Physiological Parameters of Bone Health in Elite Ballet Dancers.

Stress fractures are common among elite ballet dancers whereby musculoskeletal health may be affected by energy balance and overtraining. PURPOSE: This study aimed to characterize bone health in relation to stress fracture history, body composition, eating disorder risk, and blood biomarkers in professional male and female ballet dancers. METHODS: A single cohort of 112 dancers (male: 55, 25 ± 6 yr; female: 57, 24 ± 6 yr) was recruited. All participants underwent bone and body composition measures using dual-energy x-ray absorptiometry. In a subset of our cohort (male: 30, 24 ± 6 yr; female, 29, 23 ± 5 yr), a blood panel, disordered eating screen, menstrual history, and stress fracture history were also collected. Age-matched Z scores and young-adult T scores were calculated for bone mineral density (BMD) and body composition. Independent-samples t-tests and Fisher's exact tests were used to compare BMD, Z-scores, T scores, and those with and without history of stress fractures. A 1 × 3 ANOVA was used to compare BMD for those scoring 0-1, 2-6, and 7+ using the EAT26 questionnaire for eating disorder risk. Regression was used to predict BMD from demographic and body composition measures. RESULTS: Female dancers demonstrated reduced spinal (42nd percentile, 10%T < -1) and pelvic (16th percentile, 76%T < -1) BMD. Several anthropometric measures were predictive of BMD (P < 0.05, r = 0.65-0.81, standard error of estimate = 0.08-0.10 g·cm, percent error = 6.3-8.5). Those scoring >1 on EAT26 had lower BMD than did those with a score of 0-1 (P < 0.05). CONCLUSIONS: Professional female ballet dancers exhibit reduced BMD, fat mass, and lean mass compared with the general population whereby low BMD and stress fractures tend to be more prevalent in those with a higher risk of disordered eating. Anthropometric and demographic measures are predictive of BMD in this population.

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.

Clinical and metabolic characteristics of Turkish adolescents with polycystic ovary syndrome.

The aim of this study was to investigate the clinical, endocrine, metabolic features and prevalence of metabolic syndrome (MBS) in Turkish adolescents with polycystic ovary syndrome (PCOS) and the differences in metabolic parameters between adolescent PCOS with or without the presence of polycystic ovaries (PCO) on ultrasound. Subjects (n = 77) were classified into two groups: oligomenorrhea (O) and clinical and/or biochemical hyperandrogenism (HA) (n = 38), without PCO and O + HA with PCO (n = 39). The control group consisted of 33 age-matched adolescents. Adolescents with PCOS had a significantly higher body mass index (BMI), waist circumference and levels of LH, LH/FSH ratio, triglyceride, insulin, HOMA-IR, free androgen index and lower levels of SHBG and FSH. After adjustment for BMI, LH, LH: FSH ratio remained significantly higher. Adolescents with PCOS had a higher prevalence of MBS. No significant differences in lipid profiles, insulin levels and insulin sensitivity in both the PCOS groups were seen. HDL-C levels were lower in the O + HA + PCO group compared to the controls. BMI may be the major contributing factor in the development of metabolic abnormalities in adolescents with PCOS. Impact statement Many studies have investigated the effect of PCOS on metabolic and cardiovascular risks. It is thought that PCOS increases metabolic and cardiovascular risks. Increase in metabolic and cardiovascular risks associated with PCOS may be handled with early diagnosis and early intervention of PCOS in adolescents, although the diagnosis of PCOS in adolescents could be hard because of the features of PCOS overlapping normal pubertal physiological events. However, early identification of adolescent girls with PCOS may provide opportunities for prevention of well-known health risks associated with this syndrome and reduction of long-term health consequences of PCOS by reducing androgen levels and improving metabolic profile. Our results also support that BMI may be the major contributing factor in the development of metabolic abnormalities in adolescents with PCOS.

Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium.

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies.Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer (n = 13,719) or borderline ovarian disease (n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression.Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors (Pheterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors (Pheterogeneity < 0.0001).Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype.Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR.

A design thinking approach to primary ovarian insufficiency.

Most clinicians are not prepared to provide integrated personal care to address all the clinical needs of women with primary ovarian insufficiency. Design thinking is an engineering methodology used to develop and evaluate novel concepts for systems operation. Here we articulate the need for a seamlessly integrated mobile health system to support genomic research as well as patient care. We also review the pathophysiology and management of primary ovarian insufficiency. Molecular understanding regarding the pathogenesis is essential to developing strategies for prevention, earlier diagnosis, and appropriate management of the disorder. The syndrome is a chronic disorder characterized by oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. There may be significant morbidity due to: 1) depression and anxiety related to the loss of reproductive hormones and infertility; 2) associated autoimmune adrenal insufficiency or hypothyroidism; and 3) reduced bone mineral density and increased risk of cardiovascular disease related to estrogen deficiency. Approximately 5% to 10% of women with primary ovarian insufficiency conceive and have a child. Women who develop primary ovarian insufficiency related to a premutation in FMR1 are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability. In most cases of spontaneous primary ovarian insufficiency no environmental exposure or genetic mechanism can be identified. As a rare disease, the diagnosis of primary ovarian insufficiency presents special challenges. Connecting patients and community health providers in real time with investigators who have the requisite knowledge and expertise would help solve this dilemma.

Increased risk of humerus and lower leg fractures in postmenopausal women with self-reported premenopausal hirsutism and/or oligomenorrhea.

OBJECTIVE: The aim of this study was to investigate the prevalence of fracture in women aged >55 years with self-reported premenopausal hirsutism and/or oligomenorrhea. STUDY DESIGN: A cross-sectional study including 1057 post-menopausal women aged >55 years who were treated in a primary care facility in Santa Maria, South Brazil, from March 2013 through August 2013. Data were collected using a standardized questionnaire for characteristics including fracture history, medication use, and reproductive history (oligomenorrhea, hirsutism, miscarriage, the diagnosis or treatment of hypothyroidism, hyperprolactinemia, or infertility). RESULTS: A non-significant trend towards an increased prevalence of all fragility fractures was observed in women with premenopausal hirsutism and/or oligomenorrhea when compared to those without (20.4% vs. 15.7%). After correction for age, falls, and comorbidities, fracture prevalence was significantly higher in the lower leg (OR 3.1 [CI 1.1-8.6]; P=0.029), and humerus (OR 2.6 [CI 1.2-5.4]; P=0.015) in the women with hirsutism and/or oligomenorrhea. CONCLUSION: This is a hypothesis-generating study which evaluated the association between hirsutism and/or oligomenorrhea and fractures in postmenopausal women. Our results suggest that premenopausal hirsutism and/or oligomenorrhea may be associated with an increased risk of fracture postmenopause, particularly in the humerus and lower leg.

A genetic risk score is associated with polycystic ovary syndrome-related traits.

STUDY QUESTION: Is a genetic risk score (GRS) associated with polycystic ovary syndrome (PCOS) and its related clinical features? SUMMARY ANSWER: The GRS calculated by genome-wide association studies (GWASs) was significantly associated with PCOS status and its related clinical features. WHAT IS KNOWN ALREADY: PCOS is a heterogeneous disorder and is characterized by oligomenorrhea, hyperandrogenism and polycystic ovary morphology. Although recent GWASs have identified multiple genes associated with PCOS, a comprehensive genetic risk study of these loci with PCOS and related traits (e.g. free testosterone, menstruation number/year and ovarian morphology) has not been performed. STUDY DESIGN, SIZE, DURATION: This study was designed as a cross-sectional case-control study. We recruited 862 women with PCOS and 860 controls. Women with PCOS were divided into four subgroups: (1) oligomenorrhea + hyperandrogenism + polycystic ovary, (2) oligomenorrhea + hyperandrogenism, (3) oligomenorrhea + polycystic ovary and (4) hyperandrogenism + polycystic ovary. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Genomic DNA was genotyped for the PCOS susceptibility loci using the HumanOmni1-Quad v1 array. Venous blood was drawn in the early follicular phase to measure baseline metabolic and hormonal parameters. A GRS was calculated by summing the number of risk alleles from 11 single-nucleotide polymorphisms (SNPs) that were identified in previous GWASs on PCOS. A weighted GRS (wGRS) was calculated by multiplying the number of risk alleles for each SNP by its estimated effect (beta) obtained from the association analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The GRS was higher in women with PCOS than in controls (8.8 versus 8.2, P < 0.01) and was significantly associated with PCOS after adjusting for age and BMI. An analysis of GRS quartiles (Q1 = 3-5, Q2 = 6-8, Q3 = 9-11, Q4 = 12-15) revealed that the subjects in the highest quartile showed a remarkable increased risk of PCOS compared with those in the lowest quartile (odds ratio = 6.28, P < 0.001). Free testosterone level, menstruation number per year, ovarian volume and ovarian follicle numbers were significantly associated with the GRS (in all cases, P < 0.01). The wGRS yielded similar results. LIMITATIONS, REASONS FOR CAUTION: We used 11 loci for the calculation of GRS, but a higher number of PCOS risk alleles was reported in previous studies. Therefore, further studies should assess the value of GRS including the additional SNPs related to PCOS. Although a GRS of ≥12 was significantly associated with PCOS, the GRS showed a poor predictive value; therefore, the use of genetic information based on current GWAS data only may present problems. WIDER IMPLICATIONS OF THE FINDINGS: The GRS could be used to identify asymptomatic individuals among people at risk and stratify them into accurate risk categories for the purpose of individualizing treatment approaches, which could potentially improve health outcomes. STUDY FUNDING/COMPETING INTERESTS: None of the authors have any conflicts of interest to declare. No funding was obtained for the study.

Diets High in Fiber and Vegetable Protein Are Associated with Low Lumbar Bone Mineral Density in Young Athletes with Oligoamenorrhea.

BACKGROUND: Associations of bone mineral density (BMD) with specific food components, including dietary fiber and isoflavones (that have a negative association with serum estrogen), are unclear and need to be determined, particularly in populations more likely to consume large amounts of these nutrients (such as young athletes). OBJECTIVE: To determine dietary intake of specific food components in athletes with oligoamenorrhea (OA) compared to athletes with eumenorrhea (EA) and nonathletes (NA), and associations of the dietary intake of these nutrients with lumbar spine BMD. DESIGN AND SUBJECTS: This cross-sectional study evaluated 68 OA, 24 EA, and 26 NA individuals aged 14 to 23 years. Measurements included 4-day food records, a dual x-ray absorptiometry scan evaluating lumbar spine BMD and body composition, and hormone levels. Multivariate analysis was used to estimate associations of nutrients with lumbar spine BMD. RESULTS: Compared with EA and NA, OA had higher intake of fiber, phytic acid, and vegetable protein (all P values <0.0001). Intake of isoflavones, genistein, and daidzein was higher in OA than NA (P=0.003 and P=0.0002, respectively). OA had lower consumption of energy from saturated fatty acids than NA (P=0.002). After controlling for confounders such as body weight, menstrual status (indicative of estrogen status), calcium intake, and serum vitamin D (known BMD determinants), lumbar spine BMD z scores were inversely associated with dietary fiber (ß=-.30; P=0.01), vegetable protein (ß= -.28; P=0.02), phytic acid (ß=-.27; P=0.02), genistein (ß=-.25; P=0.01), and daidzein (ß=-.24; P=0.01), and positively associated with percent energy from fatty acids (ß=.32; P=0.0006). CONCLUSIONS: Compared with EA and NA, OA had a higher dietary intake of fiber, vegetable protein, and phytic acid, which were inversely associated with lumbar spine BMD z scores. Further studies are needed to assess dietary recommendations for OA to optimize bone accrual.

Low-energy density and high fiber intake are dietary concerns in female endurance athletes.

Low or reduced energy availability (LEA) is linked to functional hypothalamic oligomenorrhea/amenorrhea (FHA), which is frequently reported in weight-sensitive sports. This makes LEA a major nutritional concern for female athletes. The aim of this study was to describe dietary characteristics of athletes with LEA and/or FHA. Endurance athletes (n = 45) were recruited from national teams and competitive clubs. Protocols included gynecological examination, body composition, eating disorder evaluation, and 7-day dietary intake and EA assessment. Athletes with disordered eating behavior/eating disorders (n = 11), menstrual dysfunction other than FHA (n = 5), and low dietary record validity (n = 4) were excluded. Remaining subjects (n = 25) were characterized by EA [optimal: ≥ 45 kcal (188 kJ)/kg fat-free mass (FFM)/day (n = 11), LEA: < 45 kcal (188 kJ)/kg FFM/day (n = 14)] and reproductive function [eumenorrhea (EUM; n = 10), FHA (n = 15)]. There was no difference in EA between FHA and EUM subjects. However, FHA and LEA subjects shared the same dietary characteristics of lower energy density (ED) [(P = 0.012; P = 0.020), respectively], and fat content [(P = 0.047; P = 0.027), respectively]. Furthermore, FHA subjects had a lower intake of carbohydrate-rich foods (P = 0.019), higher fiber content (P < 0.001), and drive for thinness score (P = 0.003). Conclusively, low ED together with high fiber content may constitute targets for dietary intervention in order to prevent and treat LEA and FHA in female athletes.

Clinical implications of menstrual cycle length in oligomenorrhoeic young women.

OBJECTIVE: Although menstrual irregularity is associated with insulin resistance and hyperandrogenism, the relationship between the severity of menstrual infrequency and clinical phenotypes in young women with oligomenorrhoea (OM) is unclear. We evaluated whether a longer menstrual cycle length is associated with less favourable metabolic features. DESIGN/PATIENTS/MEASUREMENTS: A total of 1174 young women (aged 19-39 years) with a menstrual cycle length over 40 days and 1430 women with regular menstrual cycles participated voluntarily. Metabolic parameters, insulin sensitivity index (ISI) and testosterone were measured. Oligomenorrhoeic women were divided into three groups: (i) polycystic ovary syndrome (PCOS) by National Institute of Health criteria, (ii) severe OM (menstrual cycle length >60 days), and (iii) mild OM (menstrual cycle length 40-60 days). RESULTS: In normal-weight women (BMI < 23 kg/m(2)), the degrees of insulin resistance and hyperandrogenaemia are the highest in PCOS and higher in severe OM compared with mild OM. In overweight or obese women, PCOS was more insulin resistant and hyperandrogenaemic, but there was no difference between severe and mild OM. After excluding PCOS, women with severe OM showed a twofold increased risk of metabolic syndrome compared with regular cycling women (odds ratio 2·4, 95% confidence interval 1·1-5·6). By linear regression analysis, a longer menstrual cycle length was associated with ISI after adjustment for age, BMI, metabolic risk factors and testosterone. CONCLUSIONS: Women with a menstrual cycle length over 60 days should be more closely monitored for the metabolic syndrome than women with a menstrual cycle length of 40-60 days, even if they have no PCOS.

Low bone density risk is higher in exercising women with multiple triad risk factors.

UNLABELLED: The cumulative effect of the female athlete triad (Triad) risk factors on the likelihood of low bone mineral density (BMD) in exercising women is unclear. PURPOSE: This study aimed to determine the risk of low BMD in exercising women with multiple Triad risk factors. METHODS: We retrospectively examined cross-sectional data from 437 exercising women (mean ± SD age of 18.0 ± 3.5 yr, weighed 57.5 ± 7.1 kg with 24.5% ± 6.1% body fat) obtained at baseline from 4 prospective cohort studies examining Triad risk factors. Questionnaires were completed to obtain information on demographic characteristics, self-reported eating attitudes/behaviors, menstrual function, sport/activity participation, and medication use. Height and body weight were measured. BMD was measured using dual energy x-ray absorptiometry. Low BMD was defined as z-scores of <-1 and ≤-2. Chi-square tests were performed to determine the percentage of women with low BMD who met the criteria for individual (current oligo/amenorrhea, late menarche, low body mass index (BMI), elevated dietary restraint, lean sport/activity participation) or multiple (2, 3, 4, or 5) Triad risk factors. RESULTS: Late menarche and low BMI were associated with the highest percentage of low BMD (z-score < -1), 55% and 54%, respectively, and low BMD (z-score ≤-2), 14% and 16%, respectively. The percentage of participants with low BMD (z-score < -1 and ≤-2) increased from 10% to 62% and from 2% to 18%, respectively, as women met the criteria for an increasing number of Triad risk factors. CONCLUSIONS: A cumulative number of Triad risk factors were associated with an increased risk of low BMD, suggesting a dose-response association between the number of Triad risk factors and BMD in exercising women. Further research should be conducted to develop a user-friendly algorithm integrating these indicators of risk for low BMD in exercising women (particularly factors associated with low BMI/body weight, menstrual dysfunction, lean sport/activity participation, and elevated dietary restraint).

The severity of menstrual dysfunction as a predictor of insulin resistance in PCOS.

OBJECTIVE: The objective of the study was to evaluate the relationship between the severity of menstrual disturbances and the degree of insulin resistance in women with polycystic ovary syndrome (PCOS). DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a tertiary care academic medical center. PATIENTS: Four hundred ninety-four women diagnosed with PCOS by the Rotterdam criteria and 138 eumenorrheic, nonhirsute, control women participated in the study. INTERVENTIONS: INTERVENTIONS in the study included history and physical examination and blood sampling. MAIN OUTCOME MEASURE(S): Physical assessment and total and free T, dehydroepiandrosterone sulfate, fasting glucose, and insulin levels and calculated homeostatic model assessment values for insulin resistance (HOMA-IR) were measured. RESULTS: Overall, 80% of PCOS subjects included had clinically evident oligomenorrhea. The remainder demonstrated vaginal bleeding intervals of fewer than 35 days (ie, with either polymenorrhea or clinically apparent eumenorrhea). Only 10% of PCOS subjects studied were ovulatory. After adjusting for body mass index, age, and race, all PCOS subjects with menstrual cycles longer than 35 days had significantly higher mean HOMA-IR levels than controls, and those with cycles longer than 3 months had the highest HOMA-IR levels. There was no difference in mean HOMA-IR levels between PCOS with regular vaginal bleeding (apparent eumenorrhea), regardless of whether they were anovulatory or not, or those with cycles fewer than 26 days, when compared with controls. CONCLUSIONS: Women with PCOS and overt oligomenorrhea comprise the vast majority of PCOS subjects seen clinically and have significantly more insulin resistance than controls. About 20% of PCOS women seen reported vaginal bleeding intervals of fewer than 35 days in length and did not generally have overt insulin resistance, regardless of whether they were ovulatory or not. Overall, the presence of clinically evident menstrual dysfunction can be used to predict the presence and possibly the degree of insulin resistance in women with PCOS.

The quality of life of adolescents with menstrual problems.

OBJECTIVE: To date, very few publications have examined the health related quality of life (HRQL) in the younger population with menstrual problems, despite their high prevalence in adolescent girls. We describe the health-related quality of life (HRQL) among adolescents with menstrual problems and identified factors that have an impact on it. METHODS: The study was a questionnaire study (using PedsQL 4.0) of adolescents aged 13-18 referred to a tertiary gynecology center for menstrual problems between June 2009 and August 2010. RESULTS: One hundred eighty-four adolescents completed the questionnaires. The mean age was 15.10 ± 1.49 with the mean body mass index (BMI) of 22.83 ± 4.82 kg/m(2). The most common menstrual problems seen in the clinic were dysmenorrhea (38.6%) followed by heavy bleeding (33.6%), oligomenorrhea (19.6%), and amenorrhea (8.2%). The mean overall score was 70.40 ± 16.36 with 42.3% having a score below 1 standard deviation (SD) from the norms. Adolescents with dysmenorrhea had the poorest score in physical function, whereas those with amenorrhea had the lowest score in psychosocial function. Maternal parenting style, parental anxiety, adolescents' ill-health behavior, and BMI have been found to have impact on the girls' quality of life (QoL). CONCLUSION: Although menstrual problems are not life threatening, they can pose a significant impact on the quality of life of these patients. Identification of these impacts might lead to the recognition of potential services or education to improve this. Understanding the characteristics that predict QoL may help a clinician identify patients who are risk for poor QoL.

Role of female reproductive hormones in musicians' dystonia.

UNLABELLED: Musicians' dystonia is an occupational focal dystonia affecting men more often than women. METHODS: We identified all patients presenting with musicians' dystonia and prospectively collected data on reproductive and menstrual history from the women with musician's dystonia and female musicians without dystonia. RESULTS: 149 men and 23 women (13.37%) with musician's dystonia where identified. We did not identify any effect of contraceptive hormones, pregnancy, or menstrual phases on dystonia symptoms, but as compared with women without dystonia, those with musician's dystonia reported oligomenorrhea and menometrorrhagia significantly less frequently. CONCLUSIONS: Our data reinforce the relation between sex hormones variations and musicians' dystonia. This link should be further explored to identify mechanisms and assess whether certain hormonal interventions might protect from the manifestation of dystonia.

A comparison of bone mineral density in normal weight and obese adolescents with polycystic ovary syndrome.

STUDY OBJECTIVE: To evaluate whether there are any differences in bone mineral density (BMD) between normal weight and obese adolescents suffering from polycystic ovary syndrome (PCOS) with oligo/amenorrhea. DESIGN: Prospective cohort study. SETTING: Adolescent gynecology clinic in a general service hospital. PARTICIPANTS: Subjects consisted of adolescents between 16 to 18 years of age presenting with oligo/ amenorrhea with ultrasound morphology of polycystic ovaries ± evidence of hyperandrogenism over 24 months. Controls consisted of consecutive eumenorrheic patients within the same age group. INTERVENTIONS: All underwent full hormonal profile assessment, and dual energy X-ray absorptiometry and peripheral quantitative computed tomography scans. MAIN OUTCOME MEASURES: Areal and volumetric BMD parameters. RESULTS: Of 37 adolescents with PCOS, 12 (32%) were obese with BMI ≥25, of which 9/12 (75%) were hyperandrogenic. The control group consisted of 40 normal weight eumenorrheic girls. The PCOS group overall had lower lumbar spine BMD values as compared to the controls (0.91 vs 0.97 g/ cm(2), P = 0.033). The normal weight PCOS group had lower BMD at the spine (0.90 vs 0.97 g/ cm(2), P = 0.027), trochanter (0.66 vs 0.71 g/ cm(2), P = 0.039) as well as volumetric distal tibial core sites (268 vs 296 mg/ cm(3)) as compared to eumenorrheic controls, but there were no significant BMD differences between the obese PCOS group and the eumenorrheic controls. CONCLUSIONS: Normal weight PCOS adolescents with oligo/amenorrhea have marginally lower BMD values than controls, but obese PCOS adolescents have BMD values compatible with eumenorrheic adolescents.

Restoration of menses with nonpharmacologic therapy in college athletes with menstrual disturbances: a 5-year retrospective study.

BACKGROUND: Functional hypothalamic amenorrhea is common among female athletes and may be difficult to treat. Restoration of menses (ROM) is crucial to prevent deleterious effects to skeletal and reproductive health. OBJECTIVES: To determine the natural history of menstrual disturbances in female college athletes managed with nonpharmacologic therapies including increased dietary intake and/or decreased exercise expenditure and to identify factors associated with ROM. STUDY DESIGN: A 5-yr retrospective study of college athletes at a major Division I university. METHODS: 373 female athletes' charts were reviewed. For athletes with menstrual disturbances, morphometric variables were noted. Months to ROM were recorded for each athlete. RESULTS: Fifty-one female athletes (19.7%) had menstrual disturbances (14.7% oligomenorrheic, 5.0% amenorrheic). In all, 17.6% of oligo-/amenorrheic athletes experienced ROM with nonpharmacologic therapy. Mean time to ROM among all athletes with menstrual disturbances was 15.6 ± 2.6 mo. Total absolute (5.3 ± 1.1 kg vs. 1.3 ± 1.1 kg, p < .05) and percentage (9.3% ± 1.9% vs. 2.3% ± 1.9%, p < .05) weight gain and increase in body-mass index (BMI; 1.9 ± 0.4 kg/m2 vs. 0.5 ± 0.4 kg/m2, p < .05) emerged as the primary differentiating characteristics between athletes with ROM and those without ROM. Percent weight gain was identified as a significant positive predictor of ROM, OR (95% CI) = 1.25 (1.01, 1.56), p < .05. CONCLUSIONS: Nonpharmacologic intervention in college athletes with menstrual disturbances can restore regular menstrual cycles, although ROM may take more than 1 yr. Weight gain or an increase in BMI may be important predictors of ROM.

Relative contributions of oligomenorrhea and hyperandrogenemia to the risk of metabolic syndrome in midlife women.

CONTEXT: Young reproductive-age women with irregular menses and androgen excess are at high risk for unfavorable metabolic profile; however, recent data suggest that menstrual regularity and hyperandrogenism improve with aging in affected women approaching menopause. OBJECTIVE: The objective of the study was to determine whether women with hyperandrogenemia (HA) and a history of oligomenorrhea (Oligo) are at an elevated risk for metabolic syndrome (MetS) at the early stages of menopausal transition. METHODS: Baseline data from 2543 participants (mean age of 45.8 yr) in the Study of Women's Health Across the Nation were analyzed. Women with a lifetime history of more than one 3-month interval of nongestational and nonlactational amenorrhea were classified as having a history of Oligo. The highest tertile of serum testosterone was used to define HA. Women with normal serum androgens and eumenorrhea were used as the reference group. Logistic regression models generated adjusted odds ratios (AOR), controlling for age, ethnicity, body mass index, smoking, and study site. RESULTS: Oligo was associated with MetS only when coincident with HA [AOR of 1.93 for Oligo and HA [95% confidence interval (CI) 1.17-3.17], AOR of 1.25 for Oligo and normal androgens (95% CI 0.81-1.93)]. In contrast, HA conferred a consistently significant risk for MetS, regardless of the menstrual frequency status [AOR of 1.48 for HA and eumenorrhea (95% CI 1.15-1.90)]. CONCLUSIONS: Our results suggest that HA but not history of Oligo is independently associated with the risk of prevalent MetS in pre- and perimenopausal women in their 40s.

A single-nucleotide polymorphism in the EAP1 gene is associated with amenorrhea/oligomenorrhea in nonhuman primates.

Current evidence suggests that the acquisition of female reproductive capacity and the maintenance of mature reproductive function are related processes transcriptionally regulated by gene networks operating within the neuroendocrine brain. One of these genes, termed enhanced at puberty 1 (EAP1), encodes an upstream regulator of these processes. Selective inhibition of EAP1 expression in discrete regions of the rat and nonhuman primate (NHP) hypothalamus, via targeted delivery of RNA interference, either disrupts (rats) or abolishes (monkeys) reproductive cycles. The striking loss of menstrual cyclicity resulting from knocking down hypothalamic EAP1 expression suggests that diminished EAP1 function may contribute to disorders of the menstrual cycle of neuroendocrine origin. Here we show that a single-nucleotide polymorphism in the 5'-flanking region of EAP1 gene is associated with increased incidence of amenorrhea/oligomenorrhea in NHP. In the presence of the risk allele, binding of the transcription factor mothers against decapentaplegic homolog 3 (SMAD3) to its recognition site contained within the polymorphic sequence in the monkey EAP1 promoter is reduced. The risk allele also diminishes the increase in EAP1 promoter activity elicited by TGFß1, a peptide that activates a SMAD3/4-mediated signaling pathway to regulate gene transcription. These findings indicate that common genetic variation in the EAP1 locus increases the susceptibility of NHP to loss/disruption of menstrual cyclicity. They also raise the possibility that polymorphisms in EAP1 may increase the risk of functional hypothalamic amenorrhea in humans.

Menstrual function in sports.

OBJECTIVE: To highlight the recent developments in the field of menstrual function in sports and to provide an overview of our current understanding in regard to the pathophysiology, evaluation and management strategies of exercise-related reproductive dysfunction. DESIGN: A PUBMED search was carried out and all articles published from 1980 to 2010 with title words related to exercise, athletes, menstrual function and primary and secondary amenorrhea were reviewed. The review structure includes a pathophysiology overview, menstrual dysfunction among different athletic disciplines, clinical manifestations, evaluation and management strategies, with particular emphasis on recent data regarding the use of oral contraceptives and hormone replacement therapy. RESULTS AND CONCLUSION: Exercise-related reproductive dysfunction appears to be multifactorial in origin and remains a diagnosis of exclusion. Recent findings underscore the endocrine role of adipose tissue in the regulation of metabolism and reproduction, providing further data on our understanding of the pathophysiology of exercise-related reproductive dysfunction. Clinical manifestations range from primary amenorrhea or delayed menarche to luteal phase deficiency, oligomenorrhea, anovulation and secondary amenorrhea. Amenorrhea constitutes the most serious clinical consequence and is associated with bone pathology. Early diagnosis, thorough evaluation and individualized management (ranging from diet and exercise, or behavior adjustments to pharmacologic treatment) should be achieved in order to preserve bone mass.