T), dehydroepiandrosterone sulfate, and sex hormone-binding globulin (SHBG). Free levels of E2 (FE2) and T (FT) were calculated based on total T and E2, SHBG, and albumin levels. Women were classified as premenopausal (FSH, less than 12 U/L) and perimenopausal (FSH greater than or equal to 12 U/L; n = 46; 16%). Bone density was measured by dual photon absorptiometry of the lumbar spine (L2-L4) and hip and by single photon absorptiometry of the wrist. Perimenopausal women were older than premenopausal women (45.5 +/- 3.5 and 41.0 +/- 3.9 yr, respectively), but did not differ in height or weight. While bone density did not correlate with age in each group, perimenopausal women had significantly lower bone density at the L2-L4 and femoral neck (L2-L4, 1.18 +/- 0.14 in perimenopausal and 1.24 +/- 0.12 g/cm2 in premenopausal women; femur, 0.84 +/- 0.11 in perimenopausal and 0.90 +/- 0.11 g/cm2 in premenopausal women; P less than 0.005). Body weight showed the strongest positive correlation with bone density. Log FT, percent FT, and FE2 percent correlated positively with bone density, even after controlling for weight. Log SHBG was negatively correlated with bone density in premenopausal women at the hip and wrist after controlling for weight. FSH was inversely correlated with bone density, and E2 and T were lower in perimenopausal than premenopausal women. These data suggest that women who are still menstruating may have relative deficiencies in both E2 and T, with reduced bone densities as a consequence.

Adult↗
PubMed1991

A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma.

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.

Adult↗
PubMed1999

Ovarian overstimulation and cystic formation in premenopausal tamoxifen exposure: comparison between tamoxifen-treated and nontreated breast cancer patients.

AIM: Tamoxifen is the antihormonal treatment of choice for premenopausal breast cancer patients with advanced breast disease. Its premenopausal administration has been shown to induce supraphysiological 17beta-estradiol serum levels and to be associated with the presence of persistent, bilateral functional ovarian cysts. However, these abnormalities have not yet been compared to controls. In this study we evaluated the possibility that the above hormonal and/or ovarian abnormalities are more frequent among premenopausal breast cancer patients treated with tamoxifen than among similar nontreated patients, and thus they may be attributed to tamoxifen effect. METHODS: We evaluated serum hormone levels of 17beta-estradiol, follicular-stimulating hormone, luteinizing hormone, and progesterone, the presence of ovarian cysts, and various demographic and clinical characteristics in 20 premenopausal breast cancer patients treated with tamoxifen (study group) and compared them to those observed in 12 similar nontreated patients (control group). RESULTS: Ovarian cysts were found in 80% of the study patients and only in 8.3% of the control patients (P = 0.001). The incidence of oligomenorrhea was nearly significantly higher in the study than in the control group (50 and 16.7%, respectively; P = 0.0651). Various serum hormone levels tested were not found to be significantly different between the two groups, except for 17beta-estradiol serum levels as detected on days 14 and 21 of the menstrual cycle, which were significantly higher among the study than in the control patients. (Day 14 serum estradiol: 757.7 +/- 372.0 pg/mL versus 206.5 +/- 275.0 pg/mL, P = 0.0012. Day 21 serum estradiol: 300.0 +/- 134.5 pg/mL versus 96.5 +/- 71.5 pg/mL, P = 0.0008.) CONCLUSIONS: Tamoxifen treatment increases the incidence of ovarian cysts and the significantly higher 17beta-estradiol serum levels in premenopausal breast cancer patients.

Adult↗