Reinhard Stege

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.

Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex

Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20-87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20-84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.

HYPOCHOLESTEROLAEMIA AND INCREASED ELIMINATION OF LOW-DENSITY LIPOPROTEINS IN METASTATIC CANCER OF THE PROSTATE

To study the influence of tumour mass on lipid metabolism, the lipoprotein pattern in untreated patients with newly diagnosed cancer of the prostate was examined. Total cholesterol levels were reduced in patients with evidence of metastasis (n = 30) compared with those without metastasis (n = 73). Since the major fraction of serum cholesterol is contained in low-density lipoproteins (LDL), turnover of LDL was studied in detail in 8 patients compared with 12 age-matched healthy men. LDL were cleared faster in the 3 patients with metastatic disease than in the patients without metastasis and in controls, indicating faster catabolism of LDL. Thus in prostatic cancer an increased tumour burden is associated with increased elimination of LDL, which contributes to reduced serum cholesterol levels.

Potential side-effects of endocrine treatment of long duration in prostate cancer

Endocrine treatment of prostate cancer has been established for more than 5 decades. Focusing on immediate or short‐term side effects, bilateral orchidectomy may cause psychological trauma, treatment with oral estrogens is combined with a high risk of severe cardiovascular complications, and the use of LH‐RH agonists and antiandrogens as monotherapies or in combination may result in tumor flare, hot flashes, and gynecomastia. In recent years an increasing number of reports on anemia and/or osteoporosis related to endocrine treatment have been published. These side effects are regular and persistant after orchidectomy, or during treatment with LH‐RH agonists, and are most often expressed with maximum androgen blockade. In contrast, anemia and/or osteoporosis are not reported with estrogen treatment or the use of nonsteroidal antiandrogens as a monotherapy regimen. Since many prostate cancer patients are treated hormonally for many years, control of Hb levels and bone mineral density before and after initiation of treatment at regular intervals is highly recommended as a standard of care. Prostate Supplement 10:38–42, 2000.

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

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.

Deoxyribonucleic Acid Ploidy and the Direct Assay of Prostatic Acid Phosphatase and Prostate Specific Antigen in Fine Needle Aspiration Biopsies as Diagnostic Methods in Prostatic Carcinoma

We used fine needle biopsies from prostatic tumors at routine examinations in 133 patients. Cytological grading was performed with a scoring system. Cellular prostatic acid phosphatase and cellular prostate specific antigen from the aspirates were quantitated. Deoxyribonucleic acid flow cytometry was performed and the tumors were subdivided into diploid, tetraploid and aneuploid groups. Tumor staging was assessed by digital examination. A decrease in the biochemical markers was significantly correlated with the increase in malignancy grade, tumor stage and a shift from diploid to aneuploid tumors. Cellular prostatic acid phosphatase and cellular prostate specific antigen as well as tumor ploidy may contribute to the objective determination of the malignancy potential of the prostatic carcinoma.

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.

Tissue PSA from fine‐needle biopsies of prostatic carcinoma as related to serum PSA, clinical stage, cytological grade, and DNA ploidy

The mechanisms behind changes in serum PSA (S‐PSA) levels in patients with prostatic carcinoma (CAP) are not completely known. To further elucidate the factors affecting the serum levels of this important tumor marker, we measured PSA concentrations in serum and in aspiration biopsies (tissue PSA; T‐PSA) from patients with prostatic disease and correlated the values to tumor stage, cytological grade, and DNA ploidy.

Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen.

The present pilot study tested the clinical performance of a new pharmacokinetically guided dosing regimen of parenteral estrogen in patients with advanced prostatic carcinoma. The aim was to accelerate endocrine effects and to avoid cardiovascular side effects.

Single drug polyestradiol phosphate therapy in prostatic cancer.

Serum concentrations of testosterone (T) and estradiol-17β (E2) were analyzed in prostatic cancer patients treated with 160, 240, or 320 mg polyestradiol phosphate (PEP) i.m. every fourth week as single drug therapy during a 6 month period. Estrogen effects on the liver were studied by analyzing serum levels of sex hormone binding globulin (SHBG) in the 320 mg group and compared with values obtained in patients treated with 80 mg PEP i.m. every fourth week + oral ethinylestradiol (EE2) 150 μg daily, or by orchidectomy. Orchidectomy levels of T were reached within 3 weeks in the 320 and 3 months in the 240 mg group. In the 160 mg group, mean T levels reached the upper limit of orchidectomy values after 6 months. Accumulation of E2 occurred to mean levels 1.300–2,500 pmol/L at 6 months. At 6 months, SHBG levels had increased to 617% of pretreatment values in the oral EE2 group, to 166% in the 320 mg group, and were unaffected by orchidectomy. No cardiovascular side effects occurred during single-drug PEP treatment.