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Higher total homocysteine concentrations and lower folate concentrations in premenopausal black women than in premenopausal white women.

BACKGROUND: Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women. OBJECTIVE: The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women. DESIGN: Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured. RESULTS: Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene. CONCLUSIONS: Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.

Adolescent↗

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part B: Reduced serum androgen levels in healthy premenopausal women with complaints of sexual dysfunction.

Androgen insufficiency has been associated with decreased libido and arousal in postmenopausal women, but rarely has been evaluated in healthy premenopausal women. In all, 32 healthy premenopausal women were enrolled in this study, 18 with one or more complaints of sexual dysfunction and 14 without. Assays of ovarian and adrenal androgens were measured before and after ACTH stimulation. The women with complaints of sexual dysfunction had significantly lower adrenal androgens than did the control women. There were no differences in the basal ovarian androgens or cortisol levels. After ACTH, both groups stimulated cortisol as well as adrenal and ovarian androgens. In conclusion, premenopausal women with complaints of sexual dysfunction had lower adrenal androgen precursors and testosterone than age-matched control women without such complaints. Further study is required to determine how lower adrenal androgens contribute to female sexual dysfunction.

Adrenal Glands↗

The comparative study of bone mineral density between premenopausal women receiving long term suppressive doses of levothyroxine for well-differentiated thyroid cancer with healthy premenopausal women.

OBJECTIVE: To compare bone mineral density (BMD) of lumbar spines (LS) and femoral neck (FN) by Dual energy X-ray absorptiometry (DEXA) in premenopausal well-differentiated thyroid carcinoma women S/P total or near total thyroidectomy with a control group and the effect of Levothyroxine (LT4) to BMD between short term and long term treatment. MATERIAL AND METHOD: DEXA were performed at LS (L1-L4) and FN in 22 premenopausal thyroid carcinoma women S/P total or near total thyroidectomy followed by 1-131 ablation and long term suppressive dose LT4 and 22 healthy premenopausal women. RESULTS: Mean BMD of LS and FN were not significantly different between thyroid cancer group and control (LS 1.023 +/- 0.088 VS 0.980 +/- 0.075 g/cm2, p > 0.05, FN 0.800 +/- 0.068 VS 0.770 +/ - 0.061 g/cm2, p > 0.05). Period of time taking suppressive doses LT4 was divided into 3 groups (2-5 6-10 yrs and 11-14 yrs). Mean LS BMD +/- S.D of 2-5 yrs, 6-10 yrs and 11-14 yrs therapy are 1.042 +/- 0.135, 1.004 +/- 0.044 and 1.042 +/- 0.055 respectively (p > 0.05). Mean FN BMD +/- S.D of 2-5 yrs, 6-10 yrs and 11-14 yrs therapy are 0.808 +/- 0.084, 0.781 +/- 0.067 and 0.816 +/- 0.013 respectively (p > 0.05). CONCLUSION: The suppressive doses LT was not the risk factor of osteoporosis. Although, there was no 4 statistically significant difference of BMD between short and long-term suppressive doses LT groups, the present sample size was not enough to conclude that long-term suppressive doses LT did not decrease BMD.

Adult↗

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↗

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↗

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↗

[Prevalence of iron deficiency in pregnant and premenopausal women in China: a nationwide epidemiological survey].

OBJECTIVE: In order to better understand the iron status in pregnant and premenopausal nonpregnant women in China. METHODS: A nationwide epidemiological survey was undertaken in the year 2000 to investigate the prevalence rates (PR) of iron depletion (ID), iron deficiency anemia (IDA) and iron deficiency (ID + IDA). 3591 pregnant women and 3721 premenopausal women were selected by multi-stratification and random sampling from 26 cities and counties of 15 provinces. Hb was measured by cyanmethemoglobin assay, zinc protoporphyrin by hemo-fluorescein assay and serum ferritin by radioimmunoassay. RESULTS: The PR of ID and IDA were 42.6% and 19.1% in pregnant women, while 34.4% and 15.1% in premenopausal nonpregnant women respectively. There were statistical differences in the PR of IDA and ID + IDA in pregnant women between different trimesters (P < 0.01), with the highest in the third trimester (33.8%, 85.4%), followed by the second and the first trimesters. The prevalence rate of ID was also the highest during late pregnancy (51.6%), which was statistically different from that of early and mid-pregnancies (39.9% and 38.8% respectively), whereas there was no significant difference between the PR in early and mid-pregnancies. The PR of ID, IDA and ID + IDA in pregnant women were all significantly higher than that in premenopausal non-pregnant women (P < 0.01). The PR of ID in urban first-trimester pregnant women (41.9%) and premenopausal non-pregnant women (35.6%) were significantly higher than that in their rural counterparts (36.1% and 32.4% respectively P < 0.05). On the other hand, the PR of IDA in rural pregnant women in first-trimester (12.2%) and premenopausal non-pregnant women (17.4%) were significantly higher than that in their urban counterparts (8.2% and 13.8% respectively, P < 0.05). However, there was no significant difference between the PR of ID + IDA in urban pregnant women (62.0%), premenopausal nonpregnant women (49.4%) and then rural counterparts (61.1% and 49.7%). CONCLUSIONS: IDA and latent iron deficiency are still quite common in Chinese pregnant and premenopausal nonpregnant women. Pregnant women in mid and late pregnancies are at risk for iron deficiency. Latent iron deficiency is more prevalent in urban pregnant and nonpregnant premenopausal women, but their rural counterparts were prone to the development of IDA.

Adult↗

Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor.

OBJECTIVE: To establish whether sexual dimorphism in tumor necrosis factor (TNF) concentration in lipopolysaccharide (LPS)-stimulated whole blood culture is related to menopausal status or hormone concentrations. METHODS: Healthy volunteers (72 premenopausal female, 159 male, and 62 postmenopausal female) completed questionnaires and gave peripheral blood specimens for whole blood LPS-stimulated TNF assay and for selected hormone levels. TNFab microsatellite markers were genotyped. RESULTS: Mean LPS-stimulated TNF level in the premenopausal female group was 18% lower than the postmenopausal female mean (1579 +/- 913 pg/ml compared with 2257 +/- 881 in the men and 1965 +/- 950 in the postmenopausal women; p < 0.0003 and p 0.058, respectively). Analyzing a subset for which blood counts were obtained, mean stimulated TNF per monocyte was lower in the premenopausal female group than in the postmenopausal female group and appeared lower than in the male group (2.67 +/- 1.96 pg/ml per 10(3) monocytes vs 4.44 +/- 2.16 and 3.60 +/- 1.40; p = 0.018 and p = 0.12, respectively). Total plasma cortisol was higher in premenopausal women than men, and, in turn, higher in men than postmenopausal women (mean +/- SD 16.1 +/- 5.7, 12.2 +/- 3.6, and 10.4 +/- 4.3 microg/dl, respectively; p < 0.05 for each comparison). Using multiple linear regression to correct for covariates and TNF allelic effects, premenopausal status predicted TNF level independently from potential confounders or TNF genetic markers (covariate-adjusted decrement of 408 pg/ml; p = 0.0241). In the male group, total cortisol predicted lower TNF level (coefficient -67.5 pg/ml for each microg/dl cortisol; p = 0.0006 after stepwise selection), but total testosterone had no effect. In premenopausal women, LPS-stimulated TNF was not related to total estradiol, testosterone, or cortisol level. CONCLUSION: Premenopausal women had a lower mean whole blood LPS-stimulated TNF level than postmenopausal women, but there was no significant relation to total estradiol, testosterone, or cortisol levels in premenopausal women.

Adult↗

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↗

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↗

Premenopausal social status and hormone exposure predict postmenopausal atherosclerosis in female monkeys.

OBJECTIVE: To determine whether premenopausal social subordination in female monkeys predicts postmenopausal atherosclerosis, and whether any such effect is altered by chronic exposure to contraceptive steroids or postmenopausal hormone replacement. METHODS: One hundred seventy-seven (177) premenopausal cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six were fed an atherogenic diet that, for half of the animals, also contained an oral contraceptive (OC). Individuals were judged socially dominant or subordinate based on behavioral observations. After 26 months animals were oophorectomized, biopsied for iliac atherosclerosis, and for the next 36 months were fed one of three atherogenic diets containing soy protein: 1) phytoestrogen-free; 2) phytoestrogens intact; and 3) phytoestrogen-free plus conjugated equine estrogens. Plasma lipids and menstrual cyclicity were also assessed. Finally, all animals were necropsied and the extent of atherosclerosis measured in the coronary and iliac arteries. RESULTS: The interaction of premenopausal social status and OC exposure predicted postmenopausal coronary artery atherosclerosis (P =.02). Subordinate animals not receiving OCs developed twice the coronary atherosclerosis of similarly untreated dominants (P <.01), an outcome mitigated by premenopausal OC exposure (P <.01). These effects occurred across postmenopausal treatment groups and independent of variation in plasma lipids. The same associations were observed in the iliac arteries, and, to a similar extent, both pre- and post-menopausally. Hormone data suggest that untreated premenopausal subordinates may have been estrogen deficient. CONCLUSION: Premenopausal social subordination exacerbates postmenopausal atherosclerosis, an effect possibly mediated by estrogen deficiency and shown here to be prevented by premenopausal OC exposure. These results occur irrespective of postmenopausal treatment.

Animals↗

Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes.

Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 +/- 3 fmol/mL in controls v 23.1 +/- 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (beta,E2) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.

Adolescent↗

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↗

Comparison of HER-2/neu, ER and PCNA expression in premenopausal and postmenopausal patients with breast carcinoma.

We attempted to compare the pattern of HER-2/neu, ER and PCNA in premenopausal and postmenopausal patients with breast carcinoma to identify potential biological differences. Five hundred and forty-eight samples from 318 premenopausal and 230 postmenopausal women with invasive ductal carcinoma of the breast were evaluated for HER-2/neu, ER and PCNA expression by immunohistochemistry. HER-2/neu expression showed 27.4% positivity in premenopausal and 24.8% in postmenopausal women; there was no significant difference between the two groups (p>0.05). In contrast, HER-2/neu expression was found to be significantly associated with ER negativity in the two groups (p<0.05 in premenopausal, p<0.001 in postmenopausal patients). However, it was significantly associated with PCNA expression only in the postmenopausal group (p<0.001). 54.4% showed premenopausal tumor cell ER positivity, whereas 64.3% of the postmenopausal group showed positivity. ER expression showed a significant correlation with patient menopausal status (p<0.05). The prevalence of PCNA positivity in the tumor cell components is slightly higher in postmenopausal compared to premenopausal women (p>0.20). The current study is consistent with reports from other groups regarding the correlation of HER-2/neu with adverse pathologic features and with expression of other markers in carcinoma. We also observed there was no trend toward increased HER-2/neu expression in either premenopausal or postmenopausal patients, i.e. there was similar HER-2/neu expression in the two groups. This suggests that HER-2/neu status could be used to determine assignment to specific intensive adjuvant therapy and evaluation of biological behavior in both pre- and postmenopausal patients with breast carcinoma.

Biomarkers, Tumor↗

Premenopausal advantages in postprandial lipid metabolism are lost in women with type 2 diabetes.

OBJECTIVE: Women with type 2 diabetes appear to lose the protection against cardiovascular disease afforded by estrogens. We examined the effects of menopausal status on postprandial clearance of dietary fat in healthy and diabetic women. RESEARCH DESIGN AND METHODS: Fasting subjects (premenopausal and postmenopausal control subjects, premenopausal and postmenopausal diabetic women, all n = 8) were given a meal containing the stable isotope 1,1,1-(13)C-tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the postprandial period. Lower levels of (13)C-palmitic acid ((13)C-PA) in the triglyceride fraction implies more efficient chylomicron clearance, lower levels of (13)C-PA in the nonesterified fatty acid (NEFA) fraction implies improved dietary NEFA entrapment, and higher levels of (13)CO(2) in the breath denote more efficient of oxidation of dietary-derived lipid. RESULTS: In diabetic women, there were no differences between the pre- and postmenopausal groups for any of these parameters. In contrast, premenopausal control subjects, compared with postmenopausal control subjects, had lower (13)C-PA in the triglyceride fraction area under the curve (AUC) (premenopausal median [range] 25.2 [12.1-49.4 mmol/l] per 6 h, postmenopausal 48.5 [15.5-77.2 mmol/l] per 6 h; P < 0.01) and higher (13)CO(2) levels in the breath AUC (premenopausal 22.5 [18.0-31.5%] of administered dose, postmenopausal 17.2 [11.2-31.5%] of administered dose; P < 0.01) with no difference between groups in levels of (13)C-PA in the NEFA fraction AUC. CONCLUSIONS: The premenopausal advantage in clearance of dietary lipid is not seen in premenopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of cardiovascular disease protection seen in diabetic women.

Area Under Curve↗

Osteoporosis and low bone mass in premenopausal and perimenopausal women.

OBJECTIVE: To characterize the historical, clinical, and biochemical features of 111 young women (age, <55 years) referred for evaluation of osteoporosis or low bone mass. METHODS: Women with a bone mineral density T score < or = -2.0 (N = 111) at one or more anatomic sites (by dual-energy x-ray absorptiometry) were assessed relative to anthropomorphic and biochemical characteristics and risk factors for osteoporosis. RESULTS: Of 111 women with low bone mass or osteoporosis, 73 (66%) had identifiable causes of bone loss, of which estrogen deficiency (menopause, premenopausal estrogen deficiency) and conditions associated with estrogen deficiency (anorexia nervosa, cancer chemotherapy) were the most common. Prolonged use of glucocorticoids was the most common secondary cause of osteoporosis. Of 38 women with no identifiable cause of bone loss, 21 were premenopausal (mean age, 38 +/- 10 years [standard deviation]) and 17 were perimenopausal (mean age, 50 +/- 3 years). The mean lumbar spine T score was -2.18 +/- 1.0 in the premenopausal and -2.51 +/- 0.6 in the perimenopausal women. Nontraumatic fractures were reported by 42% of the premenopausal women and 18% of the perimenopausal women. A family history of osteoporosis was reported by 71% of the premenopausal and 47% of the perimenopausal women. CONCLUSION: Most young women with osteoporosis or low bone mass had estrogen deficiency or another secondary cause of premature bone loss (or both). A subset of premenopausal and perimenopausal women, however, had no identifiable cause of bone loss. The strong family history of osteoporosis, especially in the premenopausal women, provides further support for current theories of a genetic predisposition to osteoporosis.

Adult↗

Premenopausal women and low bone density.

OBJECTIVE: To review the evidence and provide an approach to management of low bone density among premenopausal women. QUALITY OF EVIDENCE MEDLINE: was searched from January 1990 to November 2004 and articles graded by level of evidence (I to III). Diagnosis and management recommendations were based on evidence from randomized controlled trials and expert consensus. MAIN MESSAGE: Bone mineral density (BMD) testing among premenopausal women should be completed only in the presence of approved indications. Current evidence does not support screening for osteoporosis among premenopausal women. Low BMD in premenopausal women is associated with a lower fracture risk than seen in postmenopausal women. In the absence of fragility fractures, low BMD might reflect low peak bone mass based on genetic predisposition, environment, and lifestyle factors. Clinical evaluation enables distinction between low peak bone mass and a systemic disorder resulting in low BMD and skeletal fragility. Common causes of low bone density among premenopausal women include ovulatory disturbances and low body weight. CONCLUSION: Bone mineral density alone is insufficient for diagnosis of osteoporosis among premenopausal women in the absence of fragility fractures. Antiresorptive therapy has been evaluated and shown to benefit premenopausal women using glucocorticoid therapy or those with primary hyperparathyroidism.

Bone Resorption↗

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↗