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At least 19 recordsLinked to original sources

Alternating tamoxifen and medroxyprogesterone acetate in postmenopausal advanced breast cancer patients--short and long term endocrine effects.

The endocrine effects of alternating tamoxifen and medroxyprogesterone acetate have been evaluated in 26 post-menopausal patients with metastatic breast cancer. Endocrine evaluations included the RIA determination of plasma levels of sex-hormone binding globulin, follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, cortisol, and testosterone. The evaluation of the study parameters at different intervals during therapy indicates that with this schedule an alternate sequential effect on the endocrine system is achievable because each drug exerts its own endocrine activity that is completely reversed when the other drug is administered. We can hypothesize that the same alternate activity as seen on the endocrine system could be obtained also on other tissues and organs including tumors.

Breast Neoplasms↗

Workshop on perinatal exposure to dioxin-like compounds. III. Endocrine effects.

Studies involving endocrine effects in humans and experimental animals resulting from the exposure to dioxin-like (non-ortho-substituted PCBs, PCDDs/PCDFs) and nondioxin-like (PCBs, OC pesticides) compounds (DLCs and NDLCs) were presented. A variety of reproductive and hormonal parameters, including androgen status, sexual differentiation, and thyroid functionality, were discussed. As in utero and lactational exposure of the human fetus/neonate to these environmental contaminants is inevitable, continued research to identify sensitive biomarkers of effect and susceptibility, as well as to define dose-response relationships, is required.

Animals↗

[Alkylphenols: assessment of risks for aquatic ecosystems and for human health with particular reference to endocrine effects].

(Alkylphenols: evaluation of the risk to aquatic ecosystems and human health with reference to endocrine effects).--Endocrine disrupting chemicals (EDC) are a heterogeneous group of substances that can interfere with many endocrine functions. Their effects have been demonstrated in different taxa and they are suspected to affect human health. Alkylphenols are an important group of EDC. They are formed from the degradation of alkylphenol polyethoxylates in the environment or in the sewage treatment plants. They are generally characterized by a high bioconcentration factor (BCF) and accumulate both in sediments and aquatic species. Alkylphenols (APE) show estrogenic activity: studies on fish and rodents put into evidence on both reproductive and developmental effects. In a recent study, the levels of APE detected in seafood from the Adriatic Sea showed a no negligible human health risk for strong fish consumers.

Animals↗

Hydrocortisone alone vs hydrocortisone plus aminoglutethimide: a comparison of the endocrine effects in postmenopausal breast cancer.

The endocrine effects of replacement doses of hydrocortisone in postmenopausal women with advanced breast cancer were compared with the same doses of hydrocortisone plus aminoglutethimide. Fifteen patients received aminoglutethimide (AG) 250 mg three times a day plus hydrocortisone (HC) 20 mg twice a day for 2 weeks, then AG was increased to 250 mg four times a day. Another 13 patients received HC alone for 2 weeks, then AG was added. HC alone significantly suppressed oestrone (75% of baseline) and oestradiol (50% of baseline). Addition of AG to these patients produced further oestrone suppression (50% of baseline) significantly greater than HC alone. HC alone suppressed dehydroepiandrosterone sulphate as much as AG + HC. delta 4-androstenedione (delta 4A) and dehydroepiandrosterone (DHA) were suppressed by HC alone. Addition of AG produced a rise of delta 4A to basal levels. These results show that 3-beta-ol de hydrogenase is not induced by AG. AG plus HC together from day 1 produced significantly greater oestrone suppression (50% of baseline) than HC alone. Because high-dose steroids may induce aromatase and replacement doses produced marked peripheral endocrine effects, the use of replacement hydrocortisone should be reassessed in advanced breast cancer.

Aminoglutethimide↗

Evidence of reproductive endocrine effects in women with occupational fuel and solvent exposures.

Hydrocarbons (HCs) found in fuels and solvents are ubiquitous in the environment, yet we know little about their effects on the endocrine system. The objective of this study was to assess the potential reproductive endocrine effects of low-dose HCs encountered by female U.S. Air Force personnel with fuel (primarily JP-8 jet fuel) and solvent exposures (n = 63). We estimated the internal dose of HCs in fuels and solvents by measuring their levels in exhaled breath, including the sum of aliphatic HCs (C6H14-C16H34) and the sum of aromatic HCs (benzene, ethylbenzene, toluene, and m,p,o-xylenes). Adverse outcome measures included urinary endocrine markers that have been associated with nonconceptive (vs. conceptive) menstrual cycles in ovulatory women: lower preovulatory luteinizing hormone (LH) and mid-luteal phase pregnanediol 3-glucuronide (Pd3G) and estrone 3-glucuronide, and higher follicle phase Pd3G. We also obtained reproductive and exposure information from baseline questionnaires and daily diaries. Toluene was the most frequently found analyte in the breath, with values up to 52.0 ppb, and benzene breath levels were up to 97.5 ppb. Regression analysis revealed that preovulatory LH levels were significantly lower (p = 0.007) among women whose total aliphatic HC levels were above the median. The relationship between elevated aliphatic HC exposure and lowered preovulatory LH levels in the present study suggests that compounds in fuels and some solvents may act as reproductive endocrine disruptors. Confirmation of these findings is needed, not only to determine if fuel and solvent exposure may impact other LH-dependent physiologic functions but also to examine effects of fuels and solvents on conception.

Adult↗

Anti-tumor and endocrine effects of non-steroidal aromatase inhibitors on estrogen-dependent rat mammary tumors.

The non-steroidal aromatase inhibitor CGS 20,267, at maximally effective doses in non-tumor bearing adult female rats, elicits endocrine effects mimicking those seen after surgical ovariectomy and thus induces a "medical" ovariectomy. We now report on studies characterizing the anti-tumor and endocrine effects of three orally active non-steroidal aromatase inhibitors, CGS 20,267, CGP 45,688 and CGP 47,645, in adult female rats bearing estrogen-dependent DMBA-induced mammary tumors. Doses ranging from 3 to 3000 micrograms/kg were given by gavage once daily for 6 weeks. After 6 weeks of treatment, the ED50 for suppression of tumor volume was 10-30, 100 and 3-10 micrograms/kg for CGS 20,267, CGP 45,688 and CGP 47,645, respectively. The maximally effective dose for anti-tumor efficacy was 300, 1000 and 100 micrograms/kg for each of the three inhibitors, respectively. The observed potent anti-tumor efficacy was accompanied by potent endocrine effects. Thus, disruption of ovarian cyclicity (at maximal doses rats remained in constant diestrus) was observed in all animals from the 2nd or 3rd week of treatment to the end of the 6-week treatment period. Uterine weight, at the maximally effective doses for each of the three inhibitors, was suppressed to between 42 and 28% of pre-treatment levels. This suppression was similar to the suppression of uterine weight (27% of pre-treatment) seen after ovariectomy. Serum estradiol concentrations in rats treated with 300 micrograms/kg CGS 20,267 were significantly suppressed to 12% of pre-treatment levels and serum luteinizing hormone (LH) concentrations were elevated 3 to 4-fold over pre-treatment levels. Thus the potent anti-tumor efficacy seen with each of the three non-steroidal aromatase inhibitors was accompanied in each case by a variety of endocrine effects corresponding to those seen after ovariectomy.

9,10-Dimethyl-1,2-benzanthracene↗

The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors.

SIGNIFICANCE: There are 2.2 million breast cancer survivors, and approximately 25%-30% of newly diagnosed women each year are <50 years of age. Adjuvant therapy has prolonged survival, but the quality of that survival is influenced by persistent and late effects of therapy. Knowledge of treatment outcomes will assist in the design of interventions to prevent or manage persistent and late effects in survivors. PURPOSE: The purpose of this paper is to review the incidence of gonadal toxicity associated with adjuvant chemotherapy, side effects of endocrine therapy, quality of life outcomes, fertility concerns, and options to preserve fertility in young (<35 years) and young midlife (35-50 years) breast cancer survivors. RESULTS: Alkylating agent-based chemotherapy causes destruction of primordial follicles and impairment of follicular maturation resulting in temporary preservation of menses, reversible amenorrhea, irregular menses (perimenopause), or irreversible amenorrhea (ovarian failure--menopause). Younger women have a lower risk for amenorrhea with chemotherapy because of sufficient follicular stores, although the gonadal toxicity will result in an earlier than expected menopause. Premature menopause is associated with poorer quality of life, decreased sexual functioning, menopausal symptom distress, psychosocial distress related to fertility concerns, infertility, and uncertainty about late effects of premature menopause. Routine discussion about the menopausal experience, risks for infertility, and fertility preservation options is recommended. IMPLICATIONS FOR PRACTICE: This review identified adverse treatment outcomes for young and young midlife breast cancer survivors that can be minimized or prevented with targeted interventions.

Adult↗

Endocrine effects of vasectomy.

In order to provide information on the endocrine effects of vasectomy, unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were analysed in the blood plasma of twenty Mexican men on two occasions before and 1, 3, 6 and 12 months after vasectomy. Vasectomy appeared to be associated with a significant decrease in the plasma levels of pregnenolone, dehydroepiandrosterone and androstenedione and a significant increase in the levels of dihydrotestosterone and oestrone. A probably significant increase in oestradiol levels took place 12 months after vasectomy but not before. No consistent changes were found in testosterone (up to 12 months) or in FSH and LH levels (up to 6 months) after vasectomy. The unconjugated steroids indicated above, except oestrone, were also estimated, whenever possible, in seminal plasma specimens obtained from thirty-nine subjects (including the twenty indicated above) on the same occasions. Vasectomy was associated with a highly significant decrease of seminal plasma dihydrotestosterone levels on all occasions and a significant decrease in androstenedione levels after 6 and 12 months. After 12 months there was a decrease in dehydroepiandrosterone and an increase in oestradiol; these changes were both probably significant. In another preliminary study, the levels of pregnenolone sulphate, dehydroepiandrosterone sulphate, testosterone glucuronide, testosterone sulphate and dihydrotestosterone sulphate were estimated before and 1 month after vasectomy in the seminal plasma of fourteen to seventeen subjects. Testosterone glucuronide fell, probably significantly, but other conjugates were unchanged. The data indicate that vasectomy may be associated with significant changes in the circulating and in seminal plasma levels of several steroids. The gradual nature of some of the changes observed suggests the necessity of conducting in several centres large-scale, long-term studies on vasectomized subjects and on a carefully matched control group. During the last decade vasectomy has been widely practised in several parts of the world as a method of fertility control. However, information on the endocrine effects of this intervention appears to be scanty. In most of the human studies reported, a small number of individuals were investigated and the studies have been confined to the assessment of the short-term effects of the operation. Moreover, the hormonal indices assessed by the various investigators have been limited, in most cases, to gonadotrophins and testosterone in blood. The present study was designed to assess in the same subjects the levels of a number of unconjugated steroids, FSH and LH on two occasions before and 1, 3, 6 and 12 months after vasectomy. The studies were extended to include steroid analyses in seminal plasma in the hope that such assays might yield information as to the effects of vasectomy on the distribution of steroids in the fluids of the male reproductive tract.

Adult↗

Acute and subacute metabolic and endocrine effects of clenbuterol in female pigs.

The aim of the study was to assess the relationship between acute and subacute metabolic and endocrine effects after intravenous administration of the beta2-adrenergic agonist clenbuterol in a growth-promoting dose to female pigs. Acute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and nonesterified fatty acid (NEFA) concentrations during 300 min after a single administration of clenbuterol. Significantly higher serum insulin and NEFA concentrations (19.90 +/- 2.50 microU/ml, p<0.01, and 0.69 +/- 0.04 mmol/L, p<0.001, respectively) were measured 30 min after the preprandial administration of clenbuterol in female pigs. Over the same period, the levels of blood glucose (4.42 +/- 0.30 mmol/L) showed no difference from those of control pigs. The postprandial serum NEFA concentration decreased moderately during 210 min after feeding. Postprandial blood glucose and insulin concentrations increased and reached maximal levels 120 min after clenbuterol administration (10.91 +/- 0.60 mmol/L and 85.22 +/- 7.24 microU/ml, respectively), and returned to basal levels at 300 min (4.20 +/- 0.21 mmol/L and 7.75 +/- 1.60 microU/ml, respectively) after the administration of clenbuterol. Subacute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and NEFA concentrations for 21 days after the repeated doses of clenbuterol. In addition, the influence of clenbuterol administration on the endocrine regulation of the onset of the next expected oestrus in female pigs was assessed by measuring their serum 17beta-oestradiol and progesterone concentrations. Blood glucose, serum insulin and NEFA concentrations after the last administration of clenbuterol did not differ significantly from those in control animals. The onset of the next expected oestrus occurred regularly without any significant difference in serum 17beta-oestradiol or progesterone concentrations between the treated (9.83 +/- 2.60 pg/ml and 0.15 +/- 0.03 ng/ml) and control pigs (8.52 +/- 2.70 pg/ml and 0.25 +/- 0.06 ng/ml). The study results suggest the duration of intravenous administration of clenbuterol in a growth-promoting dose necessary to influence the metabolic and endocrine activities in female pigs.

Adrenergic beta-Agonists↗

Treatment with formestane alone and in combination with aminoglutethimide in heavily pretreated breast cancer patients: clinical and endocrine effects.

We studied the clinical and endocrine effects of the aromatase inhibitor formestane (4-hydroxyandrostenedione, 4-OHA) in heavily pretreated breast cancer patients (median number of previous endocrine treatments 2, range 1-4). Of 30 patients eligible for response evaluation, 3 patients (10%) showed a partial response while 11 patients (36.7%) experienced stable disease over a time period of at least 6 months. Plasma levels of oestrone, oestradiol and oestrone sulphate were found suppressed to a mean of 33.9, 35.6 and 24.2% of control values. 4 of 6 patients experienced a further substantial reduction in plasma oestrone sulphate to < 5% of pretreatment values when aminoglutethimide (AG) was added after relapse on 4-OHA monotherapy. Our findings suggest that these aromatase inhibitors may suppress plasma oestrogen levels by a percentage approaching the percentage inhibition of in vivo aromatisation measured by tracer techniques.

Adult↗

Endocrine effects of cyproterone acetate in patients with prostatic cancer.

Cyproterone acetate was given to patients with stages C and D prostatic cancer and its effect on endocrine parameters was studied. At a daily oral dose of 100 mg. cyproterone acetate induced marked reduction in the size and consistency of tumor, while it caused moderate suppression of serum luteinizing hormone, follicle-stimulating hormone and testosterone levels. Elevation of serum prolactin levels was observed after treatment with cyproterone acetate but was to a lesser degree than that caused by estrogens.

Aged↗

Metabolic and endocrine effects of sleep deprivation.

Sleep deprivation has multiple effects on endocrine and metabolic function. In particular, sleep restriction is accompanied by increased cortisol levels in the afternoon and early evening and a shorter quiescent period compared with extended sleep periods. Those alterations could facilitate central and peripheral disturbances that are associated with glucocorticoid excess, such as memory deficits, and are similar to those observed in aging. Thus, chronic sleep loss could contribute to acceleration of the aging process. Sleep restriction is also associated with an impairment of carbohydrate tolerance, similar to that observed in individuals with clinically significant impaired glucose tolerance. Thus, chronic sleep deprivation may increase the risk for diabetes. Finally, sleep plays an important role in energy balance. Partial sleep deprivation was found to be associated with a decrease in plasma levels of leptin and a concomitant increase in plasma levels of ghrelin; subjective ratings of hunger and appetite also increased (the appetite for protein-rich foods was not significantly affected). Moreover, a remarkable correlation was found between the increase in hunger and the increase in the ghrelin:leptin ratio. Thus, the neuroendocrine regulation of appetite and food intake appears to be influenced by sleep duration, and sleep restriction may favor the development of obesity.

Appetite↗

Changes in the hypothalamic serotonergic function may mediate the endocrine effects of melatonin.

The effects of a single injection of melatonin on serum thyroxine, corticosterone and prolactin levels, and the associated changes in the metabolism of serotonin (5-HT) in several hypothalamic regions of male rats kept under a 14-h light 10-h dark cycle (lights on at 08:00 h), are investigated. Melatonin (500 micrograms/kg, s.c.) or replacing saline was injected at 18:00 h, and 8 animals from treated and control groups were killed 1 h (19:00 h), 12 h (06:00 h) and 18 h (12:00 h) later. Melatonin significantly reduced serum thyroxine, corticosterone and prolactin levels within 1 h of treatment, indicating the existence of an acute inhibitory effect on hormonal secretion. Serum prolactin levels were increased 18 h after treatment, suggesting the implication of a different long-term regulatory mechanism. Injected melatonin induced several acute changes in the metabolism of 5-HT in the hypothalamus. Thus, a significant increase of 5-HT content in the preoptic area-anterior hypothalamic (POA-AH) and medial hypothalamic regions of melatonin-treated rats was observed within 1 h of treatment. The content of 5-hydroxyindoleacetic acid (5-HIAA) increased in medial hypothalamus, and the ratio 5-HIAA/5-HT decreased in POA-AH. The results show that melatonin acutely modifies the serotonergic activity in POA-AH and medial hypothalamus, and simultaneously inhibits thyroid, adrenal and pituitary hormonal secretion. The results are discussed suggesting that the hypothalamic serotonergic system could be an ideal mechanism underlying short-term melatonin effects on endocrine function.

Animals↗

[Endocrine effects of doping with androgenic anabolic steroids].

We describe two case histories that highlight some of the endocrine effects of doping with androgenic anabolic steroids. The main endocrine effect observed after use of androgenic anabolic steroids is the development of hypogonadotrope hypogonadism, characterized by low levels of gonadotrophins, suppression of testosterone production and azoospermia. If testosterone is used alone, or in combination with synthetic anabolic steroids, the circulating levels of testosterone are normal or high. Oestrogen levels may be elevated owing to aromatization of testosterone. The level of sex hormone binding globulin is suppressed. These endocrine parameters are of practical use in evaluating patients misusing androgenic anabolic steroids.

Adult↗

Acute and chronic endocrine effects of noise: Review of the research conducted at the Institute for Water, Soil and Air Hygiene.

This is a review of the research into endocrine effects of noise since the early 1980s at the Institute for Water, Soil and Air Hygiene. According to our knowledge, no other group has studied systematically the endocrine effects of acute and chronic noise exposure. Mechanisms of acute noise-induced stress reactions as well as long-term increase of stress hormones in animal and persons under chronic noise exposure were studied. Our theoretical background was Henry's psychophysiological stress model with the two reaction alternatives : (i) The fight-flight reaction, characterised by an increase in adrenalin and noradrenaline (ii) The defeat reaction with increased cortisol. Extremely intense acute noise exposure near the threshold of pain caused an increased release of cortisol from the suprarenal cortex but acute noise exposure with levels between 90 and 100 dB(A) caused an increase of catecholamines. Non-habituated noise increased primarily the release of adrenalin from the suprarenal medulla, whereas habituated noise caused a chronic increase of noradrenaline from the sympathetic synapses under longterm noise exposure at work. Environmental noise exposure (Leq >/= 60 dB(A)) caused catecholamine increase if activities such as conversation, concentration, recreation etc were disturbed through noise. In sleeping persons, traffic noise with only Leq >/= 30 dB (A) and Lmax >/= 55 dB(A) caused significant acute increase of cortisol, which developed into chronic increase if the noise exposure was repeated consistently. Parallel to cortisol, chronic noradrenaline increase was also observed. Based upon the empirical results, a noise stress model was developed which is a first step forward in the theoretical understanding of endocrine noise effects.

Journal Article↗

Ecdysteroid synthesis and imaginal disc development in the midge Chironomus riparius as biomarkers for endocrine effects of tributyltin.

Acute effects of the endocrine disruptor bis(tri-n-butyltin) oxide (TBTO) on molting-hormone biosynthesis and imaginal-disc development were investigated in larvae of the midge Chironomus riparius (Meigen). Ecdysteroid synthesis was measured by 24-h incubation of molting-hormone-synthesizing tissues (prothoracic glands) in vitro with or without the addition of TBTO. The amount of ecdysteroids produced was analyzed by radioimmunoassay. Developmental effects in vivo were investigated by determining the developmental phase of the genital imaginal discs before and after a 48-h exposure to TBTO in water. Sex-specific effects were found with both endpoints. Ecdysteroid synthesis was significantly reduced (analysis of variance [ANOVA], p < or = 0.005) in female larvae at all concentrations (TBTO-Sn at 50, 500, and 5,000 ng/L), whereas a significant elevation of the biosynthesis rate occurred in male larvae in the 500-ng/L treatment (ANOVA, p < or = 0.05). In vivo experiments with development of the genital imaginal disc within a 48-h exposure period revealed a significantly slower development in female larvae and a significantly faster development in male larvae (contingency tables, p < or = 0.001) at all concentrations tested (TBTO-Sn at 10, 50, 200, and 1,000 ng/L). These results partly coincided with the in vitro effects on molting-hormone synthesis. The 48-h median lethal concentration (LC50) was 25 microg/L (20-30 microg/L 95% confidence intervals). The combination of in vitro and in vivo methods has proven to be a useful approach for the detection of endocrine effects of TBTO in C. riparius at levels 2,000-fold below the LC50 value. High sensitivity and short test duration suggest that chironomids may have potential as freshwater sentinel organisms for endocrine-disrupting chemicals.

Animals↗

Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats.

The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally exposed male rats. Di(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DINP) are currently being evaluated as potential substitutes for DEHP, but similarities in structure and metabolism of DEHP with DEHA and DINP have led to the hypothesis that similarities in action may also exist. Pregnant Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg bodyweight per day), DINP (750 mg/kg bodyweight per day), DEHP (750 mg/kg bodyweight per day) in combination with DEHA (400 mg/kg bodyweight per day), or DEHP (300 mg/kg bodyweight per day) in combination with DINP (750 mg/kg bodyweight per day). DINP and DEHP were both shown to reduce testicular testosterone production ex vivo and testosterone levels in testes and plasma of male fetuses at gestation day 21, indicating a similar mechanism of action for DINP and DEHP. Additionally, plasma LH levels in male fetuses were elevated. Neonatal anogenital distance was reduced and the number of nipples at postnatal day 13 increased in DEHP-exposed male offspring. Serum inhibin B levels were significantly reduced in DEHP-exposed prepubertal male offspring, and in a few adult males. No modulating effects of DEHA on the endocrine effects of DEHP were detected, but a tendency towards an accumulating effect of DEHP and DINP in combination on suppression of testosterone synthesis was seen.

Adipates↗

The clinical and endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer.

The aromatase inhibitor, 4-hydroxyandrostenedione (4OHA) is an effective treatment for advanced post-menopausal breast cancer. The clinical and endocrine effects of 4OHA treatment were studied in five pre- and perimenopausal women with metastatic breast cancer. Serum oestradiol levels were not significantly reduced as a result of treatment with 500 mg of 4OHA by weekly i.m. injections and no patient had a tumour response. Four patients were subsequently treated with the luteinising hormone releasing hormone (LHRH) analogue, gosereline, and three had objective responses. The endocrine effects of combined treatment with goserelin (Zoladex), and 4OHA were studied in a further five premenopausal women. Serum oestradiol levels after treatment with goserelin alone were typical of post-menopausal women. Addition of 4OHA led to a further suppression of oestradiol to within the range observed in post-menopausal patients treated with further suppression of oestradiol to within the range observed in post-menopausal patients treated with 4OHA. Six patients whose tumours had regressed as a result of goserelin treatment and who subsequently relapsed were then given combined treatment. Four of the six experienced a second remission. We conclude that while 4OHA alone is unlikely to be a satisfactory treatment for premenopausal patients with advanced breast cancer, 4OHA in conjunction with goserelin leads to profound suppression of oestradiol. The combination of LHRH analogue and aromatase inhibitor may prove to be a superior treatment to LHRH analogue alone in these patients.

Adult↗