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F Callies

Publications and source records attributed to F Callies.

13 recordsLinked to original sources
PubMed2003

Testosterone undecanoate: a useful tool for testosterone administration in rats.

A major obstacle of testosterone (T) treatment in experimental animals is the difficulty of maintaining long-term physiologic/anabolic steady serum levels after exogenous T administration. In two complementary studies we investigated the pharmacokinetic properties of different T formulations in male rats. Study I. Mature male Wistar rats (> 380 g, n = 4 - 7/group) were divided into four treatment groups: (1) sham-operated non orchiectomised (non-ORX) and placebo; (2) orchiectomised (ORX) and subcutaneous testosterone pellets (TP) (15, 25, 75 mg/60 days release or placebo pellets); (3) ORX and a single injection of testosterone undecanoate (TUD) (31, 62.5 or 125 mg/kg body weight subcutaneously (s.c.) or vehicle; (4) ORX and testosterone propionate (Tprop) (10, 20, 40 mg/month) or vehicle as a single injection s.c. Serum T was measured at baseline and in weekly intervals for 4 weeks. Study II. Mature male Wistar rats (180 - 200 g) were randomly assigned to one of 5 experimental groups (n = 5 - 6/group): (1) normal untreated rats (controls); (2) ORX untreated rats, and non-ORX rats receiving one of three treatment options; (3) 250 mg/kg body weight TUD i.m. (TUD 250); (4) 500 mg/kg body weight TUD i.m. (TUD 500); (5) 100-mg testosterone pellet/90 days release s.c. (TP 100). Serum T was measured at baseline and in intervals for 6 weeks after T administration. In both studies, the kinetic profile of TUD showed favourable continuous steady state levels over several weeks. In contrast, testosterone release by subcutaneous pellets resulted in a shorter than expected duration of elevated serum T levels with high inter-individual variability. Tprop administration led to only a short-lasting serum T increase with low serum T levels already 14 days after injection. In conclusion, a single injection of TUD (100 mg/kg body weight s.c.) is effective in inducing physiological testosterone levels in ORX rats for a minimum of four weeks. High dose TUD (500 mg/kg body weight i.m.) given as a single injection results in supraphysiological anabolic testosterone concentrations for up to six weeks in non-ORX rats. TUD was superior to other T release preparations and represents a convenient and effective tool for T administration in experimental animals.

Anabolic Agents↗
PubMed2001

Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion.

Serum dehydroepiandrosterone declines with age. Whether this represents a harmful deficiency or an age-related adaptation is not known. Dehydroepiandrosterone replacement in adrenal insufficiency, a state of pathological loss of dehydroepiandrosterone production, improves well-being, mood, and sexuality. To determine the effects of dehydroepiandrosterone in healthy men with a physiological, age-related decline in serum dehydroepiandrosterone sulfate, we conducted a double blind cross-over study in 22 healthy male volunteers (age range, 50-69 yr) with endogenous dehydroepiandrosterone sulfate levels below 4.1 micromol/liter (1500 ng/ml) receiving 4 months of dehydroepiandrosterone (50 mg/d) and 4 months of placebo treatment in random order, with a 1-month washout period. Dehydroepiandrosterone treatment increased serum dehydroepiandrosterone and dehydroepiandrosterone sulfate to concentrations usually found in young men. Circulating androgen levels did not change; however, androgen metabolites increased, indicating enhanced peripheral androgen synthesis. At baseline, psychometric assessment revealed normal well-being and sexuality scores. After 4 months of dehydroepiandrosterone, no effect on sexuality was observed, whereas some mood scores improved slightly, but were not significantly different from scores after placebo. Compared with placebo, dehydroepiandrosterone had no effect on serum lipids, bone markers, body composition, or exercise capacity. Thus, in contrast to previous findings in adrenal insufficiency, we found no obvious benefit of 4 months of dehydroepiandrosterone supplementation in healthy men with a physiological decline of dehydroepiandrosterone production.

Affect↗
PubMed2001

Dehydroepiandrosterone replacement in women with adrenal insufficiency: effects on body composition, serum leptin, bone turnover, and exercise capacity.

Studies in animals and humans using supraphysiological doses of dehydroepiandrosterone (DHEA) reported significant changes in body composition and carbohydrate metabolism. To investigate the metabolic action of a physiological DHEA replacement dose, we studied 24 women with adrenal insufficiency (AI; mean +/- SD age, 42.3 +/- 9.3 yr; duration of disease, 9.2 +/- 8.4 yr; body mass index, 23.4 +/- 4.0 kg/m(2)) in a double blind, placebo-controlled, randomized, cross-over design. They received 50 mg DHEA/day and placebo orally for 4 months each, with a 1 -month washout period. Measurements included fasting serum glucose, insulin, leptin, bone markers, anthropometric parameters determined by bioimpedance analysis, and exercise capacity as assessed by an incremental cycling test. DHEA did not induce any change in body mass index (placebo vs. DHEA, 23.3 +/- 4.1 vs. 23.2 +/- 3.9 kg/m(2); P = 0.39), parameters of body composition, or exercise capacity. However, compared with placebo, DHEA replacement led to a significant decrease in serum leptin (absolute change after 4 months, DHEA vs. placebo, -5.3 +/- 8.0 vs. 1.1 +/- 5.7 ng/mL; P = 0.01). This is most likely the result of the DHEA-induced normalization of circulating androgens. DHEA had no effect on fasting glucose, insulin, or the glucose/insulin ratio. Compared with placebo, serum osteocalcin increased slightly, but significantly, during DHEA treatment (absolute change after 4 months DHEA vs. placebo, +1.6 +/- 5.3 vs. -1.2 +/- 6.2 ng/mL; P = 0.02). However, urinary cross-links excretion did not change. In conclusion, replacement of DHEA in a physiological dose in patients with pathological DHEA deficiency does not have a significant effect on carbohydrate metabolism, body composition, or exercise capacity. The biological relevance of the changes in leptin and osteocalcin levels remains to be determined.

Adrenal Insufficiency↗
PubMed2000

Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females.

Oral dehydroepiandrosterone (DHEA) replacement therapy may have a multitude of potential beneficial effects and exerts its action mainly via peripheral bioconversion to androgens (and estrogens). A daily dose of 50-mg DHEA has been shown by us and others to restore low endogenous serum DHEA concentrations to normal youthful levels followed by an increase in circulating androgens and estrogens. As the hepatic first-pass effect may lead to a non physiological metabolism of DHEA after oral ingestion we studied the influence of two single DHEA doses (50 and 100 mg) on the excretion of steroid metabolites in 14 elderly males [age 58.8+/-5.1 years (mean +/- SEM)] with endogenous DHEAS levels <1500 ng/ml and in 9 healthy females (age 23.3+/-4.1 years) with transient suppression of endogenous DHEA secretion induced by dexamethasone (dex) pretreatment (4x0.5 mg/day/4 days). Urinary steroid profiles in the elderly males were compared to the steroid patterns found in 15 healthy young men (age 28.9+/-5.1 years). In the females the results were compared to their individual baseline excretion without dex pretreatment. Urinary steroid determinations were carried out by semiautomatic capillary gas-liquid chromatography. In both genders DHEA administration induced significant increases in urinary DHEA (females: baseline vs. 50 mg vs. 100 mg: 361+/-131 vs. 510+/-264 vs. 1541+/-587 microg/day; males: placebo vs. 50 mg vs. 100 mg: 434+/-154 vs. 1174+/-309 vs. 4751+/-1059 microg/day) as well as in the major DHEA metabolites androsterone (A) and etiocholanolone (Et). Fifty mg DHEA led to an excretion of DHEA and its metabolites only slightly above baseline levels found in young females and in young men, respectively, whereas 100 mg induced clearly supraphysiological values. After 50 mg DHEA the ratios of urinary DHEA metabolites (A/DHEA, Et/DHEA) were not significantly different between elderly males vs. young male volunteers and young healthy females versus their individual baseline levels. In conclusion, an oral dose of 30 to 50 mg DHEA restores a physiological urinary steroid profile in subjects with DHEA deficiency without evidence for a relevant hepatic first-pass effect on urinary metabolites.

Administration, Oral↗
PubMed2000

DHEA replacement in women with adrenal insufficiency--pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition.

Standard replacement for adrenal insufficiency (AI) consists of glucocorticoids and mineralocorticoids while DHEA deficiency is routinely ignored. Thus, AI represents the ideal pathophysiological model of isolated DHEA deficiency. We investigated the effects of DHEA replacement in 24 women with primary and secondary AI employing a double blind, placebo-controlled, randomized crossover design. A DHEA dose of 50 mg/d was chosen based on preceding single-dose pharmacokinetics and bioconversion studies. Each patient received four months of treatment with DHEA and four months placebo, with a one-month washout period. Measurements included serum steroid hormones, somatotropic parameters and psychometric assessment of well-being, mood, cognition and sexuality. Treatment with DHEA raised the initially low serum concentrations of DHEA, DHEAS, androstenedione, and testosterone into the normal range. DHEA induced a slight increase in serum IGF-I, but only in patients with primary AI, suggesting a growth hormone-mediated effect. DHEA treatment significantly improved overall wellbeing as well as scores for depression, anxiety, and their physical correlates. Furthermore, DHEA significantly increased both sexual interest and the level of satisfaction with sex. DHEA replacement had no influence on the cognitive performance, which was already on a high level at baseline. In conclusion, DHEA replacement improves well-being and sexuality in women with adrenal insufficiency. If this is due to a direct effect of DHEA on the brain, an indirect effect via increased androgen synthesis, or both, remains to be elucidated. Long-term studies in patients of both sexes are needed to further define the role of DHEA in standard replacement for adrenal insufficiency.

Adrenal Insufficiency↗
PubMed1999

[A hairy case].

Explore the source record for details and available documents.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Dehydroepiandrosterone replacement in women with adrenal insufficiency.

BACKGROUND: The physiologic role of dehydroepiandrosterone in humans is still unclear. Adrenal insufficiency leads to a deficiency of dehydroepiandrosterone; we therefore, investigated the effects of dehydroepiandrosterone replacement, in patients with adrenal insufficiency. METHODS: In a double-blind study, 24 women with adrenal insufficiency received in random order 50 mg of dehydroepiandrosterone orally each morning for four months and placebo daily for four months, with a one-month washout period. We measured serum steroid hormones, insulin-like growth factor I, lipids, and sex hormone-binding globulin, and we evaluated well-being and sexuality with the use of validated psychological questionnaires and visual-analogue scales, respectively. The women were assessed before treatment, after one and four months of treatment with dehydroepiandrosterone, after one and four months of placebo, and one month after the end of the second treatment period. RESULTS: Treatment with dehydroepiandrosterone raised the initially low serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone into the normal range; serum concentrations of sex hormone-binding globulin, total cholesterol, and high-density lipoprotein cholesterol decreased significantly. Dehydroepiandrosterone significantly improved overall well-being as well as scores for depression and anxiety. For the global severity index, the mean (+/-SD) change from base line was -0.18+/-0.29 after four months of dehydroepiandrosterone therapy, as compared with 0.03+/-0.29 after four months of placebo (P=0.02). As compared with placebo, dehydroepiandrosterone significantly increased the frequency of sexual thoughts (P=0.006), sexual interest (P=0.002), and satisfaction with both mental and physical aspects of sexuality (P=0.009 and P=0.02, respectively). CONCLUSIONS: Dehydroepiandrosterone improves well-being and sexuality in women with adrenal insufficiency.

Adrenal Insufficiency↗
PubMed1999

Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.

The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P < 0.0001); AUC 0-12 h for estrone, 1443 +/- 269 vs. 2537 +/- 434 vs. 3254 +/- 671 pmol/L x h (P < 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.

Aged↗
PubMed1998

Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression.

Women with adrenal insufficiency suffer from chronic dehydroepiandrosterone (sulfate) [DHEA(S)] deficiency. To define a suitable dose for DHEA replacement, we studied the pharmacokinetics and biotransformation of orally administered DHEA in nine healthy female volunteers (mean age 23.3 +/- 4.1 yr, mean body mass index 22.5 +/- 1.8 kg/m2) with transient suppression of adrenal androgen secretion because of dexamethasone (dex) administration (4 x 0.5 mg/day for 4 days). Diurnal blood sampling was performed during the early follicular phase of four subsequent menstrual cycles (study period 1: baseline; study periods 2-4: dex + placebo, dex + 50 mg DHEA or dex + 100 mg DHEA in a randomized cross-over design). Dex induced not only a significant suppression of serum cortisol (to 8% of baseline) but also of DHEA (18%), DHEA(S) (16%), and androstenedione (26%), as well as of testosterone (28%), dihydrotestosterone (43%), and estrone (54%). Oral administration of 50 mg DHEA led to restoration of DHEA(S) baseline levels, whereas 100 mg induced supraphysiological concentrations [baseline vs. 50 mg DHEA vs. 100 mg DHEA: area under the concentration-time curve (AUC) 0-12 h DHEA: 280 +/- 85 vs. 241 +/- 73 vs. 383 +/- 106 nmol/L x h; AUC 0-12 h DHEA(S): 89.1 +/- 48.4 vs. 139.6 +/- 43.5 vs. 213.3 +/- 21.6 mumol/L x h). Serum concentrations of dihydrotestosterone and estrone were restored to baseline after 50 mg DHEA, whereas baseline testosterone and androstenedione levels were only achieved by administration of 100 mg DHEA. In conclusion, 50 mg DHEA seems to be a suitable replacement dose in females with adrenal insufficiency. Furthermore, the rapid and lasting conversion to potent androgens demonstrates a potential role of DHEA for androgen replacement in females in general.

Administration, Oral↗
PubMed1998

Management of hypoparathyroidism during pregnancy--report of twelve cases.

There is no established therapeutic regimen for treatment of hypoparathyroidism during pregnancy. This is due particularly to uncertainty about the use of vitamin D or its analogues, as in animal experiments teratogenic side-effects have been reported. Nevertheless, vitamin D or its analogues are required to control tetany predisposing to abortion and preterm labour. We herein report the course of two pregnancies in a hypoparathyroid woman treated with calcitriol (1,25(OH)2D3). Additionally, we describe the outcome of pregnancy in ten women receiving calcitriol, reported to the Drug Safety Department (DSD), Hoffmann-La Roche AG. A 29-year-old hypoparathyroid woman receiving chronic treatment with calcitriol (0.25 microg/day) and calcium (1.5 g/day) was referred in the 6th week of her first pregnancy. Calcitriol was initially discontinued, but during the 20th week of pregnancy recurrent tetany occurred (serum calcium 1.74 mmol/l). Calcitriol (0.25 microg/day) was added, stabilizing serum calcium around 2.15 mmol/l with 1,25(OH)2D3 concentrations around 60 ng/l (normal range 35-80 ng/l). To maintain normocalcaemia the calcitriol dose was increased to 0.5 microg/day during the 33rd week and to 0.75 microg/day shortly before delivery of a healthy girl in the 3 7th week. During her second pregnancy calcitriol was given initially at a dose of 0.25 microg/day with further adaptation to 0.5 microg/day during the 20th and to 1.00 microg/day in the 31st week. Serum calcium and 1,25(OH)2D3 were continually within the lower normal range. She gave birth to another healthy girl during the 39th week. In eight of the ten pregnancies reported to the DSD no adverse effects of calcitriol (0.25-3.25 microg/day) were seen and healthy babies were delivered. In two retrospectively reported cases, serious adverse events were described: premature closure of the frontal fontanelle, and stillbirth in the 20th week due to complex fetal malformation respectively. However, in both cases the causative role of calcitriol administration remains highly questionable. We conclude that, during pregnancy, management of maternal hypoparathyroidism with calcitriol and calcium is feasible, if the 1,25(OH)2D3 concentrations are adapted to the physiological needs during pregnancy and serum calcium levels are kept in the lower normal range.

Adult↗
PubMed1997

Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro.

A desmopressin-induced ACTH increase has been recently suggested to be specific for pituitary-dependent Cushing's disease. We present the case of a 47-year-old woman with Cushing's syndrome due to ectopic ACTH production by a bronchial carcinoid. While CRH failed to induce an ACTH or cortisol response, intravenous administration of desmopressin led to a 47% increase in serum ACTH and a 42% increase in serum cortisol concentration. After surgical removal of the tumour, the desmopressin response became negative. In vitro, ACTH production by tumour cells obtained at surgery was also stimulated by desmopressin but not by CRH. Additional receptor mRNA expression studies using RT-PCR revealed expression of both V2 and V3 vasopressin receptor subtypes in the carcinoid tumour at a level comparable to that recently described in pituitary corticotroph adenomas. This case illustrates that ACTH stimulation by desmopressin is not specific for pituitary-dependent Cushing's syndrome as vasopressin receptor subtypes known to interact with desmopressin may also be found in ectopic tumours producing ACTH.

ACTH Syndrome, Ectopic↗