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Biomedical subjects

C Longcope

Publications and source records attributed to C Longcope.

At least 37 records · Page 2Linked to original sources
PubMed1998

Low dehydroepiandrosterone sulfate and heart disease in middle-aged men: cross-sectional results from the Massachusetts Male Aging Study.

PURPOSE: Serum concentrations of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS), both of which decline with age more markedly than other sex hormone levels, have been alternately credited and discredited as "protective" correlates of heart disease. Baseline data from the Massachusetts Male Aging Study (MMAS), collected in 1987-89, provided a large population-based random sample (n = 1709) in which to examine cross-sectionally the relation of DHEA and DHEAS levels to heart disease, while controlling for a comprehensive set of potential confounders including serum lipid and hormone levels as well as smoking, alcohol intake, obesity, hypertension, diabetes, diet, medication, physical activity, and psychological measures. METHODS: The subjects were men aged 40-70 years, randomly sampled from the Massachusetts state census listing, measured and interviewed at home. Nonfasting blood samples were assayed for hormones and lipids. RESULTS: In all strata of age, smoking, and alcohol intake, the age-adjusted odds ratio for self-reported heart disease was between 0.55 and 0.85 per standard deviation (SD) of log DHEA and DHEAS concentration. Multiple logistic regression analysis indicated a strong independent role for DHEAS as a predictor of self-reported heart disease, controlling for age and the potential confounders listed above. The multiply-adjusted odds ratio for heart disease was 0.64 per SD log DHEAS concentration, with 95% confidence interval (CI) 0.50-0.83 (P = 0.0002). The DHEAS effect was not diminished by controlling for use of cardiac, vasodilator, antihypertensive, or lipid-lowering medication. CONCLUSIONS: These findings suggest that serum DHEAS levels bear an inverse relationship to heart disease, independently of a large set of established cardiovascular risk factors. The cross-sectional nature of this study requires that the findings be interpreted with caution.

Aged↗
PubMed1998

Androgen metabolism and the menopause.

The concentration of androgens in the blood peaks in early adulthood. While the concentrations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) decline steadily, the concentrations of androstenedione (A) and testosterone (T) decline just before or at the menopause. DHEAS is bound strongly to albumin, resulting in a very low metabolic clearance rate (MCR) of about 12 L/day. DHEA and A are bound weakly to albumin and their MCRs are 1800 to 2000 L/day. T is bound strongly to sex hormone-binding globulin (SHBG), and the MCR of T is about 500 L/day. There are no significant changes in the MCRs at the menopause or with age. The pathways of metabolism are not altered at the menopause but aromatization of DHEA, A, and T to estrone and estradiol all increase with age. Thus, androgen metabolism in general is affected more by age than by the menopause itself.

Adult↗
PubMed1998

Dehydroepiandrosterone sulfate does not prevent spontaneous and iodine-induced lymphocytic thyroiditis and diabetes mellitus in the BB/Wor rat.

Chronic feeding of dehydroepiandrosterone (DHEA) and its sulfated metabolite, dehydroepiandrosterone sulfate (DHEAS), has previously been reported to decrease hyperglycemia, obesity, cancer, and autoantibody generation in a number of animal models and to increase muscle mass and physiological and psychological well-being in elderly humans, although these latter studies remain controversial. The present study was carried out to determine whether large amounts of DHEAS given orally would prevent the occurrence of spontaneous and iodine-induced autoimmune lymphocytic thyroiditis (LT) and/or spontaneous insulin-dependent diabetes mellitus (DM) in male and female BB/Wor rats. DHEAS was administered by gavage (44 mg/rat/day) or in the chow (133 mg/rat/day) to LT- and DM-prone rats from 30 to 120 days of life; some of these rats also received iodine in the drinking water to enhance the incidence and intensity of LT. Onset of DM requiring protamine zinc insulin and its maintenance dose were assessed. Rats were killed at 90 or 120 days of age and blood, thyroid, adrenals, pancreases, testes, and ovaries were removed. Serum glucose, DHEA, DHEAS, thyroxine (T4), tri-iodothyronine (T3) and thyrotropin (TSH) concentrations were measured in all rats in both experiments. Serum DHEAS concentrations were 10-fold higher in the rats given the steroid by gavage or in the diet compared with levels in control rats. DHEAS administered over a prolonged period of time had no significant effect on body weight, incidence and severity of DM, incidence and intensity of spontaneous and iodine-induced LT, and thyroid, pancreas and testes weights but did significantly decrease adrenal and ovarian weights. Serum T4, T3, and TSH concentrations were similar in control and DHEAS-treated rats. In conclusion, DHEAS did not prevent the occurrence of iodine-induced or spontaneous autoimmune LT or spontaneous DM in the BB/Wor rat, at variance with its reported immunosuppressive effects in other animal models.

Analysis of Variance↗
PubMed1998

Changes in reproductive hormones and sex hormone-binding globulin in a group of postmenopausal women measured over 10 years.

OBJECTIVE: As part of a study on hormones and bone density in older women, we measured a number of steroid and polypeptide hormones at 4- to 6-month intervals in 32 women over a 10-year period. DESIGN: All women were postmenopausal during this time and all measurements from 12 months after the menopause to the end were used in the analysis. To determine whether there was a significant trend in steroid or polypeptide hormones over the years, the data were analyzed by random coefficient linear regression against number of months since menopause. RESULTS: There was no significant trend in the concentrations of estrone, estrone sulfate, dehydroepiandrosterone, and follicle stimulating hormone. There was a significant decline in the concentrations of estradiol, dihydrotestosterone, dehydroepiandrosterone sulfate, and luteinizing hormone. There was a rise in the levels of androstenedione and testosterone. CONCLUSIONS: The changes in the concentration of sex hormone-binding globulin could be fitted to a quadratic equation with an initial rise in the concentration followed by a decline. Thus, the trend in hormone concentrations shows no set pattern with aging in the postmenopausal years.

Androstenedione↗
PubMed1997

Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

The purpose of this study was to determine whether bone density in older men was associated with serum sex steroids or sex hormone binding globulin (SHBG). Bone density and sex steroids were measured in men over age 65 at 6-mo intervals for an average of 2.1 yr. Bone density was significantly positively associated with greater serum E2 concentrations (+0.21 < r < +0.35; 0.01 < P < 0.05) at all skeletal sites. There were weak negative correlations between serum testosterone and bone density (-0.20 < r < -0.28; 0.03 < P < 0.10) at the spine and hip. SHBG was negatively associated only with bone density in the greater trochanter (r = -0.26, P < 0.05). Greater body weight was associated with lower serum testosterone and SHBG, and greater E2. Because of these associations, regression models which adjusted for age, body weight, and serum sex steroids were constructed; these accounted for 10-30% of the variability in bone density, and showed consistent, significant positive associations between bone density and serum E2 concentrations in men, even after adjustments for weight and SHBG. These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case for the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men.

Aged↗
PubMed1997

Serum sex hormone levels are related to breast cancer risk in postmenopausal women.

We conducted a nested case-control study to prospectively evaluate the relationship of serum estrogens and androgens to risk of breast cancer in postmenopausal women. From 1977 to 1987, 3375 postmenopausal women free of cancer and not taking replacement estrogens donated blood to the Breast Cancer Serum Bank in Columbia, Missouri. Of these, 72 were subsequently diagnosed with breast cancer. For each case, two controls matched on age and date and time of day of blood collection were selected using incidence density matching. The median age of subjects at blood collection was 62 years; the time from blood collection to diagnosis ranged from less than 1 to 9.5 years with a median of 2.9 years. Risk of breast cancer was positively and significantly associated with serum levels of estrogens and androgens. Compared to women in the lowest quartile, those in the highest quartile for non-sex hormone-binding globulin (non-SHBG) bound (bioavailable) estradiol had a relative risk of 5.2 (95% confidence interval [CI] = 1.5-18.5) and those in the highest quartile for testosterone had a relative risk of 6.2 (95% CI = 2.0-19.0). Our results lend considerable support to the hypothesis that serum concentrations of estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women.

Aged↗
PubMed1997

Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3 beta, 17 beta-diol to risk of breast cancer in postmenopausal women.

Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) in mammary tumor growth. Serum DHEA also has been related to breast cancer in postmenopausal women, but the relationship of ADIOL to risk has not been evaluated previously. To assess the relationship of serum DHEA, its sulfate (DHEAS), and ADIOL with breast cancer risk in postmenopausal women, we conducted a prospective nested case-control study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included 71 healthy postmenopausal volunteers not taking replacement estrogens when they donated blood and who were diagnosed with breast cancer up to 10 years later (median, 2.9 years). Two randomly selected controls, who also were postmenopausal and not taking estrogens, were matched to each case on exact age, date (+/-1 year), and time (+/-2 h) of blood collection. Significant (trend P = 0.02) gradients of increasing risk of breast cancer were observed for increasing concentrations of DHEA and ADIOL, and women whose serum levels of these hormones were in the highest quartiles were at a significantly elevated risk compared to those in the lowest; their risk ratios were 4.0 [95% confidence interval (CI), 1.3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to breast cancer was less consistent, but women whose serum DHEAS concentration was in the highest quartile also exhibited a significantly elevated risk ratio of 2.8 (95% CI, 1.1-7.4). Results of this prospective study support a role for the adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer.

Aged↗
PubMed1997

Assay reproducibility of hormone measurements in postmenopausal women.

As part of a breast cancer case-control study of serum hormones conducted in Columbia, MO, we included several replicate quality control samples to monitor the consistency of laboratory assays. Sera were obtained from three postmenopausal women; from each woman, three samples were placed randomly in each of nine batches with the laboratory unaware of which sample corresponded to whom. Laboratory assays for estrone (E1), estradiol (E2), testosterone, androstenedione (Adione), E1SO4, dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), and percentages of free and albumin-bound E2 were done at a single academic facility. ANOVA results showed that hormone values varied considerably from one batch to the next. The overall coefficients of variation (CVs) estimated for E2, percentage of unbound E2, and percentage of albumin-bound E2 were higher than 15%, but of these, only percentage of unbound E2 had both inter- and intra-assay CVs greater than 10%. Intraclass correlations (ICC) for FSH, SHBG, and DHEAS were high, suggesting that these assays are suitable for population-based studies attempting to link hormone levels to disease risk. The ICC estimated for E1SO4 was quite low due to aberrant values reported in a single batch. For the remaining hormones, the ICCs were fair (ranging from 47% for albumin-bound E2 to 67% for Adione), and studies using these assays would require a substantial increase in the sample size to detect small case-control differences.

Analysis of Variance↗
PubMed1996

Hormone levels during dietary changes in premenopausal African-American women.

BACKGROUND: In the United States, 5-year survival rates of 69% and 84%, respectively, have recently been reported for African-American and Caucasian women diagnosed with breast cancer. Differences in the levels of endogenous sex hormones in these populations could explain some of the variation in survival rates, since estrogen is recognized as a risk factor for this type of cancer. PURPOSE: Dietary factors are known to affect endogenous hormone levels; therefore, our study was designed to determine the serum hormone levels of African-American women consuming a typical North American diet, to determine the effect of a low-fat and high-fiber diet on their serum hormone levels, and to compare the base-line serum hormone levels in the African-American women with hormone data from our study of Caucasian women (n = 68) consuming the same control diet. METHODS: Twenty-one healthy, premenopausal, African-American women who agreed to eat only food prepared in a clinical study unit were recruited into the study. The control diet was similar to their usual diet, being high in fat (40% of calories from fat) and low in fiber (12 g/day), and was consumed on average for 3 weeks. The concentrations of estrone (E1), estrone sulfate (E1SO4), estradiol (E2), free E2, androstenedione, and sex hormone-binding globulin (SHBG) in serum samples obtained from the participants during the last week of the control diet and during the follicular phase of their menstrual cycle were determined. The women were then switched to a diet low in fat (20% of calories as fat) and high in fiber (40 g/day); they consumed this diet for two menstrual cycles before blood samples were collected for determination of serum hormone levels. Repeated-measures regression modeling was used to investigate the relationship between diet and hormone levels in African-American and Caucasian women. All P values resulted from two-sided statistical tests. RESULTS: Analysis of serum hormone levels in the African-American women indicated that the change in diet caused a significant decrease in E2 (-8.5%; 95% confidence interval [CI] = -16.1% to -0.3%; P < or = .03) and E1SO4 (-16.2%; 95% CI = -22.1% to -9.8%; P < .0001) and a significant increase in androstenedione levels (+18.3%; 95% CI = +10.3% to +26.8%; P < .0001). SHBG levels of the African-American women were 5.6% (95% CI = -14.0% to +3.7%) lower for those on the experimental diet compared with those on the control diet, but the difference was not statistically significant. Comparison of control serum hormone values in the African-American women in this study with those in Caucasian women previously studied indicated that the Caucasian women had statistically significant lower levels of E1 (-37%; 95% CI = -61.2% to -16.4%; P < or = .0002), E2 (-54.5%; 95% CI = -90.9% to -25.1%; P < or = .0001), free E2 (-30.2%; 95% CI = -65.7% to -2.3%; P < .03), and androstenedione (-48.3%; 95% CI = -83.7% to -19.7%; P < or = .0004). CONCLUSION: African-American women appear to have higher levels of serum hormones than Caucasian women, and dietary modification can result in a lowering of serum estrogens.

Adult↗
PubMed1996

Prospective study of sex hormone levels and risk of prostate cancer.

BACKGROUND: Sex steroids, particularly androgens, have been implicated in the pathogenesis of prostate cancer. Data from previous studies comparing circulating hormone levels in men with and without prostate cancer are difficult to interpret, since the studies were limited in size, hormone levels were analyzed in blood drawn after the diagnosis of cancer, nonrepresentative control subjects were used, and hormone and hormone-binding protein levels were not simultaneously adjusted. PURPOSE: We conducted a prospective, nested case-control study to investigate whether plasma hormone and sex hormone-binding globulin (SHBG) levels in healthy men were related to the subsequent development of prostate cancer. METHODS: Among participants in the Physicians' Health Study who provided plasma samples in 1982, we identified 222 men who developed prostate cancer by March 1992. Three hundred ninety control subjects, matched to the case patients on the bases of age, smoking status, and length of follow-up, were also identified. Immunoassays were used to measure the levels of total testosterone, dihydrotestosterone (DHT), 3 alpha-androstanediol glucuronide (AAG), estradiol, SHBG, and prolactin in the stored (at -82 degrees C) plasma samples. Correlations between individual hormone levels and between hormone levels and SHBG in the plasma of control subjects were assessed by use of Spearman correlation coefficients (r). Odds ratios (ORs) and 95% confidence intervals (CIs) specifying the prostate cancer risk associated with quartile levels of individual hormones, before and after adjustment for other hormones and SHBG, were calculated by use of conditional logistic regression modeling. Reported P values are two-sided. RESULTS: No clear associations were found between the unadjusted levels of individual hormones or SHBG and the risk of prostate cancer. However, a strong correlation was observed between the levels of testosterone and SHBG (r = .55), and weaker correlations were detected between the levels of testosterone and the levels of both estradiol (r = .28) and DHT (r = .32) (all P < .001). When hormone and SHBG levels were adjusted simultaneously, a strong trend of increasing prostate cancer risk was observed with increasing levels of plasma testosterone (ORs by quartile = 1.00, 1.41, 1.98, and 2.60 [95% CI = 1.34-5.02]; P for trend = .004), an inverse trend in risk was seen with increasing levels of SHBG (ORs by quartile = 1.00, 0.93, 0.61, and 0.46 [95% CI = 0.24-0.89]; P for trend = .01), and a non-linear inverse association was found with increasing levels of estradiol (ORs by quartile = 1.00, 0.53, 0.40, and 0.56 [95% CI = 0.32-0.98]; P for trend = .03). No associations were detected between the levels of DHT or prolactin and prostate cancer risk; for AAG, a marker of 5 alpha-reductase activity, only suggestive evidence of a positive association was found. The results were essentially unchanged when case patients diagnosed within 4 years of plasma collection, case patients diagnosed with localized (i.e., nonaggressive) disease, or control subjects with elevated prostate serum antigen levels (> 2.5 ng/mL) were excluded from the analyses. CONCLUSIONS: High levels of circulating testosterone and low levels of SHBG-both within normal endogenous ranges-are associated with increased risks of prostate cancer. Low levels of circulating estradiol may represent an additional risk factor. Circulating levels of DHT and AAG do not appear to be strongly related to prostate cancer risk.

Adult↗
PubMed1996

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

Although bone loss around the time of menopause is driven by estrogen deficiency, the roles of estrogens and androgens in the preservation of skeletal mass at other stages of life are less well understood. To address this issue we studied 231 women between the ages of 32 and 77 with multiple measurements of sex steroids and bone mass over a period of 2-8 yr. In all women bone mass was negatively associated with concentrations of sex-hormone binding globulin, and positively associated with weight. Bone loss occurred from all skeletal sites in peri- and postmenopausal women, but premenopausal women lost bone only from the hip (-0.3%/yr) and had positive rates of change in the radius and spine. Bone loss was significantly associated with lower androgen concentrations in premenopausal women, and with lower estrogens and androgens in peri- and postmenopausal women. Sex steroids are important for the maintenance of skeletal integrity before menopause, and for as long as 20-25 yr afterwards.

Adult↗
PubMed1996

Dehydroepiandrosterone metabolism in the female rhesus monkey: oral versus intravenous administration.

Because of the biologic effects on a variety of end points reported for dehydroepiandrosterone (DHA) and its sulfate (DHAS) after oral administration, we studied the metabolism of DHA in six female rhesus monkeys after oral and after intravenous administration. We administered [4-14C]DHA p.o. and [7-3H]DHA i.v. simultaneously, drawing blood samples at increasingly longer intervals for 24 h. The mean +/- SE metabolic clearance rate of the intravenous DHA was 404 +/- 49 L/day. The mean metabolic clearance rate was 2,601 +/- 261 L/day after oral administration, and the calculated absorption was 16.3 +/- 2.5%. There was rapid conversion of p.o. DHA to DHAS, as the conversion ratio of the orally administered DHA measured in the blood as [4-14C]DHAS was 63.3 +/- 13.6, whereas the conversion ratio of intravenously administered DHA to DHAS was 9.3 +/- 2.0. Small amounts of DHA were measured in the blood as testosterone and androstenedione after both forms of administration. We conclude that there is marked metabolism in splanchnic tissue of orally administered DHA to DHAS prior to its entry into the bloodstream, and the absorption of DHA itself is minimal when administered by mouth to the rhesus monkey.

Administration, Oral↗
PubMed1996

Does collecting repeated blood samples from each subject improve the precision of estimated steroid hormone levels?

Measuring levels of steroid hormones in epidemiologic studies is difficult because pulsatile release can cause the levels of many hormones to vary markedly over short intervals, leading to a loss of precision in between-subject comparisons. Clinicians often control this variation by collecting several samples from each subject at defined intervals and pooling these samples for assay. The number of samples per subject that would adequately control such variation in an epidemiologic study has not been fully investigated. This study examines the effects of collecting 1, 2, or 3 samples per subject on the variances of 11 hormones and sex hormone binding globulin in men and 6 hormones in women. Three samples were collected at 30-minute intervals from each of 20 men and 59 women and were assayed separately. Variances that would be obtained in studies collecting one, two, or three samples per subject were then estimated. Collecting more than one sample substantially reduced the variances of several hormones in men but not in women.

Adult↗
PubMed1996

Relation of energy, fat, and fiber intakes to plasma concentrations of estrogens and androgens in premenopausal women.

To evaluate whether diet may influence the incidence of hormone-dependent cancers through an effect on blood estrogen and androgen concentrations, we analyzed diet-blood hormone relations in a cross-sectional study. Dietary energy, fat, and fiber intakes were estimated from 7-d food records completed by 90 premenopausal women on days 14-20 of their menstrual cycles. Fasting blood specimens were collected on days 5-7, 12-15, and 21-23 of each participant's cycle and pooled to create follicular-, midcycle-, and luteal-phase samples, respectively, for analysis. Energy intake was associated inversely with plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS), averaged across the three menstrual cycle phases, and directly with the probability of a luteal-phase rise in progesterone. For each additional 1 MJ (239 kcal) consumed, androstenedione decreased by 6.0% (95% CI: -8.4%, -3.6%), DHEAS decreased by 5.1% (95% CI: -9.6%, -0.4%), and the probability of a progesterone rise increased by 60% (95% CI: 5%, 145%). After energy intake was adjusted for, the ratio of polyunsaturated to saturated fat (P:S) in the diet was significantly inversely associated with plasma estradiol and estrone during the luteal phase of the menstrual cycle. For each 0.1 increment in the P:S, there was a 7.6% (95% CI: -14.3%, -0.5%) decrease in estradiol and a 6.8% (95% CI: -12.7%, -0.6%) decrease in estrone. Results of this cross-sectional study support a relation between both energy and fat ingestion and plasma sex hormone concentrations in premenopausal women.

Adult↗
PubMed1996

Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study.

We conducted a controlled feeding study to evaluate the effects of fat and fiber consumption on plasma and urine sex hormones in men. The study had a crossover design and included 43 healthy men aged 19-56 y. Men were initially randomly assigned to either a low-fat, high-fiber or high-fat, low-fiber diet for 10 wk and after a 2-wk washout period crossed over to the other diet. The energy content of diets was varied to maintain constant body weight but averaged approximately 13.3 MJ (3170 kcal)/d on both diets. The low-fat diet provided 18.8% of energy from fat with a ratio of polyunsaturated to saturated fat (P:S) of 1.3, whereas the high-fat diet provided 41.0% of energy from fat with a P:S of 0.6. Total dietary fiber consumption from the low- and high-fat diets averaged 4.6 and 2.0 g.MJ-1.d-1, respectively. Mean plasma concentrations of total and sex-hormone-binding-globulin (SHBG)-bound testosterone were 13% and 15% higher, respectively, on the high-fat, low-fiber diet and the difference from the low-fat, high-fiber diet was significant for the SHBG-bound fraction (P = 0.04). Men's daily urinary excretion of testosterone also was 13% higher with the high-fat, low-fiber diet than with the low-fat, high-fiber diet (P = 0.01). Conversely, their urinary excretion of estradiol and estrone and their 2-hydroxy metabolites were 12-28% lower with the high-fat, low-fiber diet (P < or = 0.01). Results of this study suggest that diet may alter endogenous sex hormone metabolism in men.

Adult↗
PubMed1996

Analysis of differential gene regulation in adequate versus inadequate secretory-phase endometrial complementary deoxyribonucleic acid populations from the rhesus monkey.

The ability to create artificial menstrual cycles in the rhesus monkey provides a model for studies on the regulation of genes and gene networks by estradiol or progesterone (P) in the primate endometrium. This model allowed us to create both a normal level of secretory phase P or an inadequate level of secretory phase P, i.e. endometria that cannot support implantation. The objective of our present study focused on PCR analyses of genes for several factors that are believed to be important in the proper maturation of the endometrium. Complementary DNA (cDNA) populations were prepared from endometria harvested on day 13 (peak E level), days 21-23 of an adequate secretory phase (PcDNA) and days 21-23 of an inadequate secretory phase (IcDNA). Although placental protein 14, leukemia inhibitory factor and 17-beta hydroxysteroid dehydrogenase displayed highly upregulated levels in PcDNA (P-activated genes), there was little or no up-regulation in IcDNA. Transforming growth factor-beta 2 and its receptor and insulin growth factor-I and its receptor were up-regulated in PcDNA, whereas little or no expression was observed in IcDNA. Regulators of the cell cycle and transcription, such as retinoblastoma, c-fos, and c-jun genes, were also greatly underexpressed in IcDNA compared with PcDNA. Interestingly, one gene that we studied, keratinocyte growth factor, that was up-regulated by P (peak E levels vs. PcDNA) was more highly expressed in IcDNA. This latter result suggests that low levels of circulating P are sufficient for expression of this gene, whereas high sustained P levels result in an autologous down-regulation. These data show that the regulation of genes that may play pivotal roles in endometrial maturation are differentially expressed in IcDNA vs. PcDNA and may, in part, characterize improper endometrial maturation.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk.

To evaluate the relation of serum sex hormones to breast cancer risk, we conducted a prospective nested case-control study using the Breast Cancer Serum Bank (Columbia, MO). This bank included serum from 3375 postmenopausal women free of cancer and not taking replacement estrogens when they donated blood between 1977 and 1987. Of these, 71 were diagnosed subsequently with breast cancer. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched to the case on age and on date and time of day of blood collection were selected as controls. The median age of subjects at blood collection was 62 years, and the time from blood collection to diagnosis ranged from less than 1 to 9.5 years, with a median of 2.9 years. Postmenopausal women with elevated serum levels of total and non-sex hormone-binding globulin-bound E2 were at an increased risk of developing breast cancer. For non-sex hormone-binding globulin-bound E2, risks were elevated 4-5 fold for women in the upper three quartiles relative to those in the lowest quartile. Although breast cancer was not related to estrone or estrone sulfate concentration, the ratio of estrone sulfate to estrone was significantly inversely associated with risk, suggesting that women who develop breast cancer may be less able to metabolize estrone to its less active form. Serum testosterone was significantly positively associated with postmenopausal breast cancer; the relative risk for women in the highest versus the lowest quartile was 6.2 (95% confidence interval, 2.0-19.0). Our results support the hypothesis that prediagnostic serum estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women.

Adult↗