Endocrine effects of high-dose ketoconazole therapy in advanced prostatic cancer

1985 ◽  
Vol 110 (2) ◽  
pp. 276-283 ◽  
Author(s):  
W. Heyns ◽  
A. Drochmans ◽  
E. van der Schueren ◽  
G. Verhoeven
Keyword(s):  
Serum Concentration ◽  
Prostatic Cancer ◽  
Inverse Correlation ◽  
Serum Testosterone ◽  
Feedback System ◽  
Sex Hormone Binding Globulin ◽  
High Dose ◽  
Endocrine Effects ◽  
Advanced Prostatic Cancer ◽  
The Mean

Abstract. The endocrine effects of ketoconazole (400 mg orally every 8 h) were studied in 9 previously untreated patients with advanced prostatic cancer. Five of these patients were followed for 12 months. A rapid fall in the serum concentration of testosterone was noted in all patients studied. Minimal values were observed on day 4 of treatment but thereafter serum testosterone increased slowly. The effect of the drug on unbound testosterone was relatively more important, since sex hormone binding globulin increased markedly during treatment. An increase in progesterone and LH was observed in all patients. This suggests that ketoconazole limits the conversion of C21-precursors into androgens. This block is compensated in part by activation of the hypothalamo-hypophyseal feedback system. Urinary 17-ketosteroids were decreased but 17-hydroxysteroids were unaffected by the treatment. In 5 patients followed monthly over a period of 12 months the mean testosterone concentration ranged from 69 ng/100 ml in one patient to 428 ng/100 ml in another. An excellent inverse correlation could be demonstrated between the mean serum concentration of testosterone and the mean concentration of ketoconazole. The change of serum dehydroepiandrosterone sulphate also correlated inversely with the mean ketoconazole level. Increased concentrations of oestradiol were noted in 2 patients with slight gynaecomastia. It is concluded that long-term suppression of androgen production can be realized by high-dose ketoconazole treatment and that the degree of suppression is proportional to the serum levels of the drug.

scholarly journals Bioavailable testosterone is associated with symptoms of depression in adult men

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094171
Author(s):  
Zhongbao Chen ◽  
Xubo Shen ◽  
Kunming Tian ◽  
Yijun Liu ◽  
Shimin Xiong ◽  
...  
Keyword(s):  
Depressive Symptom ◽  
Serum Testosterone ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Levels ◽  
Adult Men ◽  
Depressed Group ◽  
The Mean ◽  
Symptom Group ◽  
The Relationship

Objective This study aimed to determine the relationship between serum testosterone levels and depressive symptoms in an adult male population. Methods We conducted a cross-sectional study of 1166 male participants from Zunyi, Guizhou, China. Each participant completed a questionnaire, a brief clinical exam, and had a fasting blood sample taken. We measured serum testosterone, sex hormone-binding globulin, and luteinizing hormone levels. Multiple linear regression was used to evaluate the effect of demographic factors on the relationship between the depressive symptom score and serum sex hormone levels. Results Mean testosterone, sex hormone-binding globulin, and luteinizing hormone levels were significantly higher in the depressive symptom group than in the non-depressed group. The mean calculated free serum testosterone level and free testosterone index (FTI) were significantly lower in the depressive symptom group than in the non-depressed group. Additionally, the mean FTI was significantly negatively correlated with the Beck Depression Inventory scale score in the multiple linear regression model (95% confidence interval: −3.274 to −0.406). Conclusions Decreased bioactive testosterone levels might be a contributing factor of depression in adult men. The FTI could be the most sensitive biomarker reflecting the level of bioavailable testosterone in patients with depression.

High-dose ketoconazole treatment in advanced prostatic cancer

1988 ◽  
Vol 20 (4) ◽  
pp. 383-393 ◽  
Author(s):  
S. Scultéty ◽  
J. Oszlánczy ◽  
I. Faredin ◽  
I. Tóth
Keyword(s):  
Prostatic Cancer ◽  
High Dose ◽  
Advanced Prostatic Cancer

High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.

1989 ◽  
Vol 7 (8) ◽  
pp. 1093-1098 ◽  
Author(s):  
D L Trump ◽  
K H Havlin ◽  
E M Messing ◽  
K B Cummings ◽  
P H Lange ◽  
...  
Keyword(s):  
Prostatic Cancer ◽  
Dehydroepiandrosterone Sulfate ◽  
Plasma Testosterone ◽  
High Dose ◽  
Clinical Effects ◽  
Advanced Prostatic Cancer ◽  
Androgen Ablation ◽  
Days Of Therapy ◽  
Hormone Refractory ◽  
Moderate Nausea

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

scholarly journals High-dose levocetirizine for the treatment of refractory chronic spontaneous urticaria and the effect on the serum inositol triphosphate level

2019 ◽  
Vol 47 (9) ◽  
pp. 4374-4379 ◽  
Author(s):  
Xianqiong Huang ◽  
Zhaoyang Li ◽  
Renshan Sun
Keyword(s):  
Serum Concentration ◽  
Cell Types ◽  
Chronic Spontaneous Urticaria ◽  
Inositol Triphosphate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Before And After ◽  
The Mean ◽  
Urticaria Activity Score

Objective The second messenger inositol triphosphate (IP3) is involved in signal transduction in multiple cell types. We evaluated the effects of high-dose levocetirizine on chronic spontaneous urticaria (CSU) and examined the significance of serum IP3 level in the pathogenesis of CSU. Methods Fifteen patients with refractory CSU were given oral levocetirizine at a dose of 15 mg once daily for 7 days, and treatment efficacy was determined using the Urticaria Activity Score and by evaluating wheal-and-erythema reactions and itching. The serum concentration of IP3 at specific time points was determined by enzyme-linked immunosorbent assay. Results The mean serum concentration of IP3 was 43.54 ± 41.97 pg/mL prior to treatment, 18.40 ± 17.53 pg/mL after treatment, and 1.31 ± 0.92 pg/mL in a healthy control group. The mean concentration of IP3 was significantly higher before treatment than after treatment, and the level of IP3 in the patient group before and after treatment was significantly higher than that in the control group. Conclusion High-dose levocetirizine was shown to be effective in the treatment of CSU. The level of serum IP3 was positively correlated with CSU activity, indicating that IP3 may play an important role in the pathogenesis of this condition.

PITUITARY-THYROID FUNCTION IN SPIRONOLACTONE TREATED HYPERTENSIVE WOMEN

1979 ◽  
Vol 90 (3) ◽  
pp. 577-584 ◽  
Author(s):  
A. G. H. Smals ◽  
P. W. C. Kloppenborg ◽  
W. H. L. Hoefnagels ◽  
J. I. M. Drayer
Keyword(s):  
Thyroid Function ◽  
Bolus Injection ◽  
Serum Testosterone ◽  
High Dose ◽  
Enhancing Effect ◽  
Basal Serum ◽  
The Mean ◽  
17 Hydroxyprogesterone ◽  
Lh Rh ◽  
Serum Tsh

ABSTRACT Four weeks high dose spironolactone treatment (Aldactone® Searle, 100 mg q. i. d.) significantly enhanced the TSH (Δ max. 8.5 ± 4.1 vs. 4.6 ± 3.1 μU/ml, P < 0.05) and T3 (Δ max. 32±27 vs. 11 ± 16 ng/100 ml, P < 0.05) responses to an intravenous TRH/LH-RH bolus injection in 6 eumenorrhoeic euthyroid hypertensive women, without affecting basal serum TSH, T3 or T4 levels or the basal and stimulated LH, FSH and prolactin values (P > 0.10). The mean serum testosterone, 17-hydroxyprogesterone and oestradiol levels were also similar before and during therapy. Spironolactone, possibly by virtue of its antiandrogenic action, may exert its enhancing effect on pituitary-thyroid function by modulating the levels of receptors for TRH in the thyrotrophs or by altering the T3 receptor in the pituitary permitting a greater response to TRH.

Effects of human serum on transport of testosterone and estradiol into rat brain

1980 ◽  
Vol 239 (1) ◽  
pp. E103-E108 ◽  
Author(s):  
W. M. Pardridge ◽  
L. J. Mietus ◽  
A. M. Frumar ◽  
B. J. Davidson ◽  
H. L. Judd
Keyword(s):  
Human Serum ◽  
Plasma Proteins ◽  
Inverse Correlation ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
Normal Male ◽  
Injection Technique ◽  
Shbg Level ◽  
The Mean

The effect in vivo of the plasma proteins in human serum on the transport of [3H]testosterone (T), [3H]-dihydrotestosterone (DHT), and [3H]estradiol (E2) through the brain capillary wall, i.e., the blood-brain barrier, was studied in anesthetized rats using a tissue-sampling-single-injection technique, In the absence of plasma proteins, approximately 90% of plasma T, DHT, or E2 was transported into brain on a single pass after a bolus carotid injection of labeled hormone. Serum was obtained from 57 patients in seven different clinical conditions: pregnancy, oral contraceptive use, thin and obese postmenopausal, follicular phase female, hirsutism, and normal male; the level (mean +/- SD) of sex hormone-binding globulin (SHBG) varied from 17 +/- 5 nM (hirsutism) to 323 +/- 83 nM (pregnancy). When the carotid injection solution was made 67% serum, the amount of T, DHT, or E2 transported into brain was inhibited in proportion to the concentration of SHBG. Among the patient groups, an overall linear inverse correlation between the mean SHBG level and the mean extraction of unidirectional influx of testosterone (r = 0.99) and estradiol (r = 0.98) was observed. These studies indicate that a) the undirectional clearance by brain of both testosterone and estradiol is inversely related to the SHBG level and b) the fraction of hormone transported into brain greatly exceeds the free (dialyzable) moiety and is essentially equal to the albumin-bound fraction of plasma testosterone or estradiol.

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