Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations.

INTRODUCTION: Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. MATERIAL AND METHODS: Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. RESULTS: Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [3 H]thymidine in cultured granulosa cells. CONCLUSIONS: Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.

Serum anti-Müllerian hormone and ovarian morphology assessed by magnetic resonance imaging in response to acupuncture and exercise in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial.

OBJECTIVE: To investigate whether electro-acupuncture or physical exercise influence serum anti-Müllerian hormone (AMH), antral follicle count (AFC) or ovarian volume in women with polycystic ovary syndrome (PCOS). DESIGN: Secondary analyses of a prospective, randomized controlled clinical trial. SETTING: University Hospital, Sweden. PATIENTS: Seventy-four women with PCOS recruited from the general population. INTERVENTIONS: Women with PCOS were randomized to 16 weeks of electro-acupuncture (14 treatments), exercise (at least three times/week), or no intervention. MAIN OUTCOME MEASURES: Serum AMH recorded at baseline, after 16 weeks of intervention, and at follow up at 32 weeks. AFC, and ovarian volume assessed by magnetic resonance imaging at baseline and at follow up at 32 weeks. RESULTS: After 16 weeks of intervention, serum levels of AMH were significantly decreased in the electro-acupuncture group by 17.5% (p < 0.001), and differed from the change in the exercise group. AMH remained decreased by 15% (p = 0.004) also at follow up at 32 weeks, but did not differ from the exercise or the no intervention groups. There was a decrease by 8.5% (p = 0.015) in ovarian volume between baseline and follow up in the electro-acupuncture group, and by 11.7% (p = 0.01) in AFC in the physical exercise group. No other variables were affected. CONCLUSIONS: This study is the first to demonstrate that acupuncture reduces serum AMH levels and ovarian volume. Physical exercise did not influence circulating AMH or ovarian volume. Despite a within-group decrease in AFC, exercise did not lead to a between-group difference.

Ovarian morphology assessed by magnetic resonance imaging in women with and without polycystic ovary syndrome and associations with antimüllerian hormone, free testosterone, and glucose disposal rate.

OBJECTIVE: To characterize ovarian morphology and perfusion by magnetic resonance imaging (MRI) in women with and without polycystic ovary syndrome (PCOS) and to investigate associations with antimüllerian hormone (AMH), free T, and glucose disposal rate (GDR). DESIGN: Explorative cross-sectional study. SETTING: University hospital. PATIENT(S): Fifty-eight women with PCOS and 31 controls from the general population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Antral follicle count (AFC), ovarian/stromal volume, perfusion, AMH, free T, and GDR. RESULT(S): Antral follicles of 1-3 and 4-6 mm, but not 7-9 mm, were more numerous, and total AFC (1-9 mm) was higher in women with PCOS. Ovarian volume was larger in women with PCOS. AMH and free T were higher and GDR was lower in women with PCOS. All values were more deranged in classic compared with nonclassic PCOS. There was a positive correlation between AMH and AFC, 1-3 mm (r = 0.81), and between AMH and total AFC (r = 0.87). In receiver operating characteristic analyses, the area under the curve was 0.89 for total AFC, 0.86 for AMH, and 0.90 for free T. PCOS was independently associated with AFC and free T but not with AMH or GDR when adjusted for age and body mass index. CONCLUSION(S): Counting antral follicles down to 1 mm in size by MRI yielded higher AFCs than previously reported. AFC, AMH, and free T discriminated with high accuracy between women with PCOS and controls, but AMH was not independently associated with PCOS. CLINICAL TRIAL REGISTRATION NUMBER: NCT00484705.

Acupuncture and physical exercise for affective symptoms and health-related quality of life in polycystic ovary syndrome: secondary analysis from a randomized controlled trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have symptoms of depression and anxiety and impaired health related quality of life (HRQoL). Here we test the post-hoc hypothesis that acupuncture and exercise improve depression and anxiety symptoms and HRQoL in PCOS women. METHODS: Seventy-two PCOS women were randomly assigned to 16 weeks of 1) acupuncture (n = 28); 2) exercise (n = 29); or 3) no intervention (control) (n = 15). Outcome measures included: change in Montgomery Åsberg Depression Rating Scale (MADRS-S), Brief Scale for Anxiety (BSA-S), Swedish Short-Form 36 (SF-36), and PCOS Questionnaire (PCOSQ) scores from baseline to after 16-week intervention, and to 16-week post-intervention follow-up. RESULTS: A reduction in MADRS-S and BSA-S from baseline to 16-weeks post-intervention follow-up was observed for the acupuncture group. The SF-36 domains role physical, energy/vitality, general health perception and the mental component of summary scores improved in the acupuncture group after intervention and at follow-up. Within the exercise group the role physical decreased after treatment, while physical functioning and general health perception scores increased at follow-up. The emotion domain in the PCOSQ improved after 16-weeks of intervention within all three groups, and at follow-up in acupuncture and exercise groups. At follow-up, improvement in the infertility domain was observed within the exercise group. CONCLUSION: There was a modest improvement in depression and anxiety scores in women treated with acupuncture, and improved HRQoL scores were noted in both intervention groups. While not a primary focus of the trial, these data suggest continued investigation of mental health outcomes in women treated for PCOS. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT00484705.

Quality of life after adopting compared with childbirth with or without assisted reproduction.

OBJECTIVE: This study compares quality of life among couples who had adopted a child 4-5.5 years previously with couples whose conception was spontaneous, as well as with couples who had successful or unsuccessful in vitro fertilization (IVF) treatment. DESIGN: Cross-sectional study. SETTING: Tertiary level university hospital. SAMPLE: From the following groups, 979 responses were obtained: adoption; successful IVF; unsuccessful IVF-living with children; unsuccessful IVF-living without children; and childbirth after spontaneous conception (controls). METHODS: Quality of life was studied with the Psychological General Well Being (PGWB) and Sense of Coherence (SOC) instruments. Demographic, socio-economic and health data were obtained with additional questionnaires. Multiple variance analysis was applied. MAIN OUTCOME MEASURES: The PGWB and SOC scores. RESULTS: After adjustment for seven confounders, the adoption group had higher PGWB scores than the unsuccessful IVF-living without children and the controls and higher SOC scores than all other groups. The unsuccessful IVF-living without children had lower PGWB and SOC scores than all other groups. The PGWB and SOC scores among controls did not differ from those with successful IVF or unsuccessful IVF-living with children. CONCLUSIONS: Adjusted PGWB and SOC scores revealed a high quality of life in the adoption group. However, the group unsuccessful IVF-living without children had low quality of life scores. Quality of life appears to be independent of the outcome of IVF treatment as long as there are children in the family.

Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial.

OBJECTIVE: To investigate the possible effects of low-frequency electroacupuncture (EA) and physical exercise on markers of coagulation and fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women with polycystic ovary syndrome (PCOS). DESIGN: Secondary analyses of a prospective, randomized controlled clinical trial. SETTING: Department of Physiology and Department of Obstetrics and Gynecology, University of Gothenburg. PATIENT(S): Eighty-four women with PCOS were randomized. INTERVENTION(S): Women with PCOS were randomized to 16 weeks of low-frequency EA (14 treatments), physical exercise (at least 3 times/wk), or no intervention. MAIN OUTCOME MEASURE(S): Anthropometrics, circulating coagulation and fibrinolytic markers, insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and adipose tissue morphology/function recorded at baseline, after 16 weeks of intervention, and after a 16-week follow-up. RESULT(S): In the low-frequency EA group, circulating plasminogen activator inhibitor 1 activity decreased by 21.8% after 16 weeks of intervention and by 31.1% at the 16-week follow-up and differed from the physical exercise and the no intervention groups. The EA group had decreases in circulating fibrinogen and tissue plasminogen activator (t-PA), sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen remained lower at the 16-week follow-up. In the physical exercise group, lipoprotein lipase activity increased and diastolic blood pressure decreased after treatment, and both diastolic and systolic blood pressure were lower at follow-up. No other variables were affected. CONCLUSION(S): Low-frequency EA counteracted a possible prothrombotic state in women with PCOS, as reflected by a decrease in plasminogen activator inhibitor 1 activity. Despite within-group improvements, there were no between-group differences in anthropometric, metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at the dose/intensity studied.

Alterations of follicular microcirculation and apex structure during ovulation in the rat.

OBJECTIVE: We utilized methods for intravital microscopy and microcirculation measurements to study changes during ovulation. STUDY DESIGN: Immature gonadotrophin-primed rats were laparotomized and one ovary was examined for morphological alterations during a 3 h period (covering a period from 1h before to 27 h after hCG) through water-immersion lenses (maximum magnification 812×). Microcirculatory blood flow was assessed by measurements of blood cell velocity and laser Doppler flowmetry. RESULTS: Follicular hyperaemia was observed 30 min after hCG and then vasomotion was observed. A gradual decline of apical blood flow was seen, which later was associated with an avascular area over the top of the apex. Cells from the surface over the follicular apex were then detached from the exterior of the follicle and this phenomenon was initiated more than one hour prior to follicular rupture. The subsequent structural alterations varied with or without formation of a cone over the stigma. In ovulations with a stigma-cone, a translucent, irregular mass formed over the stigma. Prior to follicular rupture, granulosa cells and follicular fluid were extruded from the follicular cavity at a velocity of around 70 µm/s. Occasionally, intra-antral haemorrhage occurred prior to or during follicular rupture. CONCLUSION: Characteristic features of ovulation in the rat are microcirculatory vasomotion, gradual formation of apical avascular area, specific changes of the stigma, and extrusion of the oocyte-granulosa cell complex with or without haemorrhage.

Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

CONTEXT: Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. OBJECTIVE: To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. DESIGN AND METHODS: Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). RESULTS: Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17ß-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. CONCLUSION: Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation.

Coagulation and fibrinolytic disturbances in women with polycystic ovary syndrome.

CONTEXT: Studies of fibrinolysis/coagulation status in women with polycystic ovary syndrome (PCOS) are contradictory. OBJECTIVES: The aim of the study was to investigate whether women with PCOS have disturbed circulating levels of fibrinolysis/coagulation markers and, if so, whether the disturbances are related to hemodynamics, metabolic variables, sex steroids, SHBG, lipids, and inflammatory variables in women with PCOS. DESIGN/MAIN OUTCOME MEASURES: Anthropometric variables, hemodynamics, circulating hemostatic and inflammatory markers, and serum lipid profile were measured in women with untreated PCOS (n = 74) and controls (n = 31). RESULTS: After adjustments for age and body mass index (BMI), circulating plasminogen activator inhibitor 1 (PAI-1) activity and fibrinogen levels were higher in women with PCOS than controls; lipid profile, blood pressure, and levels of D-dimer, von Willebrand factor, factor VIII, tissue plasminogen activator, and inflammatory markers were comparable in the two groups. In multiple linear regression analyses including women with PCOS, low SHBG and high insulin predicted high PAI-1 activity (R(2) = 0.526; P < 0.001); elevated high-sensitivity C-reactive protein and soluble E-selectin in combination with heart rate predicted high fibrinogen (R(2) = 0.333; P < 0.001). Differences in PAI-1 activity were not significant after adjustments for age, BMI, SHBG, and insulin. CONCLUSIONS: PCOS is characterized by a prothrombotic state, as reflected by increased PAI-1 activity and fibrinogen, without signs of dyslipidemia or a proinflammatory state. Low SHBG and high insulin may partly explain the BMI-independent difference in PAI-1 activity between women with PCOS and controls. High-sensitivity C-reactive protein and E-selectin may be involved in regulating fibrinogen in PCOS.

Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17ß-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Sexual function and surgical outcome in women with congenital adrenal hyperplasia due to CYP21A2 deficiency: clinical perspective and the patients' perception.

CONTEXT: Females with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency are exposed to androgens during fetal development, resulting in virilization of the external genitalia. Little is known about how these women feel that the disease has affected their lives regarding surgery and psychosexual adaptation. OBJECTIVE: Our objective was to investigate the correlation between the surgical results, the self-perceived severity of the disease, and satisfaction with sexual life and relate the results to the CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire, and a composite score for sexual function was constructed. The surgical outcome, including genital appearance and clitoral sensitivity, was evaluated by clinical examination. The patients were divided into four CYP21A2 genotype groups. RESULTS: The sexual function score, but not for genital appearance, was higher in the patients satisfied with their sexual life. This was also true of the patients who were satisfied with the surgical result. There were discrepancies between the patients' perception of the impact of the condition on their sexual life and what health professionals would assume from clinical examination. The patients in the null genotype group scored lower on sexual function and satisfaction with their sexual life and had more surgical complications, also compared with the slightly less severe I2-splice genotype group. CONCLUSION: Our data show that the null genotype group was considerably more affected by the condition than the other groups and should be regarded as a subgroup, both psychologically and from a surgical perspective. Genotyping adds clinically valuable information.

Gender perspective on quality of life, comparisons between groups 4-5.5 years after unsuccessful or successful IVF treatment.

OBJECTIVE: To describe and compare quality of life in men and women who had in vitro fertilization (IVF) within the Swedish public health system 4-5.5 years previously, either unsuccessfully and were subsequently living without children, or successfully, having children aged 4-5.5 years. These groups were compared to a control group of men and women with children born at the same time as in the successful group. DESIGN: Cross-sectional study. SETTING: Reproductive Unit, Sahlgrenska University Hospital, Gothenburg, Sweden. SAMPLE: Twenty-six men and 37 women in the unsuccessful group, 135 men and 154 women in the successful group and 93 men and 118 women in the control group. METHODS: Questionnaire study. The respective gender differences were studied in the control and study groups. MAIN OUTCOME MEASURES: Psychological general well-being (PGWB), sense of coherence (SOC), experience of infertility, demographic-socio-economic, and health characteristics. RESULTS: Men in the unsuccessful IVF group scored lower in total PGWB and SOC indices than the successful group men. They reported more depression, lower PGWB and lower SOC than the control group men. Women in the unsuccessful IVF group reported more anxiety, depression, and lower SOC than the successful group women and more depression and lower SOC indices than control group women. Men and women in the unsuccessful IVF group did not differ in any of the parameters. Men in the successful IVF group had higher PGWB, less signs of depression and more self-confidence than women in that group. CONCLUSION: Quality of life in men seems more negatively affected by involuntary infertility than reported in earlier studies.

Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome?

CONTEXT: Despite the high prevalence of hyperandrogenemia, the principal biochemical abnormality in women with polycystic ovary syndrome (PCOS), a definitive endocrine marker for PCOS has so far not been identified. OBJECTIVE: To identify a tentative diagnostic marker for PCOS, we compared serum levels of sex steroids, their precursors, and main metabolites in women with PCOS and controls. DESIGN AND METHODS: In this cross-sectional study of 74 women with PCOS and 31 controls, we used gas and liquid chromatography/mass spectrometry to analyze serum sex steroid precursors, estrogens, androgens, and glucuronidated androgen metabolites; performed immunoassays of SHBG, LH, and FSH; and calculated the LH/FSH ratio. RESULTS: Androgens and estrogens, sex steroid precursors, and glucuronidated androgen metabolites were higher in women with PCOS than in controls. In multivariate logistic regression analyses, estrone and free testosterone were independently associated with PCOS. The odds ratios per sd increase were 24.2 for estrone [95% confidence interval (CI), 4.0-144.7] and 12.8 for free testosterone (95% CI, 3.1-53.4). In receiver operating characteristic analyses, the area under curve was 0.93 for estrone (95% CI, 0.88-0.98) and 0.91 for free testosterone (95% CI, 0.86-0.97), indicating high sensitivity and specificity. CONCLUSION: Women with PCOS have elevated levels of sex steroid precursors, estrogens, androgens, and glucuronidated androgen metabolites as measured with a specific and sensitive mass spectrometry-based technique. The combination of elevated estrone (>50 pg/ml) and free testosterone (>3.3 pg/ml) appeared to discriminate with high sensitivity and specificity between women with and without PCOS.

Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency.

CONTEXT: Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. OBJECTIVE: The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. RESULTS: The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. CONCLUSION: We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.

Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome.

We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity (MSNA). Animal studies support the concept that low-frequency electroacupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. In a randomized controlled trial, 20 women with PCOS were randomly allocated to one of three groups: low-frequency EA (n = 9), physical exercise (n = 5), or untreated control (n = 6) during 16 wk. Direct recordings of multiunit efferent postganglionic MSNA in a muscle fascicle of the peroneal nerve before and following 16 wk of treatment. Biometric, hemodynamic, endocrine, and metabolic parameters were measured. Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared with the untreated control group. The low-frequency EA group reduced sagittal diameter (P = 0.001), while the physical exercise group reduced body weight (P = 0.004) and body mass index (P = 0.004) compared with the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for body mass index and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine, and metabolic variables. For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.

Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

The aims were assessing liver function tests (LFT) in women with congenital adrenal hyperplasia (CAH) on glucocorticoids. Sixty-one women with genetically verified CAH due to 21-hydroxylase deficiency, aged 18-63 years were compared to 61 controls. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), anthropometry and fat mass (dual energy X-ray absorptiometry) were measured. ALT and GGT were higher in the entire patient group (p=0.01 and 0.002); AST, GGT and ALP in patients > or =30 years (p=0.007-0.045); all LFT in salt-wasting (p<0.001-0.042); GGT in simple virilizing (p=0.008); ALT, GGT and ALP in Null/Null genotype (p=0.018-0.040); ALT and GGT in I2splice genotype (p<0.001 and 0.011). Using a recently proposed cut-off level for ALT (>0.317 microkat/L), 54% of patients vs 23% of controls had elevated levels (p=0.028). In patients, GGT and ALP correlated with waist circumference and with total body and trunk fat (r=0.274-0.406, p=0.001-0.043). However, ALT, GGT and ALP were increased even in non-obese patients (waist circumference < or =88 cm and body mass index <30 kg/m(2)) (p=0.012-0.045) mainly attributed to the patients > or =30 years who also demonstrated elevated insulin levels and HOMA-indices. In conclusion, compared with controls, women with CAH have higher LFT, in particular patients > or =30 years and those with severe forms, probably reflecting a higher lifetime glucocorticoid exposure. LFT were positively correlated to measurements of body fat. These women might have increased frequency of NAFLD. The finding of higher LFT also in non-obese patients suggests that not only central obesity but also glucocorticoids per se may influence.