So similar and so different: Circulating androgens and androgen origin in bulimic women.

Hyper androgen state frequently can be diagnosed in bulimic women. Eating disorder not otherwise specified (EDNOS) recognized as a less severe form of bulimia nervosa (BN). The objective of the study was to determine whether androgen levels and androgen origin differs in bulimic women compared to control subjects. Forty-six women with bulimia nervosa (BN), 31 with eating disorder not otherwise specified, purging type (EDNOS P) and 56 matched healthy controls were studied with respect to serum testosterone (T), 5alpha-dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), deyhydroepiahndrosterone sulfate (DHEAS) and luteinizing hormone (LH) and to ovarian morphology. Despite all groups had almost identical androgen and SHBG levels; there were differences in the origin of circulating T and DHT. Correlation analysis suggest major differences in the formation of circulating testosterone (T) and 5α-dihydrotestosterone (DHT) with BN being more like the control subjects with peripheral formation from 4-androsterne-3,17-dione (A-4), dehydroepiandrosterone sulfate (DHEAS) and also from T. While in EDNOS group a possible direct ovarian T secretion and a DHEAS modulating action of androgens on pituitary gonadotropin secretion is present. The origin of circulating T and DHT differs between bulimics. Our findings do probably not reflect direct actions of circulating DHT on pituitary LH secretion in the women with EDNOS, but rather the effect of A-4, T via conversion to DHT in the central nervous system, indicating psych/endocrine differences between the two groups of bulimic women.

Dehydroepiandrosterone and/or its metabolites: possible androgen receptor antagonistic effects on digitized mammographic breast density in normal breast tissue of postmenopausal women.

Background Androgens, notably testosterone inhibit breast cell proliferation and negative correlations between free testosterone (fT) and breast cell proliferation as well as mammographic density have been described. Dehydroepiandrosterone (DHEA) is reported to be a partial androgen antagonist in breast tumor cells in vitro. Our aim was to investigate if circulating DHEA had any effects on the association between circulating fT and mammographic density in vivo in the normal postmenopausal breast. Methods We measured visual and digitized mammographic density and serum DHEA, testosterone, sex-hormone-binding globulin and calculated fT in 84 healthy untreated postmenopausal women. Results Significant negative correlations between fT and both visual and digitized mammographic density were strengthened when the median DHEA level decreased from 10.2 to 8.6 nmol/L. Thereafter, correlations became weaker again probably due to decreasing fT levels and/or sample size. There were no correlations between mammographic density and DHEA, at any of the DHEA concentration ranges studied. Serum levels of fT and DHEA were positively correlated. Conclusion Our findings demonstrate that circulating DHEA and/or its metabolites counteract the inhibitory action of fT on mammographic breast density.

Serum androgen profile and physical performance in women Olympic athletes.

BACKGROUND: The role of endogenous androgens for body composition and physical performance in women athletes is still not elucidated. AIM: To examine the serum androgen profile in relation to body composition and physical performance in women Olympic athletes and to compare endocrine variables and body composition to controls. STUDY DESIGN: Cross-sectional study, conducted between 2011 and 2015 at the Women's Health Research Unit, Karolinska University Hospital, Stockholm. METHODS: Swedish women Olympic athletes (n=106) and age-matched and body mass index-matched sedentary controls (n=117) were included in the study. Blood sampling was performed in a rested, fasting state for the measurement of serum androgens and their metabolites by liquid chromatography-tandem mass spectrometry. Body composition was determined by dual-energy X-ray absorptiometry (controls n=100, athletes n=65). The athletes performed standardised performance tests (n=59) (squat jump (SJ) and countermovement jump (CMJ). RESULTS: The athletes demonstrated significantly higher levels of the precursor androgens dehydroepiandrosterone (DHEA) and 5-androstene-3ß, 17ß-diol (5-DIOL) and the metabolite etiocholanolone glucuronide (Etio-G), significantly lower levels of estrone (p<0.05, respectively), higher bone mineral density (p<0.001) and more lean mass (p<0.001) compared with controls. Serum levels of DHEA, 5-DIOL and Etio-G correlated positively to lean mass variables and physical performance in the athletes. DHEA and lean mass legs explained 66% of the variance in SJ, whereas lean mass explained 52% of the variance in CMJ. CONCLUSIONS: The present data suggest that endogenous androgens are associated with a more anabolic body composition and enhanced performance in women athletes. These results are of importance for the current discussion regarding hyperandrogenism in women athletes.

Circulating androgens and SHBG during the normal menstrual cycle in two ethnic populations.

The objective of this study was to study possible ethnic differences in steroid hormones and sex hormone-binding globulin (SHBG) during the menstrual cycle. Serum levels of the ovarian steroids estradiol (E2) and progesterone (P) and of follicle-stimulating hormone (FSH), luteinizing hormone (LH), SHBG, dehydroepiandrosterone (DHEA) and testosterone (T-ria) were all measured by immunoassay during the menstrual cycle in 15 Swedish and 11 West Asian regularly menstruating women. Testosterone (T-ms) was also measured by LC-MS/MS and so were 4-androstene-3,17-dione (A-4) and 17-alpha-hydroxyprogesterone (17-OHP). There were no ethnic differences in levels of ovarian steroids, gonadotrophins, A-4, 17-OHP and T-ms. DHEA were significantly higher and SHBG significantly lower in West Asian than in Swedish women. Surprisingly, T-ria was significantly higher in West Asian than in Swedish women and higher than T-ms (47% in Swedish and 107% in West Asian women). The difference (T-ria - T-ms) showed strong positive correlations to DHEA in the total and in West Asian but not in Swedish women, indicating an influence of DHEA/DHEAS metabolites on the T-ria results. In conclusion, ethnic differences in cross reacting steroids may cause erroneous results in one ethnic group by a steroid immunoassay having reasonable specificity in another. The reasons for the lower SHBG and the higher DHEA levels in West Asian women are not known. The results raise the question about establishing different reference values for certain analytes in different ethnic groups.

Estrone - a partial estradiol antagonist in the normal breast.

Oral hormone replacement therapy (HRT) based on estradiol-17ß (E2) greatly increases circulating estrone (E1) levels. E1 is an estrogen receptor agonist but may also be a partial E2 antagonist. We investigated the effects of circulating E1 on the association between circulating E2 and the increase in mammographic density (∂MD) in 46 healthy post-menopausal women treated with E2 2 mg and norethisterone acetate 1 mg daily. MD and serum E1 and E2 were measured before and after 6 months of treatment. At high E1 levels, ∂MD showed significant positive correlations leading to increase (∂-values) in both E1 and E2. Lowering the upper serum E1 limit strengthened the correlations to ∂E2 while the significant correlations to ∂E1 disappeared. E1 at high concentrations may act as a partial E2 antagonist also in the normal breast in vivo and disturb relationships between circulating E2 and biological estrogen effects. When investigating the relations between circulating steroids and their effects, structurally related compounds, which may act as partial antagonists, have to be considered, at least when they are present in higher concentrations.

Serum antimüllerian hormone in response to dietary management and/or physical exercise in overweight/obese women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial.

OBJECTIVE: To investigate whether randomized diet and/or physical exercise influence serum levels of antimüllerian hormone (AMH) in obese women with polycystic ovary syndrome (PCOS). DESIGN: Randomized, 4-month trial with three interventions. SETTING: Women's health clinical research unit at a university hospital. PATIENT(S): Fifty-seven overweight/obese women with PCOS. INTERVENTION(S): Diet, physical exercise, or both, using programs individually adapted and supervised by a dietician and/or a physiotherapist. MAIN OUTCOME MEASURE(S): Serum AMH levels before and after the interventions and correlations to reproductive function, body composition, and endocrine and metabolic variables. RESULT(S): After intervention, serum levels of AMH were significantly decreased only in the diet group, and the levels were significantly lower than in the exercise group. The strongest predictor of decreased AMH was a decrease in free T, whereas weight loss had no significant influence. Normalized levels of AMH were associated with improvements in menstrual cyclicity and hyperandrogenism but not in metabolic variables. CONCLUSION(S): This randomized study supports that diet reduces serum AMH in association with decreased androgen levels in obese women with PCOS. Increased serum AMH may be used as a marker of ovulatory dysfunction and hyperandrogenism but not as a marker of insulin resistance. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN48342048.

Megestrol acetate may stimulate the production of insulin-like growth factor 1 in breast tissues of women with breast cancer.

BACKGROUND: In women with breast cancer who were treated with either continuous tamoxifen alone or sequential tamoxifen followed by megestrol acetate (MA), we demonstrated significant positive associations between the breast tumor estrogen receptor (ER) and an increase in serum sex hormone-binding globulin (SHBG) during tamoxifen treatment. We interpreted this as "ER uniformity" in different tissues, e.g., breast, liver. No other associations with ER were found. In the same study, the breast tumor progesterone receptor (PR) was determined. Our aim was to see if there were any associations between PR and endocrine changes during MA treatment. METHODS: The breast tumor PR before treatment and serum insulin-like growth factor I (∂IGF-1), steroids, steroid-binding proteins, and insulin before and during treatment were measured in 17 postmenopausal women with breast cancer who were treated sequentially with tamoxifen 40 mg/day followed by MA 160 mg/day in alternating 3-month periods. RESULTS: During MA treatment periods, the levels of IGF-1 and insulin increased significantly, whereas the levels of androgens, SHBG, corticosteroid-binding globulin, and cortisol decreased significantly. Significant positive correlations were found between the PR content and increments in ∂IGF-1 but not between PR and any other endocrine change. CONCLUSIONS: PR expression in human liver is very weak, but malignant and normal breast tissues secrete considerable amounts of growth hormone and IGF-1 in vitro and in vivo. This activity is stimulated by progestogens. The association between PR and ∂IGF-1 may therefore reflect a direct PR-mediated action of MA on malignant and normal human breast tissues in vivo.

Cognitive function in association with sex hormones in postmenopausal women.

Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.

The influence of menstrual phases on pain modulation in healthy women.

UNLABELLED: This study investigated if conditioned pain modulation (CPM) varies across the menstrual cycle in healthy, normally menstruating women and investigated correlations between sex hormone levels and CPM across the menstrual cycle. Thirty-six normally menstruating women were tested during 3 phases of the menstrual cycle: early follicular, ovulatory, and midluteal, confirmed by hormone determinations. Mechanical pressure (test stimulus) was applied to the masseter muscle and the induced pain assessed before, during, and after immersion of the hand into ice water (conditioning stimulus) to activate CPM or tepid water (control). Conditioning pain, ie, pain in the hand during CPM/control experiment, and tolerance time were also measured. Test pain intensity was suppressed during CPM in all phases (P < .001), but with more effective suppression during the ovulatry than during the early follicular phase (P < .05). There were no changes in test pain intensity during the control experiment and no significant differences in conditioning pain, or tolerance time between phases. In conclusion, our results showed more effective pain modulation in the ovulatory phase of the menstrual cycle, when estradiol levels are high and progesterone levels are low, than in the early follicular phase when both these hormones are low. PERSPECTIVE: Deficient pain modulation is believed to be an important pathogenic factor in many chronic pain conditions that affect women. This article shows that sex hormones modulate conditioned pain modulation, because pain inhibition was more effective in the ovulatory phase of the menstrual cycle than in the early follicular phase.

The extreme male brain revisited: gender coherence in adults with autism spectrum disorder.

BACKGROUND: The 'extreme male brain' theory suggests that autism spectrum disorder (ASD) is an extreme variant of male intelligence. However, somewhat paradoxically, many individuals with ASD display androgynous physical features regardless of gender. AIMS: To assess physical measures, supposedly related to androgen influence, in adults with and without ASD. METHOD: Serum hormone levels, anthropometry, the ratio of 2nd to 4th digit length (2D:4D) and psychiatric symptomatology were measured in 50 adults with high-functioning ASD and age- and gender-matched neurotypical controls. Photographs of face and body, as well as voice recordings, were obtained and assessed with respect to gender coherence, blindly and independently, by eight assessors. RESULTS: Women with ASD had higher total and bioactive testosterone levels, less feminine facial features and a larger head circumference than female controls. Men in the ASD group were assessed as having less masculine body characteristics and voice quality, and displayed higher (i.e. less masculine) 2D:4D ratios, but similar testosterone levels to controls. Androgynous facial features correlated strongly and positively with autistic traits measured with the Autism-Spectrum Quotient in the total sample. In males and females with ASD dehydroepiandrosterone sulfate did not decrease with age, in contrast to the control group. CONCLUSIONS: Women with ASD had elevated testosterone levels and several masculinised characteristics compared with controls, whereas men with ASD displayed several feminised characteristics. Our findings suggest that ASD, rather than being characterised by masculinisation in both genders, may constitute a gender defiant disorder.

Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome.

OBJECTIVE: To compare the influence of dietary management and/or physical exercise on ovarian function and metabolic variables in women with polycystic ovary syndrome (PCOS). DESIGN: Randomized 4-month trial with three interventions and a long-term follow-up. SETTING: Women's health clinical research unit at a university hospital. PATIENT(S): Fifty-seven overweight/obese women with PCOS. INTERVENTION(S): Dietary management, physical exercise, or both, using programs individually adapted and supervised by a dietician and/or a physical therapist. MAIN OUTCOME MEASURE(S): Ovarian function, endocrinologic, and metabolic status and body composition. RESULT(S): On average, body mass index was reduced 6% by the dietary management, 3% by the exercise, and 5% by the combined interventions. Lower body fat and lean body mass were significantly decreased in the dietary groups, whereas upper body fat was lowered and lean body mass maintained by exercise alone. The menstrual pattern was significantly improved in 69% and ovulation confirmed in 34% of the patients, with no differences among the groups. The strongest predictor of resumed ovulation was a high serum level of insulin-like growth factor-binding protein 1 after the intervention. Follow-up of one-half of the patients for a median of 2.8 years revealed sustained weight reduction and improvement in menstrual pattern. CONCLUSION(S): Dietary management and exercise, alone or in combination, are equally effective in improving reproductive function in overweight/obese women with PCOS. The underlying mechanisms appear to involve enhanced insulin sensitivity. Supportive individualized programs for lifestyle change could exert long-term beneficial effects.

Women with bulimia nervosa exhibit attenuated secretion of glucagon-like peptide 1, pancreatic polypeptide, and insulin in response to a meal.

BACKGROUND: The eating disorder bulimia nervosa (BN) is characterized by frequent episodes of binge eating, followed regularly by inappropriate compensatory behavior, such as self-induced vomiting. OBJECTIVE: The current investigation was designed to examine possible alterations in the secretion of the gastrointestinal satiety peptides glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) in women with BN. DESIGN: Twenty-one women with BN and 17 healthy control subjects of comparable age and BMI were recruited. After fasting overnight, the subjects provided blood samples during ingestion of a standardized meal and self-rated their appetite on a visual analog scale. Fasting and meal-related secretion of the incretin GLP-1 and the meal-related feedback signal PP and insulin and glucose as indicators of the metabolic homeostasis were analyzed. RESULTS: Women with BN had significantly lower fasting and postprandial serum concentrations of GLP-1 (P < 0.01) and PP (P < 0.05) than did the control subjects. Furthermore, both the basal (P < 0.001) and peak (P < 0.05) concentrations of insulin were significantly attenuated in the bulimic subjects, whereas glucose concentrations were normal. As a consequence, the bulimic homeostasis model assessment of insulin index values were also lower (P < 0.001). CONCLUSIONS: Women with BN secrete abnormally low amounts of GLP-1 and PP, possibly because of the adaption to large meals in the form of enlarged gastric capacity and reduced muscle tone in the gastric wall. Attenuated secretion of these gastrointestinal satiety peptides may play a role in the maintenance of bulimic behavior.

Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry.

OBJECTIVE: To compare steroid concentrations and steroid product-to-precursor ratios in ovarian follicular fluid (FF) from women with polycystic ovary syndrome (PCOS) and from regularly menstruating women in their early follicular phase, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polycystic ovary syndrome involves abnormal regulation of the steroidogenic enzymes, leading to arrest of follicle development. DESIGN: Case-control study. SETTING: University hospital clinic. PATIENT(S): Follicular fluid from size-matched ovarian follicles (5-8 mm) in 27 nonstimulated women with PCOS and in 21 women without PCOS was sampled. Thirteen steroids were quantitated from 40 µL of FF, using LC-MS/MS. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Concentrations of steroids in the FF and product-to-precursor ratios (enzyme activity) were compared between the groups. RESULT(S): In women with PCOS, ovarian FF contained higher concentrations of individual and total androgens, lower individual and total estrogens (E), and a lower total E-to-androgen ratio, compared with regularly menstruating women. The product-to-precursor concentration ratios indicated higher CYP17-linked and lower CYP19-linked (aromatase) enzyme activity. Receiver operating characteristic plots indicated the early CYP17 step (17-OH5P/5P) being highly important for the prevalence of PCOS (c=0.95). CONCLUSION(S): The women with PCOS had higher ovarian CYP17-linked and lower CYP19-linked (aromatase) enzyme activity, confirming previous data. Multiple steroid assessments from minute volumes including FF from nonstimulated ovaries, using LC-MS/MS, might be useful in research, clinical endocrinology, and in IVF.

Different estrogen sensitivity of urogenital tissue from women with and without stress urinary incontinence.

AIMS: Oral hormone replacement therapy (HRT) based on estradiol-17beta (E2), E2 esters or conjugated equine estrogens gives rise to huge amounts of circulating estrone (E1) as a result of the first liver pass. E1 is an estrogen (ER) receptor agonist but has also been reported to act as a partial E2 antagonist in vitro. Our aim was to investigate the influence of circulating estrogens on estrogen sensitivity of urogenital tissue collagen turnover in patients with stress urinary incontinence (SUI) and in urologically healthy women, with and without HRT, in view of possible effects of E1 as a partial E2 antagonist. METHODS: Markers of collagen turnover, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and E1 and E2 were analyzed in serum from 54 patients with SUI and 29 urologically healthy women. RESULTS: In the total control group only a significant positive correlation was found between E2 and T-PICP. Lowering the upper serum E1 limit resulted in significant positive correlations also between E2 and T-PIIINP and finally also between E2 and T-ICTP. This pattern was found also in subgroups of post- and premenopausal controls. No association between serum E2 and collagen turnover markers and no effects of lowering the upper serum E1 limit was found in the total and postmenopausal SUI patients, while the correlation pattern in premenopausal SUI patients showed some resemblance to that in the controls. CONCLUSION: At physiological E1 levels E2 increases collagen turnover in urogenital tissue in urologically healthy women but not in women with SUI in general; however, there was a certain effect of E2 in premenopausal but not in postmenopausal SUI patients. Urogenital tissue in SUI patients and in urologically healthy women may differ in estrogen sensitivty and in SUI patients this difference may be related to menopause. Circulating E1, which is present in huge amounts during oral HRT, may act as an estrogen receptor agonist as well as a partial E2 antagonist also in humans in vivo.

Gonadal hormones in men with rheumatoid arthritis--from onset through 2 years.

OBJECTIVE: To evaluate changes over a 2-year course in the hypothalamic-pituitary-gonadal (HPG) axis in men with early rheumatoid arthritis (RA) from start of treatment with disease modifying antirheumatic drugs. METHODS: Forty-one men with early RA and with joint symptoms less than 1 year were studied. Mean age at inclusion was 53 years and mean disease duration 6 months. They were followed prospectively for 2 years for disease activity [Disease Activity Score 28 (DAS28)], physical impairment (Health Assessment Questionnaire), total serum testosterone, non-sex hormone-binding globulin-bound testosterone, and luteinizing hormone (LH). A group of 131 healthy, medicine-free men served as controls for baseline hormone concentrations. RESULTS: The men with RA already had mean testosterone levels lower than controls early in the disease course. Patients older than 50 years also had significantly lower LH levels compared with controls, consistent with mild hypogonadotropic hypogonadism. In patients who responded to treatment at the 2-year followup the testosterone levels increased significantly. A decrease in DAS28 during the 2 years correlated significantly with increased testosterone levels (r(s) = -0.46, p = 0.006). LH levels were low and stable and did not correlate with disease activity. CONCLUSION: In early RA, current inflammation seemed to affect the HPG axis, mainly at the gonadal rather than the hypothalamic-pituitary level. Prospective studies are indicated to determine if low HPG activity may be a cause rather than a consequence of a chronic inflammatory state.

Steroid profiles in ovarian follicular fluid from regularly menstruating women and women after ovarian stimulation.

BACKGROUND: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA). METHODS: We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-microL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups. RESULTS: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013). CONCLUSIONS: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.

Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis.

The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status--or dysfibrinolysis--in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status (high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P < 0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P < 0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women.

Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue in postmenopausal women.

Progestogens and progesterone receptors (PR) may play an important role in increased breast proliferation following combined estrogen/progestogen hormone therapy, while androgens may counteract this effect. In 50 untreated healthy postmenopausal women and 48 untreated postmenopausal breast cancer patients, we measured serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estrone (E(1)) and adrenal androgens; and additionally, in the breast cancer patients, cortisol and corticosteroid-binding globulin and endocrine data related to breast proliferation (assessed using the Ki-67/MIB-1 monoclonal antibody) and PR levels (determined by enzyme immunoassay) in the breast cancer tissue. In the healthy women the percentage of MIB-1(+) cells showed significant negative correlations with serum levels of total T, calculated free T (fT) and the fT/E(1) ratio; while in the breast cancer patients PR content showed significant negative correlations with fT level, the fT/E(1) ratio and the T/SHBG ratio. No other correlations were found in any of the groups. Our findings in healthy women confirm previous reports of an antiproliferative effect of androgens in breast tissue and our finding in breast cancer patients suggests that this antiproliferative effect may be mediated via downregulation of PR.

Increased DHEAS levels in patients with rheumatoid arthritis after treatment with tumor necrosis factor antagonists: evidence for improved adrenal function.

OBJECTIVE: To determine if major reduction of inflammation with longterm tumor necrosis factor (TNF) antagonist treatment has any influence on the adrenal and gonadal axes in patients with rheumatoid arthritis (RA). METHODS: Forty-eight patients with RA were treated with infliximab or etanercept for 2 years. Disease activity, clinical response, and physical function were evaluated and serum levels of high sensitivity C-reactive protein and interleukin 6 were analyzed before start of treatment and after 1 and 2 years. At the same timepoints adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) were analyzed; luteinizing hormone (LH), estradiol, and testosterone were analyzed as well in 18 male patients. RESULTS: DHEAS increased (p

Conversion of circulating estrone sulfate to 17beta-estradiol by ovarian tumor tissue: a possible mechanism behind elevated circulating concentrations of 17beta-estradiol in postmenopausal women with ovarian tumors.

AIM: Elevated serum levels of 17beta-estradiol (E2) are frequently found in postmenopausal women with ovarian tumors not classified as estrogen-producing. Conversion of circulating estrone sulfate (E1S) to E2 is one alternative way of E2 formation in target tissues in postmenopausal women. Our aim was to find out if conversion of circulating E1S to E2 by the tumor tissue could be a reason for elevated serum E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors. METHOD: Serum E2 was measured in 12 postmenopausal women with 'non-estrogen-producing' ovarian tumors (nine benign, three malignant). Total hydrolysis of and [3H]E2 formation from [3H]E1S by the tumor tissue homogenates was studied in vitro. RESULTS: Serum E2 showed significant positive correlations with total hydrolysis of and [3H]E2 formation from [3H]E1S in the total material as well as in the benign tumor subgroup. [3H]E2 formation was the most important independent variable. CONCLUSION: Conversion of circulating E1S to E2 by the tumor tissue could be one important reason for elevated S-E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.