Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean women with polycystic ovary syndrome: insights from a large Caucasian cohort.

PURPOSE: Polycystic ovary syndrome (PCOS), considered a lifelong condition, manifests mainly as a cluster of hyperandrogenic symptoms during the early reproductive years, with the affected woman gradually developing an adverse cardiometabolic profile over the years. However, some data point to the possibility of differences in the evolution of PCOS according to a woman's weight. The aim of the present study was to evaluate the metabolic and hormonal profiles of women with PCOS over time. METHODS: A total of 763 lean women with PCOS (BMI 20-25 kg/m2) and 376 controls were included. The study group was further divided into three age groups representing women post-adolescence, of reproductive age, and of late reproductive age. All subjects were assessed clinically, biochemically, and hormonally. RESULTS: Waist circumference, lipids, androgens, and insulin resistance index (homeostasis model assessment of IR index (HOMA-IR)) were significantly higher in the PCOS group compared with controls. Age subgroup analysis showed a progressive decrease of HOMA-IR and waist circumference, and lipid levels were comparable between PCOS and controls in all age groups. Androgens remained significantly higher in PCOS, but they gradually decreased through time. A significant negative association of age with waist circumference, androgens, insulin, and HOMA-IR was revealed. Univariate and multivariate regression analysis disclosed a strong correlation of HOMA-IR with age (p = 0.014, ß - 0.19, SE coefficient 0.008) as a single parameter or in combination with total cholesterol (TC) (p < 0.001, age: ß - 0.023, SE 0.10; TC: ß 0.084, SE 0.027). CONCLUSION: Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean PCOS women. We hypothesize that if these women do not gain weight with the passage of time, there is a high probability that their cardiometabolic risk will be attenuated.

In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis.

BACKGROUND: Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). MATERIAL AND METHODS: We measured serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and adiponectin, TSH, free T4 (FT4) and free T3 (FT3) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3). RESULTS: In Group 1 there was no significant change in concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 or adiponectin, despite a fall in FT4 and FT3 (8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT3, and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT4, p<0.001). In Group 2 RIT did not cause any acute change in serum MMP-2, MMP-9, TIMP-1 and TIMP-2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP-2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ml (V3), p<0.01]. There was no significant change MMP-2, MMP-9 and TIMP-1 between V1 and V3. There was a decrease in FT4 and FT3 from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT4 and FT3, respectively. CONCLUSIONS: Radioiodine therapy of thyrotoxicosis does not alter serum MMP-2, MMP-9 or TIMP-1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin might reflect favourable effects of radioiodine administration on cardiovascular risk factors, while an increase in TIMP-2 (principal MMP-2 inhibitor) might lead to a decrease in free MMP-2 concentrations.

Evolution of bone disease at 2 years after transplantation: a single-center study.

Posttransplant bone disease is caused by renal osteodystrophy. We sought to examine bone mineral density (BMD) among 90 renal allograft recipients of mean age 42.7 +/- 11.4 years to identify factors preventing bone loss at 2 years posttransplant. Subjects treated with cyclosporine or tacrolimus plus azathioprine/MMF and prednisone underwent BMD estimates of the lumbar spine (LS) and of the proximal femur using dual energy x-ray absorptiometry (DEXA) at 3 months and every 6 months for 2 years. We assayed markers of bone remodeling: intact parathyroid hormone (iPTH), calcitriol, osteocalcin, and carboxyterminal telopeptide of type I collagen on day 3, as well as month 1 and every 6 months after transplantation. At the initial measurement, we observed osteopenia (OSP) among 35% in the LS and 52% in the femur: there was osteoporosis in 8.3%. The prevalence of OSP increased during the first year, thereafter decreasing to the initial value, but the rate of osteoporosis did not change significantly (8.3% vs 6.0%). BMD and Z-score decreased during the first and increased in the second year; 27% of patients regained initial values and 38% higher ones. BMD gains in the LS and femur were observed among subjects with higher calcitriol levels during the first 6 months (P < .01), higher osteocalcin (P < .05), higher estimated glomerular filtration rate during 1-24 months and in the tacrolimus group. Improvement of LS BMD occurred in younger patients (38 vs 46 years; P < .027); BMD gain in the femur correlated with higher levels of iPTH from 1-12 months (P < .01). The tacrolimus group showed higher Z-scores in the LS and femur at 24 months (P < .05). Two years after transplantation >60% of recipients showed stabilization or gain in bone mass. A sufficient calcitriol level in the early transplant period, an adequate iPTH, good renal function, and tacrolimus therapy prevented BMD disease progression.

Metastases to the internal mammary lymph nodes as the only spread of ductal breast cancer: case description.

The present paper describes a case of a breast cancer patient in whom lymphoscintigraphy identified metastases in the internal mammary nodes whilst the axillary lymphatic center was tumor-negative. Because of the lymph node involvement, cancer was restaged from original I to IIIc. Consequently, the patient was qualified for chemotherapy with docetaxel and doxorubicin. The case described is another contribution for the routine application of sentinel lymph node biopsy (SLNB) in breast cancer patients.

Serum lipid peroxides and total antioxidant status in postmenopausal women on hormone replacement therapy.

Estradiol (E2) has antioxidant properties. The role of progestins in antioxidant defense is still unknown. We have evaluated the influence of E2 and E2 plus medroxyprogesterone acetate (MPA) on serum lipid peroxide (LPO) levels, a marker of free radical reactions, and serum total antioxidant status (TAS) in postmenopausal women. Subjects consisted of 26 women with surgical menopause, before and after 4 months of estrogen replacement therapy (ERT; E2), and 54 women with natural menopause on hormone replacement therapy (HRT; E2 plus MPA). Forty premenopausal women served as a control group. Serum E2 was estimated by radioimmunoassay, follicle-stimulating hormone by IRMA methods, LPO and TAS by colorimetric methods. Before therapy, LPO levels in the postmenopausal women were significantly higher (p < 0.001) than in the control group. After both ERT and HRT, LPO decreased significantly and did not differ between both groups and the control group. TAS was significantly lower in postmenopausal women (p < 0.001) than in the control group before therapy. After both ERT and HRT, TAS increased significantly and did not differ between both groups and the control group. We conclude that oxidative stress is increased after menopause. ERT and HRT inhibit the generation of free radicals and raise antioxidant potential to the levels found in premenopausal women. MPA did not influence the antioxidant action of E2.

Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism.

Many animal and human studies show that supraphysiological doses of dehydroepiandrosterone (DHEA) can influence body composition and carbohydrate and lipid metabolism. Most studies have concentrated on women and have not been randomized, thus creating controversial results. With this in mind, we designed a cross-over double-blind placebo-controlled study of 12 men aged 59.0 +/- 4.8 years, who received either 50 mg/24 h DHEA or placebo for 3 months to assess the influence of DHEA on the content and distribution of fat tissue and serum insulin, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels, as well as testosterone, estradiol, DHEA-sulfate (S), prostate-specific antigen (PSA) concentrations and indexes of insulin sensitivity and resistance. Patients were recruited from university employees attending for periodic health checks, with normal hepatic and renal function with endogenous DHEA-S level < 1500 ng/dl. Our results did not reveal any significant changes in study parameters, apart from a statistically significant increase in DHEA-S levels after therapy with active substance.

Influence of dietary and genetic factors on metabolic status in obese and lean postmenopausal women.

This preliminary study addressed the possible associations between dietary, genetic and hormonal factors that are involved in the development of menopausal obesity and its metabolic consequences. We performed anthropometrical, hormonal and biochemical measurements and used a nutritional questionnaire on 43 postmenopausal women who were non-HRT-users (14 obese and 29 non-obese subjects, mean age +/- SD of 52.8 +/- 4.6 years, mean body mass 74.6 +/- 4.6 kg). All of the women also had fat mass assessed by DPX-Lunar. From the 24-h dietary recall, the nutrient intake in daily food rations was calculated using a computer program (Nutritionist IV, San Bruno, CA, USA) based on our own database. Restriction fragment length polymorphism of the estrogen-receptor-alpha gene was determined with the PvuII restriction enzyme. Obese women widely under-reported their daily food intake. The analysis of body fat distribution showed that the total body weight and the percentage of total fat mass were significantly increased in the obese group (p = 0.001). We observed significantly higher leptin (20.56 +/- 11.9 vs. 9.02 +/- 2.8 ng/ml) and total cholesterol (but lower cholesterol HDL), triglycerides levels in the obese subjects (261.89 +/- 48.8 vs. 248.23 +/- 55.9; 52.17 +/- 13.6 vs. 60.92 +/- 13.04; 142.82 +/- 61.02 vs. 106.61 +/- 27.7 mg/dl). Except for diastolic blood pressure, clinical variables were not significantly different between subjects with and without the PvuII ERalpha polymorphism. Allele frequencies of the ERalpha polymorphism did not differ from those previously reported (P-0.48, p-0.52) in our study. In this preliminary study we failed to find dietary and genetic factors involved in the pathogenesis of menopausal obesity. However, our results provide support for the notion that the perimenopausal increase in visceral fat is a significant factor involved in the increased cardiovascular risk in postmenopausal women.

Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery.

A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid is reported. A 61-year-old woman presented with typical symptoms and signs of acromegaly for at least 10 years. She suffered from recurrent pneumonias, but repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown an enlarged pituitary gland without focal lesions together with a cerebral meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was confirmed by histology carried out after bronchoscopy and tumor excision. We observed partial suppression of GH secretion following short-term oral bromocriptine administration in this patient. Surgical removal of the carcinoid tumor resulted in a complete clinical, hormonal and radiological cure of acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial carcinoid differs from others described in the literature by an atypical large tumor size, the suppression of elevated GH secretion by oral bromocriptine and a concomitant meningioma.

Quantitative ultrasound of the heel and some parameters of bone turnover in patients with acromegaly.

Acromegaly caused by growth hormone (GH) hypersecretion is characterized by enhanced skeletal growth and soft tissue enlargement. Insulin-like growth factor-1 (IGF-1) is the main peripheral mediator of GH action and it has a crucial role in the maintenance of a normal bone mass. However, in some patients with acromegaly, secondary osteoporosis is observed, despite the strong anabolic effect of GH and IGF-1 in bones. It is thought to be due to hypogonadism. The bone changes are accompanied by increased turnover. The aim of this study was to assess bone properties by ultrasound and turnover in patients with acromegaly. The study was carried out in 26 patients (13 men, 13 women): 14 with active acromegaly and 12 cured by surgery who had non-active disease. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and their combination Stiffness Index (SI) by quantitative ultrasound (QUS) of the heel, hormonal status, serum osteocalcin (OC) concentration and the urinary excretion of pyridinoline collagen crosslinks (PYR) were all studied. Controls were 20 age- and sex-matched healthy persons. We observed statistically significantly lower QUS values in patients with active disease than in those whose disease was cured. The differences were more pronounced in men. QUS values were lower in the entire group of patients compared with the controls; however, the differences were not statistically significant. Serum OC concentrations and urinary PYR excretion were higher in active disease. Statistically significant inverse correlations between serum GH levels and SOS (r = -0.58, p = 0.002); BUA (r = -0.66; p = 0.0001); T-score (r = -0,65, p = 0.0001) and Z-score (r = -0.66, p = 0.0001) were found only in male patients. No correlations between IGF-1, duration of the disease, OC, PYR and other data studied were observed. In conclusion, we have shown decreased QUS parameters suggesting impaired bone properties and quality in terms of density and elasticity in men, but not in women, with active acromegaly. This finding suggests osteoporosis with increased bone turnover. The above-mentioned changes might be caused by the action of GH on trabecular bone and its metabolism, since no hypogonadism in male patients was shown. Moreover, the influence of acromegaly on heel geometry and soft tissue swelling should also be considered.

Polish consensus: procedure in case of estrogen deficiency in women after breast cancer therapy.

Women surviving breast cancer in the postmenopausal period suffer from hormonal alternations with adverse effect on mental status and functioning of a number of organs and systems. Two thirds of these women had menopause before the diagnosis of breast cancer. In the remaining one-third ovarian failure is natural or induced by chemotherapy. Doctors cautiously approach the use of estrogen therapy in this group of patients. Their fears are not unsupported bearing in mind known epidemiological data exist linking breast cancer with the use of hormonal therapy. The purpose of this review is to evaluate current data on hormonal use and breast cancer risk.

Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women.

Free radical reactions are involved in processes connected with aging. Estradiol acts as antioxidant and free radical scavenger, but the mechanism of this action remains unknown. Estradiol has a hydroxyphenolic structure and may donate hydrogen atoms to lipid peroxyradicals to terminate chain reactions. There are a few reports concerning the influence of estradiol on natural antioxidant enzyme activity, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The aim of this study was to estimate the relationship between the levels of estradiol and lipid peroxide (LPO), a marker of membrane lipid peroxidation, and the correlation between estradiol and erythrocyte SOD and GSH-Px activity. The study included 13 premenopausal and 13 postmenopausal healthy women. Serum levels of estradiol, follicle-stimulating hormone (FSH) and LPO, and erythrocyte SOD and GSH-Px activity were estimated in all subjects. Premenopausal women revealed significantly higher estradiol levels and lower LPO concentrations, as well as significantly higher GSH-Px activity than the postmenopausal group. SOD activity did not differ between the two groups. There was a negative correlation between serum estradiol and LPO levels as well as a positive correlation between estradiol and GSH-Px activity. These results support the hypothesis that estradiol exerts its antioxidant action not only through its chemical structure but probably also through its influence on natural cellular antioxidant enzyme activity.

Coexistence of parathyroid carcinoma and non-medullary carcinoma of the thyroid.

A case of 35-year-old woman with parathyroid cancer is presented. Five years ago she underwent surgery for follicular thyroid cancer. Parathyroid cancer was evidenced by palpable, solid, irregularly shaped cervical tumor 5 cm in diameter. The patient had severe hyperparathyroidism confirmed by biochemical findings of hypercalcemia reaching 16 mg%, hypophosphatemia and hyperphosphatasemia. Serum parathormone level was 23-fold higher than the norm. These findings were accompanied by polyuria, polidypsia, symptoms of bone damage and renal calcification. After the surgery the patient's condition improved significantly despite persistent hyperparathyroidism. The level of parathormone decreased, but was still 11 times higher than the norm. Two months after the surgery she noticed a single node on her neck. The patient was re-operated for recurrence of parathyroid cancer. Serum parathormone level was then 6-8 times above the norm. Medical treatment with furosemide, calcitonin and biphosphonate resulted in normalization of calcemia and phosphatemia. Further management will aim at localization of foci of hyperactive parathyroid tissue in order to enable radical reoperation. The case is reported because of rare occurrence of parathyroid carcinoma as well as because the carcinoma occurred in a patient who previously had follicular thyroid cancer. There are no reports of coexistence of these two neoplasms in available literature.

Surgery for ovarian masses in infants, children, and adolescents: 102 consecutive patients treated in a 15-year period.

BACKGROUND/PURPOSE: Ovarian pathology, although rare in children, must be included in the differential diagnosis of all girls who present with abdominal pain, an abdominal mass, or precocious puberty. METHODS: To improve clinical appreciation of these lesions, the authors reviewed the presentation, evaluation, and outcome of all patients with ovarian pathology surgically treated at their institution since 1985. RESULTS: One hundred two girls (aged 9.8 +/- 5.5 years; range, 2 days to 20 years) underwent 106 separate ovarian operations (43 salpingo-oophorectomies, 21 oophorectomies, 33 ovarian cystectomies, and 9 ovarian biopsies). Of those presenting with acute abdominal pain (n = 59), 25 (42%) had ovarian torsion (14 associated with a mature teratoma), and only 1 (2%) had a malignant tumor. In contrast, of those presenting with an abdominal mass (n = 23), 6 (26%) had malignancies. There was no age difference between those with benign disease (9.9 +/- 5.6 years; n = 96) and those with malignant tumors (8.6 +/- 3.9 years, n = 10). Nine children had 10 operations for presumed malignant tumors (3 dysgerminomas, 2 immature teratomas with foci of yolk sac tumor, 2 juvenile granulosa cell tumors, 1 yolk sac tumor, and 1 Sertoli-Leydig cell tumor). These patients all had unilateral salpingo-oophorectomy, 4 had chemotherapy, and all are now disease free at 8.4 +/- 4.1 years follow-up. CONCLUSION: Ovarian pathology remains a rare indication for surgery in girls less than 20 years of age. Because most of these lesions are benign, ovarian-preserving operations should be performed whenever feasible.

[Characteristic features of primary hyperparathyroidism caused by parathyroid cancer--based on 2 cases]. / Cechy charakterystyczne pierwotnej nadczynnosci przytarczyc spowodowanej rakiem przytarczyc--na podstawie dwóch przypadków.

Two cases of women with primary hyperparathyroidism caused by parathyroid cancer were presented. The authors noticed the following characteristic features of primary hyperparathyroidism in the course of the cancer: rich clinical symptomatology usually in form of considerable bone destruction, renal stones and nephrocalcinosis, biochemically very high level of calcium, above 14-16 mg%, threatening with hypercalcemic crisis and considerably higher parathormone serum concentration even up to twenty times above the norm. Parathyroid cancer, more often than adenoma, is a stiff and large neck tumour accessible for palpation. There are no specific biochemical and imagining examination techniques to recognise beyond any doubt the cancer character of primary hyperparathyroidism before operation. The histopathological diagnosis of this cancer is difficult and is not usually done intraoperatively. The recurrences of the malignancy are typical and they require reoperations after stating places of relapse or metastases.

Modified dexamethasone and gonadotropin-releasing hormone agonist (Dx-GnRHa) test in the evaluation of androgen source(s) in hirsute women.

INTRODUCTION: Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (COH) are heterogeneous disorders, in which excess of androgens may be caused by improper function of ovaries and/or adrenals. In many cases an overlap between ovarian and adrenal type of functional hyperandrogenism has been observed. The relationship between adrenal and ovarian metabolism in hyperandrogenic women is not totally known and etiologic diagnosis of female hyperandrogenism is often difficult. The aim of the present study was to evaluate the usefulness of combined Dexamethasone-Triptoreline testing in distinguishing ovarian and adrenal type of functional hyperandrogenism, and checking if the test could be shortened in order to economise it. MATERIALS AND METHODS: We have examined 57 women with androgen excess divided into two groups: ovarian (n = 42) and adrenal (n = 15) and 20 women with idiopathic hirsutism. There was also one patient suffering from Morris syndrome taken under examination just for curiosity. The blood for hormonal assay was taken in baseline conditions at 8.00 a.m. for LH, FSH, PRL, cortisol, T, DHEAS, 17OHP, E2. Dx was given for 4 days 0.5 mg p.o. every 6 hours. 8 hours after the last Dx administration, the blood was taken for 17OHP and T. Immediately after that Triptorelin 100 mg was given s.c. Then the blood was collected every 4 hours during 24 hours for 17OHP estimation. RESULTS: Decrease in T levels (from 1.65 +/- 0.52 to 0.73 +/- 0.25 ng/ml) after Dexamethasone administration was observed in adrenal group, which indicates adrenal glands as a source of excessive androgen production. No significant differences were seen in ovarian group. But in women from ovarian group supranormal 17OHP response after Triptoreline administration was seen: (ng/ml): at 8.00 am-0.68 +/- 0.44, 12.00--1.21 +/- 0.7*, 16.00--1.71 +/- 1.19*, 20.00--2.39 +/- 1.81*, 24.00--3.41 +/- 2.64*, 4.00--3.91 +/- 2.82*, 8.00--6.06 +/- 2.43* (*p < 0.01, **p < 0.001). Such a response is typical for women with well defined PCOS and other forms of functional ovarian hyperandrogenism and indicates ovary as a source of androgens. Significant differences were also noticed in idiopathic group: 8.00--0.31 +/- 0.09, 12.00--0.38 +/- 0.17, 16.00--1.41 +/- 0.62*, 20.00--1.52 +/- 0.97*, 24.00--1.89 +/- 0.83*, 4.00--2.17 +/- 0.83*, 8.00--1.83 +/- 0.71** (*p < 0.01). 17OHP levels did not change significantly during the whole test in adrenal group: 8.00--1.83 +/- 1.24, 12.00--1.91 +/- 1.37, 16.00--1.95 +/- 0.86, 20.00--2.19 +/- 0.93, 24.00--2.63 +/- 1.58, 4.00--2.56 +/- 1.78, 8.00--237 +/- 0.94. But patients from this group had exaggerated 17OHP response to ACTH (from 4.32 +/- 1.31 to 15.34 +/- 4.1 ng/ml). In patient suffering from Morris syndrome, after Triptoreline, serum 17OHP levels reminded on the same level as they were before drug administration. CONCLUSIONS: Combined Dx-Triptorelin test can be very useful to distinguish ovarian and adrenal type of functional hyperandrogenism. The number of times of blood collection for 17OHP can be reduced to 4 times a day (during 24 hours): at 8.00, 20.00, 24.00, 8.00.

[Parathyroid cancer]. / Rak przytarczyc.

Parathyroid cancer is a rare disease, causing 0.5% to 5.2% of primary hyperparathyroidism cases. Hyperparathyroidism accompanying a cancer is usually more severe with richer clinical symptomatology then hyperparathyroidism in the course of benign lesions. Every palpable neck tumour with high blood plasma calcium level should suggest the presence of parathyroid cancer. Development of cancer is slow but life prognosis depends on the extent of the first surgery. The prognosis is most favourable in case of 'en bloc' resection of tumour during the first surgical procedure. Therefore, diagnosis of cancer before operation is very important. If the surgery fails, the treatment should be aimed at lowering hypercalcaemia, which is the most common cause of the fatal sequel.

Influence of dehydroepiandrosterone on platelet aggregation, superoxide dismutase activity and serum lipid peroxide concentrations in rabbits with induced hypercholesterolemia.

UNLABELLED: Special interest in the role of DHEA dates back to the finding of a correlation between low serum DHEA concentrations and a higher morbidity and mortality rate due to coronary diseases in humans. Animal studies with experimental atherosclerosis confirmed the anti-sclerotic effect of DHEA. The mechanism of DHEA action remains unclear. We determined the influence of dehydroepiandrosterone (DHEA) administration, a potential anti-atherogenic agent, on platelet aggregation, platelet superoxide dismutase (SOD) activity and serum lipid peroxide (LPO) levels in male rabbits fed on a normal and atherogenic diet. 44 adult male New Zealand white rabbits were divided into 4 groups: 1--control group fed on standard rabbit food, 2--fed on an atherogenic diet, 3--fed on an atherogenic diet with DHEA, 4--fed on standard food with DHEA. We detected blood platelet aggregation following (ADP) and collagen activation by means of photometry. Platelet SOD activity was detected by means of fluorometry determining the inhibition of adrenaline auto-oxidation. The serum LPO concentration was measured by means of the colorimetric method. The serum DHEA-S concentration was measured by means of RIA methods, and serum lipid levels were measured by means of Biomérieux manufactured kits. Results demonstrate that (1) elevated LPO concentrations in rabbits with hyperlipidemia did not decrease following DHEA administration. (2) In rabbits fed on a normal diet, DHEA caused a decrease of LPO, which emphasizes the positive influence of this steroid on the oxidative stress in healthy animals. Such a result was not seen in the group with severe hyperlipidemia. (3) Rabbits with hyperlipidemia demonstrated a significantly decreased SOD activity. (4) In healthy animals as well as in those with hyperlipidemia, DHEA administration caused an increase of platelet SOD activity, the main enzyme of the antioxidant defence system, which protects the organism against free radical damage (5) (DHEA had no influence on platelets aggregation in both tested groups). IN CONCLUSION: DHEA administration improves platelet SOD activity, which protects cells against oxidative damage. The hypothesis that DHEA administration leads to an increase in antioxidant potency requires further investigations.

Intratumoral levels of estrogens in breast cancer.

Breast cancer tissue is an endocrine organ and particularly the estrogen biosynthetic properties of this tissue have been well studied. The concentration of estradiol in breast cancer tissue from postmenopausal patients is considerably higher than that in the circulation and appears to depend largely on local production. Androgenic precursor steroids are abundantly present, but estrogen storage pools like fatty acid derivatives appear to be less important than initially thought. New, potent and highly specific aromatase inhibitors effectively inhibit peripheral conversion of androgens to estrogens (Cancer Res. 53: 4563, 1993) as well as intratumour aromatase, median aromatase activity being 89% lower in the tissue from patients pretreated with aromatase inhibitor 7 days prior to surgery (P < 0.001). Also the intratissue concentrations of estrogens were decreased (64% and 80% reduction, respectively for estrone and estradiol; P = 0.001 and <0.05; Cancer Res. 57: 2109, 1997). These results illustrate that intratissue estrogen biosynthesis is effectively inhibited by the new generation of aromatase inhibitors. The pathophysiological consequences of this finding are currently under study.

Concentration of sex steroids in adipose tissue after menopause.

Adipose tissue is a site of uptake, storage, action, and metabolism of sex steroids. After menopause aromatization of androgens to estrogens in adipose tissue is one of the most important sources of estrogen in the circulation and for peripheral tissues. The aim of this study was to estimate local sex steroid concentrations in breast and abdominal subcutaneous (s.c.) adipose tissue, to compare them with plasma concentrations and to investigate possible correlations with body mass index (BMI). The patients were postmenopausal women undergoing surgery for non-oncological reasons (Group A; n = 35) and breast cancer patients (group B; n = 19). The concentrations of estrone, 17 beta-estradiol, estrone sulfate, 17 beta-estradiol sulfate, androstenedione, androstenediol (androst-5-ene-3 beta, 17 beta-diol), testosterone and dehydroepiandrosterone were measured. The method was based on frozen tissue homogenization, extraction with ethanol: acetone, delipidation, extraction of estrogens with ether, and of androgens with iso-octane in toluene, followed by RIA. The mean levels of steroids were higher in fat than in plasma, apart from testosterone. Levels of sulfates of estrogens and androstenediol were higher in breast than abdominal adipose tissue, and levels of estradiol lower. Positive correlations were found between BMI and tissue and plasma concentration of both estrone and androstenedione.

Perimenopausal obesity.

In recent years perimenopausal obesity has attracted much attention, because it affects as many as 60% of women of menopausal age. The severe clinical implications of obesity directed our efforts to establish etiological factors and possible ways of treatment. It is clear that there are numerous conditions that underly perimenopausal obesity. Among these, genetic factors, neuropeptides, adrenergic nervous system activity and hormones play a role. Reproductive hormones are also an important factor, but their influence on adipose tissue is only indirect because there are no receptors for sex steroids in fatty tissue. Reports of hormone replacement therapy in women of postmenopausal age have come to different conclusions, so its influence on the etiology of perimenopausal obesity cannot be completely excluded. However, the potential benefit of this kind of treatment in female patients at menopausal age must always be considered.