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Biomedical subjects

R Stege

Publications and source records attributed to R Stege.

At least 19 recordsLinked to original sources
PubMed1997

Transurethral microwave thermotherapy in symptomatic benign prostatic hyperplasia: a possible association between androgen status and treatment result?

BACKGROUND: Nothing is yet known of possible endocrine effects of transurethral microwave thermotherapy (TUMT) or of possible influence of endocrine status on the result of thermotherapy. METHODS: Serum levels of testosterone (T), SHBG, estradiol, LH, and PSH were measured in 48 men with BPH before and 2-3 months after TUMT (Prostatron, Prostasoft 2.0; Technomed International, Lyon, France). Assessment of results was based on the patients' own estimations. RESULTS: The treatment did not alter hormone levels. Patients who reported response after 12 months (n = 21) had significantly lower outset levels of calculated free testosterone (fT) than in the nonresponders (n = 27). In the patients aged < 70 years (n = 13), both the fT and T values were lower than in the nonresponders (n = 15). There was no age difference between responders and nonresponders. CONCLUSIONS: TUMT did not influence hormone levels. These observations suggest that androgen status may influence the final result of treatment.

Aged↗
PubMed1997

Possible bone-preserving capacity of high-dose intramuscular depot estrogen as compared to orchidectomy in the treatment of patients with prostatic carcinoma.

BACKGROUND: Treatment of prostatic disease with GnRH agonists or by orchidectomy affects bone mass negatively. Estrogen treatment has beneficial effects on bone mass in women and might hypothetically have a bone preserving capacity also in patients with prostatic cancer. METHODS: We followed serum markers for bone and collagen metabolism and sex steroids for 18 months in patients with prostatic cancer treated by orchidectomy (N = 13) or by single-drug parenteral polyestradiol phosphate (240 mg intramuscularly every second week for the first two months, and then every fourth week; N = 17). RESULTS: Total and free testosterone reached castration levels within 1.5 months of estrogen treatment. Four patients developing progressive disease and/or signs of metastasis were excluded from the analysis. In the remaining patients, serum osteocalcin, procollagen IIIP (PIIINP), procollagen (PICP), and the crosslinked carboxyterminal telopeptide of type I collagen (ICTP) increased significantly over time following orchidectomy (N = 11). Serum osteocalcin and PICP decreased significantly over time during estrogen treatment (N = 15). Treatment values of all four markers were significantly lower in estrogen-treated than in orchidectomized patients. CONCLUSIONS: The changes in serum bone and collagen markers indicate an increased bone turnover in orchidectomized subjects. The opposite pattern was found in the estrogen-treated patients, indicating a reduced turnover. Estrogens may also have a bone mass-preserving capacity in elderly males with prostatic cancer.

Aged↗
PubMed1997

Use of a hormone-sensitive (LNCaP) and a hormone-resistant (LNCaP-r) cell line in prostate cancer research.

BACKGROUND: In order to develop a hormone-resistant analog to the hormone sensitive cell-line LNCaP, different methods were tried. METHODS: After almost one year of continuous culture in RPMI-1640, containing a low concentration of androgens, the hormone sensitive cell-line LNCaP became hormone resistant and was named LNCaP-r. RESULTS: We used the LNCaP/LNCaP-r model system in order to study methods for the parenteral treatment of prostate carcinoma with estrogens, to study the mechanism of action of estramustine, and to identify markers useful as predictive tests for prostate carcinoma. CONCLUSIONS: A model system made up of the hormone sensitive prostate LNCaP cell-line and the hormone resistant LNCaP-r subline was developed and characterized. This system is, despite a number of limitations, easy to use as a first step to test different hypotheses that can be studied further in later clinical trials.

Androgens↗
PubMed1997

Testicular and adrenocortical function in men with prostatic cancer and in healthy age-matched controls.

OBJECTIVE: To compare the endocrine status of patients with prostate cancer with that of age-matched healthy controls. PATIENTS, SUBJECTS AND METHODS: Basal serum concentrations of sex steroids, sex hormone-binding globulin (SHBG) and gonadotrophins, and the basal levels and response to adreno-corticotropic hormone (ACTH) of adrenocortical steroids, were measured before treatment in 72 patients with prostate cancer and in 42 age-matched healthy controls. RESULTS: Patients aged < 60 years with prostate cancer had significantly elevated levels of total testosterone and unconjugated (E1) and total (tE1) oestrone while patients aged > or = 60 years had significantly elevated levels of total and non-SHBG-bound testosterone (NST). 17 alpha-hydroxyprogesterone and tE1. Gonadotrophins, SHBG levels and relationships between total testosterone and SHBG were normal in both age groups of patients, as were basal levels and ACTH-induced increments of adrenocortical steroids. The patients had normal age-related variations in SHBG and NST and in basal levels and ACTH-induced increments of adrenocortical steroids. There was a significant age-related increase in serum E1 in the control subjects but not in the patients. Patients with metastatic disease had significantly lower tE1 levels than had patients without metastases. CONCLUSIONS: The results suggest an increased sensitivity of the testis to gonadotrophic stimulation, as well as an increased peripheral oestrogen synthesis in patients with prostate cancer, the latter being most pronounced in younger subjects. Men developing prostate cancer may have been exposed to a combination of elevated endogenous oestrogen and androgen levels for a long time. These findings support the theory of a synergism between oestrogens and androgens as an important factor in the aetiology of prostate cancer.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Pharmacokinetics and testosterone suppression of a single dose of polyestradiol phosphate (Estradurin) in prostatic cancer patients.

The pharmacokinetics and endocrine effects of polyestradiol phosphate (PEP; Estradurin) were studied by determination of the concentrations of estradiol (E2), unconjugated (E1) and total estrone (tE1; > or = 85% estrone sulfate), and testosterone in serum from 11 prostatic cancer patients after administration of a single intramuscular injection (320 mg). After injection of PEP, serum concentrations of E2, E1, and tE1 increased during 2-3 weeks. Thereafter serum E2 declined monophasically with a mean half-life of 70 days. The elimination of E1 and tE1 seemed to be governed by the formation of E2. The testosterone concentration decreased inversely to the raising E2 level and reached castration levels within 3 weeks and remained at this level for about 2 weeks, whereafter it increased inversely to the decreasing E2 concentrations.

Aged↗
PubMed1996

Profound decrease of in vivo formation of thromboxane during oestrogen therapy.

Oestrogen has been proposed to influence platelet activity and formation of the vasoactive eicosanoids thromboxane and prostacyclin. Previous studies have been based on ex vivo techniques with well-known artifacts during blood sampling and ex vivo conditions. The present study is the first to assess in vivo formation through gas chromatographic/mass spectrometric analysis of the major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha. Ten consecutive male patients with prostatic carcinoma participating in a randomized study comparing the effects of parenteral oestrogen therapy (n = 5) with orchidectomy (n = 5) were included. Oestrogen was given as polyestradiol phosphate 240 mg i.m. every month, 2,3-dinor thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha were analysed with the help of tetradeuterated internal carriers/standards. We found a consistent decrease of in vivo formation of thromboxane by approximately 40% during parenteral oestrogen therapy (P = 0.008) and a doubling after surgical castration. The ratio of prostacyclin to thromboxane increased by approximately 50% (P = 0.023) during oestrogen therapy. In conclusion, oestrogen induced a marked decrease of in vivo formation of thromboxane and a marked increase in the ratio of prostacyclin to thromboxane formation in all patients. According to current knowledge this should be beneficial for the cardiovascular system. Furthermore, thromboxane formation increased after surgical castration. The latter fact should direct attention to the influence of androgens on thromboxane synthesis. Our findings discloses a marked sex-hormone sensitivity of the thromboxane-forming system.

Aged↗
PubMed1996

Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males.

When given orally, estrogens, as well as androgens, lower serum lipoprotein (a)[Lp(a)]levels. To determine whether these effects occur also after parenteral administration of steroids, Lp(a) levels were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with parenteral estrogen (n = 8) or orchidectomy (n = 6). One group of healthy male volunteers (n = 9) was studied after parenteral administration of testosterone. Estrogen was given as im polyestradiol phosphate, 240 mg twice monthly, and testosterone was given as im injections, 250 mg/week. In the orchidectomized subjects, Lp(a) levels increased by 20% by month 3 after treatment (P < 0.05). In spite of drastic changes in serum hormone levels, no change in Lp(a) levels was observed in the estrogen-treated subjects. Concomitantly, low-density lipoprotein cholesterol levels were lowered by 15% and high-density lipoprotein cholesterol levels increased by 20%. Testosterone administration lowered Lp(a) levels by 20% (P < 0.05). No significant changes in serum lipid levels were observed in the testosterone-treated subjects or in the orchidectomy group. Thus, during parenteral administration of estrogens or androgens, diverging effects on Lp(a) and serum lipoproteins were observed. In particular, the mode of administration of estrogen influenced the response in Lp(a) levels. This suggests that the regulatory role of sex hormones on serum Lp(a) levels may depend on their capability to influence hepatic metabolic pathways of Lp(a).

Adult↗
PubMed1995

Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens.

Bone mineral density (BMD) and bone mineral content (BMC) were measured in the femoral neck area, trochanteric area and Wards triangle, and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer. Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens. The patients were free from metastases during the entire observation period. In the orchidectomized patients, BMD and BMC of the distal radius decreased significantly following treatment, whereas no changes were observed in the estrogen-treated patients. These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients.

Aged↗
PubMed1995

[Intramuscular depot estrogens (Estradurin) in treatment of patients with prostate carcinoma. Historical aspects, mechanism of action, results and current clinical status].

More than 50 years ago, orally given estrogen was already used in the treatment of prostate cancer. Due to cardiovascular side-effects with a high morbidity of 25%, this treatment has not become standard. Recent investigations show that parenteral application reduces the risk of cardiovascular side-effects, because it avoids the first passage through the liver with high concentrations of estrogen which normally occur after oral application. Therefore, an increased synthesis of so-called "steroid-sensitive" liver proteins, such as coagulation factors (especially factor VII) can be avoided. This newer parenteral estrogen application shows encouraging results of a cheap and effective hormonal therapy with a low rate of side-effects in patients with prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed1993

[Endocrine treatment of prostatic cancer. A renaissance for parenteral estrogen].

The standard treatment for advanced cases of cancer of the prostate is castration. Oestrogens, administered per os may have serious side effects, in particular thrombosis and cardiovascular complications. If the oestrogens are administered parenterally, changes in liver function can be avoided and risk of side effects markedly reduced. 38 patients have been treated at Huddinge Hospital in Stockholm, and 14 patients at Aker Hospital in Oslo, with polyoestradiol phosphate (Estradurin) 240 mg injected intramuscularly every 4th week (initial dose 320 mg). We can sum up our own experience as follows: Plasma testosterone is reduced to castration level after 2-3 weeks. Liver function, evaluated by the sexual hormone binding globulin level in plasma, remains unchanged. Morbidity and mortality from cancer are the same as may be achieved by surgical orchidectomy. The only side effect of significance is gynaecomastia. Follow-up of the patients does not indicate any increased risk of thrombosis or cardiovascular disease. The treatment is fairly cheap compared with other alternative methods of endocrine treatment.

Estradiol↗
PubMed1993

Neoadjuvant GnRH-agonist treatment (triptorelin and cyproterone acetate for flare protection) and total prostatectomy.

The effects of 3 months treatment with the GnRH agonist triptorelin as a neoadjuvant to total prostatectomy in 40 men with localized prostatic cancer have been evaluated. The study included 1 patient with a stage T1b tumour, 25 patients with stage T2 tumours and 14 with stage T3 tumours. The patients were examined by digital rectal examination, transrectal ultrasound before and after treatment. Serum testosterone and prostate-specific antigen (PSA) levels were followed. The totally removed prostate gland was step-sectioned at 5-mm intervals and the whole-mount sections were assessed for tumour pathology stage (pT stage). Triptorelin treatment resulted in a significant decrease in total gland and tumour volume and in a reduction in the serum levels of PSA and testosterone. In comparison with the findings from a previous study, in which neoadjuvant treatment was not used, it appears that the proportion of tumours invading the margins of the surgical specimen decreased.

Adenocarcinoma↗
PubMed1992

[A study on prostatic cancer. The patient can decide himself: medical or surgical treatment].

In a multicentre study, 101 consecutive patients with advanced prostate cancer were offered the choice of orchiectomy or treatment with an LHRH analogue. Together with the cancer diagnosis the patients were given verbal information about the treatment alternatives, and detailed written information to peruse at home. One week later the patients informed the attending physicians of their choice. Information as to the reasons for the patients' choice, and their views on their choice after the start of treatment were elicited by questionnaire. Of the 101 patients, 48 chose orchiectomy, and 48 treatment with an LHRH analogue, five patients being excluded owing to their inability to decide. Mean age was about 73 years in both treatment groups, and about two thirds of each group lived with a partner. The level of education was higher among those who chose medical treatment. The predominant reasons for the choice of treatment were as follows: Orchiectomy, simpler (31 per cent), troublesome having to have monthly injections (19 per cent), simple to perform (15 per cent); medical treatment, possibility of change in treatment (27 per cent), simpler (17 per cent), fear of surgery (15 per cent). Most patients in both groups had no difficulty deciding, chose quickly, felt sure about their choice, appreciated the opportunity of choosing, and had discussed their choice with their partners or intimates. Three months after the start of treatment, almost all patients were still satisfied with their choice, and had no wish to change their choice even if that were possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Testicular and adrenocortical function in healthy men and in men with benign prostatic hyperplasia.

The influence of aging upon serum concentrations of testicular steroids, sex hormone binding globulin (SHBG) and pituitary hormones and on adrenal steroid levels and adrenal steroid response to ACTH was studied in 81 healthy men aged 20-87 years. These endocrine variables were also compared in 43 patients with benign prostatic hyperplasia (BPH), aged 58-89 years and in a subgroup of 41 men, aged 58-87 years, from the above mentioned reference population. The normal endocrine aging was characterized by a rise in SHBG levels, decreasing levels of testicular steroids and non-SHBG-bound testosterone (NST) and increasing gonadotropin levels and decreasing concentrations of total estrone. Adrenal androgen levels decreased in the presence of unchanged levels of cortisol and the adrenal steroid response to ACTH changed by decreasing increments in dehydroepiandrosterone (DHA) and increasing increments in 17 alpha-hydroxyprogesterone (17OHP). With the exception of the alterations in SHBG and adrenal androgens, all these changes were finished before the seventh decade of life. BPH patients had elevated levels of testosterone and NST in the presence of normal SHBG and gonadotropin levels, elevated levels of DHA and DHA sulfate (DHAS) in the presence of normal cortisol levels, a "younger" pattern of adrenal steroid response to ACTH as judged from the increments in DHA and 17OHP, elevated ratios between estrone and 4-androstene-3,17-dione suggesting an increased peripheral aromatization and subnormal prolactin levels. BPH patients may be considered as "endocrinologically younger" than healthy subjects. DHA and especially its proximate metabolite 5-androstene-3 beta, 17 beta-diol exert powerful estrogenic effects on the receptor level. Thus the elevated levels of DHA and DHAS in the BPH patients may create an hyperestrogenic condition in addition to the slight hyperandrogenicity caused by the elevated NST levels. Both endocrine aberrations may play a role in the etiology of BPH, in accordance with the dual sex steroid sensitivity of the periurethral glands.

Adrenal Cortex↗
PubMed1992

Quantitative estimation of tissue prostate specific antigen, deoxyribonucleic acid ploidy and cytological grade in fine needle aspiration biopsies for prognosis of hormonally treated prostatic carcinoma.

The prognostic value of deoxyribonucleic acid (DNA) flow cytometry, cytological grading and the direct assay of prostate specific antigen (PSA) in the material of fine needle aspirates was studied in 67 consecutive patients with newly detected prostatic carcinoma. All patients were hormonally treated (castration in 27 and luteinizing hormone-releasing hormone agonist or parenteral estrogens in 40). The patients were followed for a minimum of 2 years. PSA was analyzed in the biopsy material by a direct radioimmunoassay and related to the total amount of DNA. In parallel biopsies DNA ploidy using flow cytometry and cytological grade were established. Patients with a geometric mean value of greater than or equal to 0.12 microgram. PSA/microgram. DNA had a progression rate of 7%, compared to 59% for those with less than 0.12 microgram. PSA/microgram. DNA. In Cox multivariate analysis cytology and tissue PSA content were the most important factors in expressing the difference for interval to progression in hormonally treated patients.

Antigens, Neoplasm↗
PubMed1991

Effects of orchidectomy and different modes of high dose estrogen treatment on circulating "free" and total 1,25-dihydroxyvitamin D in patients with prostatic cancer.

Serum levels of total 1,25-dihydroxyvitamin D (1,25(OH)2D), vitamin D binding protein (DBP), sex hormone binding globulin (SHBG), testosterone, estradiol 17 beta (E2) and the "free" 1,25(OH)2D index were measured before and during treatment in prostatic cancer patients treated by orchidectomy (n = 15), with combined i.m. polyestradiol phosphate (PEP) + oral ethinyl estradiol (EE) (n = 10) and with i.m. PEP only for 3 months, followed by addition of oral EE (n = 9). Total concentrations of 1,25(OH)2D and DBP were unaffected by orchidectomy and treatment with i.m. PEP only, but were significantly elevated during treatment including oral EE. SHBG levels were unaffected by orchidectomy, slightly increased by i.m. PEP only and greatly increased by oral EE. The free 1,25(OH)2D index was slightly elevated by treatment including oral EE. Evidence was obtained that the increase in 1,25(OH)2D levels observed during oral estrogen treatment was secondary to the estrogen-augmented increase in DBP and not a result of an estrogen-stimulated synthesis of 1,25(OH)2D. Furthermore, the stimulatory effect of estrogen on DBP concentrations seemed to be dependent on the route of administration of the hormone.

Aged↗
PubMed1991

Cost comparison of parenteral estrogen and conventional hormonal treatment in patients with prostatic cancer.

The present study compares the cost of antitumor therapy and adverse cardiovascular effects during the first year of treatment with oral estrogens, nonoral estrogens, or surgical castration in patients with prostatic cancer. We found a much higher cost for patients treated with orchidectomy and oral estrogens than for patients treated with nonoral estrogens. Twenty-five percent of the patients treated with oral estrogen suffered cardiovascular complications, compared to none of the patients treated by orchidectomy or nonoral estrogens. The initial cost of orchidectomy as compared to nonoral estrogen treatment was shown not be balanced within the expected survival time of patients with advanced prostatic cancer. Furthermore, surgical castration causes psychological trauma to the patient. We recommend parenteral estrogen therapy as a low-cost therapeutic regimen in patients with prostatic cancer.

Administration, Oral↗