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.

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.

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.

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 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.

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.

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.

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.

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.

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.

Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.

CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.

Bone mineral density in bulimic women--influence of endocrine factors and previous anorexia.

OBJECTIVE: Data concerning bone mineral density (BMD) in bulimia nervosa are contradictory and include both low and normal values. The aim of the present study was to elucidate possible endocrine-and nutrition-related factors predicting BMD in bulimic women. DESIGN: Cross-sectional study. METHODS: Seventy-seven bulimic patients and 56 age- and body mass index (BMI)-matched healthy controls were examined with respect to BMD (dual energy X-ray absorptiometry) and to serum levels of hormones and metabolic factors. RESULTS: Bulimics had significantly lower spinal BMD and higher frequency of osteopenia in the total body than controls. Furthermore, bulimic women had significantly lower levels of estradiol-17beta and free thyroxine and significantly higher cortisol levels compared with controls. Among the bulimics, 31.2% had present menstrual disturbance, 51.9% had a history of amenorrhea and 23.4% had previous anorexia nervosa. Subgroups of bulimics with a history of amenorrhea and previous anorexia nervosa had significantly lower total and spinal BMD than controls, whereas those without such history did not differ from the controls. In univariate analysis, a history of amenorrhea, cortisol, testosterone, previous anorexia nervosa, and BMI showed significant associations with spinal BMD. Multiple regression analysis including all significant variables revealed previous anorexia nervosa to be the strongest determinant of spinal BMD, accounting for 34% of the variance, while associations between endocrine factors and BMI disappeared. CONCLUSIONS: Low bone mass in bulimics may be explained by previous anorexia nervosa, whereas endocrine variables related to BMD seem to be secondary determinants that are dependent on previous anorexia nervosa and BMI.

Conjugated estrogen/progestagen versus tibolone hormone replacement therapy in postmenopausal women: Effects on carbohydrate metabolism and serum sex hormone-binding globulin.

OBJECTIVE: To study the effects of different types of continuous hormone replacement therapy on carbohydrate metabolism. METHOD: Postmenopausal women were treated with conjugated estrogens, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg (CEE/MPA) or tibolone 2.5 mg daily for 13 28-day cycles. Serum glucose and insulin were measured before and during a 75 g oral glucose tolerance test (OGTT) at baseline and after 3, 6 and 13 cycles and areas under the curve (AUC) were calculated. Sex hormone-binding globulin (SHBG) was measured as an additional marker of nutritional and insulin status. RESULTS: Neither CEE/MPA 2.5mg nor tibolone had any effects on carbohydrate metabolism while AUC(insulin), AUC(glucose) and also body mass index (BMI) increased after 13 cycles of treatment in the CEE/MPA 5 mg group. SHBG increased significantly during CEE/MPA treatment and decreased significantly during treatment with tibolone. The effects on SHBG were less pronounced in the CEE/MPA 5mg group. Pretreatment SHBG showed significant negative correlations to BMI and to variables that may reflect a certain degree of insulin resistance, the most pronounced being fasting glucose. Changes in SHBG during treatment with tibolone were negatively correlated to pretreatment SHBG and positively to BMI, AUC(insulin) and fasting insulin resistance index, while no such correlations were found in the CEE/MPA groups. There were no correlations between changes in AUC(insulin) and AUC(glucose) on one hand and basal variables or treatment SHBG on the other in the CEE/MPA groups. CONCLUSION: The effects of tibolone and CEE/MPA on carbohydrate metabolism were considered to have clinical significance only for CEE/MPA 5mg, indicating a less favourable role of the higher progestagen dose. The results further support the important role of metabolic and insulin status in the physiological regulation of SHBG and also indicate that the suppressive effect of tibolone on circulating SHBG is mainly depends on pretreatment SHBG levels. SHBG does not reflect changes in carbohydrate metabolism during CEE/MPA treatment.

Basal release of urokinase plasminogen activator, plasminogen activator inhibitor-1, and soluble plasminogen activator receptor from separated and cultured endometriotic and endometrial stromal and epithelial cells.

OBJECTIVE: To investigate whether separated and cultured endometriotic and endometrial stromal and epithelial cells release urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and soluble plasminogen activator receptor (suPAR) antigens in vitro. DESIGN: In vitro study. SETTING: University hospital clinic. PATIENT(S): Regularly menstruating women with and without endometriosis. INTERVENTION(S): Tissue samples were collected at surgery performed for clinical reasons. MAIN OUTCOME MEASURE(S): The antigen concentrations of uPA, PAI-1, and suPAR in culture medium were assayed by enzyme-linked immunosorbent assay. RESULT(S): Both stromal and epithelial cells from endometriotic and endometrial tissue released the three types of antigens, but the release of PAI-1 was significantly higher from stromal cells in the three types of tissue than from epithelial cells. Furthermore, the release of PAI-1 was significantly higher from endometriotic cells than from endometrial stromal cells. CONCLUSION(S): This study has demonstrated the basic capacity of separated epithelial and stromal cells from all three types of tissue to release uPA, PAI-1, and suPAR without any paracrine influence, as in vivo. The higher release of PAI-1 from endometriotic stromal cells might have importance for the invasive growth.

Diurnal profiles of testosterone and pituitary hormones suggest different mechanisms for menstrual disturbances in endurance athletes.

The aim of this study was to evaluate the diurnal pattern of testosterone and pituitary hormones in endurance female athletes with different types of menstrual disorder. Age- and body mass index-matched groups of endurance athletes with amenorrhea (n = 10) and oligomenorrhea (n = 6), regularly cycling athletes (n = 8), and sedentary controls (n = 8) were compared with respect to 24-h hormonal profiles of testosterone, LH, prolactin (PRL), GH, insulin, IGF binding protein 1 (IGFBP-1), and cortisol. The 24-h hormone profiles in amenorrheic athletes were characterized by decreased LH pulsatility and peak amplitude of PRL and increased baseline levels of GH and cortisol. However, oligomenorrheic athletes displayed a significantly different pattern with higher diurnal testosterone secretion than all other groups. Furthermore, LH, PRL, GH, and cortisol secretions were comparable with regularly menstruating subjects. In the combined group of athletes with menstrual disturbances, diurnal secretions of testosterone, LH, and PRL were positively, whereas cortisol was negatively correlated with the number of menstruations the last year. Although this could be explained by a gradual inhibition of the hypothalamic-pituitary-gonadal axis, our results indicate that the symptoms of amenorrhea and oligomenorrhea may reflect two hormonally distinct conditions. Thus, amenorrheic athletes displayed a hormonal pattern in agreement with hypothalamic inhibition due to energy deficiency, whereas oligomenorrheic athletes demonstrated increased diurnal secretion of testosterone, suggesting a different mechanism, e.g. essential hyperandrogenism.

Effects of oral contraceptives on body composition and physical performance in female athletes.

Menstrual disturbances are common among female athletes, and oral contraceptives (OCs) are often recommended as estrogen substitution. However, there is little information about the effects of OC use in athletes, and there is great concern that OCs might impair physical performance. The aim of this study was to investigate the effects of OC use on body composition and physical performance in female athletes. Twenty-six endurance athletes (13 with oligo-/amenorrhea and 13 regularly menstruating athletes) and 12 sedentary controls were examined before and after 10 months of treatment with a low dose, monophasic, combined OC. Significant changes in body composition were recorded in the athletes, but not in the controls. There was an increase in weight and fat mass only in athletes with oligo-/amenorrhea. These changes were associated with a decrease in ovarian androgens. OC treatment also increased bone mineral density, with the largest increase in athletes with a low bone mineral density at baseline. Despite significant changes in body composition, little impact on physical performance was recorded. We have demonstrated that OC treatment in female athletes has predominantly beneficial effects on body composition without adverse effects on physical performance and could be used for the prevention of osteoporosis in athletic amenorrhea. However, it cannot be excluded that a marked increase in fat mass might have unfavorable effects for athletic performance in individual women.

Infiltration of morphine into an abnormal wound; effects on pain relief and endocrine/immune response.

We wanted to evaluate pain relief and endocrine/immune response after local administration of morphine into an abdominal wound. In a randomised double blind design 29 patients undergoing hysterectomy received two blinded injections of morphine and saline. Before surgery the patients in the control group (n = 15) got 10 mg of subcutaneous morphine into an arm and at skin incision 30 ml of saline was infiltrated directly into the wound. The patients in the wound group (n = 14) received 1 ml of saline into an arm before surgery and 10 mg of morphine in 30 ml of saline into the wound at skin incision. Patient controlled analgesia (PCA) with i.v. morphine was used after surgery. Repeated blood samples were obtained from the day before the surgery until 3 days later and analysed for cortisol and interleukin-6 (IL-6). There were no differences between the groups either in pain relief or in the consumption of PCA morphine. The wound group used 47 +/- 15 mg of i.v. morphine and the control group used 50 +/- 16 mg. Peak values for IL-6 and cortisol appeared at 4 h. The area under the curve (AUC) of cortisol at 0-6, 0-10 and 0-20 h was significantly lower in the control group than in the wound group (P < 0.05). High doses of i.v. morphine reduced cortisol and IL-6 levels in the early hours after surgery. The injection of morphine into the wound did not improve pain relief or reduce the consumption of i.v. morphine after surgery. The endocrine stress response to trauma was modified by preoperative administration of morphine.

Repolarization measures and their relation to sex hormones in postmenopausal women with cardiovascular disease receiving hormone replacement therapy.

Women are more susceptible to the development of Torsades de Pointes ventricular tachycardia and have a longer heart rate-corrected QT interval than men. A causal role for estrogen has been implicated. The purpose of this study was to investigate if hormone replacement therapy (HRT) resulted in any changes in noninvasive depolarization and repolarization measurements, and to study their relation to circulating concentrations of sex hormones. Sixty postmenopausal women with cardiovascular disease (mean age 59 +/- 7 years; range 44 to 75) were randomized to receive oral conjugated estrogens, transdermal estradiol-17-beta (both with addition of progestins), or placebo. QRS, QT, and JT intervals and their dispersion on 12-lead electrocardiograms were analyzed at baseline, and after 6 and 12 treatment cycles of HRT. Blood samples for analyses of serum concentration of estrogens and androgens were obtained on the same occasions. Neither mean RR, QT, QTc, JT, and JTc intervals, nor QT and JT dispersion changed during treatment. There was a significant inverse relation between the mean JTc interval and the serum concentration of estradiol-17-beta, independent of age, testosterone levels, and abdominal obesity. There was also a significant inverse relation between the change in androstenedione levels and the change in QT interval (Spearman -0.35, p = 0.028) or JT interval (Spearman -0.41, p = 0.009) at 6 treatment cycles compared with baseline. In conclusion, treatment with oral conjugated estrogens or transdermal estradiol-17-beta combined with progestins did not alter depolarization or repolarization measurements. However, the inverse relation between repolarization and androgens fits with an effect of androgens on repolarization in postmenopausal women.

Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance.

OBJECTIVE: To evaluate endocrine mechanisms underlying oligomenorrhea or amenorrhea in female athletes. DESIGN: Cross-sectional study. SETTING: Women's health clinical research unit at a university hospital. PATIENT(S): Age- and BMI-matched groups of athletes active in endurance sports with and without menstrual disturbances and regularly cycling sedentary controls. INTERVENTION(S): Groups were compared with respect to endocrine status, body composition, and physical performance. MAIN OUTCOME MEASURE(S): Identification of a subgroup of oligomenorrheic or amenorrheic athletes with increased androgen levels and anabolic body composition. RESULT(S): A subgroup of 8 of 25 athletes with menstrual disturbances had significantly higher serum levels of free and total testosterone, androstenedione, LH-FSH ratio, and lower SHBG levels than did all other groups. Other oligomenorrheic or amenorrheic athletes had normal values comparable to those in regularly menstruating athletes and controls. The hyperandrogenic subgroup showed a more anabolic body composition, with higher total bone mineral density and upper-lower fat mass ratio than did oligomenorrheic or amenorrheic athletes with normal androgen levels. The hyperandrogenic subgroup had the highest VO2 max and the highest performance values in general. CONCLUSION(S): Menstrual disturbances in female athletes are often explained as a consequence of hypothalamic inhibition and caloric deficiency. We suggest that essential hyperandrogenism is an alternative mechanism underlying oligomenorrhea or amenorrhea in some female athletes and may imply an advantage for physical performance.