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Biomedical subjects

P Henriksson

Publications and source records attributed to P Henriksson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma.

To characterize the effects of estrogen treatment on the metabolism of LDL we studied six males with metastatic prostatic carcinoma before and during the initiation of therapy; a repeated study was performed in five participants after 3-6 mo of treatment. The fractional catabolic rate (FCR) of autologous 125I-LDL was calculated both from elimination curves of plasma radioactivity and from urine/plasma (U/P) radioactivity ratios. Within 1-2 d of onset of estrogen therapy a more rapid decay of plasma radioactivity occurred, and FCR measured from U/P ratios increased by 20%. Concomitantly, LDL cholesterol levels decreased by 16%. After 3-6 mo of treatment FCR determined by both techniques was almost doubled, and LDL cholesterol was reduced by 34%. This occurred despite a 29% increase in the calculated synthesis rate of LDL. Tissue culture studies demonstrated that the receptor affinity of LDL isolated from patients on long-term estrogen therapy was reduced. We conclude that a profound increase in LDL catabolism is induced through administration of pharmacological doses of estrogen in males, and hypothesize that this is the consequence of an increased expression of hepatic LDL receptors. This enhanced catabolism of LDL leaves LDL particles in plasma with lower affinity for the LDL receptor.

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PubMed1989

Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma.

To assess if and by which mechanisms pharmacological estrogen treatment induces gallstone disease, we examined patients with recently diagnosed prostatic cancer randomly allocated to estrogen therapy (n = 37) or orchidectomy (n = 35). According to gallbladder ultrasonography, after 1 yr new gallstones had developed in 5 of 28 estrogen-treated patients, compared with 0 of 26 orchidectomized patients (P = 0.03). Estrogen therapy for 3 mo increased the relative concentration of cholesterol and cholesterol saturation of bile by approximately 30% (n = 10). Serum LDL cholesterol was reduced by approximately 40%, and its relative change related inversely to that of bile cholesterol (Rs = -0.77). There were no changes in biliary or serum lipids after orchidectomy (n = 9). Secretion rates of biliary lipids were measured with a duodenal perfusion technique. Patients on chronic estrogen therapy (n = 5) had approximately 40% higher biliary excretion rates of cholesterol than age-matched controls (n = 7). Phospholipid secretion was also higher, but no difference in bile acid secretion was found. We conclude that an increased hepatic secretion of cholesterol results in increased cholesterol saturation of bile and an enhanced rate of gallstone formation during estrogen treatment. The changes in bile cholesterol seem to be related to the induced changes in serum lipoprotein metabolism.

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PubMed1988

Effects of intermittent treatment with aspirin on thromboxane and prostacyclin formation in patients with acute myocardial infarction.

Thromboxane and prostacyclin formation were monitored in twenty patients with acute myocardial infarction. Ten received 500 mg acetylsalicylic acid (ASA) orally starting 12 h after admission and then intermittently every third day for one month; the other ten did not receive ASA or any other drug known to interfere with the synthesis of prostanoids. In the ASA group thromboxane formation, initially raised, fell rapidly and remained low. In the control group thromboxane formation decreased very slowly and was not normal by the end of the study period. Prostacyclin formation seemed identical in the two groups. Thus intermittent ASA, in this dosage, efficiently inhibited the enhanced thromboxane formation in acute myocardial infarction without interfering with prostacyclin formation.

Administration, Oral↗
PubMed1988

Cardiovascular follow-up of patients with prostatic cancer treated with single-drug polyestradiol phosphate.

Thirty-eight patients with cancer of the prostate were treated with strict parenteral estrogen in the form of monthly polyestradiol phosphate injections--160 mg, 240 mg, and 320 mg--in this nonrandomized study. In contrast to studies with oral estrogens, there have been no cardiovascular complications at a mean follow-up of 12.9 +/- 0.7 months (SEM). Twenty-nine of the 38 patients (76%) have responded to therapy.

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PubMed1988

Improved working capacity following theophylline infusion in patients with ischaemic heart disease.

The effect of theophylline on the working capacity of patients with ischaemic heart disease was evaluated in a double-blind, randomized cross-over study. Eight patients, receiving no medication, with stable effort-provoked angina pectoris and typical exercise-induced ST depressions were studied. Following intravenous administration of theophylline or placebo, the patients did a supine leg exercise limited by intolerable chest pain. The workload was continuously increased by 10 W/min. Following theophylline treatment the workload at the onset of chest pain increased from 71 +/- 9 to 114 +/- 14 W (P less than 0.002). The ST depression was less pronounced following theophylline at submaximal exercise (-0.01 +/- 0.00 vs. -0.09 +/- 0.02 mV, P less than 0.005, at 70 W). The maximum tolerable workload increased from 129 +/- 15 after placebo infusion to 153 +/- 12 W after theophylline infusion P less than 0.01). It is speculated that this beneficial effect of the adenosine receptor antagonist theophylline may possibly be due to inhibition of a pathophysiological coronary steal induced by elevated levels of adenosine during ischaemia.

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PubMed1988

Single drug polyestradiol phosphate therapy in prostatic cancer.

Serum concentrations of testosterone (T) and estradiol-17 beta (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 micrograms 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.

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PubMed1987

Increased aortic thromboxane production in experimental atherosclerosis.

It is of great importance to clarify the role of thromboxane and prostacyclin in the process of atherosclerosis. In order to study this we induced atherosclerosis in rabbits through cholesterol feeding (1% w/w) for three to 12 weeks. After sacrifice the aorta was quickly removed and incubated. The in vitro thromboxane production measured as immunoreactive thromboxane B2 increased by 86 per cent in atherosclerotic vessels compared to control vessels (p less than 0.0005). The in vitro production of prostacyclin measured as immunoreactive 6-keto-prostaglandin F1 alpha showed a tendency to higher values in the atherosclerotic vessels compared to the control vessels (31%, p less than 0.025). This suggests that an increased thromboxane production rather than a decreased prostacyclin production might be important for the progression of atherosclerosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Cost-effectiveness comparison of estrogen therapy and orchidectomy in patients with prostatic cancer.

This study compares the cost of antitumor therapy and adverse cardiovascular effects during the first year of treatment with either exogenous estrogens or orchidectomy of patients with prostatic cancer. We found that the higher costs for the orchidectomy patients were partially outweighed by the costs of treating cardiovascular complications in the estrogen-treated patients; the net overcost of orchidectomy is balanced after two and a half years by the ongoing costs of estrogen treatment. The fact that 25% of the patients treated with estrogen suffered cardiovascular complications, but no difference in mortality rates between the two groups was observed, speaks in favor of orchidectomy as the preferred treatment for prostatic carcinoma.

Cost-Benefit Analysis↗
PubMed1987

Deleterious effects of low-dose oestrogen therapy on coronary status in patients with prostatic cancer.

The effects of oestrogen therapy and of orchidectomy on coronary status, as reflected by exercise ECG-testing before and after one year of treatment, were assessed in a randomized study of patients (N = 100) with prostatic cancer. Oestrogen was given as polyestradiol phosphate 80 mg i.m. per month in combination with 150 micrograms ethinylestradiol p.o. per day. There were no significant inter-group differences in conventional risk factors or in pre-treatment exercise test results. Twelve months after the start of therapy the oestrogen group showed a significantly greater depression of the ST-segment during maximal exercise in leads CH2 (P less than 0.0005) and CH5 (P less than 0.01) compared with the pre-treatment depression. Twenty-five per cent (N = 13) of the patients in the oestrogen group suffered cardiovascular complications during the year of therapy, whereas no such complications were observed in the orchidectomy group. However, even the patients in the oestrogen group who had not suffered cardiovascular complications had significantly greater depressions of the ST-segment during exercise both in lead CH2 (P less than 0.0005) and in CH5 (P less than 0.05). There was no significant change in the ST-segment level in the orchidectomy group twelve months after surgery. In summary, we found evidence of an induction of myocardial ischaemia during treatment with exogenous oestrogens at low dosage in patients with prostatic cancer. This deleterious effect of oestrogen on the coronary status argues against oestrogen therapy, since oestrogen has not been shown to be more beneficial than orchidectomy against prostatic carcinoma.

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PubMed1987

Prediction of cardiovascular complications in patients with prostatic cancer treated with estrogen.

The authors made a randomized prospective study of estrogen therapy versus orchidectomy in patients with prostatic cancer (n = 100, Huddinge Hospital, Sweden) to investigate the possibility of predicting cardiovascular events during hormonal treatment. Patients with preexisting cardiovascular morbidity were excluded (16%). Prior to the allocation of therapy, the following were performed: exercise stress test; physiologic evaluation of the peripheral circulation; blood volume estimation; chest x-ray; blood tests, including hormones, lipoproteins, and antithrombin III; and a physical examination and history by a cardiologist. Thirteen (25%) of the patients given estrogen therapy (n = 53) had cardiovascular complications during the first year of treatment compared with none in the orchidectomy group. The authors made a multivariate discriminant analysis of the pretreatment examinations of the estrogen-treated patients; this resulted in a discriminant function including S-T segment depression in lead CH2 during the exercise stress test and blood tests for cholesterol, follicle-stimulating hormone, and luteinizing hormone. This function correctly classified 84% of the estrogen-treated patients as patients with or without risk of a cardiovascular complication. Briefly stated, if patients with prostatic cancer are examined by means of exercise stress tests and blood tests for luteinizing hormone, cholesterol, and follicle-stimulating hormone prior to treatment, the discriminant function enables the authors to identify an extremely high-risk group for cardiovascular complications if estrogen therapy is commenced. The strong association of an increased luteinizing hormone with cardiovascular complications during estrogen treatment makes it mandatory to investigate its role in the pathogenesis of atherosclerosis and cardiovascular events.

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PubMed1987

Orchidectomy or oestrogen treatment in prostatic cancer: effects on serum levels of adrenal androgens and related steroids.

Peripheral serum levels of dehydroepiandrosterone (DHA) and its sulphate (DHAS), 4-androstene-3, 17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and albumin were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Orchidectomy caused a pronounced decrease in 17-OHP levels and minor but significant decreases in the levels of A-4 and DHAS. Dehydroepiandrosterone, cortisol and albumin were unaffected by treatment. Oestrogen treatment caused a pronounced decrease in the serum levels of DHA, DHAS, 17-OHP and A-4 and a small but significant decrease in serum albumin. Cortisol levels increased, probably due to elevated transcortin levels. The ratio of DHA to DHAS was unaffected by either orchidectomy or by oestrogen treatment. These results confirm that the testis contributes to circulating DHAS. The mechanism behind the more pronounced decrease in adrenal androgens during oestrogen treatment is not known but, for DHAS, increased metabolic clearance due to the decrease in albumin levels may contribute in this respect. The unchanged values for the ratio of DHA to DHAS indicate that this sex-specific sulphatase/sulphotransferase balance is insensitive to endocrine manipulations in adult men. The results further invalidate the hypothesis that there is a 'compensatory' increase in adrenal androgen output following orchidectomy.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Serum prolactin assays have no prognostic value in treatment of prostatic cancer by orchidectomy or estrogens.

Eighty patients (54-75 years) with cytologically and/or histologically confirmed cancer of the prostate (CAP) were randomly allocated to either orchidectomy (ORX, n = 41) or combined intramuscular and oral estrogen treatment (ESTR, n = 39). Serum levels of prolactin (PRL) were determined prior to treatment and 6, 12 and 24 months after initiation of the treatment. In the ORX group, 32 patients responded to the treatment and 9 did not. In the ESTR group, 27 patients responded and 12 did not. Serum PRL levels were significantly increased by ESTR treatment in responders as well as in nonresponders, but were not affected by ORX. There were no differences in PRL values between responders and nonresponders at any time in any of the two treatment groups. It is concluded that serum PRL assays have no prognostic value in the employed endocrine treatment of CAP.

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PubMed1986

Activators and inhibitors of coagulation and fibrinolysis in patients with prostatic cancer treated with oestrogen or orchidectomy.

The treatment of prostatic cancer with oestrogen has been reported to be associated with cardiovascular side effects. Twenty patients with recently diagnosed prostatic cancer were randomly allocated to oestrogen therapy or orchidectomy. As compared to healthy age matched controls the patients with prostatic cancer had increased base-line levels of fibrinogen (5.2 +/- 1.9 g/l versus 3.7 +/- 1.0 g/l; p less than 0.002) and factor VIII:C (166 +/- 62% versus 110 +/- 29%; p less than 0.001). During oestrogen therapy factor VII increased from 99 +/- 22% to 150 +/- 47% (p less than 0.001), while the antithrombin III level fell from 93 +/- 10% to 81 +/- 13% (p less than 0.001). Both these changes are in the direction of a hypercoaguable state. Concomitantly plasminogen increased from 113 +/- 14% to 142 +/- 18% (p less than 0.001), urokinase inhibiting activity fell from 105 +/- 10% to 90 +/- 9% (p less than 0.001) and C1-esterase inhibitor fell from 110 +/- 17% to 86 +/- 22% (p less than 0.05) in the oestrogen therapy group. After orchidectomy there were no changes in the activators and inhibitors of coagulation and fibrinolysis studied as compared to base-line values. Furthermore the D dimer, a specific degradation product of crosslinked fibrin increased from a normal to a pathological value in 4 out of 8 tested patients after 6 weeks of oestrogen therapy, but in none out of 9 tested patients in the orchidectomy group. Briefly stated, patients with prostatic cancer treated with oestrogen have increased levels of factor VII, factor VIII:C and fibrinogen and a decreased level of antithrombin III.(ABSTRACT TRUNCATED AT 250 WORDS)

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