Discriminating hypothalamic oligomenorrhea/amenorrhea from hyperandrogenic oligomenorrhea/amenorrhea in exercising women.

The mechanism underlying oligo/amenorrhea in exercising women is often presumed as hypothalamic inhibition secondary to energy deficiency; however, hyperandrogenism may provide an alternative mechanism in some exercising women. Our purpose was to compare reproductive, metabolic, and androgen profiles of exercising women with eumenorrheic, ovulatory menstrual cycles (n = 91), oligo/amenorrhea without evidence of hyperandrogenism (Oligo/Amen; n = 83), and oligo/amenorrhea with evidence of hyperandrogenism (Oligo/Amen-HA; n = 17), and determine the prevalence of oligo/amenorrhea with evidence of hyperandrogenism in exercising women. Self-reported menstrual history and quantification of daily estrogen and progesterone urinary metabolites determined reproductive status. Resting energy expenditure, body composition, and metabolic hormone concentrations determined metabolic status. Serum androgens and calculated free androgen index (FAI) determined androgen status. Groups were similar in age (22.4 ± 0.3 years), height (165.1 ± 0.5 cm), resting energy expenditure (1198.4 ± 12.0 kcal/day), and total triiodothyronine (85.0 ± 1.5 ng/dL) concentration. Oligo/Amen-HA had greater weight (60.0 ± 1.6, 56.1 ± 0.7 kg), body mass index (22.3 ± 0.4, 20.6 ± 0.2 kg/m2), percentage body fat (27.3% ± 1.4%, 24.4% ± 0.6%), fat mass (16.2 ± 1.0, 13.8 ± 0.4 kg), insulin (5.8 ± 0.7, 4.2 ± 0.3 µIU/mL), leptin (12.2 ± 2.3, 6.6 ± 0.7 ng/mL), FAI (6.1 ± 0.3, 1.7 ± 0.1), and luteinizing hormone/follicle-stimulating hormone (1.9 ± 0.3, 1.3 ± 0.2) compared with Oligo/Amen, respectively. In our sample, 17% of those with oligo/amenorrhea had concurrent hyperandrogenism. This study supports that oligo/amenorrhea in some exercising women is related to hyperandrogenism. Novelty Caution must be utilized when discriminating hypothalamic oligo/amenorrhea from hyperandrogenic oligo/amenorrhea. In our sample, 17% of those with presumed hypothalamic oligo/amenorrhea had concurrent hyperandrogenism. Exercise and/or mild energy deficiency may be protective against developing severe hyperandrogenic symptoms.

Challenging diagnosis of thyroid hormone resistance initially as Hashimoto's thyroiditis.

Background Resistance to thyroid hormone (RTH) commonly presents with goiter, attention deficit hyperactivity disorder (ADHD), short stature and tachycardia. However, due to its variable presentation with subtle clinical features, a third of the cases are mistreated, typically as hyperthyroidism. Case presentation A 15-year-old female with ADHD and oligomenorrhea was initially diagnosed as Hashimoto's thyroiditis but found to have a rare heterozygous mutation in c803 C>G (p Ala 268 Gly) in the THRß gene, confirming resistance to thyroid hormone. Conclusions Fluctuating thyroid function tests in addition to thyroid peroxidase antibody (TPO Ab) positivity complicated the diagnosis of RTH, initially diagnosed as Hashimoto's thyroiditis. A high index of suspicion is needed to prevent misdiagnosis and mistreatment.

Resección laparoscópica de un tumor virilizante suprarrenal derecho / Laparoscopic approach in an adrenal right virilizing tumour

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Hormonal and psychosocial correlates of psychological well-being and negative affectivity in young gynecological-endocrinological patients.

To study the relationship between hormones, psychosocial factors and psychological well-being or negative affectivity (NA), 102 women (aged 15-31) responded to the 12-item well-being questionnaire (W-BQ12), with subscales for positive well-being (PWB), negative well-being (NWB) and energy (ENE); the Hospital Anxiety and Depression Scale (HADS), consisting of depression (HADS-D) and anxiety (HADS-A) subscales; the Beck Depression Inventory (BDI), and the Hamilton Depression Scale (HAMD). The univariate analysis revealed significant negative correlations between luteinizing hormone (LH) and HADS-T, HADS-D and HADS-A, and between follicle stimulating hormone (FSH) and HADS-A. Positive correlations were shown for thyroid stimulating hormone (TSH), HADS-T, and HADS-A. Cortisol and prolactin levels strongly correlated with BDI and HAMD scores, respectively. In a multivariate analysis, TSH significantly predicted the mood impairment in HADS-T (ß = 0.68) and HADS-A (ß = 0.68), while economic status predicted the general well-being (ß = 0.75), NWB (ß = -0.83), ENE (ß = 0.89), and HADS-A (ß = -0.63). We could not detect any significant differences in NA or well-being in patients with versus without PCOS or with versus without hirsutism, but almost all psychometric parameters differed significantly according to the economic status. In conclusion, TSH was the only hormonal predictor of overall NA and anxiety, and low-economic status overtrumped the impact of hormones on the psychological well-being.

Obesity and menstrual disorders.

Obese women often present with oligomenorrhoea, amenorrhoea or irregular periods. The association between obesity and heavy menstrual bleeding is not well documented and data on its prevalence are limited. While the investigation protocols should be the same as for women of normal weight, particular focus is required to rule out endometrial hyperplasia in obese women. The treatment modalities of menstrual disorders for obese women will be, in principle, similar to those of normal weight. However, therapeutic outcomes in terms of effectiveness and adverse outcomes need special consideration when dealing with women with a high body mass index (BMI). Here, different treatment strategies are reviewed paying particular attention to the effect of weight on their efficacy and the challenges of providing each treatment option. This chapter aims to review the current literature and address areas where further evidence is needed, which will subsequently influence clinical practice.

Hyperandrogenic oligomenorrhea and metabolic risks across menopausal transition.

CONTEXT: Although there is evidence of metabolic risks in young women with irregular menses and androgen excess, persistence of risks after menopause is unclear. OBJECTIVE: The objective of the study was to determine the impact of menopause on the cardiometabolic profile in women with high androgens and a history of menstrual irregularity. METHODS: Study of Women's Health Across the Nation is a longitudinal cohort study. Data from 1929 women without metabolic syndrome (MetS) at baseline were analyzed for incidence of MetS, self-reported stroke, and myocardial infarction. Cox hazard ratios (HRs) were estimated, adjusting for age, ethnicity, body mass, smoking, menopausal status, and study site. RESULTS: Among MetS-free women at baseline, 497 new cases were identified during 20 249 woman-years of follow-up over 12 years. Women with hyperandrogenemia (HA) and oligomenorrhea (Oligo) developed incident cases of MetS at a comparable rate compared with their counterparts: eumenorrheic, normoandrogenic women [HR 1.4 (0.9-2.2)], oligomenorrheic, normoandrogenic women [HR 1.3 (0.8-2.2)], and eumenorrheic hyperandrogenic women [HR 1.2 (0.7-1.8)]. Smoking and obesity were the strongest predictors of incident MetS. There was no significant difference in incidence of self-reported stroke or MI by HA/Oligo status. CONCLUSIONS: Longitudinal evidence suggests that a history of androgen excess and menstrual irregularity is not associated with worsening of metabolic health after menopause. Our findings challenge the notion that a history of concurrent HA and Oligo reflects ongoing cardiometabolic risk in postmenopausal women.

Comparison of the phenotype of Chinese versus Dutch Caucasian women presenting with polycystic ovary syndrome and oligo/amenorrhoea.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex disorder with variable prevalence and clinical presentation in different populations, which may be mediated by geographical and ethnic background. METHODS: We performed a comparison of phenotypic characteristics between 547 Chinese and 427 Dutch women with PCOS and oligo/amenorrhoea attending University Reproductive Centers in China and the Netherlands. RESULTS: Chinese women presenting with a clinical diagnosis of PCOS were observed to have a higher incidence of hyperandrogenism (HA) (P < 0.001) and amenorrhoea (P < 0.001) compared with Dutch women, but no difference was observed in the incidence of polycystic ovaries (PCOs). Using population-specific cut-off values, Chinese women with PCOS demonstrated a higher incidence of increased BMI (P < 0.001), waist circumference (WC) (P < 0.001) and waist-hip ratio (P < 0.001) than Dutch women. In both groups, HA was associated with increased age, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and serum LH while PCOs correlated with BMI, WC, HOMA-IR, fasting insulin and elevated total testosterone. Associations specific for ethnic background were found between LH and HA, and between both BMI and HOMA-IR, and PCOs. CONCLUSIONS: Reproductive and metabolic characteristics differed between the two ethnic groups. Chinese women were found to present more frequently with a phenotype associated with increased risk of metabolic complications later in life, compared with Dutch Caucasian women. Ethnicity seems to determine part of the specific phenotypical presentation of PCOS.

Endocrine and metabolic characteristics of polycystic ovary syndrome in Chinese women with different phenotypes.

OBJECTIVE: The aim of this study was to describe the endocrine and metabolic characteristics of Chinese women with polycystic ovarian syndrome (PCOS) according to different phenotypes, including menstrual cycle pattern and body mass index (BMI). DESIGN: Retrospective study. PATIENT(S): A total of 3539 patients with PCOS and 590 controls were recruited from the Centre for Reproductive Medicine. Patients with PCOS were divided into three groups according to the characteristics of the menstrual cycle (amenorrhoea, oligomenorrhea and eumenorrhea) and the BMI (<25 kg/m(2) ; 25 ≤ and ≤ 30 kg/m(2) ; and BMI > 30 kg/m(2) ). MEASUREMENTS: Waist circumference, hip circumference, weight, height, Ferriman-Gallwey score, and endocrine and metabolic variables were measured. RESULTS: The serum testosterone, luteinizing hormone (LH) and oral glucose tolerance test 2 h-glucose levels were increased in the amenorrhoea group (P < 0·05). The triglycerides (TG) and low-density lipoprotein-cholesterol (LDL) levels were the highest in the amenorrhoea group (P < 0·05). The same trend existed in total cholesterol and non- high-density lipoprotein-cholesterol (HDL) levels, although there was no statistical significance (P > 0·05). Subjects with a BMI<25 kg/m(2) had higher values of follicle stimulating hormone (FSH), LH, LH/FSH and prolactin (P < 0·001) than the other two groups. The levels of TG, LDL and non-HDL and the indices of glucose and insulin metabolism increased with the change in BMI (P < 0·001). CONCLUSIONS: The amenorrhoea group had severe endocrine and metabolic abnormalities, which appeared to be related to latent long-term complications and higher morbidity. The degree of dysbolism was positively associated with the change in BMI.

Skeletal muscle mitochondrial function in polycystic ovarian syndrome.

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance (IR), which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry. METHODS: Hyperinsulinemic-euglycemic clamps (40  mU/min per m(2)) and muscle biopsies were performed on 23 women with PCOS (nine lean (body mass index (BMI) <25 kg/m(2)) and 14 obese (BMI >25 kg/m(2))) and 17 age- and weight-matched controls (six lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function. RESULTS: Insulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex I+II were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mitochondrial DNA/genomic DNA. We found no correlation between mitochondrial function and indices of insulin sensitivity. CONCLUSIONS: In contrast to previous reports, we found no evidence that skeletal muscle mitochondrial respiration is reduced in skeletal muscle of women with PCOS compared with control subjects. Furthermore, mitochondrial content did not differ between our control and PCOS groups. These results question the causal relationship between reduced mitochondrial function and skeletal muscle IR in PCOS.

Adolescent oligomenorrhea in a biracial schoolgirl cohort: a simple clinical parameter predicting impaired fasting glucose plus type 2 diabetes mellitus, insulin, glucose, insulin resistance, and centripetal obesity from age 19 to 25 years.

We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to <126 mg/dL) plus type 2 diabetes mellitus (T2DM; ≥126 mg/dL), insulin and glucose levels, and insulin resistance (IR) in young adulthood (ages 19-25). A prospective 15-year follow-up of 370 schoolgirls starting at age 10 was performed. Age 14 waist circumference was the most important explanatory variable for IFG + T2DM during ages 19 to 24 (P = .002; odds ratio, 1.06; 95% confidence interval, 1.02-1.10), along with oligomenorrhea category from ages 14 to 19 (0, 1, 2, ≥3 reports over 6 years; P = .032; odds ratio, 1.82; 95% confidence interval, 1.05-3.14). Impaired fasting glucose + T2DM at ages 19 to 24 were more common in girls having 1 (6%), 2 (11%), and ≥3 (38%) oligomenorrhea reports from ages 14 to 19 than in girls without oligomenorrhea (3%; P = .0003). Positive explanatory variables (all Ps ≤ .05) for homeostasis model assessment of IR at ages 19 to 24 included age 14 waist (partial R(2) = 30.1%), oligomenorrhea with hyperandrogenism (polycystic ovary syndrome; partial R(2) = 4.1%), black race (3.8%), and oligomenorrhea frequency during ages 14 to 19 (0.8%); sex hormone binding globulin was a negative explanatory variable (0.7%). This is the first prospective study to report an independent association of adolescent oligomenorrhea with young adult IFG + T2DM, with insulin and glucose levels, and with IR. Age 14 waist circumference, oligomenorrhea with hyperandrogenism (polycystic ovary syndrome), black race, oligomenorrhea frequency at ages 14 to 19, and age 14 sex hormone binding globulin were independently associated with IR at ages 19 to 24, potentially facilitating primary prevention of IFG, T2DM, and hyperinsulinemia.

Clinical evidence for predominance of delta-5 steroid production in women with polycystic ovary syndrome.

CONTEXT: In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway. OBJECTIVE: This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women. DESIGN: We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women. SETTING: The study was conducted in a General Clinical Research Center in an academic medical center. PARTICIPANTS: Women with PCOS (age, 18-37 yr; n = 10) and normal ovulatory controls (age, 18-37 yr; n = 11) were recruited. INTERVENTIONS: For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 µg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 µg of recombinant hCG. MAIN OUTCOME MEASURE(S): We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration. RESULTS: In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women. CONCLUSION: In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.

The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase-deficient nonclassic adrenal hyperplasia.

OBJECTIVE: To test the hypothesis that women with polycystic ovary syndrome (PCOS) are distinguishable from those with 21-hydroxylase-deficient nonclassic adrenal hyperplasia on the basis of having polycystic ovaries and metabolic dysfunction. DESIGN: Prospective observational. SETTING: Tertiary care center. PATIENT(S): Fifty-two lean and 54 obese women with PCOS according to the 1990 National Institutes of Health criteria, 23 women with nonclassic adrenal hyperplasia, and 27 controls. INTERVENTION(S): History and physical examination, blood sampling, ovarian sonography, oral glucose tolerance, and acute adrenocorticotropin stimulation testing. MAIN OUTCOME MEASURE(S): The frequency of clinical, biochemical, and metabolic features. RESULT(S): Women with PCOS had a higher frequency of oligomenorrhea or amenorrhea than those with nonclassic adrenal hyperplasia. Mean androstenedione and DHEAS levels were highest in nonclassic adrenal hyperplasia. The degree of metabolic dysfunction was greatest in obese women with PCOS; women with nonclassic adrenal hyperplasia and lean women with PCOS did not differ in degree of metabolic dysfunction. Women with nonclassic adrenal hyperplasia had a lower prevalence of polycystic ovaries than those with PCOS. The proportion of patients with an LH/FSH ratio >2 was greater in women with PCOS, compared with those with nonclassic adrenal hyperplasia. Basal 17-hydroxyprogesterone levels >2 ng/mL were found in 87%, 25%, 20%, and 7% of women with nonclassic adrenal hyperplasia, lean women with PCOS, obese women with PCOS, and controls, respectively. CONCLUSION(S): Nonclassic adrenal hyperplasia should be excluded in all women presenting with hirsutism, with use of a basal follicular phase 17-hydroxyprogesterone level, regardless of the presence of polycystic ovaries or metabolic dysfunction; however, women with nonclassic adrenal hyperplasia have a higher prevalence of normal ovulation and lower likelihood of having an LH/FSH ratio >2 or polycystic ovaries.

Hyperandrogenism in oligomenorrhoea with minimal or nil 'unwanted hair growth'.

AIM: To detect whether oligomenorrhoea with minimal or nil 'unwanted hair growth' is a hyperandrogenic problem. MATERIALS AND METHODS: Fifty-nine women with oligomenorrhoea with modified Ferriman Gallway score (m FG) = <5 (Group A), 40 women with oligomenorrhoea with m FG score = > 6 (Group B) and 22 eumenorrhoeic non-hirsute 'control' women (Group C) were studied. Body mass index, Waist-hip ratio were noted during clinical examination. Serum testosterone, Sex hormone binding globulin, fasting insulin levels were measured in each woman. Free androgen index (FAI) was calculated. RESULTS: No significant differences were noted in the clinical parameters. Though serum testosterone levels were within the normal ranges in Group A and Group B, they were significantly higher than that of Group C. Groups A and B had significantly higher FAI values and fasting insulin levels than Group C. Between Groups A and B there were no significant differences in any of the androgenic parameters studied. CONCLUSION: Oligomenorrhoea without definite hirsutism is an androgen excess disorder. Definition of biochemical hyperandrogenism needs more clarity. Hirsutism is not a sensitive indicator of hyperandrogenism. The role of insulin in this type of hyperandrogenism needs further studies.

Effect of oral contraceptives on weight and body composition in young female runners.

PURPOSE: To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners. METHODS: The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively. RESULTS: Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results. CONCLUSION: This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.

Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome.

OBJECTIVE: Application of the newly introduced Rotterdam criteria for polycystic ovary syndrome (PCOS) generates four phenotypic subgroups, defined by the presence/absence of three diagnostic elements: polycystic ovarian (PCO) morphology (P); hyperandrogenism (H); and oligo-amenorrhoea (O). Whilst PCOS is associated with adverse metabolic features, the strength of the association within individual subgroups is not established. We characterized the metabolic and endocrine profiles of PCOS women who are oligomenorrhoeic but normoandrogenaemic, and compared these to other PCOS women and controls. DESIGN: Retrospective dataset analyses. PATIENTS: A total of 309 Europid PCOS women, all with PCO morphology, of whom 191 were also hyperandrogenaemic and oligomenorrhoeic (PHO), 76 hyperandrogenaemic with normal menses (PH) and 42 oligomenorrhoeic but normoandrogenaemic (PO); plus 76 Europid control women without PCOS. MEASUREMENTS: Metabolic parameters: fasting insulin, lipids, homeostasis model assessment (HOMA) measures of insulin sensitivity; endocrine variables: LH, FSH; prevalence of metabolic syndrome. RESULTS: Insulin sensitivity: PO women were indistinguishable from controls, and markedly less insulin-resistant than PHO women (vs. controls, P = 0.38 after adjustment for BMI and age; vs. PHO, P = 0.003). Metabolic syndrome: the prevalence in PO women (7.1%) was similar to that in controls (3.9%), and lower than in PHO women (29.3%, P < 0.0001). LH levels: PO women were intermediate between controls (vs. controls, P = 0.008) and PHO women (vs. PHO, P = 0.06). CONCLUSIONS: Normoandrogenaemic, oligomenorrhoeic women with PCOS are metabolically similar to control women with significantly fewer metabolic features than PCOS women who are also hyperandrogenaemic. However, higher than normal LH and lower sex hormone-binding globulin (SHBG) concentrations in the PO women support the view that they form part of the spectrum of PCOS.

Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.

The metabolic cardiovascular disease (CVD) risk factors of women with self-reported oligomenorrhea and/or hirsutism, which are symptoms of polycystic ovary syndrome (PCOS), were investigated in a general population-based Northern Finland Birth Cohort 1966 Study to determine whether women with PCOS symptoms at 31 yr would be distinguishable from asymptomatic controls in terms of CVD risk factors. A total of 518 cases with oligomenorrhea and/or hirsutism and 1036 randomly selected controls were analyzed. C-Reactive protein (CRP; median, 0.70 vs. 0.60 mg/liter; P = 0.026), triglycerides (mean, 0.97 vs. 0.91 mmol/liter; P = 0.039), body mass index (BMI; mean, 25.1 vs. 24.2 kg/m(2); P < 0.001), and waist/hip ratio (mean, 0.82 vs. 0.81; P = 0.001) were significantly higher, and high-density lipoprotein cholesterol levels were lower (mean, 1.60 vs. 1.66 mmol/liter; P = 0.002) in the cases compared with the controls. Total cholesterol, low-density lipoprotein cholesterol, and blood pressure showed no statistically significant differences between the cases and the controls. In terms of metabolic CVD risk factors, women reporting hirsutism alone were indistinguishable from the control group, and those who reported both oligomenorrhea and hirsutism had the most severe changes in risk factor profiles. Because obesity is strongly related to PCOS symptoms, the analyses were stratified by BMI. After stratification into normal weight (BMI, <25 kg/m(2)), overweight (25 kg/m(2) or=30 kg/m(2)) groups, the waist/hip ratio was significantly higher among the overweight cases (mean, 0.84 vs. 0.83; P = 0.04). Among the obese women, high-density lipoprotein cholesterol was significantly lower (mean, 1.32 vs. 1.48 mmol/liter; P = 0.002) among the cases, and triglycerides tended to be higher (mean, 1.43 vs. 1.27 mmol/liter; P = 0.068) than in controls. In conclusion, these results indicate that self-reported symptoms of oligomenorrhea and/or hirsutism, particularly in the presence of both symptoms, may be helpful to identify women with metabolic cardiovascular risk factor accumulation associated with PCOS.

Is there an association between athletic amenorrhea and endothelial cell dysfunction?

PURPOSE: To test the hypothesis that young females with athletic amenorrhea and oligomenorrhea show signs of early cardiovascular disease manifested by decreased endothelium-dependent dilation of the brachial artery. METHODS: Ten women with athletic amenorrhea (mean +/- SE, age 21.9 +/- 1.2 yr), 11 with oligomenorrhea (age 20.8 +/- 1.1 yr), and 11 age-matched controls (age 20.2 +/- 1.1 yr) were studied. Study subjects were amenorrheic an average of 2.3 (range 0.6-5) yr and oligomenorrheic an average of 6.2 yr. All ran a minimum of 25 miles.wk. They were nonpregnant and free of metabolic disease. Brachial artery flow-mediated dilation (endothelium-dependent) was measured with a noninvasive ultrasound technique in each group. RESULTS: Endothelium-dependent brachial artery dilation was reduced in the amenorrheic group (1.08 +/- 0.91%) compared with oligomenorrheic (6.44 +/- 1.3%; P< 0.05) and eumenorrheic (6.38 +/- 1.4%; P< 0.05) groups. CONCLUSION: Athletic amenorrhea is associated with reduced endothelium-dependent dilation of the brachial artery. This may predispose to accelerated development of cardiovascular disease.

The Effect of sex steroid hormones on substrate oxidation during prolonged submaximal exercise in women.

In animals, female sex steroid hormones (SS, estrogens-progesterone) influence the energy substrate that is metabolized. Human research on this issue is controversial. This study examined whether changes in circulating SS hormone levels affected the carbohydrate-lipid metabolism during submaximal prolonged (60 min) exercise. Young, physically active females were studied. Four were classified as anovulatory-oligomenorrheic and four were classified as ovulatory-eumenorrheic. Subject responses were pooled to form one group (n = 8) and then their responses under low (L) and high (H) pharmaceutically manipulated SS hormone conditions were examined. During exercise, the mean oxygen consumption levels were 1.70 +/- 0.10/ x min(-1) for L-SS and 1.75 +/- 0.11/ x min(-1) for H-SS (p = 0.07), respectively. The respiratory exchange ratio (RER) responses were significantly different during exercise between the conditions: 0.93 +/- 0.04 for L-SS and 0.90 +/- 0.04 for H-SS (p < 0.05), respectively. RER responses were utilized to calculate substrate oxidation. Significantly less carbohydrate oxidation was found in the H-SS condition as compared to the L-SS condition (p < 0.05). Lipid oxidation was also significantly different, but for this measure, the levels of oxidation were greater in the H-SS than in the L-SS condition (p < 0.05). Finally, total energy expenditure for the 60 min of exercise was not significantly different between the hormonal conditions. Results suggest that sex steroid hormones have an impact upon substrate oxidation in women during exercise. Specifically, high circulating concentrations of the SS hormones result in an enhanced reliance upon the oxidation of lipid as an energy substrate and consequently induce a reduction in carbohydrate oxidation. The mechanism inducing this "metabolism shift" appears due to sex steroid hormones directly and indirectly increasing lipid mobilization and lipolysis.

Expression of insulin-receptor substrate-1 and -2 in ovaries from women with insulin resistance and from controls.

OBJECTIVE: To evaluate the role of insulin-receptor substrate (IRS)-1 and -2 in ovary dysfunction in women with insulin resistance. DESIGN: Immunoblotting and immunohistochemical analyses of the localization and staining intensity of IRS-1 and IRS-2 in the ovaries of women with the polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. SETTING: Department of Obstetrics and Gynecology, Turku University Central Hospital. PATIENT(S): Sections of ovary were obtained at the time of cesarean section from five volunteers without medical complications and three patients with gestational diabetes mellitus. Paraffin-embedded ovary sections were selected from those on file from the department of pathology; four were from women with a histologic diagnosis of PCOS and seven were from women with endometriosis (controls). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Protein expression of IRS in human ovary samples. RESULT(S): Immunoblotting with specific monoclonal and polyclonal antibodies showed the presence of 165-kDa and 183-kDa proteins that corresponded to the size of IRS-1 and IRS-2, respectively, in normal pregnant ovaries and human cultured follicles. Immunohistochemical staining showed that positive IRS-2 expression in antral follicles was restricted to theca internal cells in ovulatory ovaries but was distributed widely in all compartments of follicles in different stages in polycystic ovaries. Compared with follicles at a similar stage of development in ovulatory ovaries, follicles in polycystic ovaries showed decreased staining for IRS-1 in granulosa cells but increased staining for IRS-2 in theca internal cells. These features of IRS-1 and -2 expression were also noted in preantral and atretic follicles from patients with gestational diabetes mellitus compared with those who had uncomplicated pregnancy. CONCLUSION(S): This study highlights a shift of the follicular insulin signal protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestational diabetes mellitus.

Decreased resting metabolic rate in ballet dancers with menstrual irregularity.

We studied 21 ballet dancers aged 19.4 +/- 1.4 years, hypothesizing that undernutrition was a major factor in menstrual irregularity in this population. Menstrual history was determined by questionnaire. Eight dancers had always been regular (R). Thirteen subjects had a history of menstrual irregularity (HI). Of these, 2 were currently regularly menstruating, 3 had short cycles, 6 were oligomenorrheic, and 2 were amenorrheic. Subjects completed a weighed dietary record and an Eating Attitudes Test (EAT). The following physiological parameters were measured: body composition by anthropometry, resting metabolic rate (RMR) by open-circuit indirect calorimetry, and serum thyroid hormone concentrations by radioimmunoassay. R subjects had significantly higher RMR than HI subjects. Also, HI subjects had lower RMR than predicted by fat-free mass, compared to the R subjects. Neither reported energy intake nor serum thyroid hormone concentrations were different between R and HI subjects. EAT scores varied and were not different between groups. We concluded that in ballet dancers, low RMR is more strongly associated with menstrual irregularity than is current reported energy intake or serum thyroid hormone concentrations.