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Earlier menarche and irregular periods, among other markers of sex-hormone levels, have been associated with a higher risk of asthma and allergic diseases. This has suggested an etiologic role of sex hormones in the development of these conditions. The authors investigated the association of age at menarche, irregular periods, duration of menstruation, and acne with reported medical history of asthma and/or atopy (hay fever and/or eczema/urticaria) in a historical cohort of students born before the rise in asthma prevalence in the United Kingdom and attending university in 1948-1968. Finding consistent associations in a cohort that has experienced different life-course exposures and has different confounding structure can help to identify causal associations. In the Glasgow Alumni Cohort, irregular periods were associated with atopic asthma (multinomial odds ratio (MOR) = 2.79, 95% confidence interval (CI): 1.33, 5.83) and atopy alone (MOR = 1.40, 95% CI: 1.06, 1.84) but not with nonatopic asthma (MOR = 1.02, 95% CI: 0.45, 2.30), compared with students reporting no asthma and no atopy. The authors found no association with acne, a marker of high testosterone levels, that they hypothesized could point to polycystic ovary syndrome underpinning these associations. In summary, the authors found evidence for a potentially etiologic role of irregular menstruations with some specific asthma phenotypes, namely, atopic asthma and atopy, but not with nonatopic asthma.

Objectives: To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM)., Methods: Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years., Results: High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls., Conclusions: Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.

Background: PCOS is presented by a broad spectrum of menstrual irregularities appearing often at puberty or later on during the reproductive years in women suffering from this multifaceted syndrome. To our knowledge, there is no evidence to suggest whether the time of onset of menstrual irregularities (peri or post pubertal) indicates a differential metabolic and/or hormonal profile as well as ovarian ultrasonographic findings, in adulthood in women with PCOS., Aim of the Study: To compare anthropometric, hormonal-metabolic profile and ultrasound findings in PCOS women with peripubertal onset of menstrual disorders with the corresponding data obtained from PCOS patients with post pubertal onset of menstrual irregularities, matched for BMI and age., Patients-Methods: 89 PCOS women were evaluated cross-sectionally at the age of 25 years. In 49 subjects menstrual irregularities were present from menarche, whereas in 40 women the irregularities appeared at least 3 years post menarche., Results: Anthropometric parameters were comparable between the 2 groups. The 2 groups did not differ on metabolic and hormonal profile as well as ovarian ultrasound findings., Conclusions: These data indicate that the timing of menstrual irregularities, do not appear to have an impact, on hormonal/metabolic profile and ovarian ultrasound morphology in patients diagnosed with PCOS, later in life., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Background: There have been few studies examining the associations between menstrual irregularity, androgens and bone mass in population-based samples of premenopausal women. This study aimed to describe the associations between menstrual pattern, testosterone, sex hormone binding globulin (SHBG) and bone mass in a population-based sample of premenopausal women., Methods: Cross-sectional study (N = 382, mean age 31.5 years). Menstrual pattern was assessed by questionnaire, bone mass measured by quantitative ultrasound (QUS) and androgen status was assessed by levels of serum testosterone, SHBG and the free androgen index (FAI)., Results: Women with irregular cycles (n = 41, 11%) had higher free androgen index (FAI, P = 0.01) and higher QUS measurements including speed of sound (SOS, 1%, P < 0.05), quantitative ultrasound index (QUI, 7%, p < 0.05), and broadband ultrasound attenuation (BUA, 7%, p = 0.10). These associations persisted after adjustment for age and body mass index (BMI). After further adjustment for hormonal factors (either testosterone, SHBG or FAI), the strength of the associations was moderately attenuated, however, women with irregular cycles still had a 6% increase in mean QUS. Total testosterone, FAI and SHBG were also associated with QUS measures (testosterone and FAI, r +0.11 to +0.21, all p < 0.05; SHBG r -0.14 to -0.16, all p < 0.05) and the associations remained significant after adjustment., Conclusion: Irregular menstrual cycles were associated with higher bone mass in this population-based sample of premenopausal women suggesting menstrual disturbance should continue to be evaluated but may be less harmful for bone mass. The association between menstrual irregularity and bone mass was partially mediated by markers of androgen status especially free testosterone.

Background: Alterations in circulating steroids are believed to be important mediators of the impact that diet and exercise have on breast cancer risk and changes in bone density. This study aimed to test the hypothesis that moderate exercise training combined with caloric restriction would produce significant menstrual disturbances and alterations in ovarian steroids in premenopausal women., Methods: Sedentary premenopausal women (25-40 years; body mass index: 23.6 +/- 0.6 kg/m(2)) assigned to either a light conditioning (LC, n = 9) or an exercise combined with caloric restriction group (EX + CR, n = 24) were studied for one screening, one baseline and four intervention periods equivalent to the length of subjects' menstrual cycles. Exercise consisted of supervised training sessions, i.e. two LC or four EX + CR times per week, 30-60 min at a moderate intensity. The EX + CR group was prescribed a diet representing a caloric restriction of 20-35% below baseline energy requirements, whereas the LC group remained eucaloric. Ovarian steroid exposure was determined with daily urinary estrone-1- and pregnanediol glucuronides (E1G and PdG, respectively) and mid-cycle urinary LH measures. Fitness, body composition, and serum sex hormone binding globulin (SHBG) and serum estradiol (E2) were assessed repeatedly., Results: The intervention produced significant increases in VO(2) max and decreases in both body weight (-3.7 +/- 0.5 kg; ranged from -8.8 to +1.8 kg) and percent body fat (-4.5 +/- 0.7%; ranged from -12 to +0.3%), which were attributable primarily to changes in the EX + CR subjects (time x group; P < 0.05). Serum E2 and urinary E1G and PdG concentrations declined significantly across the intervention period (time; P < 0.05), whereas SHBG increased transiently (time; P < 0.05) in the EX + CR subjects, with no significant changes observed in the LC group. The decrease in E1G area under the curve was significantly related to the daily energy deficit (R =0.61; P = 0.003), not the amount of weight lost. There was no significant impact of the intervention on menstrual cyclicity or the incidence of menstrual disturbances in either group., Conclusions: A moderate aerobic exercise training program combined with modest weight loss in accordance with recommended guidelines produces significant reductions in ovarian steroid exposure without disrupting menstrual cyclicity in premenopausal women aged 25-40 years. Exposure to a daily energy deficit is a stronger predictor of the decline in estrogen exposure than decreases in body weight.

Objective: Wujijing Oral Liquid (WJJ) contained principally the flesh essence of the black-boned chicken. As a kind of food and medicine in China, it was used to treat the menstrual disturbance traditionally, but the exact mechanism of the action was not yet clear. The clinical effects of the WJJ on the symptoms of the menstrual disturbance and the reproductive hormones were studied in this paper., Materials and Methods: The 53 women with the menstrual disturbance were selected as the study object, and then they were randomly divided to receive either WJJ 10mL twice daily (n=28) or the placebo (n=25) from the 1st day after menstrual flow for 2 menstrual cycles. On the 1st day after the discontinuation of the medication but before the treatment, the scores for the menstrual pattern and the related symptoms were obtained and the blood samples were collected to test the reproductive hormones. The serum levels of the follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and estradiol (E2) were examined by enzyme-linked immunosorbent assay (ELISA). The levels of progesterone (P) and testosterone (T) in serum were measured by the radioimmunoassay., Results: The score for the primary and related symptoms of the menstruation was increased significantly among patients treated with the WJJ. The differences on the FSH, PRL, and E2 levels of patients were significant before and after the treatment with WJJ. Comparing the WJJ group and the placebo group, the levels of P and T differed significantly after treatment. The oral liquid of WJJ was found to be safe, as it did not cause any change in the hepatic and renal functional parameters., Conclusion: The oral liquid of Wujijing could improve the menstrual disturbance and were generally safe and well tolerated. The possible mechanism could be associated with its effects in reinforcing the kidney and regulating the hypothalamus-pituitary-ovary axis (HPOA)., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Context: Serum anti-Müllerian hormone (AMH) levels are significantly elevated in adolescents with polycystic ovary syndrome (PCOS) compared to normal controls. Whether adolescents with oligomenorrhea have elevated AMH levels is unknown., Objective: This study was performed to assess serum AMH levels in oligomenorrheic (OLIGO) girls without evidence of hyperandrogenism., Design: This was a prospective study comparing AMH levels in OLIGO, PCOS, and normal control adolescents., Setting: The study was conducted through four tertiary academic medical centers., Participants: The study groups were comprised of OLIGO (n = 24), PCOS (n = 153), and normal adolescent girls (n = 39), as well as PCOS (n = 73) and normal adult women (n = 36)., Interventions: In each subject, serum AMH levels were assessed in the early to midfollicular phases for regularly menstruating subjects and on an arbitrary day for OLIGO or PCOS subjects., Main Outcome Measure(s): Basal serum AMH levels were assessed among OLIGO, PCOS, and normal girls, in addition to PCOS and normal women., Results: OLIGO girls had serum AMH levels (5.33 +/- 0.47 ng/ml) that were significantly greater than the normal adolescents (3.05 +/- 0.31 ng/ml) and adults (2.33 +/- 0.22 ng/ml), but similar to values seen in the PCOS adolescents (5.28 +/- 0.26 ng/ml) and adults (6.36 +/- 0.47 ng/ml). Obese adolescents and PCOS women had significantly lower AMH levels compared to lean controls (P < 0.02)., Conclusion: In OLIGO adolescents, elevated serum AMH levels suggest increased antral follicle number similar to that observed in girls with PCOS.

The relationship between the menstrual cycle and risk for suicidal behaviors is not clear. The aim of this study is to determine whether perimenstrual phases in fertile women are associated with acute risk for suicide attempt and explore whether risk is elevated during low estradiol/low progesterone states. Women (N=431) recruited within 24h of a suicide attempt were assessed for psychopathology, suicidal behavior and LH, FSH, estradiol and progesterone blood levels. Among fertile women (N=281/431), suicide attempts were more likely to occur during menses (26%, 72/281 observed vs. 15%, 43/281 expected attempts; p<0.001). Compared to women whose attempts occurred during other phases, women who attempted suicide during low estradiol/low progesterone states (menstrual phase, amenorrhea and menopause) reported severe suicide intent, a measure that may be predictive of eventual suicide death. Suicide attempts among women are more likely when estrogen and progesterone levels are low and attempts made under these conditions are associated with greater severity. Low gonadal hormone levels may constitute a key factor in the neurobiological basis of suicidal behavior among women, suggesting a novel, testable hypothesis regarding the underpinnings of suicidal acts., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Menstrual cycle irregularities are often observed among physically active women and athletes who participate in physical activity ranging from recreational to competitive exercise training. Further, such irregularities have been casually linked to an energy deficiency where caloric intake is inadequate for exercise energy expenditure resulting in a suppressive effect on growth and reproduction. Adaptations consistent with chronic energy deficiency, including reductions in resting energy expenditure and total triiodothyronine, have been observed in exercising women with functional hypothalamic amenorrhea (FHA). Gut peptides and adipocytokines also appear to be altered in exercising women with FHA and have been hypothesized to be involved in the etiology of FHA. Ghrelin concentrations are elevated in exercising women with FHA. Interestingly, while fasting ghrelin, an orexigenic peptide, is elevated in women with FHA, PYY, an orexigenic peptide, is paradoxically also elevated in women with anorexia nervosa and exercising women with FHA. Leptin, an adipocytokine, is also suppressed in FHA associated with exercise and anorexia. A critical leptin concentration threshold is suggested to be necessary for regular menses to occur. Ghrelin, PYY, and leptin all have the ability to cross the blood brain barrier and, in the hypothalamus, can modulate appetite and food intake, and are hypothesized to affect the hypothalamic-pituitary-ovarian axis. Future studies are needed to determine if ghrelin, PYY, or leptin play a direct role in the regulation of the hypothalamic-pituitary-ovarian axis, and if these signals can be altered by improving energy status secondary to increasing caloric intake and initiate the reversal of amenorrhea., (Copyright © 2010 S. Karger AG, Basel.)

Background: Menstrual disturbances in female athletes are often explained as a consequence of energy deficiency. Oral contraceptive (OC) treatment may have favorable metabolic effects. We evaluated effects of OCs on diurnal secretions of insulin, insulin-like growth factor binding protein 1 (IGFBP-1), growth hormone (GH) and cortisol in relation to changes in body composition in athletes with menstrual disturbance compared with regularly menstruating athletes and controls., Methods: Age- and BMI-matched groups of endurance athletes with menstrual disturbance (OAM, n = 9) and regularly cycling athletes (RM, n = 8) and sedentary controls (CTRL, n = 8) were examined, and hormone levels measured, before and after 8 months of treatment with a low-dose combined OC (30 microg ethinyl estradiol + 150 microg levonorgestrel)., Results: Before OC treatment, the diurnal profile of insulin was lower (P < 0.01) and levels of IGFBP-1 (P < 0.05) and cortisol (P < 0.05) were higher in OAM athletes than in CTRL, whereas GH secretion was higher than in RM athletes (P < 0.05). After treatment, diurnal secretions of these hormones were similar between groups with an increase of IGFBP-1 in the regularly menstruating subjects only (P < 0.001). OC treatment increased body fat mass in OAM athletes (P < 0.01 versus baseline). The change in total fat mass correlated positively with pretreatment diurnal levels of GH (r(s) = 0.67, P < 0.01) and cortisol (r(s) = 0.64, P < 0.01)., Conclusions: OC treatment in endurance athletes with menstrual disturbance increases body fat mass and results in diurnal levels of insulin, IGFBP-1, GH and cortisol that are comparable to those in regularly menstruating subjects. These results suggest that OCs improve metabolic balance in OAM athletes.

Multiple sclerosis is a chronic inflammatory disease of central nervous system.Women are more susceptible to this disease. One of the obvious clinical complaints in women with multiple sclerosis specially treated with Beta Interferones is menstrual cycle irregularity. The aim of this study was to determine the prevalence of menstrual irregularities and probable changes in blood levels of related hormones (FSH, LH, PRL, TSH, T4, T3) in 58 females with definite MS treated with beta interferones versus 58 healthy women. In comparison to the control group, the patients had higher prevalence of irregular menstruation (P=0.001), oligomenorrhea (p=0.03), abnormal amount of menstrual blood flow (P=0.001), abnormal duration of menstrual flow (P=0.01) and missed period (P=0.04). Mean LH level in patients group was higher than control group (P=0.04). Hyperprolactinemia (>25.5 ng/ml) was more prevalent in patients group. There were not a significant difference in plasma levels of FSH and thyroid hormones between two groups. There were some relations between the type of Beta interferones and the subtype of menstrual irregularities in the patients. In conclusion, the results of this study emphasized the high rate of menstrual problem and changes of related plasma hormone levels in MS patients.

Introduction: Progressive condylar resorption has been described for many years. Because condylar resorption favors women over men, many have thought that a prominent systemic factor for the pathogenesis of this disease might be related to sex hormones., Methods: Over a 3-year period, 27 women without autoimmune disease came to our office for orthognathic surgical correction of their skeletal deformity secondary to severe condylar resorption. They all showed radiographic evidence of severe condylar resorption. Sex hormone dysfunction was evaluated, and midcycle serum levels of 17beta-estradiol were measured. Use of exogenous hormones was also documented., Results: Twenty-six of the 27 women with severe condylar resorption had either laboratory findings of low 17beta-estradiol or a history of extremely irregular menstrual cycles. Of the 27 women, 25 showed abnormally low levels of serum 17beta-estradiol at midcycle. Two subsets were identified in the group with low 17beta-estradiol. The first did not produce estrogen naturally (8 of 27), and the second had low 17beta-estradiol levels secondary to oral contraceptive pill (OCP) use (19 of 27). Of the 19 OCP users, all 19 reported that chin regression and open bite changes occurred after starting OCP use. Nine of the 19 reported these condylar resorption symptoms within the first 6 months of starting the OCP., Conclusions: Whether induced by ethinyl estradiol birth control or by premature ovarian failure, low circulating 17beta-estradiol makes it impossible for the natural reparative capacity of the condyle to take place in the face of local inflammatory factors. This leads to cortical and medullary condylar lysis.

The objective of this study was to evaluate serum prostate specific antigen (PSA) levels in women with menstrual disturbances and fibrocystic mastopathy. A total of 114 women with fibrocystic breast disease with cysts <10 mm (group I), 62 with macrocysts >10 mm (group II) and 46 healthy volunteers, who served as control subjects, were recruited for this prospective study. Each patient underwent complete gynecological examination and had performed sonography of the breasts. Moreover menstrual pattern, serum levels of free and total PSA, LH, FSH, SHBG, PRL, estradiol, progesterone, TSH, T4, as well as serum total testosterone, were evaluated in each subject. We compared serum free and total PSA levels between women with different menstrual pattern within groups of women with micro- and macrocysts. We also evaluated correlations between serum free and total PSA and hormonal/descriptive variables. We found that, in group II, women with regular menses and polymenorrhea revealed significantly higher serum free PSA than women with oligomenorrhea and secondary amenorrhea. Moreover, we found a positive correlation between serum total testosterone and total PSA in the control group and between progesterone and total PSA in group II. Our data show that serum free PSA is increased in women with regular menstrual cycles and polymenorrhea. This later relationship refers to women with macrocysts. Further studies are required to clarify the relationships between serum PSA and menstrual disturbances in women with mastopathy.

Background: The purpose of this study was to test the hypothesis that menstruation is associated with a higher concentration of endometrial cells in peritoneal fluid(PF) and with increased white and red blood cell concentration in PF when compared to nonmenstrual phases of the cycle., Methods: PF was obtained at laparoscopy from 107 women with endometriosis (n = 59) and controls with a normal pelvis (n = 48) during the luteal (n = 46), follicular (n = 38) or menstrual (n = 23) phase of the cycle. Endometriosis was classified according to the classification of the American Society for Reproductive Medicine (rAFS into minimal (n = 25), mild(n = 20), moderate(n = 6) and severe(n = 8) disease. Cell counts (leucocytes, erythrocytes, thrombocytes) were determined on a cell counter. In a subset of 32 patients (13 controls and 19 women with endometriosis), PF was fixed, processed and thinlayers were prepared and stained with Papanicolaou method and with immunocytochemistry using monoclonal antibodies against cytokeratin 7(CK 7), CK 8/18, Ber-Ep4, vimentin, calretinin and CD68. Ber-Ep4 is a marker for cells with epithelial origin (in some cases for mesothelial cells as well). CD68 is specific for cells from monocyte/macrophage lineage; CK7 and CK8/18 are markers for both endometrial epithelial and mesothelial cells, whereas calretinin and vimentin are markers for both endometrial stromal and mesothelial cells., Results: In comparison with the nonmenstrual phase of the cycle, analysis of PF during menstruation showed an increased concentration of leucocytes (3.3 x 109/L vs 0.8 x 109/L, P = 0.03), erythrocytes (0.3 x 1012/L vs 0.02 x 1012/L, P = 0.006), hematocrit (0.03 L/L vs 0.003 L/L, P = 0.01) and hemoglobin (0.8 g/dL vs 0.1 g/dL, P = 0.01). Mesothelial cells stained positively with CK7, CK8/18, vimentin, and calretinin. Cells positive for Ber-Ep4 were not observed, except in 2 patients with endometriosis investigated during menses. In all patients 50-98% of single cells were strongly positive for both vimentin and CD68., Conclusion: When compared to nonmenstrual phases of the cycle, menstruation is associated with an increased concentration of red and white blood cells in PF. However, the presence of EM cells that are detectable by immunohistochemistry in PF is low during all phases of the cycle, including menstruation.

Reproductive disorders and psychological distress are common co-morbidities of obesity in young women. Psychological and reproductive disturbances may also be associated with increased food cravings but the relationships between these factors have not been explored. This study aimed to explore the pattern of food cravings and to determine the relationship between psychological distress, reproductive health and food cravings in overweight and obese young women using baseline data in a weight loss trial. A total of 198 young women were included in this analysis (BMI 33.3+/-0.3 kg/m(2), age 28+/-0.3 years). The most frequently craved food item was chocolate (3.9+/-0.08 i.e., sometimes-often). The most frequently craved food categories were fast foods (2.6+/-0.07) and sweets (2.5+/-0.05). Psychological distress was significantly correlated with food cravings (R(2)=0.18, P<0.05). High fat (r=0.2), sweets (r=0.17) and overall cravings (r=0.20) were significantly correlated with energy intake (P<0.05). Psychological distress did not correlate with energy intake (P>0.05). Participants with menstrual disturbances had greater fast food cravings independent of age, BMI and PCOS status (P<0.05). Participants with hyperandrogenemia had greater high fat food cravings independent of age, BMI and PCOS status (P<0.01). Energy intake did not differ with menstrual disturbances or hyperandrogenemia (P>0.05). These results suggest that psychological distress, hyperandrogenemia and menstrual disturbances are associated with greater food cravings. Further investigations are required to elucidate the relationship between hyperandrogenemia and food cravings in young women.

Background: Anti-Müllerian hormone (AMH) has been proposed as a clinical predictor of improvements in reproductive function following weight loss in overweight and obese women with polycystic ovary syndrome (PCOS). This study aimed to assess whether baseline and/or change in AMH levels with weight loss predict improvements in reproductive function in overweight and obese women with PCOS., Methods: Fifty-two overweight and obese women with PCOS and reproductive impairment (age 29.8 +/- 0.8 years, BMI 36.5 +/- 0.7 kg/m(2)) followed a 20-week weight loss programme. AMH, weight, menstrual cyclicity and ovulatory function were assessed at baseline and post-intervention., Results: Participants who responded with improvements in reproductive function (n = 26) had lower baseline AMH levels (23.5 +/- 3.7 versus 32.5 +/- 2.9 pmol/l; P = 0.03) and experienced greater weight loss (-11.7 +/- 1.2 versus -6.4 +/- 0.9 kg; P = 0.001) compared with those who did not respond (n = 26). Logistic regression analysis showed that weight loss and baseline AMH were independently related to improvements in reproductive function (P = 0.002 and P = 0.013, respectively). AMH levels did not change with weight loss in both responders and non-responders., Conclusions: In overweight and obese women with PCOS and reproductive dysfunction, a 20-week weight loss intervention resulted in improvements in reproductive function but no change in AMH levels., Clinical Trials Registration Number: ACTRN12606000198527.

This cross-sectional study aimed to examine the association between different body composition measures, menstrual cycle characteristics, and hormonal factors in a population-based sample of young women. The study sample included 726 Australian women aged 26-36 years who were not currently taking hormonal contraceptives and were not currently pregnant or breast feeding. Anthropometric measures included BMI, waist circumference (WC), and waist-hip ratio (WHR). Menstrual cycle characteristics were self-reported and usual cycles defined as short (or=35 days). Cycles were defined as irregular if there were >or=15 days between the longest and shortest cycle in the past 12 months. Fasting serum levels of sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose were measured and the free androgen index (FAI) derived. Compared with those of normal weight, obese women had at least a twofold greater odds of having an irregular cycle, whether defined by BMI (odds ratio (OR) = 2.61; 95% CI = 1.28-5.35), WC (OR 2.28; 95% CI = 1.16-4.49), or WHR (OR = 2.27; 95% CI = 1.09-4.72). Body composition measures were significantly positively associated with fasting insulin, testosterone, and FAI, and negatively associated with SHBG (P < 0.01). Fasting insulin, SHBG, and FAI had the strongest influence on the associations between obesity and irregular cycles, with statistically significant ORs of having an irregular cycle being attenuated to near null values following adjustment. In conclusion, both overall and central obesity were significantly associated with having an irregular menstrual cycle. This association was substantially influenced by hormonal factors, particularly insulin and SHBG.

The objective of this study was to assess the nutritional adequacy of sub-elite runners with irregular menstrual function (n=10) and that of a comparable group of runners with regular menstrual function (n=10), with a special focus on vitamin E. Based on 3 days' records of weighed dietary intake, the mean energy intakes of micro- and macronutrients were estimated. Both estimated daily energy intake (irregular: 9.9+/-0.4 MJ; regular: 12.2+/-0.7 MJ; mean+/-sx) and intake of dietary fat (irregular: 61+/-6 g; regular: 98+/-12 g) were lower in athletes with irregular menstrual function than in athletes with regular menstrual function (P=0.01). Estimated intake of vitamin E was below recommended values in both groups. Serum concentrations of alpha-tocopherol were used to evaluate vitamin E status, which were normal in athletes with regular menstrual function (27.3+/-3.6 micromol.l(-1)) but below normal values in athletes with irregular menstrual function (15.7+/-0.8 micromol.l(-1); P=0.01). Furthermore, post-exercise osmotic fragility in red blood cells was inversely related to resting alpha-tocopherol concentrations. Our results indicate that irregular menstrual function in athletes on a low-fat diet is associated with low concentrations of circulating alpha-tocopherol, rendering the red blood cells more susceptible to haemolysis in connection with physical activity.

Purpose of the Work: To assess bone mineral density (BMD) in girls with menstruation disorders in the first years after menarche and to demonstrate that BMD value may be one of the indicators confirming an early diagnosis of hypothalamic hypogonadism or androgenisation complex., Material and Methods: The research included 155 girls at the ages of 16-17, observed due to rare menstruation or secondary amenorrhea. In case of 71 girls functional, hypothalamic disorders were found (Group A), in 35 girls increasing androgenisation features were diagnosed additionally (Group B), and 49 healthy girls represented Group C--control group. BMI was determined, as well as FSH, LH, T, E2, PRL concentrations and the BMD test of lumbar spine section was made in all of the cases. RESEARCH RESULTS: The average values of BMI and BMD in Group A were the lowest compared to Group B (p<0.001) and Group C (p<0.001). E2 concentrations in Group A was the lowest and in Group B--the highest (p<0.001). T concentrations in Group B girls was the highest and SHBG--the lowest compared to Groups A and C (p<0.001; p<0.01). FSH concentrations in Group A were the lowest compared to Groups B and C (p<0.01), while LH in Group B was the highest (p<0.001; p<0.01). Basic PRL concentrations were not essentially different. In groups (A + B + C) together, a statistically significant correlation between BMD and BMI values was found (r=0.67; p<0.001), E2 (r=0.38; p<0.01) and T (r=0.56; p<0.001)., Conclusions: Low bone mineral density value compared to the age value may signify long-term hypoestrogenism, and high value - a complex of metabolic disorders with high concentration of androgens. Therefore, bone mineral density may be a reliable and highly sensitive metabolic and hormonal indicator of menstruation disorders of hypothalamic, functional type or androgenisation complex.

Today, serum antimullerian hormone (AMH) is considered as an interesting marker of fertility potential in women to determine follicular status and in men to evaluate testicular function. We study analytical and clinical characteristics of two AMH commercialized immunoassays: Immunotech and DSL methods. The detection limits (close to 0.13 ng/mL), functional sensitivities (close to 0.30 ng/mL) are equivalent, and imprecision results are acceptable for entirely manual assays. The Immunotech method is linear within the calibration range (up to 21 ng/mL) and the DSL method presents a lack of linearity making it accurate only up to 11 ng/mL (and not up to 14 ng/mL as it is indicated by the manufacturer). The two methods allow to measure human AMH, don't cross react with TGF-beta superfamily proteins and the DSL immunoassay recognize mouse (25%), rat (68%) and calf (100%) AMH. The comparison between the two methods (from 0.3 to 200 ng/mL) shows a good correlation (r = 0.979) with not statistically different results (p = 0.31). From a clinical point of view, the two methods allow the evaluation of follicular status in normo-ovulatory women and in women with polycystic ovary syndrome. Results are in agreement with studies showing that AMH serum concentration is strongly correlated with the number of antral follicles. In conclusion, the Immunotech method seems to be more efficient than the DSL method even if the two methods are suitable for clinical applications needing AMH measurements.

Objective: To examine the efficacy of sibutramine together with brief lifestyle modification for weight reduction in obese women with polycystic ovary syndrome (PCOS)., Design: Investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial., Setting: Departments of Obstetrics and Gynecology in primary care, referral centers, and private practice., Patient(s): Forty-two patients with confirmed PCOS were included in the study, and 34 patients completed the study., Intervention: Sibutramine 15 mg once daily together with brief lifestyle modification was compare with placebo together with brief lifestyle modification., Main Outcome Measure(s): The primary endpoint was to assess weight loss. Secondary endpoints included the efficacy of sibutramine for treatment of menstrual pattern and cardiovascular risk factors., Result(s): After 6 months the sibutramine group had lost 7.8 +/- 5.1 kg compared with a weight loss of 2.8 +/- 6.2 kg in the placebo group. Sibutramine treatment resulted in significant decreases in apolipoprotein B, apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C levels., Conclusion(s): Sibutramine in combination with lifestyle intervention results in significant weight reduction in obese patients with PCOS. In addition to the weight loss, sibutramine seems to have beneficial effects on metabolic and cardiovascular risk factors.

The androgen theory of autism proposes that autism spectrum conditions (ASC) are in part due to elevated fetal testosterone (FT) levels, which are positively correlated with a number of autistic traits and inversely correlated with social development and empathy. A medical questionnaire was completed by n=54 women with ASC, n=74 mothers of children with ASC, and n=183 mothers of typically developing children to test whether women with ASC have an increased rate of testosterone-related medical conditions, and to see whether mothers of children with ASC show similar abnormalities, as part of the 'broader autism phenotype'. Compared to controls, significantly more women with ASC reported (a) hirsutism, (b) bisexuality or asexuality, (c) irregular menstrual cycle, (d) dysmenorrhea, (e) polycystic ovary syndrome, (f) severe acne, (g) epilepsy, (h) tomboyism, and (i) family history of ovarian, uterine, and prostate cancers, tumors, or growths. Compared to controls, significantly more mothers of ASC children reported (a) severe acne, (b) breast and uterine cancers, tumors, or growths, and (c) family history of ovarian and uterine cancers, tumors, or growths. These results suggest current hormone abnormalities in women with ASC and their mothers. Direct investigations of serum testosterone levels and genetic susceptibility to high testosterone production or sensitivity in women with ASC would illuminate the origin of these conditions. The relationship between FT and current testosterone levels also needs to be clarified. The present results may be relevant to understanding the increased male risk to developing autism.

Aims: To assess the prevalence of hormonal dysfunction in women addicted to alcohol during first week following drinking cessation; to determine whether fluctuations of hormone levels in follicular, ovulation and luteal phases in addicted women are equal to those normally found in healthy women; to determine the association between hormonal imbalances with selected clinical features., Methods: Biochemical parameters of liver function and hormone levels were assessed in 30 women treated for 30 days in a Short Term Therapy and Detoxification Ward. The following hormones were measured: prolactin (PROL), folliculotropin (FSH), luteotropin (LH), estradiol (ES) and testosterone (TEST)--(i) after menstruation, at follicular phase, between 5th and 7th day of the cycle; (ii) around ovulation, 11-14th day of the cycle; and (iii) before menstruation, at luteal phase, between 19th and 22th day of the cycle., Results: Mean PROL levels in all three cycle phases and progesterone level in follicular phase were above, while mean TEST level was below, the reference values. Over 50% of women had abnormally increased PROL values in all phases of the cycle while decreased values of PROG or LH were found in approximately 50% and >30% of study women., Conclusions: The menstrual cycle disturbances in alcoholic women are most prominent around the middle part of the cycle and age influences the pattern of hormonal changes.

Background: Menstrual disturbances are common among teenagers and are often explained by immaturity of the hypothalamic-pituitary-gonadal axis. However, little is known about the underlying causes. The aim of this study was to evaluate endocrine mechanisms of menstrual disturbances and associated factors among adolescent girls visiting a Swedish youth clinic. METHODS. All adolescent girls visiting the youth clinic during a five-year period due to menstrual disturbances, except those with primary amenorrhea, were included in this retrospective study. These 203 girls were evaluated in a standardized manner by the same gynecologist. One third also met a psychologist and/or a dietician at the clinic., Results: Secondary amenorrhea was diagnosed in 117 girls (58%) and oligomenorrhea in 86 girls (42%). Menarcheal age was 13 in both groups. Hypothalamic inhibition of the gonadal axis was more frequent in the girls with secondary amenorrhea, whereas a hyperandrogenic hormonal pattern as a feature of polycystic ovary syndrome was more common in the oligomenorrheic girls. Different types of eating disorders were diagnosed in 68% of the amenorrheic girls and in 38% of the oligomenorrheic girls., Conclusions: We found hypothalamic amenorrhea and hyperandrogenism to be frequent endocrine mechanisms of menstrual disorders in teenagers. Concomitant eating disorder was highly frequent and secondary amenorrhea was associated with anorectic behavior. It is important to evaluate endocrine patterns and eating behavior in adolescents with menstrual disturbances to ensure adequate medical care and treatment.

Aim: Evaluation of CCCT results and anti-Müllerian hormone (AMH) plasma levels in women with menstrual cycle irregularities and/or infertility., Patients and Methods: 70 patients with menstrual cycle disturbances were recruited to the study. Clomiphene citrate challenge test (CCCT) was carried out in each patient enrolled. At day 3 of the cycle plasma basic levels of FSH, estradiol, progesterone, IGFBP-1, TSH, prolactin, DHEAS and anti-Müllerian hormone were measured. At day 10 of the cycle plasma levels of FSH and estradiol were evaluated. Plasma levels of hormones were measured by commercially available ELISA kits., Results: 50 women with normal result of CCCT (group A) had higher mean plasma level of AMH compared to 20 women with abnormal result of CCCT (group B). Mean plasma FSH level at day 3 of the cycle was lower in group A compared to group B. There were no other statistically significant differences in mean values of assessed parameters between groups A and B. Taking into account all patients enrolled to the study AMH correlated significantly with patients' age and plasma levels of FSH at day 3 and day 10 of the cycle). Basic AMH plasma levels in group A correlated negatively with plasma levels of FSH at day 3 and day 10. In group B plasma levels of FSH at day 10 of the cycle also correlated with basic AMH plasma levels. Plasma levels of estradiol at day 10 of the cycle were related inversely with basic AMH plasma levels in group A, but directly in group B., Conclusion: It should be recommended to perform the CCCT before infertility treatment. Evaluation of the anti-Müllerian hormone plasma level reflects the results of the CCCT.

Purpose: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously., Methods: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured., Results: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone-binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women., Conclusions: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.

Objective: The study was designed to compare the follicular phase of women with recurrent pregnancy loss and a healthy control group. It is possible that a defective or aberrant follicular phase may be associated with poor oocyte quality leading to a production of an embryo with compromised quality and hence early pregnancy loss., Design: Prospective case-control study., Setting: A tertiary care hospital of Sheffield, UK., Patient(s): Thirty-four women with recurrent miscarriage and 10 women with no previous history of miscarriage and regular menstrual cycles (control group) were recruited., Intervention(s): The characteristics studied included Doppler assessment of blood flow to the follicle and the endometrium. Simultaneously, serum concentrations of biochemical markers such as anti-Müllerian hormone, inhibin B, FSH, LH, and P were compared in the two groups., Main Outcome Measure(s): Differences in the two groups., Result(s): We were unable to detect significant differences in various biochemical and ultrasound measurements in the follicular phase between women with recurrent miscarriage and a control group; however, the expected correlation between ovarian and pituitary hormones, which was observed in the control group, was absent in women with recurrent miscarriage., Conclusion(s): There may be subtle derangements of the feedback mechanism responsible for regulation of follicle development in this group of women. However, there were no obvious differences in the follicular phase of women with recurrent miscarriage and a healthy control group.

Background: Preliminary reports suggest that menstrual cycle irregularities occur more commonly in women with bipolar disorder and unipolar depression than in the general population. However, it is not always clear whether such abnormalities, reflecting disruption of the hypothalamic-pituitary-gonadal (HPG) axis, are caused by psychotropic treatments or associated with the disorder per se., Method: The prevalence of early-onset (within the first 5 postmenarchal years) menstrual cycle dysfunction (menstrual cycle length unpredictable within 10 days or menstrual cycle length<25 days or >35 days) occurring before onset of psychiatric illness was compared between subjects with DSM-IV bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and subjects with DSM-IV unipolar depression or no psychiatric illness participating in the Harvard Study of Moods and Cycles. Data from the Harvard Study of Moods and Cycles were gathered from September 1995 to September 1997, and data from STEP-BD were gathered from November 1999 to May 2001., Results: Early-onset menstrual cycle dysfunction was reported to have occurred in 101/295 women with bipolar disorder (34.2%), 60/245 women with depression (24.5%), and 134/619 healthy controls (21.7%). Women with bipolar disorder were more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2=16.58, p<.0001) and depressed women (chi2=6.08, p=.01), while depressed women were not more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2=0.81, p=.37)., Conclusions: Compared with healthy controls and women with unipolar depression, women with bipolar disorder retrospectively report early-onset menstrual dysfunction more commonly prior to onset of bipolar disorder. Future studies should evaluate potential abnormalities in the hypothalamic-pituitary-gonadal axis that are associated with bipolar disorder.

The aim of the present study was to verify the presence of anti-corpus luteum antibodies (anti-CoL) in systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis (HT) patients, as well as establish its possible correlation with menstrual and/or hormonal disturbances in both populations and with SLE activity. Forty-six patients with SLE, 31 with HT, four with both SLE and HT, and 36 healthy women were studied. Out of these, seven (15.2%) patients with SLE, three (9.7%) with HT, three (75%) with both pathologies, and none of the healthy controls tested positive for anti-CoL. The presence of anti-CoL was not significantly correlated to menstrual disturbance (P = 0.083), changes in the level of follicle stimulating hormone (P = 1.0), luteinizing hormone (P = 0.284), estradiol (P = 0.316), prolactin (P = 1.0) or SLE activity measured by SLEDAI (P = 0.756) in SLE patients. There were not enough patients testing positive for anti-luteal antibodies among those with HT or both HT and SLE (three from each group) for a statistical analysis. In conclusion, we found no association between anti-CoL and menstrual or hormonal disturbance in patients with SLE. Also anti-CoL was not specific for SLE, and was not found to be a marker of ovarian failure in SLE.

Either exogenous or endogenous glucocorticoid excess is an established cause of osteoporosis and fractures. Glucocorticoids exert their negative effects on bone through mechanisms that are not yet completely elucidated; however, as many as 50% of patients with Cushing's syndrome suffer from osteoporosis. Bone loss induced by glucocorticoids is potentially reversible after resolution of glucocorticoid excess. It is presently unknown if Cushing's disease (CD) sustained by a pituitary ACTH-producing adenoma and adrenal-dependent Cushing's syndrome (ACS) sustained by an adrenocortical adenoma have a different potential of inducing osteopenia. The aim of the present study was to retrospectively analyze bone mineral density (BMD) in 26 patients with CD (4 men, 22 women, aged 14-79 years), 12 patients with ACS (4 men, 8 women, aged 32-79 years) and 38 healthy subjects carefully matched for sex, age and body mass index (BMI). Measurement of BMD was performed by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR 4500 W instrument. Data were analyzed using absolute BMD values (g/cm2), T-score and Z-score referred to the manufacturer's normative data for the lumbar spine and to the NHANES III dataset for the hip. The patients with CD and ACS were comparable for age, BMI, estimated duration of disease, urinary free cortisol (UFC) levels, midnight serum cortisol and gonadal function. The analysis of variance demonstrated that lumbar bone densitometric parameters were significantly different among the three groups. They were more reduced in patients with ACS (BMD, 0.76+/-0.03 g/cm2; T-score, -2.78+/-0.28; Z-score, -2.25+/-0.30) while patients with CD (BMD, 0.87+/-0.02 g/cm2; T-score, -1.74+/-0.24; Z-score, -0.99+/-0.32) showed DXA values between the first group and controls (BMD, 1.02+/-0.02 g/cm2; T-score, -0.35+/-0.19; Z-score, 0.33+/-0.16). The difference in BMD at the spine remained statistically significant ( P=0.04) after adjustment for the non-significant differences in age, UFC and fat mass between CD and ACS. Conversely, femoral bone densitometric parameters were not significantly different between patients with ACS and CD, even if they were more reduced than in controls. In patients with ACS, we observed a reduction of DHEA-S levels, expressed as standard score ( Z-score) values referred to a group of 180 healthy subjects stratified by sex and different age groups (<40 years, between 40 and 60 years, >60 years) to circumvent the pronounced effect of gender and age on such hormone (ACS DHEA-S Z-score -0.88+/-1.4 versus CD DHEA-S Z-score 2.25+/-2.35, P=0.0001). DHEA-S Z-score values were significantly correlated with lumbar BMD ( r=0.41, P=0.02) and femoral BMD ( r=0.43, P=0.01). DHEA-S Z-score values were also significantly correlated with osteocalcin levels ( r=0.45, P=0.01). Our data suggest that bone loss is greater in ACS than in CD. A plausible explanation comes from the reduced DHEA-S level in ACS since DHEA-S has well known anabolic actions on bone. However, this hypothesis needs to be confirmed in large, prospective series of patients with Cushing's syndrome of different etiology.

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.

Objectives: Menstrual disorders are very common during the early postmenarcheal years. This study was undertaken to determine the causes of menstrual disorders in adolescents., Materials and Methods: In the research there were included 117 girls 14-18 years old without evidence of androgen excess (hirsutism, acne): the study group consisted of 87 adolescents with menstrual disorders and the control group of 30 girls with regular menstrual cycles. All the patients underwent gynecological and ultrasound examination and an analysis of the hormonal status., Results: The data from our investigation show that 43.7% of adolescents with menstrual dysfunction have eating disorders, 16.1%--immaturity of hypothalamic-pituitary-ovarian axis, 13.8%--polycystic ovary syndrome, 9.2%--hyperprolactinemia, 4.6%--delayed puberty, 3.4%--genetic defect and 9.2% other reasons., Conclusions: A thorough history and physical examination focusing on the basic understanding of pubertal and menstrual physiology and pathology allows to obtain an accurate diagnosis. The prognosis for later fertility depends on the preventive measures token in adolescence.

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (p<0.01) and LH (p<0.05) plasma levels higher than control group and the highest free androgen index (FAI) values (13 +/- 0.87). All patients with irregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

Objective: We evaluated menopausal symptoms, menstrual cycle bleeding characteristics and reproductive hormones for their associations with thyroid stimulating hormone (TSH) concentrations in women at the mid-life from five ethnic groups., Methods: This report is from the baseline evaluation of the Study of Women's Health Across the Nation (SWAN), a community-based multiethnic study of the natural history of the menopausal transition. Enrollees were 42-52 years old (pre- and early perimenopausal) African American, Caucasian, Chinese, Hispanic and Japanese women (n = 3242). Enrollees were interviewed about self-reported diagnosed hypo- and hyperthyroidism or thyroid treatment, menopausal symptoms and menstrual cycle bleeding characteristics. Serum was assayed for TSH, oestradiol, testosterone, FSH and SHBG., Results: There were 6.2% of women with TSH > 5.0 mIU/ml and 3.2% with TSH < 0.5 IU/ml, cutpoints that have been used to encompass clinical and subclinical hypo- and hyperthyroidism, respectively. African American women had significantly lower mean TSH concentrations than Caucasian, Hispanic and Chinese women. Of the more than 15 menopause symptoms evaluated, only fearfulness was associated with having a TSH value > 5.0 mIU/ml (P < 0.008) or < 0.5 mIU/ml (P < 0.02). Women with TSH values outside the range of 0.5-5.0 mIU/ml were more likely to report shorter or longer menstrual periods (P = 0.004 for both) than women within that range. FSH, SHBG, dehydroepiandrosterone sulphate (DHEA-S), testosterone, and oestradiol concentrations were not associated with TSH concentrations., Conclusion: In mid-aged women, there was a 9.6% prevalence of TSH values outside the euthyroid range of 0.5-5.0 mIU/ml. Although TSH was associated with bleeding length and self-reported fearfulness, it was not associated with indicators of the menopausal transition, including menopausal stage defined by bleeding regularity, menopausal symptoms or reproductive hormone concentrations.

A study presents two cases of menstrual abnormalities in women with primary biliary cirrhosis and chronic active hepatitis treated with liver transplantation. The gonadotropin, sex hormones levels and biochemical parameters were presented. The menstrual disorders we observed may be a consequence of high concentration of oestrogens in our patients.

Purpose: Polycystic ovaries and menstrual disturbances seem to be common among women taking valproate for epilepsy. The purpose of the present study was to assess the frequency of valproate-related metabolic and endocrine disorders in different groups of women with epilepsy., Subjects and Methods: Seventy-two women with epilepsy and 52 control subjects from centers in three European countries (Finland, Norway, and the Netherlands) participated in the study. Thirty-seven of the women with epilepsy were taking valproate monotherapy and 35 carbamazepine monotherapy., Results: The frequency of polycystic ovaries or hyperandrogenism, or both, among valproate-treated women with epilepsy was 70% (26 of 37) compared with 19% (10 of 52) among control subjects (P <0.001). They were found in 79% (11 of 14) of obese and 65% (15 of 23) of lean women on valproate, and in 20% (7 of 35) of carbamazepine-treated women. The obese valproate-treated women with polycystic ovaries or hyperandrogenism, or both, had hyperinsulinemia and associated unfavorable changes in serum lipid levels consistent with insulin resistance., Conclusions: Polycystic ovaries and related hyperandrogenism are frequently encountered in both obese and lean women taking valproate for epilepsy. The use of valproate is associated with risk factors for cardiovascular disease in obese women.

Purpose: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation., Methods: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured., Results: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations., Conclusions: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.

Women have become increasingly physically active in recent decades. While exercise provides substantial health benefits, intensive exercise is also associated with a unique set of risks for the female athlete. Hypothalamic dysfunction associated with strenuous exercise, and the resulting disturbance of GnRH pulsatility, can result in delayed menarche and disruption of menstrual cyclicity. Specific mechanisms triggering reproductive dysfunction may vary across athletic disciplines. An energy drain incurred by women whose energy expenditure exceeds dietary energy intake appears to be the primary factor effecting GnRH suppression in athletes engaged in sports emphasizing leanness; nutritional restriction may be an important causal factor in the hypoestrogenism observed in these athletes. A distinct hormonal profile characterized by hyperandrogenism rather than hypoestrogenism is associated with athletes engaged in sports emphasizing strength over leanness. Complications associated with suppression of GnRH include infertility and compromised bone density. Failure to attain peak bone mass and bone loss predispose hypoestrogenic athletes to osteopenia and osteoporosis. Metabolic aberrations associated with nutritional insult may be the primary factors effecting low bone density in hypoestrogenic athletes, thus diagnosis should include careful screening for abnormal eating behavior. Increasing caloric intake to offset high energy demand may be sufficient to reverse menstrual dysfunction and stimulate bone accretion. Treatment with exogenous estrogen may help to curb further bone loss in the hypoestrogenic amenorrheic athlete, but may not be sufficient to stimulate bone growth. Treatment aimed at correcting metabolic abnormalities may in fact prove more effective than that aimed at correcting estrogen deficiencies.

PRL exists in different forms in human serum. The predominant form is little PRL (molecular mass 23 kDa) with smaller amounts of big PRL (molecular mass 50--60 kDa) and at times big big or macroprolactin (molecular mass 150--170 kDa). The frequency and clinical consequences of macroprolactinemia have not been clearly established, mainly because of difficulty in identifying these patients biochemically. This previously required the use of gel filtration chromatography, which could not be used routinely. Recently, a screening test using polyethylene glycol (PEG) has been used to identify macroprolactin in serum. Consequently, this study was designed to examine the use of PEG precipitation in the identification of patients with a predominance of macroprolactin and to establish the clinical characteristics of such a cohort. Over 12 months, 18,258 requests for serum PRL were received and of these 1225 patients had a serum PRL more than 700 mU/L. A total of 322 of these patients (26%) had a percentage recovery after PEG precipitation of less than 40%, thus indicating the presence of a predominance of macroprolactin. Fifty-five of these patients were referred for detailed clinical assessment. Symptoms typical of hyperprolactinemia were not common in this cohort. None had sustained amenorrhea and eight have had oligomenorrhea at age less than 40 yr. One had galactorrhea. All had pituitary imaging, and four had a microadenoma with none having a macroadenoma. PEG precipitation allows easy identification of macroprolactin in routine clinical practice. As the clinical consequences of this entity at this stage seem relatively benign, referral and intensive investigation of these patients may not be necessary. However, follow-up of a large cohort is required to ensure that the long-term outlook is likewise benign. This would have important implications for both patients and healthcare systems.

Background: Reproductive endocrine disorders characterized by menstrual disorders, polycystic ovaries, and hyperandrogenism seem to be common among women treated with sodium valproate for epilepsy., Objective: To describe the development of valproate-related reproductive endocrine disorders in women with epilepsy., Design: Case report., Patients: Three patients developed a reproductive endocrine disorder during treatment with valproate. It was characterized by hyperandrogenism and polycystic ovaries in all cases, and it was associated with weight gain and menstrual disorders in 2 of the 3 women., Results: Replacing valproate with lamotrigine resulted in a decrease in serum testosterone concentrations in all 3 women. The polycystic changes disappeared from the ovaries in 2 of the women after valproate therapy was discontinued, and the 2 women who had gained weight and developed amenorrhea while being treated with valproate lost weight and resumed menstruating after the change in medication., Conclusions: The 3 cases presented here illustrate the development of reproductive endocrine disorders after the initiation of valproate therapy in women with epilepsy. The disorders were characterized by hyperandrogenism and polycystic ovaries in all cases, and were associated with weight gain and menstrual disorders in 2 of the 3 women. An evaluation of ovarian structure and function should be considered in women of reproductive age being treated with valproate for epilepsy, especially if they develop menstrual cycle disturbances during treatment.

Objective: We sought to establish the lowest dose of 3-keto-desogestrel, when added to a copper-releasing intrauterine contraceptive device, that is needed to reduce menstrual blood loss to a very low level and to treat (essential) menorrhagia successfully., Study Design: A double-blind group comparative study was designed in which 203 healthy women with or without menorrhagia were enrolled and randomized to four different Multiload Cu250 intrauterine contraceptive devices, releasing 0 (control), 1.5, 3, or 6 microg of 3-keto-desogestrel daily. Menstrual blood loss, hemoglobin, and serum ferritin levels were determined before and during treatment., Results: All 3-keto-desogestrel-copper intrauterine contraceptive devices reduced menstrual blood loss significantly, causing a reduction of up to 30 to 40 mL after 12 months of use. All women with essential menorrhagia were considered to have been successfully treated after 6 months of use. Serum ferritin levels rose with all three 3-keto-desogestrel-loaded devices., Conclusion: A Multiload Cu250 intrauterine contraceptive device releasing 1.5 microg of 3-keto-desogestrel daily is able to reduce menstrual blood loss to a very low level and to replete body iron stores in women with or without menorrhagia. Higher doses have no superior effect.

The objective of this cross-sectional study was to determine the relationship between hyperandrogenemia and blood pressure in women with menstrual irregularities seen at an endocrinology clinic. Women with serum testosterone levels (T) > or = 30 ng/dL were more likely to have general obesity (odds ratio [OR] = 6.8, 95% confidence intervals [CI] = 2.2-27.2) and central obesity (OR = 14.5, 95% CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women (HA) had an OR of 2.4 (95% CI = 1.0-6.2) for elevated SBP and an OR of 2.7 (95% CI = 0.8-8.8) for elevated DBP, independent of age and ovulatory status. Obese HA had an OR of 4.7 (95% CI = 2.3-10.4) for elevated SBP and an OR of 2.9 (95% CI = 1.9-9.9) for elevated DBP. In conclusion, T is associated with an increased risk for obesity and central adiposity. T predicts BP elevation independent of age and ovulatory status. There was a synergistic relationship between obesity and androgens in their affect on BP.