[Parenteral estrogen--a safe therapeutic alternative in prostatic cancer seen from the cardiovascular point of view?].
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Aged↗
Biomedical subjects
K Carlström
Publications and source records attributed to K Carlström.
[Sex hormone binding globulin--a new dimension of androgenic diagnostics].
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Androgens↗
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↗
The effect of essential fatty acid deficiency on hepatic bile salt sulphotransferase in rats.
Hepatic bile salt sulphotransferase (BSS) activity and the contents of unconjugated oestradiol-17 beta (E2) and conjugated oestrone (cE1) in liver tissue was significantly lower in young essential fatty acid (EFA) deficient female rats than in female control rats. No corresponding differences were found between male EFA deficient and control rats. A significant sex difference, with higher values in females, was found for BSS activity and E2 and cE1 contents in control rats but not in EFA deficient rats. The decrease in hepatic BSS activity in female rats caused by EFA deficiency may be mediated via a decreased estrogenic action on the liver.
Animals↗
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↗
Effects of a diet regimen on pituitary and steroid hormones in male ice hockey players.
Serum concentrations of androgens, cortisol, androgen binding proteins, pituitary hormones, together with anthropometric variables and sports performance were studied in two different elite male ice hockey teams. One of the teams (DIF, n = 22) participated in a special dietary program including reduction in fat from approximately 40 per cent of total energy intake (E%) to less than 30 E% and an increase in carbohydrate intake from 45 E% to about 55 E%, while the other (SSK, n = 21) served as a control group and had no special dietary program. The study covered a 7-month period. Basal values of serum testosterone, sex hormone binding globulin (SHBG), non-SHBG-bound testosterone (NST), cortisol, dehydroepiandrosterone sulfate (DHAS) and LH did not differ between the two teams. Serum concentrations of testosterone, SHBG, NST and cortisol increased significantly during the study period in the DIF group and were, with the exception of SHBG, significantly higher than in the SSK group at the end of the study (33.0 vs 26.8 nmol/l, p less than 0.05; 22.5 vs 18.3 nmol/l, p less than 0.05; and 548 vs 464 nmol/l, p less than 0.01). The ratio between NST and cortisol which was used as an index of anabolic/catabolic steroid balance did not change in either group during the study. A significant decrease in the serum concentrations of LH during the observation period was found in the SSK group. The endocrine differences between the teams may be explained by a relative negative energy balance in DIF, together with a reduced fat and increased carbohydrate intake.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Androstenedione as a predictor of ovarian hyperstimulation syndrome.
Serum concentrations of testosterone, 4-androstene-3,17-dione (androstenedione), dehydroepiandrosterone (DHA) and its sulphate and sex hormone-binding globulin (SHBG) were measured in 30 ovulatory women before and after down-regulation with gonadotrophin releasing-hormone analogue, prior to ovarian stimulation in a programme of in-vitro fertilization and embryo transfer. Nine of the women developed ovarian hyperstimulation syndrome (OHSS) while the others did not. Pretreatment values of androstenedione and the androstenedione:DHA ratios were higher and the testosterone:androstenedione ratios lower in the OHSS women. The decrease in androstenedione levels during down-regulation was greater and the absolute levels following down-regulation were lower in the OHSS group. Higher levels of SHBG and lower testosterone:SHBG ratios, an index of biologically active testosterone, were observed in the OHSS group. The isolated elevation in pretreatment androstenedione levels and the high SHBG levels make the OHSS group different from patients with polycystic ovarian disease. Pretreatment values of testosterone:androstenedione or testosterone/SHBG:androstenedione ratios and/or the decrease in androstenedione during down-regulation may be used as markers, prior to stimulation, for identifying women at risk of developing OHSS.
Adult↗
Serum steroids and prolactin during and after major surgical trauma.
Serum levels of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17-alfa-hydroxy-progesterone (17 OHP), testosterone (T, only in males), unconjugated (E1) and total estrone (tE1 greater than 85% estrone sulfate) were studied in six male and two female patients before, during and up to 30 days after aortic graft surgery. All steroids except 17 OHP decreased following induction of anesthesia but, except for testosterone, rose again during surgery to preoperative levels or slightly above. Extremely high peak values for E1 and tE1 and a less pronounced peak for cortisol were noted on postoperative day 2; after that, the levels of these steroids returned to normal. The levels of 17-OHP, DHA and DHAS decreased after surgery and were below preoperative values from postoperative day 4 to day 16 or (DHAS) day 30. In males, 17 OHP showed a pronounced peak 30 min after initiation of surgery, but decreased after that to below preoperative values. Testosterone levels decreased further during surgery and remained very low until postoperative day 16. Major surgical trauma has a rapid, profound and long-lasting effect on gonadal activity, as judged from decreased testosterone levels, while the effect on adrenal steroids is less pronounced. Adrenal delta 4 and delta 5-steroids showed different patterns in the postoperative period, indicating differences in their regulation. The highly elevated estrogen levels on postoperative day 2 probably reflect either transiently elevated peripheral aromatization or decreased estrogen metabolism rather than increased levels of substrate steroids (A-4). The biological significance of this remains to be elucidated.
17-alpha-Hydroxyprogesterone↗
Effect of predilatation of the uterine cervix by laminaria tent on activity of the placenta.
Serum concentrations of hCG were determined in blood samples taken 18-20 h and immediately before vacuum aspiration in 45 women in gestational weeks 7-9, admitted for legal abortion. In 35 of the women, a laminaria tent was inserted for cervical dilatation immediately after the first blood sampling. Serum hCG values decreased significantly in the women pretreated with laminaria tent, but were unchanged in the untreated women. This finding may indicate that pretreatment with a laminaria tent induces a partial placental detachment.
Abortion, Legal↗
Effect of cortisol on the secretion of testosterone and estradiol-17 beta by human granulosa-luteal cell cultures. A model system for analyzing hormonal alterations in female athletes.
The combination of hypercortisolism and usually low androgen and estrogen levels is frequently observed in female long distance athletes. In order to find a useful model system for studying the underlying mechanisms, the following studies were performed. The effect of cortisol on the secretion of testosterone (T) and estradiol-17 beta (E2) by human granulosa-luteal cells was studied in vitro in cultures of cells recovered from mature follicles of gonadotrophin stimulated women (participating in the IVF program). Following 24 hours of culture in tissue culture medium without hormonal additives, the granulosa-luteal cells were incubated for 6 hours in media with addition of 4-androstene-3,17-dione (A-4) as precursor and hMG and cortisol in different combinations. The secretion of T was significantly stimulated by cortisol but not by human menopausal gonadotrophin (hMG). Cortisol, but not hMG, also increased the secretion of E2, although this effect was not statistically significant. These in vitro findings make a direct effect of cortisol upon ovarian sex steroid secretion less likely as the mechanism behind the subnormal sex steroid levels in female long distance athletes. Instead, inadequate gonadotrophic stimulation, related to hypothalamic amenorrhea, and/or a selective decrease in the adrenal secretion of precursor steroids, may be an explanation.
Estradiol↗
Detection of testosterone administration by increased ratio between serum concentrations of testosterone and 17 alpha-hydroxyprogesterone.
An increased ratio between urinary testosterone (T) and epitestosterone (epiT) has been accepted by the International Olympic Committee as a marker for T doping. However, in a few subjects, we and others have observed constantly above-normal urinary T/epiT ratios that are unlikely to be related to exogenous T administration. To find a better test for T doping, we studied several serum and urinary androgens and androgen precursors, estrogens, and luteinizing hormone (LH) in seven healthy volunteers for 35 days after an intramuscular injection of 250 mg of testosterone enanthate. Among urinary analyses, only the T/epiT ratio was a suitable marker of T doping; of the serum assays, 17 alpha-hydroxyprogesterone (17OHP), T/17OHP ratio, LH, and T/LH ratio were fair to good markers of T doping. The serum T/17OHP ratio was the best marker of those tested, with all seven subjects having above-normal values for this in the first 3 days of the observation period. No other marker showed abnormal values in all subjects at any time. Moreover, the T/17OHP ratio was affected by neither diurnal variation nor physical stress. The value of this marker for T doping was further supported by the finding of normal T/17OHP ratios in a subject with increased urinary T/epiT ratios caused by an abnormally low testicular epiT production, probably related to genetic factors.
17-alpha-Hydroxyprogesterone↗
Atrial natriuretic peptide concentrations and hemodynamic effects of acute plasma volume expansion in normal pregnancy and preeclampsia.
Plasma atrial natriuretic peptide (ANP) and circulatory responses were studied during rapid plasma volume expansion with crystalloid solutions. Sixteen women with preeclampsia and 16 healthy controls in the third trimester were compared. Basal mean (+/- standard error of the mean) ANP levels were not significantly higher in the preeclamptics than in controls (13.6 +/- 3.5 versus 6.4 +/- 1.1 pmol/L; not significant), but the increment following volume expansion was more pronounced (12.9 +/- 2.6 versus 6.1 +/- 2.3 pmol/L; P less than .05). The mean plasma volume expansion was less in the preeclamptic group (6.1 +/- 0.8 versus 9.3 +/- 1.1%; P less than .05), reflecting a higher capillary permeability in this disease. Left ventricular posterior-wall thickness in diastole was increased in the preeclamptics under basal conditions as compared with the controls (9.8 +/- 0.3 versus 8.9 +/- 0.3 mm; P less than .05), as was the thickness of the interventricular septum in systole (14.3 +/- 0.5 versus 12.3 +/- 0.6 mm; P less than .05). Systemic vascular resistance was higher in the preeclamptic group (19.7 +/- 0.8 versus 15.1 +/- 1.1 peripheral resistance units; P less than .01). In the controls, cardiac output increased by 23 +/- 4% and systemic vascular resistance decreased by 17 +/- 3%. The preeclamptic women reacted in a similar way. Our results indicate that preeclampsia is associated with an enhanced ANP response despite a less pronounced increase in plasma volume during acute fluid challenge.
Adult↗
Formation of novel C21-bile acids from cholesterol in the rat. Structure identification of the major Di- and trihydroxylated species.
We recently showed that previously unknown di- and trihydroxylated C21-bile acids are major degradation products of sitosterol and campesterol in bile-fistulated female Wistar rats. Using a mixture of 4-14C- and 22-3H-labeled cholesterol it was shown that such C21-bile acids are formed also from cholesterol in amounts up to about 25% of the total formation of bile acids. The C21-bile acids were formed from labeled cholesterol also in perfused rat liver, demonstrating that the liver is the site of synthesis. The major trihydroxylated C21-bile acids in bile were identified, by means of mass spectrometry, NMR, stereospecific dehydrogenases, and reagents, as 5 beta-pregnan-3 alpha, 11 beta, 15 beta-triol-21-oic acid and 5 beta-pregnan-3 alpha, 11 beta, 15 alpha-triol-21-oic acid. The corresponding 11-oxo-isomers were also present. A minor trihydroxylated C21-bile acid was identified as 5 beta-pregnan-3 alpha, 11 beta, 16-triol-21-oic acid. The major dihydroxylated C21-bile acid was identified by the same means as 5 alpha-pregnan-3 alpha, 12 alpha-diol-21-oic acid. Male rats converted 4-14C-cholesterol into C21-bile acids less efficiently than did female rats. None of the C21-bile acids from male rats contained a 15-hydroxyl group. It is speculated that the novel C21-bile acids are formed both from cholesterol and from plant sterols by an initial hydroxylation at C21 followed by peroxisomal or mitochondrial beta-oxidation. The presence of a hydroxyl group at C15 may facilitate this reaction. The above formation of C21-bile acids shows that mammalian liver is able to degrade the side chain of cholesterol beyond the C24 stage, even in the absence of a blocking group at C24. C21-bile acids, or one of their precursors, are hydroxylated in the liver by a hitherto unknown 11 beta-hydroxylase. The possible physiological importance of the C21-bile acids is discussed.
Animals↗
Cortisol and androgen concentrations in female and male elite endurance athletes in relation to physical activity.
To evaluate the effect of variations in physical activity on selected hormone concentrations in male versus female athletes, fasting serum concentrations of cortisol (C), total-testosterone, free-testosterone, non sex hormone binding globulin (SHBG) bound testosterone, dehydroepiandrosterone, 4-androstene-3,17-dione and SHBG were studied. The tests were performed in nine male and seven female elite endurance athletes during the off-season (test 1), early in the competition season (test 2) and at the end of the competition season (test 3). The C concentration increased significantly during the competition season in women but not in men. Further, the mean C concentrations at test 3 as well as the mean level during the whole observation period (tests 1, 2, 3) were significantly higher in women than in men. No significant changes were found in androgen concentrations or androgen:cortisol ratios within the two groups. The differences between the sexes in C response may indicate different adaptive mechanisms to similar physical stress.
Adult↗
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↗
Sex hormone-binding globulin, oestradiol-17 beta, progesterone and testosterone at stimulation and after embryo transfer during in-vitro fertilization.
Serum concentrations of sex hormone-binding globulin (SHBG), oestradiol-17 beta progesterone and testosterone were measured in 23 gonadotrophin-stimulated menstrual cycles and in the implantation period [days 11-19 after human chorionic gonadotrophin (HCG) injection] following in-vitro fertilization and embryo transfer. Nine cycles resulted in successful pregnancies, one pregnancy ended in spontaneous abortion (week 14) and 13 cycles were without conception. SHBG levels were significantly elevated above pretreatment values from day 3 after HCG injection onwards. A significant positive correlation was found between increments in SHBG (delta SHBG) during the luteal phase and oestradiol/testosterone ratios during the follicular and luteal phases. In the pregnant cycles a significant positive correlation was also found between delta SHBG during the implantation period and oestradiol/testosterone ratios during the luteal phase and the implantation period. Significant negative correlations were found between delta SHBG and testosterone during the luteal phase in pregnant and non-pregnant women as well as between delta SHBG during the period corresponding to implantation and testosterone during the luteal phase in non-pregnant cycles. The results may reflect a modulating action of the oestrogen/androgen balance upon SHBG levels in subjects with supraphysiological oestradiol levels, such as in stimulated cycles and in very early pregnancy.
Adult↗
Evaluation of the possible interaction of the antifungal triazole SCH 39304 with oral contraceptives in normal healthy women.
The possible interaction of the newly developed triazole antifungal SCH 39304 with low-dose combined oral contraceptives (OCs) was studied in 15 healthy women. Serum levels of ovarian and adrenocortical steroids and sex hormone-binding globulin (SHBG) were analyzed in samples collected during the OC cycles immediately before, during and after the administration of SCH 39304. The drug was given as a single 400-mg oral dose on day 7 in the second cycle. SCH 39304 did not interfere with the ovulatory inhibitory action of low-dose combined OCs as judged from serum progesterone values. Administration of SCH 39304 caused minor decreases in serum SHBG, cortisol and dehydroepiandrosterone sulfate. The mechanism(s) behind these minor changes is not known.
Adult↗
Relationship between serum testosterone and sex hormone binding globulin in menstruating and postmenopausal women.
The relationship between total testosterone (T), sex hormone binding globulin (SHBG) and calculated non-SHBG-bound testosterone (NST) was studied in randomly collected blood samples from healthy menstruating (n = 61) and postmenopausal (n = 65) women. In 12 of the menstruating women, blood samples were also collected more frequently during the menstrual cycle. Total T and SHBG were positively correlated in menstruating women in random samples as well as during different phases of the menstrual cycle, but not in postmenopausal women. Upper and lower limits of NST were independent of SHBG in menstruating but not in postmenopausal women. The data are at variance with the common concept about SHBG regulation and suggest a kind of compensatory mechanism in order to maintain a constant androgen homeostasis in menstruating but not in postmenopausal women. Consequently, supranormal total T or subnormal SHBG values do not necessarily indicate hyperandrogenicity in normally menstruating women.
Adult↗