Serum DHEAS Levels Research Articles

Relation of progesterone and DHEAS serum levels to 5-HT1A receptor binding potential in pre- and postmenopausal women.

Preclinical research and clinical experience point to a modulation of 5-HT1A receptor expression by gonadal steroid hormones. We examined the effect of estradiol, progesterone and DHEAS on serotonin neurotransmission in 16 premenopausal and 28 postmenopausal women, differentiating by reproductive status. By means of positron emission tomography and the radiotracer [carbonyl-(11)C]WAY-100635, the 5-HT1A receptor binding potential (BP) was quantified in 45 brain regions of interest. Median BP was used as a surrogate marker to estimate the whole brain effect of the steroid hormones on receptor binding. We found a strong negative effect of serum progesterone and DHEAS levels on 5-HT1A receptor binding in postmenopausal women both in the Median BP and on a regional level. Furthermore, there was a non-linear, U-shaped relationship between DHEAS levels and 5-HT1A receptor binding in the pooled sample. Presynaptic 5-HT1A receptor BP in the raphe nuclei was significantly explained in a non-linear way by both progesterone and DHEAS in the pooled sample. Our study confirms in humans a preclinically suggested relation of the steroid hormones progesterone and DHEAS to 5-HT1A receptor binding. We show differential effects of the hormones with regard to reproductive hormonal status. Non-linear, U-shaped relationships between hormone serum concentrations and serotonin neurotransmission might explain paradoxical effects of these hormones on mood.

Adrenal insufficiency in a woman secondary to standard-dose inhaled fluticasone propionate therapy

SummaryA 55-year-old woman with asthma presented with adrenal insufficiency of unknown origin. She was referred to our Division of Reproductive Endocrinology to further evaluate an undetectable morning cortisol level discovered during the evaluation of a low serum DHEA-S level. She was asymptomatic other than having mild fatigue and weight gain. Her medication list included 220 μg of inhaled fluticasone propionate twice daily for asthma, which she was taking as prescribed. On presentation, the undetectable morning cortisol level was confirmed. A urinary measurement of fluticasone propionate 17β-carboxylic acid was markedly elevated. Fluticasone therapy was discontinued and salmeterol therapy initiated with supplemental hydrocortisone. Hydrocortisone therapy was discontinued after 2 months. A repeat urinary fluticasone measurement 4 months after the discontinuation of fluticasone therapy was undetectably low and morning cortisol level was normal at 18.0 μg/dl. Inhaled fluticasone is generally considered to be minimally systemically absorbed. This patient's only clinical evidence suggesting adrenal insufficiency was fatigue accompanying a low serum DHEA-S level. This case demonstrates that adrenal insufficiency can be caused by a routine dose of inhaled fluticasone. Missing this diagnosis could potentially result in adrenal crisis upon discontinuation of fluticasone therapy.Learning points Standard-dose inhaled fluticasone can cause adrenal insufficiency.Adrenal insufficiency should be considered in patients taking, or who have recently discontinued, inhaled fluticasone therapy and present with new onset of nonspecific symptoms such as fatigue, weakness, depression, myalgia, arthralgia, unexplained weight loss, and nausea that are suggestive of adrenal insufficiency.Adrenal insufficiency should be considered in postoperative patients who exhibit signs of hypoadrenalism after fluticasone therapy has been withheld in the perioperative setting.Routine screening for hypoadrenalism in patients without clinical signs or symptoms of adrenal insufficiency after the discontinuation of inhaled fluticasone therapy is not indicated due to the apparently low incidence of adrenal insufficiency caused by fluticasone.

Day 3 FSH is inversely correlated with serum DHEAS level in patients undergoing IVF

Given that circulating DHEAS levels decline with aging and that DHEA supplementation has been suggested to improve ovarian response in women with evidence of diminished ovarian reserve, we aimed to assess whether endogenous DHEAS levels relate to ovarian reserve, response and IVF outcomes.

A phase Ib trial of mushroom powder in biochemically recurrent, hormone-naive prostate cancer.

142 Background: Biochemically recurrent prostate cancer (PC) is a common presentation of relapse after primary local therapies. Strategies to delay disease progression and defer initiation of androgen deprivation therapy and associated side effects are needed. White button mushroom (WBM, Agaricus bisporus) extract suppresses prostate cancer tumor growth in animals, and prior human experience indicates favorable toxicity profile. Methods: Patients (pts) with rising PSA of ≥0.2 ng/mL after prostatectomy (RP) and/or radiation (RT) and no radiographic evidence of metastases were treated with WBM powder tablets at 4, 6, 8, 10, 12 and 14 grams po daily. Dose escalation was conducted in cohorts of 6 and continued as long as no more than 1 patient per cohort experienced dose limiting toxicity (DLT). Therapy continued until PSA increased by ≥100% and by ≥1 ng/mL, or clinically detectable metastases or unacceptable toxicity occurred. Primary objective was feasibility and toxicity, secondary objective was the effect of WBM on serum PSA and androgen levels. Results: Thirty six pts were treated. Median age was 68 (53-80).Thirty three pts (92%) had prior RP and all underwent previous RT. Median PSA was 1.9 (0.2-22.2). Mean compliance was 98.6 %. No DLT’s were encountered. The most common side effect was grade 1 abdominal bloating (39%); one patient experienced asymptomatic grade 3 hyponatremia. Overall PSA response rate was 11% (95% CI: 4%-27%). Two pts receiving 8 and 14 gm/day demonstrated a PSA complete response (CR), defined as a decline in PSA to undetectable levels that continues for 26 and 7 months respectively. Two pts, receiving 8 and 14 gm/day, experienced confirmed PSA partial responses (PR), defined as a ≥50% PSA decline on treatment. After 3 months of therapy 36% of pts (13/36) demonstrated some PSA decrease below baseline. No association between PSA response and serum testosterone, DHT or DHEA levels was observed. Median duration on therapy is 10.2 months (0.9 – 35.3). Ten pts remain on therapy. Conclusions: Therapy with WBM was well tolerated. Our data suggest that WBM intake results in durable decreases in PSA level in some patients with biochemically recurrent PC. Further studies to clarify mechanism of action are warranted. Clinical trial information: NCT00779168.

Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

BackgroundAdrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women.MethodsThe study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured.ResultsT, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol.ConclusionPCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

High Dose Paroxetine-Induced Galactorrhea with Normal Serum Prolactin Level: A case report

ABSTRACTA 33-year-old woman with no significant psychiatric history began to have depressive and anxiety symptoms that worsened over time. She had depressed mood, loss of interest in her daily household works, reduced sleep and appetite, fatigability and irritability. A provisional diagnosis of depressive disorder was made and she was prescribed 20 mg/day paroxetine with the dose being increased to 60 mg/day at her third outpatient psychiatric appointment. After 2 weeks she noticed milk secretion from both her nipples. There were no abnormalities in blood chemistry, thyroid function tests and beta human chorionic gonadotropin. Magnetic resonance imaging of the hypothalamic/pituitary area was normal. The serum prolactin, FSH, DHEAS and estradiol levels were normal.Because her galactorrhea developed after increasing the paroxetine dosage to 60 mg/day, we reduced the dosage by 10 mg per week. The discharge stopped when we reached a dosage of 30 mg/day paroxetine. The temporal relationship between the paroxet...

Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (S) levels in medicated patients with major depressive disorder compared with controls

BackgroundThere is accumulating evidence regarding gender differences in clinical symptoms or response to antidepressants in patients with depression. However, less attention has been given to sex differences in the underlying biological mechanisms of depression. The adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S), play a critical role in controlling affect, mood, and anxiety. Changes in serum adrenal androgen levels have been reported in conditions pertaining to stress as well as in psychiatric disorders. The objective of the present study was to investigate differences in serum levels of adrenal androgens in male and female patients with major depressive disorder (MDD). MethodsParticipants included 90 inpatients with MDD at the psychiatric ward of Juntendo University Koshigaya Hospital who were receiving antidepressants. Serum levels of DHEA and DHEA-S were assessed at the time of admission. Matched controls (based on sex and age) included 128 healthy individuals. First, data from male and female MDD patients and controls were compared. Second, correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients with MDD were assessed by gender. In addition, effects of various factors on adrenal androgens were analyzed using multiple regression analysis. ResultsSerum DHEA levels were significantly increased in both male and female MDD patients compared with controls. Serum levels of DHEA-S in male patients were significantly decreased compared with male controls, whereas no significant differences were seen in female patients and controls. No significant correlations among adrenal androgens were observed in male patients with MDD, whereas significant positive correlations were found in both male and female controls. No significant correlations were seen between adrenal androgens and HAM-D scores in male or female patients. Multiple regression analysis showed that both hormones were affected by the age at onset of depression. LimitationsAll subjects in the present study were on antidepressant medications. ConclusionsElevated levels of serum DHEA may be associated with the biological pathophysiology of depression, as DHEA administration has been found to be effective for the treatment of depression. Findings of differential changes in DHEA-S levels in men compared with women may suggest distinct characteristics of these hormones between men and women with depression. However, DHEA/DHEA-S may be a poor indicator for evaluating severity of depression.

The use of dehydroepiandrosterone in the treatment of hypoactive sexual desire disorder: A report of gender differences

Data regarding the efficacy of dehydroepiandrosterone (DHEA) in the treatment of hypoactive sexual desire disorder (HSDD) are scarce and inconsistent. We aimed to determine possible gender differences in the efficacy of DHEA as a treatment for HDSS. Postmenopausal women (n=27), and men (n=21) with HSDD, were randomized to receive either DHEA 100mg daily or placebo for 6 weeks in a controlled, double blind study. Primary outcome measures were sexual function questionnaires. Hormone serum levels of DHEAS, total and bioavailable testosterone, estradiol, and urine levels of DHEA and androsterone were also measured. Participants on active treatment showed a significant increase in circulating serum levels of DHEAS, while bioavailable testosterone levels increased in women only. In women only, significant interaction effects were observed for sexual arousal (p<0.05), satisfaction (p<0.05), and cognition (trend; p=0.06). For arousal, a significant improvement was observed for the DHEA treated group at 6 weeks (p=0.001). Significant correlations were observed between bioavailable T and sexual cognitions, arousal and orgasm, while DHEAS was correlated with satisfaction. In the men, significant correlations were observed between testosterone and arousal (r=.45), sexual drive (r=.50) and orgasm (r=.55). In women with HSDD, DHEA treatment had a significant beneficial effect on arousal, whereas no efficacy was demonstrated in men, indicating a possible gender difference. This improvement seems to be mediated via DHEA's metabolism to testosterone. Our positive results suggest that the neurosteroid DHEA may be effective as a treatment for women with HSDD if administered at a dose of at least 100mg per day.

Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women

The current study examines the effect of administering dehydroepiandrosterone (DHEA) on short-term memory. This experiment used a double-blind placebo-controlled cross-over design to explore the effects of a four week regimen of 50 mg oral DHEA on performance on the digit span, verbal span, and modified Sternberg (Oberauer) tasks. The results demonstrate that the current regimen of drug administration significantly increases serum levels of DHEA, DHEAS, testosterone and estrone and substantially alters the patterns of correlations among the serum levels of these hormones. Despite this substantial change in the hormonal milieu, DHEA administration produced no beneficial effects on cognitive performance in the digit span, verbal span, or modified Sternberg paradigm tasks. Ancillary analyses of the relation between hormone levels and cognitive performance demonstrated a strong positive correlation between DHEA levels and performance on digit span forward/backward and verbal span forward in the placebo drug condition, but not in the DHEA condition. We interpret the juxtaposition of the null results of DHEA administration and the correlation of DHEA levels and performance in the placebo condition to indicate that the referenced correlations arise because a third variable (i.e., age) is associated with both performance and DHEA levels. Additional analyses supported this hypothesis.

Fatigue in patients with systemic lupus erythematosus: the role of dehydroepiandrosterone sulphate

Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 female patients with SLE with low disease activity (31 using, 29 not using prednisone) and 60 age-matched healthy women, and 2) fatigue between patients with SLE with low and normal DHEAS levels. Serum DHEAS levels were determined with an Advantage Chemiluminescense System. The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue. Patients were more fatigued (p ≤ 0.001) than healthy women and more often had below-normal DHEAS levels (p < 0.001). Patients using prednisone with low and normal DHEAS levels reported a similar level of fatigue (p ≥ 0.39). Patients with low DHEAS levels not using prednisone reported less fatigue than those with normal DHEAS levels (p ≤ 0.03). Thus, our results indicate that low DHEAS levels in SLE are not - or even inversely - related to fatigue. After our previous finding that DHEA administration does not reduce fatigue, this result further indicates that low serum DHEA(S) levels alone do not offer an explanation for SLE fatigue.

The steroid metabolome of adrenarche

Adrenarche is an endocrine developmental process whereby humans and select nonhuman primates increase adrenal output of a series of steroids, especially DHEA and DHEAS. The timing of adrenarche varies among primates, but in humans serum levels of DHEAS are seen to increase at around 6 years of age. This phenomenon corresponds with the development and expansion of the zona reticularis of the adrenal gland. The physiological phenomena that trigger the onset of adrenarche are still unknown; however, the biochemical pathways leading to this event have been elucidated in detail. There are numerous reviews examining the process of adrenarche, most of which have focused on the changes within the adrenal as well as the phenotypic results of adrenarche. This article reviews the recent and past studies that show the breadth of changes in the circulating steroid metabolome that occur during the process of adrenarche.

Abstract LB-224: A randomized phase 2 study of two doses of itraconazole in men with metastatic castration-resistant prostate cancer (mCRPC)

Abstract BACKGROUND: The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling, and delays tumor growth in murine prostate cancer xenograft models. Unlike ketoconazole, it does not suppress androgen synthesis. METHODS: A phase 2 study of oral itraconazole in men with mCRPC was conducted at 4 sites. Men were randomized to low dose (LD) or high dose (HD) itraconazole (200 or 600 mg/day) until disease progression or unacceptable toxicity. The primary endpoint was PSA progression-free survival (PPFS) at 24 wk (PSA progression = 25% PSA rise above baseline/nadir); a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints were progression-free survival (PFS) at 24 wk (progression = clinical/radiographic progression or death, but not rising PSA); median PFS; median PPFS; and max PSA decline. Exploratory outcomes included CTC enumeration, analysis of adrenal androgens (serum testosterone and DHEA), VEGF analysis, and GLI1 expression in skin biopsy samples. RESULTS: The HD arm enrolled to completion (N=29), but the LD arm closed early (N=17) due to a prespecified futility analysis. Table 1 shows efficacy results. In addition, 3/5 men (60%) in the HD arm and 2/3 men (67%) in the LD arm with unfavorable (≥5) CTCs at baseline converted to favorable (&amp;lt;5) CTC counts with treatment. Itraconazole did not reduce serum testosterone or DHEA levels. It had no effect on circulating VEGF levels. In skin biopsies, downmodulation of GLI1 was seen in 33% and 68% of men in the LD and HD arms, respectively. Median PPFS was superior in men who achieved GLI1 downmodulation compared to those who did not (P=.028). Toxicities with itraconazole included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia/hypertension/edema. CONCLUSIONS: Only the HD arm met its primary endpoint. Itraconazole 600 mg/day may have activity in men with mCRPC that is not mediated by androgen suppression, and may correlate with GLI1 downmodulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-224. doi:1538-7445.AM2012-LB-224

Polikistik Over Sendromunda, Brakiyal Arter’in Endotel Bağımlı ve Bağımsız Vazodilatasyonun Araştırılması

Objective: The endothelium plays an important role in the regulation of vascular tone. Arterial distensibility is a marker of functional and structural wall properties. A decreased distensibility is an important risk factor for cardiovascular disease. Hyperandrogenism may be related to impaired systemic arterial vascular compliance. In this study, using a non-invasive ultrasonography method, we investigated endothelium dependent and endothelium independent vasodilation in the brachial artery of the patients with polycystic ovary syndrome (PCOS). Materials and Methods: Fourteen hyperandrogenemic patients with PCOS and 18 healthy age and BMI matched controls were included in the study. Serum DHEAS, androstenedione, total and free testosterone levels were measured for the diagnosis of hyperandrogenism. Brachial artery diameter was measured at baseline, during post-occlusion reactive hyperaemia (flow-mediated, endothelium dependent dilation), and after 400 mg glyceryl trinitrate sublingually (endothelium-independent dilation). Vasodilation was expressed as the percentage change relative to the baseline diameter. Results: Baseline flow and blood pressure were similar in the patients with PCOS and healthy subjects. Baseline vessel diameter (mm) was not statistically different between the patients with PCOS (3.2p0.3) and control group (3.1p0.4). Endothelium dependent dilation in PCOS patients (7.8p5.4%) was significantly (pl0.05) lower than in control subjects (14.9p7.9%). Endothelium-independent dilation in PCOS patients (10.8p4.2%) was also significantly (pl0.01) lower than in controls subjects (20.3p9.9%). Conclusion: The results of this study suggest that the patients with PCOS have impaired endothelium-dependent and independent vasodilation and it could be determined non-invasive methods. Key words: Polycystic Ovary Syndrome; Hyperandrogenism; Brachial Artery; Vasodilation.

Relationship between Dehydroepiandrosterone Sulfate and Pre-Competitive Anxiety Status in College Basketball Players

Pre-competitive anxiety plays an important role in exercise performance. Dehydroepiandrosterone (DHEA) and its sulfate product (DHEAS) have been reported to act against psychological disturbance under stress condition. However, the change in DHEAS level under pre-competitive anxiety is remains unclear. The purpose of this study was to examine the changes in serum DHEAS levels and its impact on anxiety during pre-competitive condition. Twenty male professional basketball athletes (age 19.8 ± 0.3 years) were recruited in this study. All subjects completed the modified Competitive State Anxiety Inventory-2 (modified CSAI-2) questionnaire and blood samples were collected for DHEAS measurement on two separate days; before training (training state) and prior to basketball game (pre-competitive states). According to the serum DHEAS level, all subjects were divided into DHEA-increased and DHEA-decreased groups. We found that self-confidence intensity was significantly (p ＜ .05) lower during pre-competitive state compared to training state in DHEA-increased group. Similarly, direction of somatic and cognitive anxiety was significantly decreased under pre-competitive stress in DHEA-increased group. However, self-confidence and anxiety were not significantly changed between pre-competitive and training states in DHEA-decreased group. According to above evidences, we suggested that serum DHEAS could play a role in managing the anxiety under pre-competitive stress in basketball players.

Large Adrenocortical Carcinoma Presenting as an Adenoma with Precocious Puberty

Sir, We present a case of peripheral precocious puberty due to a large adrenal mass, with hemorrhagic and necrotic areas, despite long history and no metastasis, making the distinction between carcinoma and adenoma very difficult. A 3.5-y-boy presented with progressive enlargement of penis, appearance of pubic hair and hoarseness of voice for 2 y. There was no history of focal neurological deficits, testicular swelling or chronic drug intake. There was no family history of precocious puberty. The child had a muscular look, penile length and testicular volume were 8.5 cm and 2.3 cc respectively. Child belonged to Sexual Maturity Rating stage III. He weighed 23 kg, height was 107.5 cm and arm span of 103.7 cm. The blood pressure recorded was 90/60 mmHg which was normal for his age. A 5 cm rounded, firm, non tender lump in left lumbar region was felt. The bone age was 13–15 y. CECT abdomen revealed a large well defined heterogeneously enhancing necrotic mass involving left adrenal with specs of calcifications, closely abutting spleen and left kidney, however the fat planes were maintained. No evidence of metastatis was found on MRI brain and CT chest. Per-operatively a 13×10 cm tumor was found in left suprarenal area with intact capsule and hemorrhagic areas (Fig. 1), without any evidence of invasion. Considering the Weiss criteria, weight, size and presence of necrosis and hemorrhage (Fig. 2), diagnosis of adrenocortical carcinoma was considered. The hormonal profile revealed raised 17 hydroxy progesterone (5.14 ng/ml), testosterone (30 ng/dl), DHEAS (543 μg/dl) and cortisol (104 μg/ml) levels which came down to serum cortisol level of 48 μg/dl, serum testosterone of 10 ng/dl and serum DHEAS level of 152 μg/dl which were within normal limits 3 mo after surgery. Adrenocortical carcinomas are very rare cause of gonadotropin independent precocious puberty with an incidence of 1– 2 per million populations annually. It is usually unilateral and seen in females [1]. It has a bimodal age distribution [2]. Clinically, virilization is most common and only 10% present with cushingoid features and palpable mass. In 20– 40% cases, no history of hormonal overproduction is found. Red flag signs for adrenal carcinoma are large size (>4 cm), intra-lesional calcification, hemorrhage, necrosis, tumor

Serum levels of dehydroepiandrosterone sulfate (DHEAS) in ocular toxoplasmosis

There are no previous study about ocular toxoplasmosis and serum levels of dehydroepiandrosterone sulphated hormone (DHEAS). We use the chemoluminiscence automatized Immulite assay to determine the levels of DHEAS. Four groups were studied: (1) Individuals with chronic asymptomatic infection with a positive test for IgG anti-Toxoplasma and without ocular lesions (n = 16); (2) Chronic asymptomatic patients with retinal scars of retinochoroiditis by Toxoplasma (n = 19); (3) Acute symptomatic patients with active retinochoroiditis by Toxoplasma (n = 26); (4) Individuals with negative assays for IgG anti-Toxoplasma (n = 21). Comparison of DHEAS levels between groups were adjusted by age and sex and non-parametric Kruskall Wallis statistical tests were applied. No significant differences in serum levels of DHEAS were found between groups when age and sex were controlled. DHEAS levels were not significantly different in active ocular toxoplasmosis related to non active or non infected persons.

CAG repeat polymorphism in androgen receptor gene is not directly associated with polycystic ovary syndrome but influences serum testosterone levels

Hyperandrogenemia has been the most consistent feature of polycystic ovary syndrome (PCOS). Androgens exert their effects through androgen receptors (ARs). The expansion of the codon CAG trinucleotide repeat polymorphism in exon 1 of the AR gene represents a type of genetic alteration associated with changes in the AR gene function. The purpose of this study was to establish a possible association of the AR gene CAG repeat length polymorphism with PCOS, and its influence on clinical and biochemical androgen traits. Two hundred and fourteen Croatian women with PCOS and 209 healthy control women of reproductive age were enrolled. Phenotypic hyperandrogenism, BMI and waist to hip ratio were recorded. Hormonal profiles, fasting insulin and glucose levels were measured on cycle days 3–5. Genotyping of the CAG repeat polymorphism in the AR gene was performed. We found no significant difference in the mean CAG repeat number between the PCOS patients and controls (22.1±3.4 vs. 21.9±3.2, P=0.286). There was a positive correlation between the CAG repeat length and total testosterone (TT) in the PCOS group (R=0.225, P=0.015). A multiple linear regression model using mean CAG repeat length, BMI, age and HOMA-IR as predictors explained 8.5% (adjusted R2) of the variability in serum TT levels. In this model the CAG repeat polymorphism was found to be a significant predictor of serum TT levels in PCOS patients (P=0.015). The logistic regression analysis revealed that the CAG repeat length is not a significant predictor of hirsutism and acne status (P=0.921 and P=0.437, respectively). The model was adjusted for serum TT, free testosterone, androstendione and DHEAS levels as independent variables, which were also not found to be significant predictors of hirsutism (P=0.687, P=0.194, P=0.675 and P=0.938, respectively) or acne status (P=0.594, P=0.095, P=0.290 and P=0.151, respectively). In conclusion, the AR CAG repeat polymorphism is not a major determinant of PCOS in the Croatian population, but it is a predictor of serum TT level variability in women with PCOS.

Effects of intensive glycemic control on serum levels of insulin-like growth factor-I and dehydroepiandrosterone sulfate in Type 2 diabetes mellitus.

Although accumulating evidence shows that aging hormones are involved in glucose metabolism, effects of glycemic control on serum IGF-I and DHEAS levels are still unclear. To investigate the effects of glycemic control on these hormone levels, we conducted a 1-month longitudinal study of 49 Japanese patients with Type 2 diabetes mellitus. We measured serum levels of IGF-I and DHEA-S before and after 1-month glycemic control and analyzed the association of changes in IGF-I and DHEA-S with glycated hemoglobin (HbA1c). HbA1c was decreased at 1 month with mean changes of -1.2% (p<0.001). Serum IGF-I was increased with mean changes of 11 ng/ml (p<0.05), while serum DHEA-S was decreased with mean changes of -19 μg/dl (p<0.05). Multiple regression analysis showed that changes in DHEA-S were inversely associated with changes in fasting plasma glucose (β=-0.36, p=0.027) and HbA1c (β=-0.33, p=0.028), while changes in IGF-I were not. The present longitudinal study showed that intensive glycemic control for 1 month increased serum IGF-I level and decreased serum DHEA-S level in Japanese patients with poorly controlled Type 2 diabetes. Further studies are needed to clarify the hormonal changes in IGF-I and DHEA-S after intensive glycemic control would affect diabetic complications.

Serum sex steroids measured in middle-aged European and African–Caribbean men by gas chromatography–mass spectrometry

Differences in circulating steroid hormone levels have been hypothesized to explain ethnic differences in steroid-related diseases. The aim of this study was to determine the serum levels of a wide panel of steroid hormones, both androgens and estrogens, in healthy middle-aged African-Caribbean and European men. Serum steroid hormone levels were determined in men participating in a systematic public health study funded by the French National Health Insurance system. Blood was collected in the morning from 304 healthy African-Caribbean and European men aged between 40 and 69 years. Serum steroids were measured by mass spectrometry-gas chromatography, except for DHEAS and sex hormone-binding globulin, which were determined by RIA. Data were analyzed in 10-year age intervals by analysis of covariance, with adjustment for age, body mass index, waist-to-hip ratio, tobacco and alcohol consumption, and season of sampling. Compared with Europeans, African-Caribbean men presented significantly higher serum levels of measured bioavailable testosterone, 4-androstenedione (4-dione), and estrone (E1) regardless of the age group, of 5-androstenediol (5-diol) in those aged 40-49 and 50-59 years, and of testosterone (TT) and dihydrotestosterone in those aged 40-49 years. In contrast, European men aged 40-69 years showed significantly higher serum levels of DHEA and DHEAS. Significant differences in serum steroid hormone levels were observed in middle-aged African-Caribbean and European men. Whether such differences could contribute to ethnic differences in disease risk in adult men remains to be investigated. Some steroids, such as bioavailable TT, 4-dione, 5-diol, and E1, deserve particular attention.

P02-47 - The severity and duration of depression and the anabolic balance

ObjectivesIn recent years many investigators have paid attention to anabolic balance in depression. They highlight the importance of the ratio of anabolic and catabolic processes for prognosis of the outcome of depression. Some researchers suppose that cortisol/DHEAS ratio and growth hormone (GH) are important markers of anabolic balance. The aim of the study was to investigate the impact of severity and duration of depression on the anabolic balance in depressionMethods79 patients with depressive episode were examined (F 32.0-2), 64 males and 15 females. Depressive symptoms were evaluated by the Hamilton Depression Scale (HDS). Anxiety was evaluated by Hamilton Anxiety Scale. Blood samples were drawn before antidepressant treatment. Serum DHEAS, cortisol and growth hormone levels were measured using ELISA kits.ResultsThere was a negative correlation between cortisol level and duration of depression (r = - 0,47, p = 0,037). Cortisol/DHEAS ratio in patients with severe depression was significantly lower than in patient with mild depression (287 ± 89 and 374 ± 87, respectively, P = 0,002). Patients with early stage of depression have increased levels of catabolic hormones that have positive correlation with the severity of anxiety. Patients with long duration of depression have decreased levels of both anabolic and catabolic hormones.ConclusionsOur data demonstrate that depression can cause serious changes in the balance of anabolic and catabolic hormones. We can assume that the long duration of depression can cause exhaustion of HPA-axis.