[Androgens in the treatment of women].
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Aged↗
Biomedical subjects
K Carlström
Publications and source records attributed to K Carlström.
Pharmacokinetics and testosterone suppression of a single dose of polyestradiol phosphate (Estradurin) in prostatic cancer patients.
The pharmacokinetics and endocrine effects of polyestradiol phosphate (PEP; Estradurin) were studied by determination of the concentrations of estradiol (E2), unconjugated (E1) and total estrone (tE1; > or = 85% estrone sulfate), and testosterone in serum from 11 prostatic cancer patients after administration of a single intramuscular injection (320 mg). After injection of PEP, serum concentrations of E2, E1, and tE1 increased during 2-3 weeks. Thereafter serum E2 declined monophasically with a mean half-life of 70 days. The elimination of E1 and tE1 seemed to be governed by the formation of E2. The testosterone concentration decreased inversely to the raising E2 level and reached castration levels within 3 weeks and remained at this level for about 2 weeks, whereafter it increased inversely to the decreasing E2 concentrations.
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Reduced serum cholecystokinin and increase in body fat during oral contraception.
This investigation was undertaken to explore a possible role of the "satiety peptide" cholecystokinin and some other gastrointestinal hormones for changes in appetite and weight during oral contraception. Ten young healthy women attending a youth health care center for contraceptive counseling volunteered for the study. A standardized meal test was used for recordings of appetite and gastrointestinal hormone response before and after 5 months of treatment with a monophasic combined oral contraceptive. Body fat was calculated from measurements of skin-fold thickness. Oral contraceptives caused a suppression of basal levels of serum cholecystokinin, which was correlated to an increase in body fat. Meal-related response of cholecystokinin and appetite were not affected. Serum levels of gastrin and insulin were also unchanged, whereas triglycerides and postprandial glucose levels were elevated. The results suggest a role of cholecystokinin in regulation of body composition. Cholecystokinin stimulates the release of insulin and stimulates lipolysis in adipose tissue. Reduced cholecystokinin levels may, therefore, be related to mild impairment of glucose tolerance and promote body fat storage during oral contraception.
Adipose Tissue↗
Influence of a diet regimen on glucose homeostasis and serum lipid levels of male elite athletes.
Physical training affects carbohydrate metabolism and results in an increased insulin-stimulated glucose disposal. To investigate if carbohydrate and lipid metabolism would be affected by nutritional factors in optimally trained elite athletes, during a 1-year period we studies elite ice-hockey players on two Swedish top-performance teams. Players on one team were subjected to extensive dietary monitoring and intervention, whereas players on the second team continued their ordinary diet. Blood levels of insulin, C-peptide, glucose, hemoglobin A1C (HbA1c), lipids, and lipoproteins were measured repeatedly. Basal insulin levels and insulin resistance (IR) were significantly lower among athletes on both teams compared with a sedentary group, and muscle weight and body mass index were significantly higher. During the course of the study in the intervention group, insulin levels decreased (3.6 +/- 0.3 v 6.2 +/- 0.6 [mean +/- SEM], P <.05) in conjunction with a decreased relative fat energy content, but returned toward baseline levels when relative fat energy content increased. IR decreased in parallel (0.59 +/- 0.05 v l.12 +/- 0.12, P <.05) and followed a similar pattern, reverting toward baseline levels. Also, levels of HbA1c changed during dietary manipulation. No changes in these parameters were observed among the elite players from the team not participating in the diet regimen. In contrast to the parameters for glucose homeostasis, no significant changes were found in serum lipid or lipoprotein levels in either team during the course of the study. The results verify the presence of an improved carbohydrate metabolism in elite athletes. The observed changes in glycemic control and glucose homeostasis as a consequence of dietary modification demonstrate further that nutritional factors may affect carbohydrate metabolism also in well-trained athletes.
Adult↗
Serum steroid hormone levels, sex hormone-binding globulin, and body mass index in the etiology of postmenopausal breast cancer.
Serum concentrations of estrone, androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured postoperatively in 122 postmenopausal women with incident breast cancer and 122 age-matched population controls. After mutual adjustment, through conditional logistic regression, between the hormonal variables and body mass index (BMI), the odds ratios for increasing control-defined quartiles of estrone and androstenedione, respectively, were 1.00, 1.44, 1.76, 1.94 and 1.00, 0.83, 0.97, 2.43; there was no association of testosterone with breast cancer risk. Moreover, the odds ratios for increasing quartiles of SHBG and BMI were 1.00, 0.72, 0.28, 0.25 and 1.00, 0.39, 0.28, 0.19, respectively. This study reveals sharp contrasts in breast cancer risk between women with high estrone and low BMI and SHBG, vs women with low estrone and high BMI and SHBG.
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Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males.
When given orally, estrogens, as well as androgens, lower serum lipoprotein (a)[Lp(a)]levels. To determine whether these effects occur also after parenteral administration of steroids, Lp(a) levels were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with parenteral estrogen (n = 8) or orchidectomy (n = 6). One group of healthy male volunteers (n = 9) was studied after parenteral administration of testosterone. Estrogen was given as im polyestradiol phosphate, 240 mg twice monthly, and testosterone was given as im injections, 250 mg/week. In the orchidectomized subjects, Lp(a) levels increased by 20% by month 3 after treatment (P < 0.05). In spite of drastic changes in serum hormone levels, no change in Lp(a) levels was observed in the estrogen-treated subjects. Concomitantly, low-density lipoprotein cholesterol levels were lowered by 15% and high-density lipoprotein cholesterol levels increased by 20%. Testosterone administration lowered Lp(a) levels by 20% (P < 0.05). No significant changes in serum lipid levels were observed in the testosterone-treated subjects or in the orchidectomy group. Thus, during parenteral administration of estrogens or androgens, diverging effects on Lp(a) and serum lipoproteins were observed. In particular, the mode of administration of estrogen influenced the response in Lp(a) levels. This suggests that the regulatory role of sex hormones on serum Lp(a) levels may depend on their capability to influence hepatic metabolic pathways of Lp(a).
Adult↗
Effect of growth hormone on follicular fluid androgen levels in patients treated with gonadotropins before in vitro fertilization.
Forty normally ovulating women aged 25-38 years from one private and two university in vitro fertilization (IVF) centres were used in this randomized, double-blind, parallel, placebo-controlled study to explore the effect of recombinant human growth hormone (GH) on follicular fluid (FF) levels of steroid hormones, particularly androgens. All the women had tubal factor infertility and were classified as poor responders with at least two previously performed and failed IVF treatments in which less than five oocytes had been retrieved following ovarian hyperstimulation. Growth hormone (GH 0.1 IU/kg body wt per day) or placebo was given as pretreatment during down-regulation with gonadotropin-releasing hormone agonist and during stimulation with human menopausal gonadotropin (hMG) according to the randomized protocol. Follicular fluid concentrations of steroids were measured and changes related to the levels of insulin-like growth factor I (IGF-I) and IGF binding proteins 1 and 3 and to the mode of GH administration. Pretreatment with GH, i.e. administration of GH before hMG stimulation only, caused significantly elevated follicular fluid concentrations of estrone, testosterone and dehydroepiandrosterone (DHEA) and higher values for markers of aromatase activity (ratios between estrone and androstenedione and between estradiol-17 beta and androstenedione) than in the placebo group, as well as in the two groups receiving GH during hMG stimulation. The highest values for markers of steroid sulfatase activity (ratios between DHA and DHEA sulfate and between unconjugated and conjugated estrone) were found in the patients pretreated with GH. Positive correlations were found between follicular fluid IGF-I and IGF binding protein 3 on the one hand and androgens on the other. This study showed that the administration of adjuvant GH to women who were poor responders to gonadotropins alters the endocrine/paracrine ovarian response to gonadotropins.
Adult↗
Does hyperandrogenism explain lower in vitro fertilization (IVF) success rates in smokers?
BACKGROUND: Our aims were to elucidate whether a decreased fertility in smoking women treated by in vitro fertilization (IVF) could be related to a divergent hormonal response to the controlled stimulation prior to IVF, to study the effect of smoking on the ovarian endocrine milieu and to possibly identify factors that might be detrimental to oocyte fertilization. METHODS: Serum and follicular fluid concentrations of estradiol-17 beta (E2), progesterone (P), testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), DHA sulfate (DHAS), sex hormone-binding globulin (SHBG) and serum cortisol were studied in 50 non-smoking and 50 smoking women in an IVF program. Follicular fluid concentrations were also compared in follicles which gave rise to cleaved oocytes (TYPE I) and follicles which failed to yield fertilized oocytes (TYPE II) in the same woman. RESULTS: The fertilization rate did not differ significantly between the two groups, but the live birth rate was 30% in non-smokers and 4% in smokers. During treatment, serum A-4, DHAS and the T/SHBG-ratio were significantly higher in smokers than in non-smokers. In the TYPE I follicles, smokers had higher follicular fluid concentrations of A-4 and DHA and a higher E2/P ratio. The TYPE II follicles in smokers had higher A-4 and T and lower E2 levels. CONCLUSIONS: Smoking women have a relative hyperandrogenism of ovarian origin, which may contribute to the lower pregnancy rate at IVF in this group.
Adult↗
Plasma protein changes induced by two orally administered androgen derivatives.
Epostane is a synthetic 17 alpha-alkylated 5 beta-androstane derivative, active following oral administration and devoid of any apparent androgenic, estrogenic or antiestrogenic potency. Circulating concentrations of 13 different plasma proteins were measured in eight women before and after 2 and 4 weeks of daily oral intake of 600 mg of epostane. The results were compared with those previously found during administration of the same daily dose of danazol, a synthetic 17 alpha-alkylated androgen derivative with known androgenic/anabolic activity. Epostane significantly suppressed serum levels of sex hormone-binding globulin, pregnancy zone protein and thyroxin-binding globulin and increased the levels of transthyretin. Haptoglobins, plasminogen and transferrin showed minor and/or transient changes and the levels of high density lipoproteins, alpha2-macroglobulin, albumin, C1-esterase inactivator, C3 complement and transcortin remained unaffected. The pattern of changes in plasma proteins was almost identical to that induced by administration of danazol, although the effects of epostane were somewhat weaker. Thus epostane is capable of inducing substantial changes in the pattern of steroid-sensitive plasma proteins in an androgen-like fashion despite its apparent lack of androgenic activity. The capacity of a steroid to induce such changes thus seems to be tied to the chemical structure rather than to the intrinsic hormonal activity of the molecule.
Abortifacient Agents, Steroidal↗
Low endogenous estrogen levels--analytical problems and tissue sensitivity.
Measurement of low peripheral concentrations of estradiol-17 beta with radioimmunoassay techniques has frequently produced extremely variable results, due to methodological problems. One such problem is variable non-specifically bound radioactivity (NSB) in methods using precipitation for separation of free and bound radioactivity. This problem can be overcome either by substituting the precipitation technique with dextran coated charcoal separation which drastically reduces NSB or by correcting for individual NSB values in samples and calibrators. These simple modifications of an existing commercial kit make convenient determination of estradiol-17 beta at low concentrations in postmenopausal women possible. Estrone sulfate is the quantitatively most important circulating estrogen in non-pregnant individuals. Studies of the metabolism of tritiated estrone sulfate in vitro evidently show that estrone sulfate is converted into estradiol-17 beta in several estrogen target tissues, including the vaginal mucosa. This conversion is probably important for the estradiol-17 beta supply to target organs in individuals with low circulating levels of estradiol-17 beta such as postmenopausal women.
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Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens.
Bone mineral density (BMD) and bone mineral content (BMC) were measured in the femoral neck area, trochanteric area and Wards triangle, and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer. Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens. The patients were free from metastases during the entire observation period. In the orchidectomized patients, BMD and BMC of the distal radius decreased significantly following treatment, whereas no changes were observed in the estrogen-treated patients. These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients.
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Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia.
OBJECTIVE: To determine the effects of nitroglycerin on placental circulation in severe preeclampsia. METHODS: Twelve women with severe preeclampsia were examined. Uterine and umbilical artery pulsatility indices (PI) were assessed by pulsed Doppler ultrasound before and after infusion of nitroglycerin, starting at 0.25 micrograms/kg per minute with stepwise dosage increases until a diastolic blood pressure (BP) of 100 mmHg was achieved. Blood pressure and heart rate were recorded every 5 minutes. Blood was sampled for analysis of the second messenger of nitric oxide, cyclic guanosine monophosphate (cGMP), before and at the end of the infusion. RESULTS: During the infusion, the mean systolic BP decreased from 161 (95% confidence interval [CI] 154-169) to 138 mmHg (95% CI 131-146), and the diastolic pressure decreased from 116 (95% CI 111-122) to 103 (95% CI 96-110) mmHg (P < .01). The PI of the uterine artery did not change significantly (1.23 [95% CI 1.01-1.61]) versus 1.30 [95% CI 1.01-1.88]), whereas umbilical artery PI decreased significantly (P < .01), from 1.35 (95% CI 1.09-1.73) to 1.20 (95% CI 1.05-1.40), with a more pronounced decrease in patients with high basal values. Cyclic GMP remained essentially unchanged (6.4 [95% CI 5.4-7.7] versus 5.5 [4.7-6.6] nmol/L). CONCLUSION: The reduction in the PI of the umbilical artery during nitroglycerin-induced BP reduction implies vasodilation in the umbilical circulation. The absence of an increase in cGMP does not support the view that the nitroglycerin effect is reflected by the plasma concentration of cGMP.
Blood Pressure↗
A subtle disturbance in the feedback regulation of the hypothalamic-pituitary-adrenal axis in the early phase of Alzheimer's disease.
In an attempt to find if a disturbance in the function of the feedback regulation of the hypothalamic-pituitary-adrenal axis is an early feature in Alzheimer's disease (AD), 35 outpatients (mean age 76.8 years) with a mild to moderate AD were compared to 20 controls (mean age 73.8 years) in their response to different doses of dexamethasone. After 0.5 mg dexamethasone, serum cortisol levels were significantly less suppressed in patients with early AD (p = .03) and these patients were significantly more often dexamethasone nonsuppressors (serum cortisol > or = 138 nmol/l) than controls (14/35 vs. 2/20; p = .03). Nonsuppression to 1 mg dexamethasone did not differ between groups (2/35 vs. 0/20). Plasma adrenocorticotropin levels were significantly lower in patients with Alzheimer's disease (n = 16) after 0.5 mg as well as after 1.0 mg dexamethasone (p = .01 and p < .001, respectively). The relationship between cortisol resistance to dexamethasone suppression and pathophysiology of AD is discussed.
Adrenocorticotropic Hormone↗
Serum and urinary markers of exogenous testosterone administration.
In an attempt to find optimal markers of exogenous testosterone (T) administration in male athletes, a number of compounds were measured in 11 healthy men before and after 3, 6 and 9 months of weekly administration of 250 mg i.m. T enanthate and in age-matched untreated controls. The following variables were measured in serum: T, 17 alpha-hydroxyprogesterone (17-OHP), sex hormone-binding globulin (SHBG), estradiol-17 beta, estrone (free + conjugated) and luteinizing hormone (LH). The following variables were measured in urine: T glucuronide (urinary T), epitestosterone glucuronide (urinary epiT), estrone (free + conjugated) and LH. Serum T, serum T/17-OHP ratio, serum T/LH ratio, serum T/SHBG ratio, serum and urinary estrogens, urinary T/creatinine-, T/epiT- and T/LH ratios increased whereas serum 17-OHP, SHBG and LH and urinary epiT/creatinine- and LH/creatinine-ratios decreased significantly during treatment. Levels above the upper reference limit were found in all subjects at 3, 6 and 9 months for serum T/17-OHP and serum and urinary T/LH ratios and at 6 months for the urinary T/epiT ratio. Levels below the lower reference limit were found in all subjects at 3, 6 and 9 months for serum LH and the urinary LH/creatinine ratio, at 3 months for the urinary epiT/creatinine ratio and at 9 months for serum 17-OHP. No other variable showed abnormal values in all subjects at the same occasion. Despite significant changes during treatment, steroid concentrations as such are poor indicators of T doping. Serum and urinary LH levels, T/LH ratios and serum T/17-OHP ratios seem to be the most reliable markers of exogenous T administration in males.
Age Factors↗
Effects of weight reduction on the regulation of lipolysis in adipocytes of women with upper-body obesity.
1. The regulation of lipolysis was studied in 14 upper-body obese women aged 26-55 years. Isolated subcutaneous adipocytes from the abdominal region were examined before and after an 8 to 12-week-long weight reduction programme, during which the mean body mass index (kg/m2) of the group was reduced from 36.4 +/- 0.9 to 30.3 +/- 1.0. 2. Fat cell volume was reduced from 891 +/- 39 to 655 +/- 45 pl. The sensitivity to noradrenaline stimulation of lipolysis in vitro increased fivefold after weight reduction. A corresponding increase in sensitivity was found with the beta 2-selective adrenoceptor agonist terbutaline. However, the number of beta 2-adrenoceptor binding sites as assessed by radioligand binding with 125I-labelled cyanopindolol was not changed. No changes were observed when dobutamine (a beta 1-selective adrenoceptor agonist) and clonidine (an alpha 2-adrenoceptor agonist) were used. 3. The basal lipolysis rates decreased by about 50% after weight reduction and the maximum enzyme activity of hormone-sensitive lipase was also reduced by almost 50%. 4. Plasma concentrations of insulin, noradrenaline and total testosterone decreased and sex hormone-binding globulin increased after weight reduction. Calculated apparent free testosterone levels decreased by more than 40% after weight reduction. 5. In conclusion, weight reduction leads to increased efficiency of adipocyte lipolysis with decreased resting lipolysis rate but increased sensitivity to stimulation by catecholamines, which may be attributed to a decreased activity of hormone-sensitive lipase and an increased sensitivity of beta 2-adrenoceptors. Changes in circulating levels of catecholamines, insulin and testosterone may play a role in these modifications of adipocyte function.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipocytes↗
Longitudinal study of adrenocortical function following allogeneic bone marrow transplantation in children.
Basal serum concentrations of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A4) and 17 alpha-hydroxyprogesterone (17OHP) were measured yearly in children treated with bone marrow transplantation (BMT) with or without preceding total body irradiation (TBI). Age-matched controls were used for comparison. ACTH stimulation tests were performed in the patients before and after treatment. However, in the samples taken before BMT only cortisol was measured. Basal posttreatment cortisol levels were subnormal in TBI-treated boys (n = 14, aged 5-17 years at BMT) during the adrenarcheal period (7-14 years) but became normal afterwards. All other groups had normal cortisol values. Treatment neither affected basal levels nor the ACTH-induced increment (delta-value) of cortisol. In the boys treated with TBI, normal basal levels of 17OHP and adrenal androgens were found with the exception of decreased DHA levels in the postadrenarcheal boys. However, the delta-17OHP values and had an abnormal age relation and were significantly higher than in the patients not treated with TBI. In the patients not treated with TBI (6 boys aged 2-17 years) normal responses were found for 5 years or more after treatment. In female patients treated with TBI (n = 12, aged 1-16 years) circulating levels of DHA, DHAS and A4 were significantly decreased up to 5 years or more following treatment. It is concluded that after TBI, the cortisol homeostasis is maintained at the cost of reduced adrenal androgen secretion.
17-alpha-Hydroxyprogesterone↗
Serum levels of androgens and estrogens and 'steroid-sensitive' liver proteins in early human pregnancy: influence on the gender of the offspring.
Serum androgens, estrogens, 'steroid-sensitive proteins', thyroid components, and albumin were measured twice within a 4-5 week interval in 44 cases of early normal pregnancy (gestational weeks 8-18). Positive correlations were found in the total material between dehydroepiandrosterone sulfate (DHAS) and testosterone (T), unconjugated and total estrone, albumin, tetraiodothyronine, and calculated free tetraiodothyronine concentrations and within 2-week intervals between DHAS and T, estradiol-17 beta, and unconjugated and total estrone, and between T and estradiol-17 beta and unconjugated estrone. Positive correlations were also found between the rates of change in DHAS of albumin. No significant association was found between 'steroid-sensitive proteins' and androgens or androgen/estrogen ratios. Women giving birth to girls had significantly higher serum levels of pregnancy-associated alpha 2-macroglobulin, thyroxine-binding globulin, and ceruloplasmin and lower ratios between T and sex hormone binding globulin than women giving birth to boys. The important role of placental aromatization in the metabolism of maternal androgens is well known. Albumin binding and thyroid status may also affect the metabolism of DHAS during pregnancy. The androgen/estrogen balance may be of little importance for the regulation of 'steroid-sensitive' proteins during early pregnancy. The mechanism behind the higher serum levels of pregnancy-associated alpha 2-macroglobulin, thyroxine-binding globulin, and ceruloplasmin in women giving birth to girls remains to be elucidated.
Adult↗
Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function.
Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis. Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids. In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks. Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay. Serum cortisol, osteocalcin and urinary cortisol levels were also determined. An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response. In peripheral lymphocytes, GR mRNA levels were significantly down-regulated. MTIIa mRNA levels increased significantly. Serum osteocalcin decreased significantly during treatment with both BUD and FP. Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment. In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes. These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact. Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids.
Administration, Intranasal↗