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F Jockenhövel

Publications and source records attributed to F Jockenhövel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men.

We investigated whether the androgen type or application mode or testosterone (T) serum levels influence serum lipids and lipoprotein levels differentially in 55 hypogonadal men randomly assigned to the following treatment groups: mesterolone 100 mg orally daily ([MES] n = 12), testosterone undecanoate 160 mg orally daily ([TU] n = 13), testosterone enanthate 250 mg intramuscularly every 21 days ([TE] n = 15), or a single subcutaneous implantation of crystalline T 1,200 mg ([TPEL] n = 15). The dosages were based on standard treatment regimens. Previous androgen substitution was suspended for at least 3 months. Only metabolically healthy men with serum T less than 3.6 nmol/L and total cholesterol (TC) and triglyceride (TG) less than 200 mg/dL were included. After a screening period of 2 weeks, the study medication was taken from days 0 to 189, with follow-up visits on days 246 and 300. Before substitution, all men were clearly hypogonadal, with mean serum T less than 3 nmol/L in all groups. Androgen substitution led to no significant increase of serum T in the MES group, subnormal T in the TU group (5.7 +/- 0.3 nmol/L), normal T in the TE group (13.5 +/- 0.7 nmol/L), and high-normal T in the TPEL group (23.2 +/- 1.1 nmol/L). 5 alpha-Dihydrotestosterone significantly increased in all treatment groups compared with baseline. Compared with presubstitution levels, a significant increase of TC was observed in all treatment groups (TU, 14.4% +/- 3.0%; MES, 18.8% +/- 2.5%; TE, 20.4% +/- 3.0%; TPEL, 20.2% +/- 2.6%). Low-density lipoprotein cholesterol (LDL-C) also increased significantly by 34.3% +/- 5.5% (TU), 46.4% +/- 4.1% (MES), 65.2% +/- 5.7% (TE), and 47.5% +/- 4.3% (TPEL). High-density lipoprotein cholesterol (HDL-C) showed a significant decrease by -30.9% +/- 2.8% (TU), -34.9% +/- 2.5% (MES), -35.7% +/- 2.6% (TE), and -32.5% +/- 3.5% (TPEL). Serum TG significantly increased by 37.3% +/- 11.3% (TU), 46.4% +/- 10.3% (MES), 29.4% +/- 6.5% (TE), and 22.9% +/- 6.7% (TPEL). TU caused a smaller increase of TC than TE and TPEL, whereas the parenteral treatment modes showed a lower increase of TG. There was no correlation between serum T and lipid concentrations. Despite the return of serum T to pretreatment levels, serum lipid and lipoprotein levels did not return to baseline during follow-up evaluation. In summary, androgen substitution in hypogonadal men increases TC, LDL-C, and TG and decreases HDL-C independently of the androgen type and application made and the serum androgen levels achieved. Due to the extended washout period for previous androgen medication and the exclusion of men with preexisting hyperlipidemia, this investigation demonstrates more clearly than previous studies the impact of androgen effects on serum lipids and lipoproteins. It is concluded that preexisting low serum androgens induce a "male-type" serum lipid profile, and increasing serum androgens further within the male normal range does not exert any additional effects. The threshold appears to be above the normal female androgen serum levels and far below the lower limit of normal serum T levels in adult men. These findings may have considerable implications for the use of androgens as a male contraceptive and for androgen therapy in elderly men.

Adult↗
PubMed1999

Unique alterations of thyroid function parameters after i.v. administration of alkylating drugs (cyclophosphamide and ifosfamide).

Alkylating drugs (cyclophosphamide and ifosfamide) have been in clinical use for the treatment of malignant diseases in the past. They are most useful anticancer agents and cyclophosphamide is also widely used for its immunosuppressive properties. However the effect of alkylating drugs on thyroid hormone parameters have not been evaluated so far. Three groups of patients were prospectively evaluated: Group I: 15 patients with Wegener's granulomatosis and 4 patients with severe scleritis received a single dose cyclophosphamide (15 mg/kg bw/day) and 250 mg prednisone i.v. Group II: 9 patients with malignant lymphomas were treated according to the IMVP 16-protocol. Patients received daily ifosfamide 1000 mg/m2 from day 0 to 4 and vepesid from day 0 to 2. Patients did not receive corticosteroids additionally. Group III: 6 patients with a relapse of malignant lymphomas received ifosfamide 1.500 mg/m2/day from day 0 to 4 i.v. and dexamethasone 40 mg/m2 as well as ara-c and etoposid. All patients received mesna to prevent hemorrhagic cystitis and odansetran or metoclopramide as antiemetic drugs. Alkylating drugs were given as a one hour infusion. Thyroid hormone parameters were determined before and on day 1, 2, 3, 4 after drug administration. We observed a significant increase in T4 and fT4 concentrations and a concomitant fall in TSH in either group one day after the administration of alkylating drugs. The effect was most pronounced in group III: T4 increased from 113 +/- 8 nmol/L to 175 +/- 8 (normal: 58-154) and fT4 from 14.0 +/- 0.8 to 24.8 +/- 2.5 pmol/L (normal 10-25). TSH dropped from 1.27 +/- 0.16 to 0.33 +/- 0.07 mU/L (normal 0.3-4). All changes were significant: p < 0.001. Two of the six patients displayed biochemical hyperthyroidism. Also reverse T3 increased significantly. Two days after drug administration a gradual normalization occurred. However, T3, Tg, TBG, Transthyretin and albumin levels did not change throughout the study period. One patient with coexisting hypothyroidism, who received his last thyroxine substitution therapy one day before the administration of cyclophosphamide (as in group I), also demonstrated an increase in T4, fT4 and rT3 and a fall in TSH concentrations. I.v. administrations of cyclophosphamide and ifosfamide induce a transient increase in T4 and fT4 concentrations and a concomitant fall of TSH in the presence of normal Tg, T3 and thyroid binding protein concentrations. These data suggest, that the changes are not due to a release of thyroid hormones from the thyroid itself, but is likewise related to a release of thyroxine from cellular pools such as the liver.

Adult↗
PubMed1998

[Gynecomastia in men].

Gynecomastia is a very common symptom of an underlying hormonal imbalance in men. In addition to the three age peaks, a number of pathological conditions can also lead to an increase in the ratio of estrogen to androgen in the male, and thus provoke gynecomastia. While it is not necessary to carry out a thorough diagnostic investigation in every case of gynecomastia, the presence of an underlying tumor needs to be excluded. Should appropriate treatment of associated or causal pathology fail to resolve the problem, drug treatment or surgical options are available.

Adolescent↗
PubMed1998

Sequential changes of biochemical bone parameters after kidney transplantation.

BACKGROUND: Persistent hyperparathyroidism after renal transplantation (Rtx) has been reported in several studies. However these studies evaluated biochemical bone parameters either only during a short time period (up to 6 months) or for a longer time period, but with long intervals in between. Therefore, we prospectively evaluated biochemical bone parameters of kidney-transplant recipients at short intervals for 2 years after surgery. METHODS: Biochemical bone parameters were prospectively investigated in 129 patients 2, 3, 5, 8, 12, 18 and 24 months after Rtx. All patients received prednisone and cyclosporin A as immunosuppressive therapy, and 75 patients also received azathioprine. None of the patients was treated with calcium, phosphorus, or vitamin D preparations. RESULTS: Serum creatinine levels decreased from 166.8 +/- 5.4 mumol/l to 140.0 +/- 4.9 two years after Rtx; (data are expressed as mean +/- s.e.m.). Serum phosphorus levels increased slightly from 0.9 +/- 0.022 mmol/l to 0.98 +/- 0.025 (12 m), but remained within the lower normal range. We observed a rise in total and albumin adjusted calcium concentrations 3 months after Rtx. 52% of all patients had serum calcium levels above 2.62 mmol/l (upper normal limit in our laboratory) 3 months after renal transplantation with a gradual decrease thereafter. There was no correlation of calcium and PTH levels. We observed a significant rise in biochemical bone parameters from 2 to 5 months after renal transplantation (P < 0.001): alkaline phosphatase (AP) increased from 164.3 +/- 9.4 to 236 +/- 12.7 U/l (normal 50-180), bone specific alkaline phosphatase (BAP) rose from 17.7 +/- 1.36 to 23.2 +/- 1.7 ng/ml (normal:4-20) and osteocalcin (OC) increased from 20.2 +/- 1.5 to 26.7 +/- 1.9 ng/ml (normal 4-12). AP and BAP levels values normalized 12 months after renal transplantation, whereas OC was still above normal throughout the study period. Patients were subdivided into two groups: those with good and those with impaired graft functions. Patients with good graft function had stable serum creatinine levels (< or = 132 mumol/l or < or = 1.5 mg/dl) well below the mean serum creatinine concentration during the study period. The significant changes in AP, BAP, and OC occurred irrespective of renal function. However, patients with impaired graft function (n = 65) had significantly higher PTH-levels (70 pg/ml higher) than patients with good graft function (n = 64), P < 0.01. PTH was positively correlated with serum creatinine (r = 0.81, P < 0.001). Moreover, patients with low 25 (OH) vitamin D levels (n = 63) had significantly higher PTH concentrations (between 40 and 80 pg/ml, P < 0.01) throughout the study period compared to patients (n = 66) with a sufficient 25(OH)D supply irrespective of graft function. There was a negative correlation of 25 (OH)D levels and PTH; (r = -0.49, P < 0.001). 1,25(OH)2D3 (evaluated in 24 patients) levels increased from 46.5 +/- 6.6 to 76.9 +/- 7.6 pg/ml (normal:35-90) at 12 months. CONCLUSION: Hypercalcaemia is a common phenomenon in the early period after kidney transplantation and occurs in the presence of low normal phosphorus levels. It is most probably related to improved PTH action and 1-hydroxylation of vitamin D. The rise in biochemical bone parameters between 3 and 5 months occurs irrespective of graft function and normalization is only achieved 1 year after transplantation. PTH is constantly elevated for up to 2 years after kidney transplantation and is most probably related (a) to impaired graft function and (b) to suboptimal 25 OH vitamin D supply.

Adult↗
PubMed1997

Effects of various modes of androgen substitution therapy on erythropoiesis.

In order to investigate differential effects of androgens on erythropoiesis, 55 men with clincally and biochemical confirmed hypogonadism were randomly assigned to 4 groups receiving different forms of androgen substitution: Mesterolone (MES) 100 mg/d, testosterone undecanoate (TU) 160 mg/d, testosterone enanthate (TE) 250 mg i.m./21 days or 1200 mg crystalline testosterone (TPEL) subcutaneously implanted at study begin. Previous testosterone medication had been suspended at least 3 months prior to study begin. Testosterone (T), dihydrotestosterone (DHT), hemoglobin (HB) and hematocrit (HC) were assessed before, during and after substitution of androgens. MES did not increase serum T and TU raised average T levels during substitution to 5.7 +/- 0.3 nmol/l, thereby doubling baseline concentrations. TE resulted in a 6fold increase of baseline T yielding 13.5 +/- 0.7 nmol/l and TPEL increased serum T 8.5fold to 23.2 +/- 1.1 nmol/l. Average DHT levels during substitution were 4.3 +/- 0.2 (MES), 3.3 +/- 0.2 (TU), 4.0 +/- 0.4 (TE) and 5.5 +/- 0.4 (TPEL) nmol/l. The groups receiving TPEL, TU or TE showed a significant rise of HB and HC compared to baseline, whereas in the MES group these parameters did not change significantly. MES increased HB by 5.6 +/- 1.8 g/l, TU by 12.7 +/- 2.8 g/l, TE by 21.1 +/- 2.6 g/l and TPEL by 21.7 +/- 4.0 g/l. HC was raised by 1.8 +/- 0. 4% in the MES group, 3.9 +/- 1.1% in the TU group and 6.4 +/- 0.9% and 6.5 +/- 1.6% in the TE and TPEL groups, respectively. Except for 1 subject in the TPEL group, the HB and HC stayed within the normal limits. We conclude that, T, but not DHT, stimulates erythropoiesis in a dose dependent manner. T levels within the low normal range for men are required for maximal stimulation of erythropoiesis.

Adult↗
PubMed1997

Significant changes in thyroid hormone parameters after a four week recreation period at the North Sea without alterations of iodine intake.

UNLABELLED: Many studies have been carried out evaluating thyroid hormone parameters in patients suffering from various illnessess. However data on thyroid function after a recreation period are missing. Therefore we evaluated thyroid hormone parameters in 178 patients (mostly suffering from chronic obstructive lung disease) undergoing a four week recreation period in a health spa on the island Borkum at the North Sea. We observed a subtle, but significant increase in basal TSH concentrations from 1.20 mU/l (median) to 1.50 mU/l; (p<0. 001) and a fall in T4 values from 97.5 +/- 17.7 nmol/l (mean +/- SD) to 90.3 +/- 17.0 (p<0.001) and T3 from 2.21 +/- 0.33 nmol/l to 2.09 +/- 0.33 (p<0.001). However no increase in iodine intake occurred during the four weeks: median iodine excretion 61 microg iodine/g creatinine at the beginning vs 65 microg iodine/g creatinine at the end. IN CONCLUSION: a recreation period at the North Sea is associated with subtle but significant changes in thyroid hormone parameters. However no increase in iodine intake occurs during the four week observation period.

Adult↗
PubMed1997

Triiodothyronine (T3) reflects renal graft function after renal transplantation.

OBJECTIVE: Abnormalities in thyroid function are observed in patients with end stage renal disease. However, there are no data available evaluating sequential changes of thyroid function after renal transplantation. Therefore, we have studied thyroid hormone function in the immediate post-operative period after renal transplantation in order to determine the relationship between improving renal function and changes in thyroid hormone economy. DESIGN AND PATIENTS: Thyroid function was evaluated in 22 patients before and on days 1, 3, 7 and 15 after renal transplantation. All patients received prednisone and cyclosporin as immunosuppressive therapy. Twelve patients with normal renal function undergoing comparable surgical procedures served as a control group. MEASUREMENTS: Serum creatinine and thyroid hormone parameters (total T4, total T3, free T4, free T3, thyroxin binding globulin (TBG), reverse T3, T3 sulphate and TSH) were measured. RESULTS: According to post-operative kidney function after renal transplantation, patients could be subdivided into three groups: five patients had primary graft function (group I); seven patients had delayed graft function because of acute renal failure (group II); 10 patients had delayed graft function requiring high doses of prednisone and some also of OKT3 because of acute rejection (group III). There was a significant fall in T3 and T4 concentrations with a concomitant rise in reverse T3 in all patients up to 3 days after renal transplantation. However, only patients in group I reached pre-operative values on day 15 after renal transplantation (serum creatinine 167 +/- 52 microM), whereas patients in group II (creatinine 609 +/- 118 microM) and group III (creatinine 839 +/- 71 microM) continued to have T3 concentrations well in the hypothyroid range (group I, 1.68 +/- 0.28 nM) vs 0.87 +/- 0.09 nM in group II and 0.76 +/- 0.10 nM in group III; P < 0.01). Serum T4 concentrations were also low in group III (47.7 nM vs 100.2 nM in group I; P < 0.05) 15 days after renal transplantation. These changes were accompanied by a concomitant fall in T3/TBG ratio and in free T3. Elevated reverse T3 returned to normal values in all groups on the 15th day after renal transplantation. TSH fell significantly on the first post-operative day, but did not return to pre-operative values in renal transplantation patients. In the control group, TSH did not change during the study period. T3 sulphate, known to be elevated in chronic renal failure, remained above normal in all patients irrespective of graft function during this study period. CONCLUSIONS: T3 concentrations reflect renal graft function after renal transplantation. T3 is below normal in patients with delayed graft function (acute renal failure or acute rejection). The post-operative period (up to 3 days after renal transplantation) is associated with a low T3 syndrome. TSH does not return to pre-operative values even in patients with primary graft function. This might be due to the administration of prednisone. T3-sulphate is elevated before and after renal transplantation irrespective of graft function.

Acute Kidney Injury↗
PubMed1997

Influence of coronary artery bypass surgery on thyroid hormone parameters.

UNLABELLED: The postoperative period after cardiac surgery with cardiopulmonary bypass (CPB) is associated with a low T3 syndrome, i.e. low T3 and fT3 concentrations in the presence of normal T4 and TSH concentrations. So far, results from studies evaluating thyroid function during and after CPB are rather conflicting. We therefore evaluated prospectively thyroid function in 28 patients before, during and up to 3 days after coronary artery bypass surgery. We could demonstrate the most significant changes in thyroid hormone concentrations on day 1 after CPB (low T3 and fT3 concentrations, elevated rT3 concentrations in the presence of a significant fall of TSH). T3 fell from 1.93 to 0.6 nmol/1 and fT3 from 5.5 to 1.42 pmol/1. Those patients with low cardiac output syndrome after surgery had significantly lower T3 concentrations than patients without this complication. Moreover, those patients, who already had significant lower T3 values prior to CPB, also demonstrated low T3 concentrations on day 1 after CPB. Cortisol usually has a suppressive effect on TSH secretion. However, the effect of cortisol on TSH in patients undergoing CPB seems to be not that important: those patients with high endogenous cortisol concentrations on day 1 after CPB had similar TSH values to those patients with only slightly elevated cortisol concentrations. Also, the application of high doses of catecholamines seems to have only minor effects on TSH secretion, because those patients requiring high doses of dopamine over a prolonged time period had essentially the same TSH values after CPB. Patients who had been exposed preoperatively to high doses of iodine did not demonstrate significantly different thyroid hormone concentrations. IN CONCLUSION: We could demonstrate that CPB induces a low T3 syndrome up to 3 days after surgery. Those patients with low T3 concentrations prior to surgery demonstrate postoperatively a more severe degree of nonthyroidal illness (NTI). Catecholamines and cortisol seem to have only minor effects on the TSH secretion after CPB. The influence of a previous iodine contamination is negligible.

Aged↗
PubMed1997

Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men.

The ob gene product leptin (OB) is a feedback signal from the adipocyte to the hypothalamus and is involved in regulation of food intake and energy expenditure in rodents. A major determinant of serum OB levels is fat mass. Several studies suggest that men have lower OB levels than women even after adjustment for percent body fat. We, therefore, investigated the influence of testosterone (T) substitution in hypogonadal men on serum OB levels. Hypogonadal men with T levels of 3.6 nmol/L or less and off substitution therapy for at least 3 months were assigned to two treatment groups: testosterone enanthate (TE; 250 mg, i.m., every 21 days; n = 10) or a single s.c. implantation of 1200 mg crystalline T (TPEL; n = 12). Blood samples for determination of T, 5 alpha-dihydrotestosterone (DHT), sex hormone-binding globulin, and 17 beta-estradiol were obtained before therapy and then every 21 days until day 189 and at follow-up visits on days 246 and 300. Serum OB levels were assessed on days 0, 42, 84, 126, 168, and 300. OB levels were referred to a normal range for men based on the analysis of OB levels in 393 adult men. Substitution with T led to a large rise in T and DHT in both groups compared to baseline values (average T, days 21-189: TE, 14.33 +/- 2.63 nmol/L; TPEL, 24.98 +/- 1.64; average DHT, days 21-189: TE, 4.20 +/- 0.57 nmol/L; TPEL, 5.11 +/- 0.56; P < or = 0.05). Concomitantly, 17 beta-estradiol increased in both groups, and sex hormone-binding globulin levels were significantly decreased. At baseline, serum OB levels in hypogonadal men were 3-fold elevated compared to those in normal men (12.39 +/- 2.93 micrograms/L vs. 4.28 +/- 0.52; P < 0.01) and not different between groups (TE, 13.7 +/- 5.6; TPEL, 11.3 +/- 2.9 micrograms/L). This elevation was retained after adjustment for body mass index in the normal control group [TE, 1.45 +/- 0.51 SD score (P < 0.0001); TPEL, 0.98 +/- 0.35 SD score (P < 0.0008)]. During T substitution serum OB was completely normalized (trough levels: TE, 4.6 +/- 1.0 micrograms/L; TPEL 4.3 +/- 0.9 micrograms/L). In multiple regression analysis, the androgen (T plus DHT)/estrogen ratio was the only significant determinant of OB levels (r = -0.32; P < 0.01). At baseline, OB levels did not correlate with body mass index, but during substitution, the correlation was considerably improved. We conclude that hypogonadal men exhibit elevated OB levels that are normalized by substitution with T. The only determinant of OB levels was the androgen/estrogen ratio, indicating a major influence of sex steroids on OB production. The interaction of T and OB might be part of a hypothalamic-pituitary-gonadal-adipose tissue axis that is involved in body weight maintenance and reproductive function.

Adult↗
PubMed1997

[Thyroid hormone resistance: variable clinical manifestations in five patients].

AIM: The syndrome of thyroid hormone resistance (RTH) is characterised by elevated circulating thyroid hormones, unsuppressed TSH levels and peripheral refractoriness to hormone action. Patients with RTH may be clinically hyperthyroid if the pituitary gland is more insensitive than other tissues to thyroid hormones. More often, patients have peripheral tissue resistance as well and are euthyroid. RTH is related to point mutations in the T3-binding domain of the beta-receptor gene. We report the variable clinical and biochemical features of five patients with RTH. METHODS: Five patients with RTH were clinically and biochemically evaluated: thyroid tests were done at baseline, after TRH stimulation and after T3-suppression test. Thyroid ultrasound was performed as well. Individual exons of the thyroid hormone receptor beta gene were amplified from leucocyte DNA in these patients using the polymerase chain reaction (PCR). RESULTS: Sequence analysis identified a single point mutation at a certain nucleotide position. This corresponds to aminoacids substitutions at one position in the predicted aminoacid sequence. RTH was familial in three individuals and sporadic in two. Three of the patients underwent thyroid surgery or radioiodine treatment because of recurrent goiter and/or "refractory hyperthyroidism". Moreover, one of our patients with RTH developed also hyperthyroidism due to Graves disease and underwent thyroid surgery for the third time. Her brother, besides RTH, demonstrated strongly positive TPO-antibodies and a hypoechogenic pattern on ultrasound. So the diagnosis of Hashimoto's thyroiditis was made. CONCLUSIONS: RTH has to be considered in all patients with inappropriate TSH secretion. The clinical manifestation of patients with RTH is heterogenous. Thyroid antibody measurements should be performed regularly in order to detect the development of coexisting autoimmune thyroid disease.

Adult↗
PubMed1996

Differential presentation of cortical and trabecular peripheral bone mineral density in acromegaly.

Growth hormone (GH) has been suggested as a therapeutic tool for the treatment of osteopenia. To assess the differential influence of growth hormone on cortical and trabecular bone, bone mineral densities (BMD) of the ultradistal radius were determined in 18 men and 19 women with clinically and biochemically confirmed acromegaly using peripheral computed tomography and a specialized scanner (Stratec XCT 900). The results were expressed in equivalents to hydroxyl-apatite (mg/ccm) and compared with the BMD of healthy controls (17 men, 34 women). Cortical bone mineral density was significantly higher in acromegalic women (295.2 +/- 18.4, X +/- SEM) and men (339.4 +/- 21.2) compared to healthy women (243.0 +/- 12.8) and men (272.2 +/- 15.9). In contrast, trabecular BMD did not differ between acromegalic patients (men: 161.0 +/- 16.1; women: 116.5 +/- 10.5) and controls (men: 158.0 +/- 12.2; women: 134.1 +/- 6.3). Acromegalic women showed a significant correlation between insulin-like growth factor (IGF-I) expression and cortical BMD, whereas in acromegalic men GH levels correlated significantly with cortical BMD. Greatly increased serum osteocalcin levels in both, acromegalic men (15.5 +/- 3.3 ng/ml) and women (12.9 +/- 1.8) compared to controls (men: 6.7 +/- 1.7; women: 7.7 +/- 1.0) indicates the activation of osteoblastic bone formation. This study revealed an increase in cortical BMD at the forearm; in acromegalic patients; though trabecular BMD did not differ from controls. The differential mineralization of cortical and trabecular bone in acromegaly may be indicative of the detrimental effect accompanying pituitary insufficiency can have on trabecular bone, despite substitution therapy, but could also be due to different reactivity of cortical and trabecular bone to GH and/or IGF I. The observable increase of bone mineral density in acromegaly suggests a potential use for GH in treating osteoporosis.

Acromegaly↗
PubMed1996

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men.

OBJECTIVE: There are advantages and disadvantages with all of the presently available types of testosterone replacement for hypogonadal men. We performed this investigation to establish detailed data about the pharmacokinetics, pharmacodynamics, feasibility and side-effects of subcutaneously implanted testosterone (T) pellets. DESIGN AND MEASUREMENT: In a single-dose, open-label, non-randomized study, 6 T-pellets, each containing 200 mg of fused crystalline T, were implanted in the subdermal fat tissue of the lower abdominal wall of 14 hypogonadal men. Blood samples for determination of T, LH, FSH, 5 alpha-dihydrotestosterone (DHT), sex hormone binding globulin (SHBG) and oestradiol (E2) were obtained at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hours and on day 21 after implantation and then every 3 weeks until day 189, and on days 246 and 300 during follow-up. In another 36 hypogonadal men the feasibility and side-effects of T-pellets were evaluated. PATIENTS: Fourteen patients participated in the detailed pharmacokinetic study and another 36 patients in the assessment of feasibility and side-effects. All patients (age range 18-61 years) suffered from primary or secondary hypogonadism (T < 3.6 nmol/l). RESULTS: The pharmacokinetic study in 14 hypogonadal men revealed an initial short-lived burst release of T with a peak concentration of 49.0 +/- 3.7 nmol/l at 0.5 +/- 0.13 days which was followed by a stable plateau lasting until day 63 (day 2, 35.2 +/- 2.3; day 63, 34.8 +/- 2.6 nmol/l). Thereafter serum T gradually declined and was close to baseline concentrations on day 300. Apparent terminal elimination half-life (t1/2) was 70.8 +/- 10.7 days and apparent mean residence time 87.0 +/- 4.5 days. On average, serum T was below 10 nmol/l after 180 days. Absorption of T followed a zero-order release kinetic with an absorption half-time of 74.7 days (95% confidence interval: 71.1-78.5) and was almost complete by day 189 (95.9 +/- 0.84%). Serum DHT and E2 were significantly elevated from day 21 to day 105 and correlated significantly with T (DHT, r = 0.65, P < 0.0001, E2, r = 0.67, P < 0.0001). SHBG was significantly decreased from day 21 to day 168. In 6 men with primary hypogonadism T suppressed LH and FSH to the eugonadal range from day 21 to 126 and 42 to 105, respectively, with nadirs occurring at day 84 (LH) and day 63 (FSH). LH and FSH were highly inversely correlated with T (r = -0.47 and -0.57). The only side-effect observed during 112 implantations in the total group of 50 men were 6 local infections (5.4%) leading to extrusion of 5 pellets in 3 men. When given the choice, all patients except one preferred T-pellets to their previous T medication for permanent substitution therapy. CONCLUSION: T-pellets are the androgen formulation with the longest biological action and strongest pharmacodynamic efficacy in terms of gonadotrophin suppression. The pharmacokinetic features are advantageous compared to other T preparations and the patient acceptance is high.

Adolescent↗
PubMed1995

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers.

Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full agonist at dopamine (DA)-receptors and alpha- and beta-adrenoceptors. To study whether in vivo DA-receptors mediated effects can be separated from alpha- and beta-adrenoceptor effects we compared in 10 male volunteers the effects of i.v. epinine (0.5; 1; 2; 4 micrograms/kg/min for 15 min each) on DA-receptor (changes in serum prolactin)- and alpha- and beta-adrenoceptor (changes in systolic [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects with those of dopamine before and after propranolol (5 mg i.v. 45 min pre-infusion), bisoprolol (15 mg p.o. 2 h pre-infusion) and domperidone (10 mg p.o. 1 h pre-infusion). At the 0.5 and 1 microgram doses of dopamine and epinine did not effect Psyst, Pdiast and heart rate but significantly decreased prolactin levels. At the higher dose both dopamine and epinine significantly increased Psyst and heart rate, while only epinine significantly increased Pdiast. In addition, both dopamine and epinine significantly increased diuresis and natriuresis; in contrast, only dopamine, but not epinine dose-dependently increased plasma noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked blood pressure- and heart rate-changes, but antagonized their prolactin-effects (at least at the lower doses). Bisoprolol and propranolol significantly reduced dopamine-induced Psyst- and heart rate-increases to about the same extent. Propranolol enhanced epinine-induced Psyst- and Pdiast-increases while bisoprolol reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced heart rate-increase was abolished by bisoprolol and was converted into heart rate-decrease by propranolol. We concluded that in 0.5 and 1 microgram doses (plasma levels of 20-80 nmol/l)epinine acts only at DA-receptors. Thus, ibopamine in therapeutically recommended doses (3 x 100 mg/day with peak plasma epinine-levels of 50-80 nmol/l) very likely activates only DA-receptors. In higher doses, however, epinine-like dopamine-activates alpha- and beta-adrenoceptors whereby epinine has a stronger alpha-adrenoceptor agonistic activity than dopamine. Moreover, part of the dopamine-effects are indirect via release of endogenous noradrenaline whereas epinine-effects do not appear to include an indirect component.

Adult↗
PubMed1994

The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth.

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.

Cell Division↗
PubMed1994

Ineffectiveness of kallikrein in treatment of idiopathic male infertility: a double-blind, randomized, placebo-controlled trial.

In order to clarify the potential of kallikrein for treatment of idiopathic male infertility, a double-blind, randomized, placebo-controlled study was performed. A total of 44 patients were treated with 600 IU/day kallikrein and 47 patients with placebo for 12 weeks. Following two basal investigations, control examinations were performed at 6 and 12 weeks and included conventional and computer-aided semen analysis, hormone measurements and evaluation of drug safety. No significant changes in sperm concentration, normal sperm morphology and sperm motility evaluated by conventional analysis were detected. Computer-aided semen analysis revealed a significant increase in average path velocity and lateral head displacement of spermatozoa only in the placebo group. Within the observation period of 6 months four pregnancies occurred in each group. In conclusion, kallikrein treatment at a dose of 600 IU/day leads neither to an improvement of semen variables nor does it increase the pregnancy rate of the female partners, and is therefore not suited for therapy of idiopathic male infertility.

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