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J Geller

Publications and source records attributed to J Geller.

At least 19 recordsLinked to original sources
PubMed1992

The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.

BACKGROUND: Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS: In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS: As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

5-alpha Reductase Inhibitors↗
PubMed1992

Nonsurgical treatment of prostatic hyperplasia.

BACKGROUND: Epidemiologic studies in castrates strongly support the key role of the testis in the pathogenesis of benign prostatic hyperplasia (BPH). Since the testis secretes both androgen and estrogen, both of these hormones have been implicated in BPH. Many data support the important role of dihydrotestosterone (DHT) in BPH. It is now possible to quantify prostate size and function with reliable new techniques and to utilize androgen withdrawal studies to test the validity of the DHT theory. METHODS: A variety of androgen-blocking drugs have been demonstrated to decrease prostate size by approximately 30% by either blocking secretion of circulating testosterone and adrenal androgen, inhibiting 5 alpha-reductase to prevent DHT formation, or blocking DHT binding to androgen receptors. RESULTS: Accompanying these changes in size have been significant improvement in clinical symptoms of prostatism in approximately 50% of patients when double-blind, large multicenter studies were conducted with one of these drugs. Although these results suggest a very important role for androgen, particularly dihydrotestosterone, in the pathogenesis of BPH, other abnormalities besides those of androgen metabolism may coexist since significant numbers of patients do not show a total reversal of disease. There is strong indirect evidence for a possible role for estrogen in the pathogenesis of BPH and studies are under way to test the effects of estrogen withdrawal on prostate size and symptoms. Similarly, dynamic aspects of prostatic obstruction, which are under alpha adrenergic regulation, may also be a component of this disease and amenable to therapy with alpha-adrenergic blockers. CONCLUSIONS: Therefore it would seem that BPH may be multifactorial and require combined therapy. Androgen would certainly appear to be necessary, but perhaps not sufficient, for the pathogenesis of this disorder.

5-alpha Reductase Inhibitors↗
PubMed1992

Castration-like effects on the human prostate of a 5 alpha-reductase inhibitor, finasteride.

Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BPH) and prostate cancer. 5 alpha-Reductase deficiency in humans, an experiment of nature, is an uncommon genetically transmitted disorder in which prostate size remains very small throughout adult life. A 5 alpha-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trials in patients with BPH to statistically decrease prostate size and improve clinical symptoms in comparison to placebo controls. In the untreated BPH prostate, tissue levels of dihydrotestosterone (DHT) and testosterone (T) averaged 4.2 and 0.2 ng/g, respectively. Following one week of finasteride therapy, T levels rose to a mean of 1.32 ng/g while DHT levels decreased to 0.62 ng/g. These values contrast with values in prostate tissue from surgical castrates in which DHT and T values average 1.14 ng/g and 0.1 ng/g, respectively. If we use the relative binding affinity of T and DHT to the androgen receptor as a criterion of biological androgen potency, T would appear to be one-fourth as potent as DHT. Using this 1:4 ratio to convert prostatic T to a biologically equivalent amount of prostatic DHT, the total biologically active DHT equivalent in the prostate following one week of finasteride averages 0.95 ng/g compared to a mean of 1.14 ng/g in surgical castrates.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1992

Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture.

We have adopted an in vitro three-dimensional histoculture technique for assay of androgen sensitivity in explants of human benign prostatic tissue. The assay is based on the uptake of 3H-thymidine/micrograms protein in explants of prostate incubated in parallel with dihydrotestosterone (DHT) and hydroxyflutamide (HF) controls. The ratio of 3H-thymidine/micrograms protein in DHT treated samples per 3H-thymidine/micrograms protein in HF treated samples provides an index of androgen sensitivity. The DHT/HF index measured in 24 BPH specimens averaged 3.6. To determine the specificity of the HF effect, we measured the DHT/HF index in a single prostate at different concentrations of HF in the presence of fixed concentrations of DHT (2 x 10(-8) M) and noted a dose-response relationship. In addition we noted no effects of HF on 3H-thymidine incorporation over a range of 2 x 10(-4)M compared to 2 x 10(-7)M, except at the highest concentration. Of surprise was the finding of an average DHT/HF index in 5 different nonprostate tissues, including breast, uterus, colon, kidney, and thyroid, that was similar to the index found in prostates. We plan to adapt this androgen sensitivity assay to measure the DHT/HF index in biopsy-size samples of prostate, since such an assay could then be utilized to determine androgen sensitivity in individual patients with prostate cancer.

Androgen Antagonists↗
PubMed1992

Inadequate adrenergic response to disopyramide-induced hypoglycemia.

OBJECTIVE: To report a case of disopyramide-induced hypoglycemia and to discuss the observed inadequate adrenergic response in this patient. Risk factors, possible etiologies, and preventive measures are also discussed. DATA SOURCES: References from case reports and review articles as identified by MEDLINE. DATA SYNTHESIS: A wide variety of drugs has been implicated as causing hypoglycemia. The mechanism for drug-induced hypoglycemia is known for the majority of these agents. Case reports of disopyramide-induced hypoglycemia have been reported in the literature, but the mechanism of action is unclear. We report a case of disopyramide-induced hypoglycemia in which counter-regulatory hormones, serum insulin, and C-peptide concentrations were obtained. From these data, it appears that disopyramide-induced hypoglycemia results from endogenous insulin secretion, with concomitant inadequate counterregulatory response. CONCLUSIONS: Although a rare occurrence, disopyramide-induced hypoglycemia is potentially life-threatening. Patients at risk for this reaction need to be identified prior to the institution of disopyramide therapy. Patients at risk for hypoglycemia should be monitored while on disopyramide and disopyramide blood concentrations should be maintained at the lower end of the therapeutic range, or alternative agents should be considered.

Aged↗
PubMed1992

Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia.

The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate. In the placebo group the mean concentration of prostatic dihydrotestosterone was 10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7 +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride, prostatic dihydrotestosterone declined to 15% or less of control levels, and the testosterone concentration increased in a reciprocal fashion. Compared to the placebo group, there was no significant difference in the mean prostatic dihydrotestosterone level achieved in any of the finasteride-treated groups. However, prostatic dihydrotestosterone levels were lower in the groups receiving higher doses of the drug. In two additional patients, finasteride treatment for 2 days also caused a decrease in prostatic dihydrotestosterone levels. No significant adverse experiences occurred during the study. We conclude that finasteride causes profound decrease in prostatic dihydrotestosterone.

5-alpha Reductase Inhibitors↗
PubMed1991

The influence of lactose consumption on the association of oral contraceptive use and ovarian cancer risk.

The authors investigated the joint effects of diet and oral contraceptive use on ovarian cancer risk in 194 white women aged 65 years or less with epithelial ovarian cancer and 193 age- and residence-matched controls in Boston between 1984 and 1987 by using in-person interviews and self-administered food frequency questionnaires. Use of oral contraceptives for 3 months or more was associated with a modest protective effect for ovarian cancer (odds ratio (OR) = 0.7, 95 percent confidence interval (CI) 0.5-1.1). In women who consumed 11 g or less per day of lactose, use of oral contraceptives for 3 months or more was associated with a nonsignificant increased risk (OR = 1.6, 95 percent CI 0.8-3.2). In women who consumed more than 11 g per day of lactose, use of oral contraceptives for 3 months or more was associated with a substantially decreased risk of ovarian cancer (OR = 0.3, 95 percent CI 0.1-0.7). Within this group, the strongest association occurred with more than 4 years of total oral contraceptive use (OR = 0.2, 95 percent CI 0.1-0.6) and in those who had more than 2 years of oral contraceptive use after age 30 years (OR = 0.1, 95 percent CI 0.03-0.4). These results suggest that, with respect to ovarian cancer, lactose users may be the most likely to benefit from oral contraceptive use and that the benefit may be strongest when oral contraceptive use occurs after age 30 years.

Adult↗
PubMed1991

Benign prostatic hyperplasia: pathogenesis and medical therapy.

Epidemiologic studies in castrates strongly support the key role of the testis in the pathogenesis of benign prostatic hyperplasia (BPH). Since the testis secretes androgen and estrogen, both of these hormones have been implicated in BPH. Much information supports the important role of dihydrotestosterone (DHT) in BPH, including intraprostatic activities of enzymes that regulate DHT. Although controversy still exists, DHT levels in BPH may be higher than in normal prostate tissue. Based upon these findings and the ability to quantitate prostate size and function with reliable new techniques, suppression of androgen-mediated action has been tested to assess the validity of the DHT theory. A variety of drugs has been demonstrated to decrease prostate size by approximately 30% by either blocking secretion of circulating testosterone and adrenal androgen, inhibiting 5 alpha-reductase to prevent DHT formation, or blocking DHT binding to androgen receptors. Accompanying these changes in size was significant improvement in clinical symptoms of prostatism in about 50% of patients, when double-blind, large multicenter studies were conducted with one of these drugs. Although these results suggest a very important role for androgen, particularly DHT, in the pathogenesis of BPH, other abnormalities may coexist since significant numbers of patients do not show a total reversal of disease. There is strong indirect evidence for a possible role for estrogen in the pathogenesis of BPH, and studies are under way to test the effects of estrogen withdrawal on prostate size and symptoms. Similarly, dynamic aspects of prostatic obstruction, which are under alpha-adrenergic regulation, may also be a component of this disease and amenable to therapy with alpha-adrenergic blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Stigmatizing labels.

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Attitude of Health Personnel↗
PubMed1990

Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen.

Whole tissue dihydrotestosterone (DHT) and testosterone (T) concentrations have been measured after finasteride, a 5 alpha-reductase inhibitor, and this was compared to other methods of androgen inhibition. In 10 patients treated for 1 week with finasteride, whole tissue DHT decreased to a mean of 0.302 ng/g. This value was significantly less than DHT values in control patients (mean, 4.5 ng/g) and patients treated with either surgical castration (mean, 1.14 ng/g), megestrol (160 mg/day) plus diethylstilbestrol (0.1 mg), or megestrol plus ketoconazole (1200 mg/day; mean, 0.609). Tissue T levels were significantly increased in finasteride-treated patients (1.18 ng/g) compared to a mean of 0.171 ng/g in controls and 0.105 ng/g in megestrol-treated patients. Part of the prostate tissue obtained at surgery was mechanically separated into epithelium and stroma. The epithelial cells were homogenized, the supernate was assayed for prostate-specific antigen (PSA), an androgen-dependent protein, and the pellet was assayed for DHT and DNA. Epithelial cell PSA and DHT values significantly decreased in finasteride- and megestrol- plus estrogen-treated patients compared to controls. However, the slope and position of the regression lines for DHT vs. PSA in patients treated with megestrol plus low dose estrogen (r = 0.79) differed significantly (P less than 0.05) from the regression line relating epithelial DHT to PSA in patients treated with finasteride (r = 0.82). Since the regression slope for finasteride described a greater increase in PSA per unit change in DHT compared to the slope for megestrol plus estrogen, which lowers both DHT and T, finasteride, despite its drastic lowering of DHT, may have a modest residual androgenic effect related to its effect on tissue T.

5-alpha Reductase Inhibitors↗
PubMed1990

The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects.

Chromium has been implicated as a cofactor in the maintenance of normal lipid and carbohydrate metabolism. A deficiency of chromium results from diets low in biologically available chromium. Picolinic acid, a metabolite of tryptophan, forms stable complexes with transitional metal ions, which results in an improved bioavailability of the metal ion chromium. To determine whether or not chromium picolinate is effective in humans, 28 volunteer subjects were given either chromium tripicolinate (3.8 micromol [200 micrograms] chromium) or a placebo daily for 42 days in a double-blind crossover study. A 14-day period off capsules was used between treatments. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, the principal protein of the LDL fraction, decreased significantly while the subjects were ingesting chromium picolinate. The concentration of apolipoprotein A-I, the principal protein of the high-density lipoprotein (HDL) fraction, increased substantially during treatment with chromium picolinate. The HDL-cholesterol level was elevated slightly but not significantly during ingestion of chromium picolinate. Only apolipoprotein B, of the variables measured, was altered significantly during supplementation with the placebo. These observations show that chromium picolinate is efficacious in lowering blood lipids in humans.

Adult↗
PubMed1989

Comparison of dihydrotestosterone levels in prostatic cancer metastases and primary prostate cancer.

Dihydrotestosterone (DHT) concentration, a marker for biochemical differentiation and possible clonal origin of prostate tumors, was measured in cancer present in lymph nodes (LN) from patients with untreated metastatic prostate cancer and compared to levels in untreated primary prostate cancer. The mean DHT of 2.23 ng/g in LN (S.E. = 0.28, N = 22) was significantly less (P less than .001) than the mean DHT of 4.8 ng/g in primary cancer (S.E. = 0.52, N = 20). Since primary prostate cancer may be admixed with stromal tissue, while lymph node represents pure epithelial cell tumor, we chose for this comparison only the 20 prostate cancer tissues that were judged by our pathologist to contain 90% or more epithelial cell tumor. Using this selection criteria, we found that prostate stroma, which has an average DHT concentration 1.18 times higher than prostate epithelia, would have an insignificant effect on primary prostate tumor DHT concentration. These data suggest that the decreased DHT in prostate tumor cells present in LN metastases may be a marker for a clone of cells with metastatic potential. These findings are consistent with previous reports from this laboratory indicating that DHT concentration less than 2.4 ng/g in primary prostate cancer is a predictor of a reduced disease-free interval following androgen blockade in advanced prostate cancer.

Dihydrotestosterone↗