PubMed Health⌕ Search

Biomedical subjects

F Z Stanczyk

Publications and source records attributed to F Z Stanczyk.

At least 19 recordsLinked to original sources
PubMed1998

Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility.

The prostate is an androgen-regulated organ, which has led to long-standing interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones. The international and racial-ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, have suggested that whereas environmental factors are likely to be important, genetic factors might also play a central role in determining prostate cancer risk. We are developing a polygenic model of prostate carcinogenesis focused around a series of genes involved in androgen biosynthesis and androgen activation, transport, and metabolism in the prostate. In this developing model, we have initially targeted four genes based on three main criteria: (a) all encode products that play important roles in inducing androgen stimulation in the prostate; (b) all are polymorphic; and (c) all show substantial allelic variation in the polymorphic marker among the racial-ethnic groups of greatest interest in terms of prostate cancer risk. In addition to studying how the polymorphic markers of interest are related to prostate cancer development within and between racial-ethnic groups, we are concurrently evaluating whether genotypic variations correlate in the anticipated direction with biochemical parameters in vitro and in vivo. We summarize the development of this model and the state of knowledge related to each of the genes comprising the current model. We discuss the extent to which the current model can explain demographic variation in prostate cancer risk as well as the potential for future expansion of the model to incorporate environmental risk factors as well as additional genes. The model, when fully developed, can potentially provide a basis for targeting populations for screening interventions and/or preventive strategies aimed at the multigene products or at the genes themselves.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Cytochrome P450c17alpha gene (CYP17) polymorphism is associated with serum estrogen and progesterone concentrations.

An increased level of serum estrogen is one marker of breast cancer risk. We have recently reported that increased risk of advanced breast cancer is associated with a common allele of the cytochrome P450c17alpha gene (CYP17), designated A2. We now show that CYP17 genotype is associated with serum hormone levels among 83 young, nulliparous women. Serum estradiol (E2) levels measured around day 11 of the menstrual cycle were 11 and 57% higher (P = 0.04), respectively, among women hetero- and homozygous for the CYP17 A2 allele compared to A1/A1 women. Similarly, around cycle day 22, E2 levels were 7 and 28% higher (P = 0.06), and progesterone levels were 24 and 30% higher (P = 0.04), respectively. These data provide direct evidence of genetic control of serum hormone levels.

Adult↗
PubMed1998

The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels.

Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.

Adenocarcinoma↗
PubMed1998

Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys.

Our hypothesis was that estrogen and progesterone modulate coronary artery reactivity in rhesus monkeys. Adult ovariectomized (ovx) monkeys were treated for 1, 2, or 4 wk with physiological concentrations of 17 beta-estradiol (E2), natural progesterone (P), and/or therapeutic levels of medroxyprogesterone acetate (MPA). Steroid concentrations in venous blood, coronary artery estrogen receptor (ER) and progesterone receptor (PR) localization, and isolated vascular muscle cell (VMC) Ca2+ and protein kinase C responses to serotonin and U46619 (a thromboxane A2 mimetic) were measured. Ovx monkey VMC responses were hyperreactive, showing prolonged increases in intracellular Ca2+ and protein kinase C that correlated with exaggerated in vivo coronary artery vasoconstrictor responses. The hyperreactive Ca2+ responses were abolished by in vivo treatment with E2 and/or P. However, VMC from ovx monkeys treated with the combination of E2 and MPA or E2, P, and MPA remained hyperreactive to vasoconstrictor stimuli, suggesting that MPA negated the protective effects of E2. ER were detected primarily in interstitial and endothelial cells and a minor fraction of the VMC. PR were localized to coronary artery VMC and interstitial cell nuclei. In vivo treatment of ovx monkeys with E2 tended to up-regulate PR in VMC, but MPA appeared to down-regulate PR expression. These results suggest that E2 and P replacement decreases coronary artery reactivity through direct interactions with ER and PR in coronary artery VMC.

Animals↗
PubMed1998

Rapid, convenient radioimmunoassay of estrone sulfate.

We developed a specific, simple, and rapid RIA for the direct quantification of estrone sulfate (E1S) and established its performance characteristics. The assay has a dynamic range of 0.05-90 micrograms/L with a detection limit of 0.009 microgram/L. Intraassay CVs were 9.2%, 4.5%, and 4.6% at 0.35, 9.0, and 60 micrograms/L, respectively. Interassay CVs were 8.8%, 5.1%, and 5.5% at 0.076, 0.5, and 12 micrograms/L, respectively. Linearity of dilution studies showed values of 80-105% of expected, and recovery of E1S added to serum samples ranged from 82% to 102%. Cross-reactivities with structurally related estrogens were < 5%. When compared with a conventional assay (involving hydrolysis of E1S and indirect measurement of estrone), the present RIA showed excellent correlation (r = 0.99, slope = 1.54, Sy/x = 2.14, n = 71). Mean E1S concentrations measured with this RIA for normal men (n = 20) and women in follicular (n = 20) and luteal (n = 25) phases of their menstrual cycle were 0.96, 0.96, and 1.74 microgram/L, respectively. Mean E1S concentrations for oral contraceptive users (n = 20) and postmenopausal women without hormone replacement therapy (n = 21) or on hormone replacement therapy (n = 22) were 0.74, 0.13, and 2.56 micrograms/L, respectively. Serum concentrations of E1S in pregnant women in their first (n = 14), second (n = 17), and third (n = 15) trimesters were 20, 66, and 105 micrograms/L, respectively. Availability of this simple RIA should provide a useful tool for the assessment of estrogen status in women.

Cross Reactions↗
PubMed1997

A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase.

Prostate cancer is the most common serious cancer diagnosed in men in the United States. This disease is also characterized by a striking racial/ethnic variation in incidence: highest in African-Americans, intermediate in Caucasians, slightly lower in Latinos, and lowest in Asians. Ample biochemical and epidemiological evidence suggests a role for androgens, particularly testosterone and dihydrotestosterone, in prostate cancer etiology. We have analyzed a candidate gene for prostate cancer, SRD5A2, encoding prostatic steroid 5alpha-reductase type II, which converts testosterone into the more bioactive dihydrotestosterone, for mutations. We report here one amino acid substitution, V89L, which replaces valine at codon 89 with leucine. This substitution is a "germline" (constitutional) DNA polymorphism, and it is common, panethnic, and reduces in vivo steroid 5alpha-reductase activity. This substitution is particularly common among Asians and may explain the low risk for prostate cancer in this population.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Androgen support of lacrimal gland function.

The effects of dihydrotestosterone (DHT) (1 mg/kg) on biochemical parameters related to lacrimal secretion, basal tear flow rate, and pilocarpine-stimulated lacrimal gland fluid secretion, in mature ovariectomized rabbits were studied. The effects of the synthetic estrogen diethylstilbestrol (DES) (100 micrograms/kg), on lacrimal gland biochemical parameters in normal mature female rabbits was also studied. Ovariectomy decreased the total serum levels of testosterone (T) by 88.5% and androstenedione by 35.9%, without changing the levels of dehydroepiandrosterone (DHEA) of its sulfate. Ovariectomy caused a significant regression of the lacrimal glands, decreasing total DNA by 35%, and total protein by 22%. DHT treatment of ovariectomized animals prevented lacrimal gland regression, increasing total gland DNA (31%) and total protein (18%). DHT treatment also increases Na+, K(+)-ATPase activity (29%) and beta-adrenergic receptor binding sites (23%) compared to the ovariectomized group. DHT increased pilocarpine stimulated lacrimal gland fluid secretion (13.26 +/- 1.47 microL/min) compared to the ovariectomized group (7.72 +/- 0.41 microL/min), but DHT treatment paradoxically decreased basal tear flow rate (1.02 +/- 0.04 microL/min) as compared to the ovariectomized rabbits (1.96 +/- 0.12 microL/min). DES decreased the total serum T from 59.33 +/- 10.54 pg/mL to 21.5 +/- 6.06 pg/mL. DES decreased total Na+,K(+)-ATPase by 12% and increased beta-adrenergic receptor binding sites by 83.3%. These results suggest that androgens play a major role in supporting lacrimal gland secretory function. Additionally, they suggest that estrogens may influence certain aspects of lacrimal functions, although it is not clear to what extent those actions are elicited directly or indirectly.

Acid Phosphatase↗
PubMed1997

Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein.

OBJECTIVE: To examine the independent effects on insulin sensitivity and antioxidative activity of the three most prevalent constituents in Premarin (Wyeth-Ayerst Laboratories, Philadelphia, PA): estrone sulfate (E1S), 50%; equilin sulfate (EqS), 25%, and 17 alpha-dihydroequilin sulfate (17 alpha-ES), 15%. DESIGN: Prospective randomized cross-over study. SETTING: University of Southern California Medical Center. PATIENT(S): Eight healthy postmenopausal women, mean age 53 +/- 2 years, and mean body mass index, 26 +/- 2 kg/m2, were enrolled. INTERVENTION(S): Each woman received, in randomized succession, daily oral doses of 17 alpha-ES (0.2 mg), E1S (0.625 mg), and EqS (0.3 mg) for 30 days. MAIN OUTCOME MEASURE(S): Oxidation of low-density lipoprotein (LDL) by negatively charged LDL (LDL-) and lag phase duration and measured the plasma glucose disappearance after insulin administration (K(itt)). RESULT(S): All three estrogen preparations demonstrated antioxidant effects with E1S demonstrating the most significant changes, followed by EqS and 17 alpha-ES. Using E1S, LDL-levels decreased from a baseline of 3.91 +/- 0.9 to 2.05 +/- 0.32 mg/dL and the lag time increased from 24.5 +/- 6.0 to 87.8 +/- 11.8 minutes. Changes in insulin tolerance tests revealed improved insulin action with the various estrogens. With EqS, K(itt) increased from 3.1% +/- 0.3% to 4.3% +/- 0.3% glucose/min, was intermediate with E1S and was least with 17 alpha-ES. CONCLUSION(S): All three conjugated equine estrogens demonstrated antioxidant activity. Also, some improved insulin action was demonstrated. To our knowledge, this is the first in vivo study to examine the effects of these components which may help explain, in part, some of the cardioprotective properties ascribed to Premarin.

Adult↗
PubMed1997

Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors.

OBJECTIVE: To establish levels of plasma endothelin-1 in postmenopausal women with increased CV risk as compared with healthy premenopausal women and to measure the effects of different forms of estrogen replacement on plasma endothelin-1. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENT(S): We studied 18 postmenopausal women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL divided into those with and without hypertension as well as in 10 healthy premenopausal women. INTERVENTION(S): The postmenopausal women were randomized to receive oral estrone sulfate, transdermal E2, or placebo for 30 days. MAIN OUTCOME MEASURE(S): We measured the endothelin-1 levels and total cholesterol at baseline and after 30 days of estrogen treatment. RESULT(S): In the postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women, endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate, 4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive women alone with estrogen therapy, plasma endothelin-1 showed the greatest decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in endothelin-1 with estrogen, which was statistically significant for the entire group, did appear to be influenced by the route of administration. Baseline plasma endothelin-1 levels were correlated positively to plasma cholesterol levels with a correlation coefficient of 0.632. CONCLUSION(S): These data provide another potential mechanism explaining the cardioprotective effects of hormone replacement therapy.

Administration, Cutaneous↗
PubMed1997

Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound.

Polycystic-appearing ovaries (PAO) on ultrasound have been described in a variety of endocrinopathies and also occur in ovulatory women. By some investigators this is merely referred to as 'PCO' (polycystic ovaries). Although there is controversy in this regard, we do not consider women with PAO/PCO who have no known endocrine disturbance to have polycystic ovary syndrome (PCOS) and therefore prefer not to use the term 'PCO' which is often equated with PCOS. We studied 15 ovulatory women with normal-appearing (NAO) ovaries on ultrasound and 15 matched ovulatory women with PAO/PCO. Compared to ovulatory women, 25 other women were studied who were considered to have PCOS. Of these, 15 were overweight and 10 were of normal weight. All the PCOS women had serum concentrations of luteinizing hormone (LH), testosterone, unbound testosterone, androstenedione and dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P < 0.01) than values in the normal women, regardless of ovarian morphology. These values were similar in the two groups of ovulatory women with NAO and PAO/PCO. Fasting insulin was elevated in women with PCOS with increased body weight (P < 0.01) and was higher than in ovulatory women with NAO and PAO/PCO and than in women of normal weight with PCOS. Serum insulin-like growth factor (IGF)-I and binding protein (BP)-3 were similar in all groups but serum IGFBP-1 was significantly (P < 0.01) lower in those women with PCOS with increased body weight, compared to all other groups. Compared to values in ovulatory women with NAO, serum IGFBP-1 was also significantly (P < 0.05) lower in women with PAO/PCO and those women with PCOS of normal weight. These lower values were similar in women with PAO/PCO and in normal weight women with PCOS. On an individual basis, an elevation of at least one serum androgen value was found in 33% of women with PAO/PCO. These data confirm that increased body weight accentuates the metabolic alterations in PCOS, but suggest that subtle endocrine disturbances, similar to those that are found in PCOS, may be uncovered in up to a third of ovulatory women with PAO/PCO. It appears that a disturbance of the IGF/IGFBP-1 axis is common and apparently closely associated with alterations in ovarian morphology.

Adult↗
PubMed1997

A pilot study of urinary estrogen metabolites (16alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer.

The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and 2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E1), 17beta-estradiol (E2) and estriol (E3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However, urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3 measured in urine.

Breast Neoplasms↗
PubMed1997

5 alpha-reductase activity and prostate cancer: a case-control study using stored sera.

We report a nested case-control study of serum biomarkers of 5 alpha-reductase activity and the incidence of prostate cancer. From a cohort of more than 125,000 members of the Kaiser Permanente Medical Care Program who underwent multiphasic health examinations during 1964-1971, we selected 106 incident prostate cancer cases. A control was pair matched to each case on age, date of serum sampling, and clinic location. Serum levels of total testosterone, free testosterone, androsterone glucuronide, and 5 alpha-androstane-3 alpha,17 beta androstanediol glucuronide (3 alpha-diol G) were measured on the stored samples and scored as quartiles. Potential confounders included alcohol, smoking, and body mass index. The adjusted odds ratios and 95% confidence intervals for a one quartile score increase were 1.00 (0.75-1.34) for total testosterone, 1.14 (0.86-1.50) for free testosterone, 1.13 (0.84-1.53) for androsterone glucuronide, and 1.16 (0.86-1.56) for 3 alpha-diol G. A limitation of this study is that there are two different 5 alpha-reductase isoenzymes, only one of which is expressed in high levels within the prostate, yet both of which may affect serum biomarkers. Since the two isoenzymes are encoded on different chromosomes, variation in one would act as an independent source of measurement error in any analysis of serum biomarker effects of the other. Consequently, the odds ratios may be underestimated and the study, although negative, cannot exclude the previously hypothesized possibility that a positive relationship between intraprostatic 5 alpha-reductase activity and prostate cancer may exist. A clinical trial to test this hypothesis is under way.

Aged↗
PubMed1997

Urinary progesterone and pregnanediol. Use for monitoring progesterone treatment.

OBJECTIVE: To compare progesterone (P) and pregnanediol glucuronide (PDG) levels in urine with respect to their potential use for monitoring luteal activity and P treatment. STUDY DESIGN: Two different experiments were carried out. In the first experiment, each of seven normal, ovulatory women collected first morning urines daily throughout an entire menstrual cycle. The day of ovulation was determined by transvaginal ultrasound scanning. P, PDG, estrone glucuronide, luteinizing hormone and creatinine were measured in each urine specimen. In the second experiment, each of three normal, ovulatory women was given a single oral dose of 200 mg of micronized P and, 2 days later, a single intramuscular injection of 25 mg of P during days 2-5 of the cycle. Blood and urine were collected prior to each treatment and 1, 4, 8, 12 and 24 hours after treatment. P was measured in both serum and urine; PDG was quantified only in urine. RESULTS: The mean initial rises and peak days, as well as the patterns of urinary excretion of P and PDG during the menstrual cycles, were similar; however, the variability of PDG was much greater. Concentrations of PDG were 1,000-4,000 times greater than those of P. A significant correlation was observed between urinary P and PDG. Following either intramuscular or oral P treatment, serum P levels rose rapidly and reached peak levels (7.0-11.8 ng/mL) by one hour. In contrast, both urinary P and PDG peaked considerably later (4-12 hours). Twenty-four hours after intramuscular treatment, serum and urinary P and urinary PDG were still elevated. Following oral treatment the levels of these compounds decreased after peaking and were 10- to 20- fold lower at 24 hours. Also, after oral P treatment, urinary PDG levels were considerably higher and more variable as compared to urinary P levels. CONCLUSION: Urinary P appears to be as good a clinical marker of luteal activity and therapeutic P administration as PDG and may be measured in place of this metabolite. There appears to be greater variability in urinary PDG as compared to urinary P when P is administered.

Adult↗
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

Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway.

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

Adult↗
PubMed1996

Biologic effects of 17 alpha-dihydroequilin sulfate.

OBJECTIVE: To determine the independent biologic effects of 17 alpha-dihydroequilin sulfate. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENTS(S): Twenty-one postmenopausal women, mean age 50 +/- 2 (+/-SEM) years, and mean body mass index 27 +/- 2. INTERVENTION(S): Women were randomized to receive daily oral doses of either 1.25 mg of estrone sulfate (E1S), 0.2 mg of 17 alpha-dihydroequilin sulfate, or a combination. Three blood and urine samples were obtained before and after 30 and 90 days of treatment. RESULT(S): After 30 and 90 days of treatment, E1S alone increased sex hormone-binding globulin (SHBG) levels significantly, 19.7% +/- 6.0% and 61.3% +/- 13.0%, whereas 17 alpha-dihydroequilin sulfate reduced SHBG levels, 20.8% +/- 68% and 12.4% +/- 7.5%, respectively. Nevertheless, the combination of E1S and 17 alpha-dihydroequilin sulfate significantly increased SHBG levels, 103% +/- 27.9% and 98.2% +/- 19.1%, compared with baseline at 30 and 90 days. Fewer changes were evident with corticosteroid-binding globulin (CBG). After 90 days of treatment, CBG levels significantly increased 30.9% +/- 5.5% with E1S, decreased by 7.2% +/- 5.0% with 17 alpha-dihydroequilin sulfate, and, with the combination, significantly increased by 10.5% +/- 2.4% compared with baseline. Changes in lipids and lipoproteins were more variable. However, high-density-lipoprotein cholesterol increased significantly with E1S at 30 and 90 days compared with baseline, 96.5% +/- 39% and 91.5% +/- 22.6%, and with the combination increased 66.4% +/- 13.3% and 79.2% +/- 24.4%, respectively. Fewer changes were evident with 17 alpha-dihydroequilin sulfate alone, decreasing 4.4% +/- 22% and 2.6% +/- 21.3%. Urinary ratios of bone collagen equivalents-creatinine and calcium-creatinine decreased in all three groups. However, the combination group resulted in a significantly greater percentage decrease in bone collagen equivalents-creatinine than with E1S alone. CONCLUSIONS(S): 17 alpha-Dihydroequilin sulfate could modify some of the first-pass effects of conjugated equine estrogens and act synergistically with other conjugated equine estrogens to reduce bone resorption.

Calcium↗
PubMed1996

Serum androgens and prostate cancer.

It is suspected that male hormones are associated with the risk of prostate cancer. To test this hypothesis, we conducted a nested case-control study in a cohort of 6860 Japanese-American men examined from 1971 to 1975. At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 141 tissue-confirmed incident cases of prostate cancer were identified, and their stored sera and those of 141 matched controls were assayed for total testosterone, free testosterone, dihydrotestosterone, 3-alpha-androstanediol glucuronide, androsterone glucuronide, and androstenedione. Odds ratios for prostate cancer, based on quartiles of serum hormone levels, were determined using conditional logistic regression methods. The odds ratios for the highest quartiles were 1.37 (95% confidence interval, 0.73-2.55) for 3-alpha-androstanediol glucuronide and 1.24 (95% confidence interval, 0.62-2.47) for androstenedione, but none of the differences was statistically significant. The results were unremarkable for the other four hormonal measurements. In addition, the patients and controls were compared by hormonal ratios (i.e., total testosterone:dihydrotestosterone), but the results were also unremarkable. The findings of this study indicate that none of these androgens is strongly associated with prostate cancer risk.

Aged↗