Search

BACKGROUND: Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. OBJECTIVES: The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. METHODS: Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen + Cal, n = 40, mean ± SEM age: 21.3 ± 0.5 y; weight: 55.0 ± 1.0 kg; BMI: 20.4 ± 0.3 kg/m(2)) who increased energy intake 20%–40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n = 36; mean ± SEM age: 20.7 ± 0.5 y; weight: 59.1 ± 1.3 kg; BMI: 21.3 ± 0.4 kg/m(2)). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed. RESULTS: Oligo/Amen + Cal improved energy status [increased body mass (2.6 ± 0.4 kg), BMI (0.9 ± 0.2 kg/m(2)), fat mass (2.0 ± 0.3 kg), body fat percentage (2.7% ± 0.4%), and insulin-like growth factor 1 (37.4 ± 14.6 ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P 0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (−0.006 g/cm(2); 95% CI: −0.011, −0.0002 g/cm(2) ; time main effect P = 0.043) and month 12 (−0.011 g/cm(2); 95% CI: −0.021, −0.001 g/cm(2); time main effect P = 0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (−0.006 g/cm(2); 95% CI: −0.011, −0.002 g/cm(2); time main effect P = 0.004). CONCLUSIONS: Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352 kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen. This trial was registered at clinicaltrials.gov as NCT00392873.

Objective To test the hypothesis that the polycystic ovary syndrome (PCOS) phenotype, or its component features, is less severe in adolescents than in young adult patients, in a referred (clinical) population. Design Cross-sectional study. Setting Tertiary-care academic medical center. Patient(s) Two hundred seventy-four adolescents and young adults aged 13.0–24.9 years with PCOS according to the National Institute of Health 1990 criteria. Patients were categorized as adolescents (AD: 13.0–18.9 years; n=91) and young adults (YA: 19.0–24.9 years; n=183). Adolescents were further categorized as early adolescents (Early-AD: 13.0–15.9 years; n=31) and late adolescents (Late-AD: 16.0–18.9 years; n=60). Intervention(s) History, physical examination, hormonal assays with the use of standardized protocols. Main Outcome Measure(s) Unadjusted and adjusted odds ratios (ORs; adjusted for body mass index [BMI] when applicable) were calculated for biochemical hyperandrogenism (HA), hirsutism (HIR), acne, and degree of oligo/amenorrhea (OA). PCOS phenotypes were classified as HIR+HA+OA, HA+OA, and HIR+OA. Result(s) Our analysis demonstrated minimal significant difference in the prevalence of the three PCOS phenotypes, or component features, between AD and YA patients. The risks for obesity were higher for YA versus AD, and the risk of acne was lower for YA versus AD. There was no significant difference between Early-AD and Late-AD. BMI-adjusted models did not significantly modify the main findings. Conclusion(s) The present study suggests that the PCOS phenotype is established in early adolescence, remains constant into adulthood, and is not related to BMI.

Study Objective Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and chronic anovulation, which affects 5%-10% of reproductive-age women. Diagnosis of adult patients with PCOS is made easily with clinical and laboratory methods and the anti-Mullerian hormone (AMH) level are accepted as a good indicator. However, there is still no complete consensus on the diagnosis of PCOS in adolescents. Design and Setting Prospective cohort study, December 2013 to November 2014. Participants The study was conducted on adolescent girls with oligomenorrhea, with at least 2 years since menarche. The study group consisted of adolescent girls with complete PCOS and incomplete PCOS. A control group was formed of healthy adolescent girls. Complete PCOS was diagnosed according to the Rotterdam criteria, as the presence of all the following characteristics: oligomenorrhea, hyperandrogenism, and polycystic ovarian morphology on ultrasound image. Incomplete PCOS was accepted as “oligomenorrhea and polycystic ovarian morphology,” or “oligomenorrhea and hyperandrogenism.” Interventions and Main Outcome Measures All patients underwent a physical examination and the anthropometric assessments, insulin resistance, and acanthosis nigricans were recorded. It was also noted whether or not the patient had an acne score. The Ferriman-Gallwey score was applied to evaluate hirsutism. Results The results of this study showed that no statistically significant difference was found between the PCOS and incomplete PCOS groups and the control group with respect to AMH levels. Conclusion The use of adult-specific diagnostic methods in adolescence might result in an incomplete diagnosis and inadequate treatment plan. Although the serum AMH level clearly facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in PCOS diagnosis is still controversial and further studies are needed.

Study Objective Although early diagnosis of polycystic ovary syndrome (PCOS) in adolescents might allow for earlier treatment and prevention of chronic disorders, incorrect or premature diagnosis carries risks of unnecessary treatment and psychological distress. There is no consensus concerning which diagnostic criteria to use for adolescents and current criteria vary. The objective of this study was to determine whether using different diagnostic criteria will affect PCOS diagnosis in adolescents. Design, Setting, and Participants Fifty-two patients aged 13-18 years with at least 2 of the following criteria were included in the study: (1) oligomenorrhea or amenorrhea; (2) Clinical or biochemical hyperandrogenism; and (3) polycystic ovaries on ultrasonography. Patients were then categorized according to the 6 different criteria for PCOS. National Institutes of Health, Rotterdam criteria, Androgen Excess Society, Amsterdam criteria, Endocrine Society criteria, and the Pediatric Endocrine Society criteria. The characteristics of adolescents who were diagnosed with PCOS were also evaluated. Interventions and Main Outcome Measures Forty-one patients out of 52 (78.8%) received diagnosis with National Institutes of Health and Endocrine Society criteria, all with Rotterdam criteria, 45/52 (86.5%) with Androgen Excess Society criteria, 36/52 (69.2%) with Amsterdam criteria and 34/52 (65.4%) with the Pediatric Endocrine Society criteria. Results and Conclusion This study shows that the choice of guideline used does have a great effect on whether an adolescent received the PCOS diagnosis or not. For physicians using the broader criteria, care should be taken to ensure the patient does not receive diagnosis because of the physiological changes seen during puberty, which might mimic PCOS. For those using stricter criteria, close monitoring of patients who do not receive diagnosis is necessary to prevent chronic complications.

Polycystic ovary syndrome (PCOS) is a familial heterogeneous disorder affecting 6% to 10% of reproductive-age women. The use of criteria developed for adult women is problematic for the adolescent girl because the clinical features associated with PCOS are normal pubertal events. The recent consensus statement on PCOS in adolescents stated that hyperandrogenism and oligomenorrhea need to persist for at least 2 years to consider the diagnosis of PCOS. Although insulin resistance, hyperinsulinism, and obesity are often associated with PCOS, these features are not considered valid diagnostic criteria. Recent genomewide association studies implicate genetic loci involved in the hypothalamic-pituitary-ovarian axis.

Melasma is a facial hyperpigmentation in the upper lips, cheeks, forehead and chin. It is mostly seen in women. Melasma treatments include topical methods that are not only costly, but also temporary. Melasma recurs shortly after cessation of the treatment. Considering the relationship between melasma and elevated estrogen levels in patients with oligomenorrhea, systemic anti-estrogen therapies are not used for melasma. In this study, by searching in the scientific databases such as Scopus, Pubmed and the authentic books of traditional medicine such as the Canon of medicine, melasma treatment was evaluated based on oligomenorrhea systemic therapy. The results of this study showed that if melasma is due to oligomenorrhea, the use of systemic anti-estrogenic therapies can improve melasma by reducing of Melanogenesis due to decreasing α msh (alpha-Melanocyte-stimulating hormone) in addition to oligomenorrhea improvement. However, because of the extreme attention to the advertising cosmetic creams, attention to systemic therapies has been faded. According to traditional medicine, the use of menstruation-inducing systemic therapies can be more effective in melasma than topical treatments because of removing of the disease agent. Given the important role of oligomenorrhea in creating of melasma, it is suggested conducting more studies on the effect of systemic therapy of oligomenorrhea on melasma treatment. If proven, to be considered as the treatment strategies for this disease.

Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carriers of CAH (33), respectively were selected. Forty-four females age-matched healthy controls were also enrolled and genotyped for CYP21A2. Clinical, hormonal and genetic data were collected. CYP21A2 monoallelic mutations, defining the heterozygous carriers state, were identified in subjects with clinical features including hirsutism, oligomenorrhoea, overweight and a PCO-like phenotype, particularly occurring in the age of adolescence. Consistently, levels of 17OHP and cortisol were found to be significantly different from NC-CAH. Overall, some clinical and laboratory findings including oligomenorrhea and 17OHP/cortisol ratio were observed as independent markers associated with carriers of CAH. Here we report a high prevalence of late-onset signs of polycystic ovary syndrome (PCOS) and hyperandrogenism in heterozygous carriers. The 17OHP/cortisol ratio may be a predictive tool to identify the carriers of CAH, even though specific cut-off values have not yet been identified.

Objective Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. Study design A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A – patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B – patients with H plus O (without PCO); C – patients with H plus PCO (ovulatory phenotype); D – patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. Results Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59–13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40–211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01–0.51). Conclusions The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group.

WOS: 000308511500012 PubMed: 22534402 Objective: The relationship between menstruation disorders and antidepressant drugs usage in women remains unclear. In this study, we aimed to investigate the incidence rate of antidepressant-related menstruation disorders and to examine whether or not antidepressant use is associated with menstrual disorders in women. Methods: The study sample was gathered from three centers and four hospitals. A total of 1432 women who met the criteria of inclusion were included in the study. The sample was divided into two groups: the antidepressant group (n=793) and the control group (n=639). The menstruation disorders were established with reports from the study participants on the basis of related gynecological descriptions. Results: The prevalence of menstrual disorders was significantly higher in the antidepressant group (24.6%) than the control group (12.2%). The incidence of antidepressant-induced menstruation disorder was 14.5%. The antidepressants most associated with menstrual disorders were paroxetine, venlafaxine, sertraline and their combination with mirtazapine. Overall, the incidence rate was similar in women receiving selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors. Conclusions: The results of the present study suggest that menstruation disorders are frequently observed in women taking antidepressants and that it appears to be associated with antidepressant use at least in some women. (C) 2012 Elsevier Inc. All rights reserved.

The objective was to investigate whether the associations between leptin, adiponectin, andadiposity reported in classic polycystic ovary syndrome (PCOS) are also observed in elderly women with a novel putative postmenopausal PCOS phenotype. We studied 713 postmenopausal community-dwelling women. Diagnosis of the novel phenotype required the presence of ≥3 diagnostic features including: 1) a personal history of oligomenorrhea; 2) history of infertility or miscarriage; 3) current or past clinical or hormonal evidence of hyperandrogenism; 4) central obesity; 5) biochemical evidence of insulin resistance. Women in the control group had ≤2 of these components. Mean age (±SD) was 74±8 years for the study cohort. Sixty-six women (9.3%) had the putative PCOS phenotype. Serum leptin was higher (mean 25.70±15.67 vs 14.94+9.89 ng/mL, P.01) and adiponectin lower (mean 11.72±4.80 vs 17.31±7.45 μg/mL, P.01) in cases vs controls. Leptin was positively, and adiponectin inversely, associated with an increasing number of phenotype features (P.01 for linearity). In age-adjusted regression analysis, adjustment for waist circumference eliminated the association between leptin and the PCOS phenotype, but not the association between adiponectin and the PCOS phenotype. In this novel postmenopausal PCOS phenotype, adipocytokine profiles and their associations with adiposity parallel those reported in younger women with classic PCOS. These results support our hypothesis that a putative phenotype analogous to PCOS can be identified in postmenopausal women using clinical and biochemical criteria. Use of this novel phenotype could provide a basis for studies of the delayed consequences of PCOS in older women.

Study Objective The aims of this study are to determine among female high school track athletes: (1) knowledge of the association between menstrual irregularity and bone health; (2) attitudes toward amenorrhea, specifically if amenorrhea is seen as a sign of athletic success; (3) the association between knowledge and attitudes based on athlete menstrual status. Design Cross-sectional survey. Setting Five public high schools in Texas. Participants 103 female high school track athletes ages 14–18 years. Intervention Participants completed a questionnaire that addressed menstrual history, details of track participation, knowledge of bone mineral density (BMD)/ menstrual status connection, and attitudes about the desirability of oligo/amenorrhea. Outcome Measures Frequencies of attitude and knowledge replies, summative knowledge score, and correlations between attitudes, knowledge, and menstrual status. Results Sixteen subjects (16.7%) met criteria for amenorrhea, 16 for oligomenorrhea (16.7%). Median summative knowledge score was one of six. Menstrual irregularity was associated with lower knowledge ( P = 0.035). Incorrect answers about consequences of bone loss and the link to menstrual irregularity were given by ≥90% of respondents. Lower knowledge was associated with a greater number of “don’t know” replies to attitude questions ( P = 0.002). Among more knowledgeable participants endorsing opinions, menstrual irregularity was not seen as a sign of athletic success. Conclusions The prevalence of irregular menses is high among adolescent track athletes and a larger-scale inquiry to clarify adolescent athletes’ knowledge of and attitudes about the link between menstrual patterns and BMD is indicated. Education may provide one key to improved health behavior among this at-risk population.

We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to

Objective: To investigate oligomenorrhoea in adolescents with type 1 diabetes and the possible relationship with glycaemic control. Study design: The study group consisted of 81 female adolescents with type 1 diabetes whose mean age was 15.0 years (range 12–18). The control group consisted of 205 healthy adolescents with a mean age of 15.5 years (range 12–18). Data on menstruation were collected by two parallel self-administered questionnaires. Oligomenorrhoea was defined as having a menstrual cycle longer than 36 days throughout the past year (5–6/year). The metabolic control of diabetes was evaluated by calculating the mean value of HbA1c during the past year. Results: Age of menarche was greater for adolescents with type 1 diabetes (12.2 1.4 vs. 11.7 1.2, p < 0.000) compared to healthy age-matched controls. Logistic regression analysis with oligomenorrhoea as the dependent binary variable revealed an odds ratio equal to 7.8 (95% CI 3.411–17.853) for adolescents with type 1 diabetes (p < 0.000). Finally, a second logistic regression analysis, concerning only adolescents with type 1 diabetes and with the same binary variable, estimated an odds ratio of 4.8 (95% CI 1.784–13.057, p < 0.002) for HbA1c, and an odds ratio of 5.3 (95% CI 1.821–15.130, p < 0.002) for the frequency of hypoglycaemia. Conclusion: In adolescents with type 1 diabetes, menarche occurs later and oligomenorrhoea is more frequent. The relative risk of having oligomenorrhoea is greater when there is an increased value of HbA1c or when hypoglycaemia is more frequent.

To compare the health-related quality of life (HRQOL) of women at surgical menopause with that of women at natural menopause, utilizing the Menopause Rating Scale (MRS-II).An institution-based cross-sectional study design was used, with 32 participants in each of two groups: women who had undergone surgical menopause of 9-12 months previously; and women who were more than 40 years of age and had had oligomenorrhoea for at least 1 year. The MRS-II was used to assess HRQOL. None of the women had received any hormonal therapy before assessment.Total MRS-II scores along with the scores on the somato-vegetative, psychological and urogenital sub-scales were compared between the two groups.HRQOL was rated as worse by the surgical menopause group than by the natural menopause group: the total MRS-II scores were much higher for the surgical menopause group (mean=29.4, SD=6.7) than for natural menopause group (mean=20.7, SD=6.5), and this difference was significant (p0.0001). Similar results were obtained on the three sub-scales-somato-vegetative (p=0.030), psychological (p0.0001) and urogenital (p0.0001).HRQOL is worse after surgical than in natural menopause. Routine surgical castration at hysterectomy should be avoided because of adverse short-term effects and, potentially, long-term consequences.

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.

Objective PCOS (polycystic ovarian syndrome) is a clinically heterogeneous endocrine disorder which affects up to 4–10% of women of reproductive age. A standardized definition is still difficult because of a huge variety of different phenotypes. The aim of this study was to evaluate possible correlations between the degree of cycle irregularity and the grade of endocrine and metabolic abnormalities. Study design A cross-sectional study was carried out. Hyperandrogenic and/or hirsute women with regular menstrual cycles and polycystic ovaries on ultrasound (PCOS eumenorr, n = 45), PCOS patients with oligomenorrhea (PCOS oligo, n = 42) and PCOS patients with amenorrhea (PCOS amenorr, n = 31) were recruited from the Department of Gynecological Endocrinology and Reproductive Medicine of the Women's University Hospital Heidelberg (Heidelberg, Germany). Results Normocyclic patients demonstrated significantly better metabolic parameters (BMI, fasting insulin, HOMA-IR) than patients with oligo/amenorrhea. Hormonal parameters (LH, FSH, FAI and testosterone) were significantly different between patients with different menstrual patterns and patients with regular cycles. Conclusion Determining the degree of cycle irregularity as a simple clinical parameter might be a valuable instrument to estimate the degree of metabolic and endocrine disorders. Emphasis should be given to those parameters as a first step to characterize PCOS patients with a risk of endocrine and metabolic disorders leading to consequent detailed examination.

Study Objective Oligomenorrhea in active adolescent females of normal weight is presumed to be related to hypoestrogenism secondary to physical activity and decreased fat mass. We hypothesized that active adolescents with oligomenorrhea would have lower estrogen levels than normal controls with similar levels of cardiovascular fitness. Design/Participants Twenty healthy participants between the ages of 16 and 20 years were recruited at least 2 years postmenarche. Adolescents reporting fewer than 9 cycles a year (n = 6) were compared to 14 controls with monthly menstrual cycles. Histories of eating disorder, hirsutism, severe acne, depression, or amenorrhea were cause for exclusion. Main Outcome Measures Body composition and bone density were measured by total body dual x-ray absorpitometry. Cardiovascular fitness was evaluated by measuring oxygen consumption during exercise. Control subjects were matched by age, body mass index (BMI), and fitness level. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, progesterone, and estradiol were obtained. Statistical analysis was performed using SAS 9.1. Results Cardiovascular fitness in both groups was within normal limits for age. No significant differences in BMI, estradiol concentrations, or bone density were found, but trunk fat mass was lower in adolescents with oligomenorrhea who also reported more frequent exercise. Testosterone concentrations and LH/FSH ratios were significantly higher in participants with irregular menstrual cycles (P = 0.0018 and Conclusion Adolescents with oligomenorrhea were leaner, yet they had higher testosterone levels and a greater LH/FSH ratio than their BMI-matched, cyclic counterparts. We hypothesize that, in active adolescents of normal weight, elevated androgen and LH concentrations are linked to ovarian dysfunction, which can masquerade as exercise-induced oligomenorrhea.

Objective To determine the level of plasma soluble CD40 ligand (sCD40L) in patients with polycystic ovary syndrome (PCOS). Design Prospective study. Setting Baskent University School of Medicine in Turkey. Patient(s) Thirty-one patients with PCOS and 31 non-PCOS (control) patients. Intervention(s) Determination of plasma sCD40L and homocysteine levels. Main Outcome Measure(s) Plasma sCD40L, fasting glucose, fasting insulin, homeostatic model assessment insulin resistance index (HOMA-IR), LH, FSH, E 2 , total T, DHEAS, total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, homocysteine, and high-sensitivity C-reactive protein (hsCRP). Result(s) The mean serum fasting insulin and HOMA-IR levels were significantly higher in the PCOS group. The mean serum homocysteine level was significantly higher in the PCOS group. Despite a trend for higher high-sensitivity C-reactive protein levels in the PCOS group, the difference did not reach statistical significance. The mean plasma sCD40L level in the PCOS group was significantly higher than that in the control group (5.14 ± 3.65 ng/mL vs. 3.45 ± 2.64 ng/mL, respectively). Conclusion(s) Polycystic ovary syndrome is associated with elevated levels of sCD40L and homocysteine.

Objective The study was conducted to identify predictors of oligoamenorrhea at 12 months in levonorgestrel-releasing intrauterine system (LNG-IUS) users. Design A 12-month observational study. Setting Gynecologic outpatient clinic in a large regional hospital in Flanders, Belgium. Population or Sample A total of 150 women who had made an informed decision to use a LNG-IUS either as a method of contraception or to manage menorrhagia. Methods All women were premenopausal and first-time users. The variables recorded prior to insertion on Days 1 to 5 of the menstrual cycle were age, parity, body mass index, indication for LNG-IUS use, prior contraceptive use, menstrual bleeding history, length of the uterine cavity, endometrial thickness, number of antral follicles, serum follicle-stimulating hormone, inhibin B and anti-Mullerian hormone. Menstrual bleeding pattern, patient satisfaction or wish to discontinue the method was noted at 3, 6 and 12 months of follow-up visits. Main Outcome Measures Menstrual bleeding pattern (amenorrhea, oligomenorrhea, menorrhagia) at 12 months was taken as the primary outcome measurement. Patient satisfaction was followed as a secondary outcome. Results Oligoamenorrhea was associated with a high patient satisfaction. A bleeding period less than 5 days, absence of severe uterine bleeding at baseline, LNG-IUS use for contraception and oligoamenorrhea at 3 months were predictors of a favorable outcome at 12 months in a univariate analysis. The absence of severe bleeding prior to LNG-IUS insertion was the only clinically useful predictor of favorable outcome in the multivariate analysis (odds ratio 0.13, 95% confidence interval 0.02–0.66). Conclusions Patient profiling as described is not helpful in counselling women for intentional LNG-IUS use, especially not if it is planned as a method of managing menorrhagia.

Study Objective To evaluate whether oligomenorrhea and amenorrhea in adolescent females would have a negative effect on the standard quality of life (QOL) scores as compared to eumenorrheic adolescents, and whether such scoring would differ between those with exercise related oligo/amenorrhea or those with hypothalamic/ovarian causes. Design Prospective cross-sectional observational survey. Methods Young dancers were recruited from the Sports Clinic of a collegial School of Dance, and non-dancers were recruited from a hospital-based adolescent gynecology clinic. All subjects completed a structured self-answering questionnaire recording epidemiological data and a 36-item Short Form Health Survey (SF-36). All subjects had a full hormonal profile and pelvic ultrasound to study ovarian morphology. Results Sixty-six dancers (19 with exercise-related oligo/amenorrhea and 47 eumenorrhoeic) and 90 non-dancers (45 eumenorrhoeic and 45 oligo/amenorrheic) were analyzed, all 16–20 years of age. There was no difference in the scoring between eumenorrheic dancers and non-dancers. Oligo/amenorrheic dancers did not score lower than eumenorrheic dancers. Compared with eumenorrheic subjects or to oligo/amenorrheic dancers, oligo/amenorrheic non-dancers had significantly lower QOL scores in the domains of physical functioning (PF) and general health (GH) and vitality (VT). Conclusion Compared with eumenorrheic adolescents, QOL scores were lower in non-exercising adolescents with oligo-amenorrhea, but not those with exercise related oligo/amenorrhea. The negative effects of oligomenorrhea and amenorrhea on quality of life were apparently attenuated if the menstrual dysfunction was related to physical training.

Background: A prospective cohort study was carried out to evaluate uterine volume and the volume of uterine leiomyomas in women using the levonorgestrel intrauterine system (LNG-IUS) to treat idiopathic menorrhagia (n=32) and menorrhagia due to leiomyomas (n=27). A control group used the device as a contraceptive method (n=28). Methods: Clinical and ultrasonographic evaluations were carried out at insertion and at 3, 6, 12, 24 and 36 months later. Total uterine volume and the volume of the leiomyomas were calculated using the ellipsoid formula (anteroposterior diameter)(transverse diameter)(longitudinal diameter)(4/3)(k). In the case of multiple leiomyomas, the volume of each myoma was added to calculate the total volume of leiomyomas in each patient. Menstrual bleeding episodes were recorded. Results: Uterine volume decreased significantly in both groups of menorrhagic patients but not in the control group. In the group of women with idiopathic menorrhagia, a mean reduction of 36.4F15.3 (S.D.) cm 3 (from 127.1 cm 3 to 90.7 cm 3 ) was observed (p=.041), and a greater and more significant mean reduction of 63.6F19.0 (S.D.) cm 3 (from 156.6 cm 3 to 93 cm 3 ) occurred in the group of women with leiomyomas (p=.014). In the contraception group, the reduction was of only 2.9F5.4 (S.D.) cm 3 in mean uterine volume (from 70.3 cm 3 to 67.4 cm 3 ), which was not statistically significant (p=.085). The mean volume of leiomyomas decreased by 5.2F3.1 (S.D.) cm 3 (from 12.8 cm 3 to 7.6 cm 3 ) after 3 years of use, but this difference was not significant (p=.4099). After 36 months of use, amenorrhea and oligomenorrhea were the most frequent bleeding patterns, occurring in 45–57% and 33–39% of users in the three groups, respectively. Amenorrhea was higher in the contraception group (57.1%) and in women with idiopathic menorrhagia (53.4%) than women in the group with menorrhagia due to leiomyomas (44.5%) (p=.027). Moreover, the prevalence of spotting was almost three times higher (11%) in women with menorrhagia caused by leiomyomas and nearly double (7.7%) in the idiopathic menorrhagia group when compared with 4% in the control contraception group (p=.024). Conclusion: The LNG-IUS significantly reduces uterine volume in women with menorrhagia with and without leiomyoma; however, it does not significantly reduce the volume of leiomyomas.

Objective To test the interdependence between insulin resistance (IR) and gonadotropin dissociation (GD) in polycystic ovary syndrome (PCOS). Design Cross-sectional prospective study. Setting Clinical research center. Patient(s) Thirty-two PCOS patients aged 19–34 years; 16 obese (BMI ≥ 27) and 16 nonobese (BMI Intervention(s) A 75-g oral glucose tolerance test (OGTT) and a 100-μg i.v. GnRH test were performed on different days. Blood was taken at 0, 30, 60, 90, 120, and 180 minutes in each test. Serum glucose, insulin, LH, and FSH were measured. Main outcome measure(s) Area under the curve was calculated for glucose, insulin, and glucose-to-insulin ratio (GIR), and for LH, FSH, and LH-FSH ratio. Result(s) Glucose, insulin, and GIR were not modified significantly during the GnRH test, nor LH, FSH and LH-FSH ratio throughout the OGTT. There were no significant differences in GIR response of patients with and without GD, nor in LH-FSH ratio of patients with and without IR, after OGTT and GnRH test. However, obese patients with IR had a significantly larger ( P Conclusion(s) Insulin resistance and GD do not appear to be related events in PCOS, suggesting that each one might be determined by different genetic disorders. However, IR can affect GD after chronic stimulation in obese patients.

Summary Background Polycystic ovary syndrome is the most common cause of anovulatory infertility. It has long-term health implications and is an important risk factor for type 2 diabetes. However, little is known about the cause of polycystic ovaries. We have used detailed morphological analysis to assess the hypothesis that there is an intrinsic ovarian abnormality that affects the earliest stages of follicular development. Methods We took small cortical biopsies during routine laparoscopy from 24 women with normal ovaries and regular cycles and from 32 women with polycystic ovaries, 16 of whom had regular, ovulatory cycles and 16 of whom had oligomenorrhoea. We used computerised image analysis to assess the density and developmental stage of small preantral follicles in serial sections of fixed tissue. Findings Median density of small preantral follicles, including those at primordial and primary stages, was six-fold greater in biopsies from polycystic ovaries in anovulatory women than in normal ovaries (p=0·009). In both ovulatory and anovulatory women with polycystic ovaries, we noted a significant increase in the percentage of early growing (primary) follicles and a reciprocal decrease in the proportion of primordial follicles compared with normal ovaries. Interpretation Our findings indicate that there are fundamental differences between polycystic and normal ovaries in early follicular development, suggesting an intrinsic ovarian abnormality. The increased density of small preantral follicles in polycystic ovaries could result from increased population of the fetal ovary by germ cells, or from decreased rate of loss of oocytes during late gestation, childhood, and puberty.

Nutritional status, eating behaviors and menstrual function was examined in 23 nationally ranked female adolescent volleyball players using a health/weight/ dieting/menstrual history questionnaire, the Eating Disorder Inventory (EDI), and the Body Shape Questionnaire (BSQ). Nutrient and energy intakes (El) and energy expenditure (EE) were determined by 3-d weighed food records and activity logs. Iron (Fe), vitamins C, B12, and Folate status were assessed using serum and whole blood. Mean El (2248 +/- 414 kcal/d) was less than EE (2815 +/- 306 kcal/d). Mean carbohydrate (5.4 +/-1.0g/kg/d) and protein (1.1+/-0.3g/kg/d) intakes were below recommended levels for highly active women. Mean intakes for folate, Fe, Ca, Mg, and Zn were less than the respective RDAs/DRIs and almost 50% of the athletes were consuming less than the RDAs/DRIs for the B-complex vitamins and vitamin C. Three athletes presented with Fe deficiency anemia (Hb12 mg/dL), while marginal vitamin B12 status (200 pg/ml) and vitamin C status (28 mmol/L) were found in 1 and 4 athletes, respectively. Approximately 1/2 of the athletes reported actively "dieting". Mean BSQ and EDI subscales scores were within the normal ranges; yet, elevated scores on these scales were reported by 26% and 35% of athletes, respectively. Past or present amenorrhea was reported by 17% of the athletes and 13% and 48%, reported past or present oligomenorrhea and "irregular" menstrual cycles, respectively. These results indicate that elite adolescent volleyball players are at risk for menstrual dysfunction and have energy and nutrient intakes that place them at risk for nutritional deficiencies and compromised performance.

The objectives of this study were to evaluate the bleeding patterns and clinical performance during the first 2 years of use of an intrauterine system releasing 20 μg/day of levonorgestrel (LNG-IUS, Mirena). Two-hundred-fifty-six women accepted use of Mirena from April 1998 through September 1998. The gross cumulative discontinuation rate due to pregnancy and expulsion were significantly higher in women who used the device because of heavy bleeding. There was one pregnancy at the 15th month of use after an inadvertent expulsion of the device. The continuation rate was 66.2 at the end of the second year. Forty-four percent of women reported amenorrhea at the 6th month of use. This rate maintained stability at 50% after 12 and 24 months of use. Spotting was present in 25% of the users at 6 months, decreasing to 8% and 11% at 18 and 24 months, respectively. Oligomenorrhea was described by one-quarter of women and was similar at each observation period. Removals due to menstrual bleeding problems were concentrated in the first 6 months of use and mostly due to amenorrhea or menorrhagia. In conclusion, LNG-IUS showed a high contraceptive efficacy and a good continuation rate up to 2 years. In addition, a reduction of blood loss was observed a few months after insertion.

To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS).Prospective pilot study.Outpatient.Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who hador = 1 previous pregnancy while they were not receiving metformin.Metformin, 1.5-2.55 g/day, throughout pregnancy.Rates of first-trimester spontaneous abortion and teratogenicity.Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (allor = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04).Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.

Characteristic presentation of nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency was compared between women carrying a severe and a mild CYP21 mutation (Group 1, N = 26) versus homozygotes for mild mutations (Group 2, N = 8). The diagnosis was based on elevated ACTH-stimulated 17OH-progesterone (17OHP). Genotyping for 10 mutations was performed by PCR-based techniques. Jewish patients predominated among Group 2 (25% vs 11.5% in Group 1); however, 85% of all patients were non-Jewish Caucasians. Average age of presentation was 23-25 years, and did not differ between groups. Hirsutism, and to a lesser extent oligomenorrhea and acne, were more prevalent among Group 1 women. There was a trend to higher basal 17OHP among Group 1 patients (mean +/- SEM; 1354+/-323 vs 714+/-129 ng/dl, P< or =0.25). The lack of significant difference was perhaps due to the relatively few homozygotes for 2 mild mutations (24%). V281L was carried on approximately 48% of all alleles, and about 16% carried either P30L or P453S. Approximately 38% of alleles and 77% of patients carried a classic mutation. These data have important implications for genetic counseling. In summary, we describe differences in clinical, hormonal, and genetic characteristics among a multiethnic group of females with NCAH.

A prospective cohort analysis of premenopausal women with focal epilepsy was conducted in order to determine whether polycystic ovary syndrome (PCOS) is a common finding in women treated with antiepileptic drugs (AED). This study was carried out in 93 of 150 women (aged between 20 and 53 years; mean, 34.3 years) with chronic focal epilepsy consecutively cared for at the Department of Epileptology, University of Bonn: 38 were receiving one AED (18 valproate, 20 carbamazepine), 36 more than one drug, and 19 were without medication. Patients were followed-up for 6 months. PCOS was defined as hyperandrogenism (testosterone concentration, >0.7 ng/ml) combined with oligomenorrhoea (cycle length, >35 days) or amenorrhoea. PCOS was identified in two out of 19 (10.5%) patients receiving no medication; in four of 38 (10.5%) of patients receiving monotherapy, and in none of the patients receiving more than one AED. The incidence of PCOS in patients treated with valproate monotherapy (11.1%) was similar to that in patients treated with carbamazepine (10%) and also to that in patients not treated with AEDs. The results of this study suggest that the manifestation of PCOS in women with focal epilepsy is not related to the administration of valproate or carbamazepine.

Objective: To evaluate [1] the effects of levels of sex hormone-binding globulin (SHBG), albumin, and total testosterone on the distribution of testosterone between SHBG-bound and non–SHBG-bound fractions; [2] the independent effects of polycystic ovary syndrome (PCOS) and body mass index on serum levels of total testosterone, non–SHBG-bound testosterone, SHBG, and albumin; and [3] the usefulness of levels of total testosterone and non–SHBG-bound testosterone and of the free androgen index in the diagnosis of PCOS. Design: Retrospective clinical study. Setting: An academic research environment. Patient(s): Forty-three women with oligomenorrhea and PCOS. Twenty-five women with regular menstrual cycles and without hirsutism served as controls. Intervention(s): None. Main Outcome Measure(s): Levels of non–SHBG-bound testosterone, total testosterone, SHBG, and albumin in serum. Result(s): Levels of total testosterone and non–SHBG-bound testosterone, and the free androgen index were higher in patients with PCOS than in healthy controls. PCOS did not have an effect on the levels of SHBG or albumin, or on the percentage of non–SHBG-bound testosterone. Levels of SHBG and albumin were inversely related to body mass index. The percentage and concentration of non–SHBG-bound testosterone and the free androgen index were directly related to body mass index. Hirsutism did not have an effect on any outcome measure. Conclusion(s): The distribution of total testosterone into SHBG-bound and non–SHBG-bound fractions is associated with body mass index, not with PCOS. The high levels of non–SHBG-bound testosterone and the high free androgen index in patients with PCOS reflect mainly high levels of total testosterone. Thus, the measurement of levels of non–SHBG-bound testosterone and the calculation of the free androgen index provide no further information in the diagnosis of PCOS beyond that provided by the measurement of levels of total testosterone.

Study Objective To determine the presence of impaired gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period. Design A case series study of 28 patients aged 12 to 19 years with menarche at least 2 years before the study. Setting Tertiary care public hospital. Participants Group I: 14 adolescents previously submitted to chemotherapy during the prepubertal or peripubertal period and with remission of oncologic disease for at least 2 years; Group II: 14 normal adolescents with no previous oncologic disease and with regular menstrual cycles. Interventions and Main Outcome Measures Pubertal development, menstrual cycles and serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined during the early follicular phase. Results There were no differences between the two groups in terms of age at appearance of secondary sexual characteristics or age at menarche. Menstrual irregularity was detected in 7 of the 14 patients in Group I, all 8 of whom presented oligomenorrhea. There were no differences in LH levels between the two groups ( P = 0.55), although mean FSH levels were higher in Group I than in Group II (6.71 ± 2.99 mIU/ml vs. 3.83 ± 2.01 mIU/ml, P = 0.01). Conclusion Although girls submitted to chemotherapy during the prepubertal or peripubertal period presented normal sexual development, the incidence of oligomenorrhea was higher than expected for their age, and FSH levels, although within normal limits, were higher than those seen in normally cycling girls.

Objective To examine the serum total renin in women with polycystic ovarian syndrome (PCOS) and in controls. Setting Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. Patients Forty-four oligomenorrheic women with PCOS (body mass index [BMI] 18.0 to 49.0 kg/m 2 ) and 25 control women with regular menstrual cycles (BMI 18.0 to 53.5 kg/m 2 ). Main Outcome Measures The concentrations of total renin, LH, FSH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and insulin in serum. Results The concentration of total renin in serum was higher in PCOS women than in healthy women independently of BMI, age, or serum insulin. The serum total renin measurement discriminated PCOS patients and control women to a similar extent as the previously used hormonal parameters (LH:FSH, T, A, and T:SHBG) as judged by receiver-operating characteristic analysis. Positive correlations were found between the serum total renin level and LH concentration, LH:FSH ratio, T and A levels, and T:SHBG ratio. Analysis of serum total renin in PCOS patients during oligomenorrhea and after menstruation did not reveal any significant changes. Conclusions The elevated concentration of serum total renin suggests an enhanced activity of ovarian renin-angiotensin system in PCOS. The determination of serum total renin may provide a novel tool in the diagnostics of PCOS, because its serum level is elevated in PCOS women independently of BMI and serum insulin.

1. The vast majority of bone mineralization in girls occurs by the middle of the second decade. 2. Premature bone demineralization occurs in women with hypothalamic dysfunction manifest as amenorrhea and oligomenorrhea, associated with athletics, dancing, and eating disorders. 3. In young women with amenorrhea associated with weight loss, BMD loss will be occurring soon after the amenorrhea develops. Treatment to prevent BMD loss or promote BMD accretion should begin soon, probably within 6 months after amenorrhea occurs. 4. Women who recover from anorexia nervosa at a young age (< 15 years of age) can have normal total body BMD, but regional (lumbar spine and femoral neck) BMD may remain low. The longer the anorexia nervosa persists, the less likely it is that the BMD will return to normal. Girls and women with anorexia nervosa need to be rehabilitated early in the disease to maximize BMD accretion. 5. Conjugated estrogen, in doses that improve bone mineralization in postmenopausal women and in combination with medroxyprogesterone, has not been shown to improve BMD in young women with hypothalamic amenorrhea. The role of orally administered medroxyprogesterone at a dose of 10 mg per day, 10 days per month, in improving BMD in teenage girls with hypothalamic amenorrhea or oligomenorrhea remains to be established. 6. Treatment with OCP may have a beneficial effect on BMD in young women with hypothalamic amenorrhea, but this has not been established in a double-masked, randomized, controlled trial. Doing a double-masked trial using OCP will be difficult because estrogen-deficient subjects treated with OCP will be likely to have menstrual bleeding, whereas those treated with placebo will not. In addition, the risk of pregnancy in a sexually active subject, who does not know whether she is receiving OCP, is too great for some subjects. 7. Osteoporosis is a major cause of morbidity and death. Peak bone mass is a major determinant of the risk of osteoporosis, and the second decade is the critical period of peak bone mass acquisition; thus providers of health care for adolescents need to understand the factors that affect bone mineralization during this period, and advise patients accordingly.

This study examined the relationship of premenstrual and postmenopausal symptoms with vertebral osteoporosis by means of a retrospective case control questionnaire in patients with vertebral osteoporosis and control patients. Seventy-five postmenopausal women aged 55–70 years with vertebral osteoporosis and 77 age-matched controls were interviewed at the outpatient clinics of the Royal Hallamshire Hospital, Sheffield, UK to establish the past history of premenstrual symptoms, and present and past history of postmenopausal vasomotor symptoms. The risk of vertebral osteoporosis was significantly greater in women with a history of premenstrual symptoms (RR = 1.86) or oligomenorrhoea (RR = 3.08). Significantly more patients with osteoporosis than controls recalled vasomotor symptoms at the time of the menopause (RR = 1.35). Patients were more likely than controls to describe their symptoms as severe (RR = 1.43) or persistent (RR = 2.19). We conclude that the relative risk of vertebral osteoporosis is increased in women with a history of premenstrual symptoms, irregular periods, and with severe and/or persistent menopausal vasomotor symptoms.

We compared young female figure skaters, aged 10-23, with non-athletic control subjects to ascertain whether there were differences in skeletal densities at various sites. We also compared other characteristics of body size, including height, weight and percent body fat. Although the skaters were thinner and significantly more likely to have oligo- or amenorrhea, they had similar skeletal densities at upper body sites (spine, arms, ribs) and significantly greater densities in the pelvis and legs. These differences were not evident until the mid-teens, however, suggesting that there is little likelihood of selection bias as the cause of the observed differences.

Objective To examine the clinical efficacy of low dose spironolactone in hirsute women. Design Retrospective. Setting Outpatient endocrinology clinic. Patients One hundred nine consecutive women prescribed 75 to 100 mg/d spironolactone for at least 4 months in whom adequate follow-up data were available. Results Hirsutism improved in 72% of the women. Women with regular menses, whether or not they used oral contraceptives (OCs), had the highest response rate to spironolactone (78%), whereas women with irregular menses who did not use an OC had the lowest response rate (55%). Favorable responses were associated with increased severity of hirsutism (P = 0.04) and lower serum dehydroepiandrosterone sulfate levels (P = 0.05). Responders and nonresponders did not differ significantly in age (P = 0.10), duration of hirsutism (P = 0.14), pretreatment serum testosterone (T) (P = 0.48), or body mass index (P = 0.11). However, when each parameter was divided into subsets, trends toward decreasing response were observed with increasing age, duration of hirsutism over 15 years, and increasing serum T level. Conclusion Low-dose spironolactone improves hirsutism in a majority of hirsute women, irrespective of age, severity or duration of hirsutism, menstrual status, or serum hormone levels.

Sixty-six consecutive infertility clinic patients were prospectively screened with the 26-item Eating Attitudes Test and a study questionnaire. Women identified as being at high risk for an eating disorder were then interviewed to confirm or refute the diagnosis. A total of 7.6% of infertility clinic women were found to suffer from anorexia nervosa or bulimia nervosa. If eating disorders not otherwise specified were included, a total of 16.7% of infertility patients were found to suffer from an eating disorder. Among infertile women with amenorrhea or oligomenorrhea 58% had eating disorders. Because women often fail to disclose eating disorders to their gynecologists and may appear to be of normal weight, it is recommended that a nutritional and eating disorder history be taken in infertility patients, particulary those with menstrual abnormalities. It has previously been shown that disordered eating and nutrition can affect menstruation, fertility, maternal weight gain, and fetal well-being.

Many physicians routinely measure the gonadotropins PRL, LH, and FSH and the androgens dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), an-drostenedione (ADIONE), and testosterone, as well as testosterone’s biologically active fractions in the evaluation of hirsute women. Is this cost effective? To answer this question, 38 consecutive premenopausal hirsute women were evaluated. Two women each had minor elevations in PRL and FSH, and 11 had minor elevations in LH. Three women had minor elevations in the LH/FSH ratio, and only one was above a ratio of 3, believed to be indicative of polycystic ovarian syndrome. Because these gonadotropin elevations did not correlate with the androgens measured and were of no value in the diagnosis or management of these women, they were not believed to be cost effective. Their routine measurements should be abandoned.

A recent study demonstrated that hirsute women with irregular menses had higher levels of serum androgens that hirsute women with regular menses. To investigate this finding, we measured total testosterone, biologically active testosterone, free testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in 51 hirsute women with regular menses and compared the levels found to those found in 28 hirsute women with oligomenorrhea. There was no significant difference in the degree of facial hirsutism between the two groups. Oligomenorrheic women had significantly higher levels of free testosterone (p less than 0.02) and biologically active testosterone (p less than 0.05). The other androgens did not differ significantly between the two groups. The free fractions of testosterone are the metabolically active forms of the hormone and their levels are a function of the rates of production and clearance of testosterone that are elevated in states of hyperandrogenism. This study confirms that hirsute women with oligomenorrhea have higher levels of free and biologically active testosterone than those with regular menses.

Hirsutism in women is frequently associated with increased levels of androgens. Studies of biochemical changes, however, have yielded conflicting results. This study compares the findings in 30 hirsute women with normal menses and those of 30 hirsute women with abnormal cycles. Of the women with abnormal menstruation, 73% had oligoamenorrhea only and the others had dysfunctional uterine bleeding. The abnormally menstruating group had a similar mean age but tended to have heavier body weights than those with normal cycles. Free and total testosterone levels were significantly higher in the abnormal group (total testosterone, 54 +/- 35 ng/dl vs 35 +/- 12 ng/dl, p = 0.004; free testosterone, 7.8 +/- 4.9 pg/ml vs 4.2 +/- 1.4 pg/ml, p = 0.002). The abnormal group tended to have higher levels of androstenedione than the normal group (227 +/- 116 ng/dl vs 139 +/- 59 ng/dl) but dehydroepiandrosterone sulfate (DHEAS) levels were similar (320 +/- 142 mg/dl vs 298 +/- 169 pg/dl). Levels of thyroxin, thyrotropin, and prolactin were comparable in the two groups. Among hirsute women those with abnormal menses tended to be heavier and to have higher levels of total testosterone, free testosterone, and androstenedione. This is consistent with the clinical impression, not previously documented, that of hirsute women, those with abnormal menses have more severe endocrine abnormalities than those with normal cycles.

Objective The aim of this study was to evaluate the prevalence of hyperprolactinemia in adolescents and young women with menstrual problems. Study Design This study included 1704 young women with menstruation-related problems. The patients were classified into group I (age, 11-20 years) or group II (age, 21-30 years); the prevalence of hyperprolactinemia was analyzed according to age and categories of menstruation-related problems. Results For primary amenorrhea and oligomenorrhea, the prevalence of hyperprolactinemia was low in both groups. However, hyperprolactinemia was a relatively common cause of secondary amenorrhea (5.5% for group I and 13.8% for group II, respectively); it was more frequent in group II ( P = .001); the prevalence of prolactinoma was also higher in group II ( P = .015). For abnormal uterine bleeding, hyperprolactinemia was more common in group II (2.6% for group I and 9.4% for group II; P Conclusion Hyperprolactinemia is not rare in young women with menstruation-related problems; its prevalence varies according to age and manifestations.

Objective The objective of the study was to determine the efficacy of a novel “stair-step” clomiphene protocol in women with polycystic ovarian syndrome (PCOS) who do not respond to 50 mg clomiphene. Study Design This was a retrospective analysis at an academic fertility center. The stair-step protocol is performed as follows: 50 mg clomiphene for 5 days, ultrasonography on days 11-14. If unresponsive, immediately begin 100 mg clomiphene for 5 days and repeat ultrasound in 1 week. If still unresponsive, begin 150 mg clomiphene for 5 days and repeat the ultrasound in 1 week. Stair-step cycles were compared with published historical clomiphene outcomes for women who were nonresponsive. Results The time to ovulation was 32-53 days less with the stair-step protocol compared with a traditional regimen. The dose-dependent ovulation rate was 64% at 100 mg with the stair-step protocol compared with 22% with a traditional regimen. Conclusion It is not necessary to induce menses before increasing clomiphene doses in nonresponsive PCOS patients.

Endocrine dysfunction was studied in 109 consecutive female patients with moderate to severe alopecia, mostly of a diffuse pattern. The study included an evaluation of associated hirsutism and/or menstrual dysfunction, plasma hormonal measurements, and ultrasonography of the ovaries. A control group of 24 ovulatory, nonhirsute, nonalopecia individuals was also studied. Of the 109 patients, 70 (64.2%) had no clinical evidence of hirsutism or menstrual dysfunction. Two of 44 patients tested with cosyntropin (Cortrosyn) had 21-hydroxylase deficiency, whereas two other patients had hyperprolactinemia caused by pituitary tumors. Hyperandrogenism was defined as an increase in any of the plasma androgens (testosterone, non-sex hormone-binding globulin bound testosterone, dehydroepiandrosterone sulfate, androstenedione, or dihydrotestosterone) and was noted in 42 of the 109 patients studied (38.5%). Of these 42 patients, 11 were ovulatory with no evidence of clinical hirsutism, 13 were ovulatory and hirsute, and 18 had oligomenorrhea or amenorrhea with or without hirsutism with confirmatory evidence of polycystic ovarian disease. Patients with diffuse alopecia may demonstrate hyperandrogenism, even in the absence of hirsutism, oligomenorrhea, or amenorrhea. The most common endocrine disorder in this series of patients with diffuse alopecia was polycystic ovarian disease.

Nine oligomenorrheic adolescent girls with a clinical and hormonal picture of ovarian hyperandrogenism were treated with a monophasic oral contraceptive (OC) containing 0.03 mg ethinylestradiol (EE) plus 0.150 mg desogestrel (DOG) for six months. The same treatment was administered in eight eumenorrheic adolescents. In both groups the treatment induced a decrease in LH, FSH, androstenedione (delta 4-A), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) levels associated with a significant sex-hormone-binding globulin (SHBG) increase. In oligomenorrheic adolescents a marked decrease in both the total ovarian volume and the number of cystic follicles was observed. All parameters, except SHBG and ovarian volume in hyperandrogenic girls, returned to pre-treatment values 3 months after treatment. Subjective improvement of skin problems occurred in six of the nine oligomenorrheic girls. Although temporary, the EE + DOG formulation pill is effective in the treatment of ovarian hyperandrogenism in adolescents. It may also be useful for the prevention of the progressive transformation in the 'classical' and 'irreversible' micropolycystic ovary of adult age.The hormonal effects of a combined, monophasic oral contraceptive (OC) containing 0.03 mg of ethinyl estradiol and 0.150 mg of desogestrel were compared in 9 adolescents with oligomenorrhea and ovarian hyperandrogenism and 8 controls with regular menstrual periods. All adolescents were treated for 6 consecutive months. Before treatment, the females with irregular periods had significantly higher basal luteinizing hormone (LH), delta 4-androstenedione (A), testosterone (T), and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. In addition, the oligomenorrheic females had significantly lower sex hormone binding globulin (SHBG) levels and greater mean ovarian volume. OC treatment produced a decrease in all hormones (LH, follicle-stimulating hormone, delta-4 A, T, and DHEA-S) in girls in both groups and a significant increase in SHBG levels. Oligomenorrheic subjects further manifested a significant decrease in total ovarian volume, with reduced number or disappearance of all echo-free cystic follicles in both ovaries. With the exception of SHBG and ovarian volume in hyperandrogenic subjects, all parameters returned to pretreatment values 3 months after discontinuation of the OC. 6 of the 9 oligomenorrheic subjects showed subjective improvement of skin problems; in addition, 6 reported a longterm decrease in hair growth. Post-treatment, oligomenorrhea and anovulation persisted in 7 of the 9 subjects. Although the effect of this treatment is temporary, the ethinyl estradiol-desogestrel OC appears to be effective in hyperandrogenic adolescents and may delay the progression of hirsutism and prevent adult micropolycystic ovarian disease.

An extended regimen of clomiphene consisting of 250 mg of clomiphene for 8 days followed by the administration of 10,000 IU of human chorionic gonadotropin (hCG) 6 days later was administered to 13 oligomenorrheic women who had previously failed to ovulate when treated with 250 mg of clomiphene for 5 days and hCG. Eight of these 13 women ovulated. Their postovulatory mean progesterone (P) level 7 days after hCG was 16 +/- 2 ng/ml. Three pregnancies occurred during 25 treatment cycles. Posttreatment estrogen levels were higher when women were treated for 8 days than for 5 days. Women ovulating after 8 days of treatment had increased concentrations of luteinizing hormone (LH) and testosterone (T) prior to hCG administration and higher pretreatment levels of estrogen and T, compared with women who did not ovulate. Changes in the timing of hCG administration may induce ovulation in some women who fail to ovulate when hCG is given on day 14. Because this 8-day regimen of clomiphene and hCG was successful in more than 50% of women failing to ovulate after 5 days, this regimen should be used prior to human menopausal gonadotropin (hMG) therapy.

Pituitary responses to 100 mcg. of luteinizing hormone-releasing hormone (LH-RH) administered subcutaneously were studied in 34 cases of amenorrhea or anovulatory oligomenorrhea associated with galactorrhea. Twenty-six patients had pituitary prolactin-secreting tumors (group I); eight patients had a normal sella turcica and remission of the syndrome either spontaneously or after thyroid replacement therapy (group 2). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to LH-RH were variable in each group of patients, ranging from poor to exaggerated, and no statistically significant difference could be observed between the groups. A positive correlation was found between FSH pituitary responses and basal FSH levels (r=0.50; P less than 0.01). No positive correlation was observed between either LH responses and basal LH levels or the gonadotropin responses and plasma estradiol levels, serum prolactin concentrations, duration of amenorrhea, or size of the tumor.

Forty-two patients ages 15 to 20 years (average 17.3 years) were evaluated for oligomenorrhea. Group I consisted of 19 patients with evidence of androgen excess (hirsutism, clitoromegaly, acne); and Group II included 23 patients without evidence of androgen excess. Sixteen of the 19 patients in Group I had elevated serum LH and normal FSH values. Serum total testosterone concentration was elevated in 12 patients and free T was elevated in one additional patient. In nine patients urinary 17KS excretion was elevated and dexamethasone suppressible. For the purpose of treatment, patients in Group I were divided into three subgroups: IA, polycystic ovary syndrome--12 patients; IB, adrenal block--two patients; IC, combined adrenal and ovarian hyperandrogenism--five patients. Among the 23 Group II patients, four had persistently elevated serum LH and normal FSH values, suggesting PCO; three had menopausal levels of LA and FSH; one had hyperprolactinemia and a depressed floor of the pituitary sella; and the remaining 15 patients had low to normal serum levels of LH and FSH, consistent with hypothalamic suppression. Guidelines for the diagnosis and treatment of adolescents with oligomenorrhea are discussed on the basis of these findings.

Radioligand assays have been developed for the principal reproductive steroids and peptide hormones. Specific binding reagents have included antibodies, plasma binders, and intracellular receptors. In each assay, problems of specificity, sensitivity, and nonspecific inhibitors were encountered. Many features of the endocrine physiology in childhood, during puberty, and in adulthood have been characterized. Hormonal evaluations of endocrine disorders of reproduction are characterized on the basis of their characteristic pathophysiologic alterations.

This report summarises a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA, and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience of these contraceptives. A wide range of approaches are described. The most frequently emphasised aspect of management is thorough pre-treatment counselling with further support and counselling at follow-up visits. Oestrogens in various forms are widely used for the treatment of prolonged, frequent or heavy episodes of bleeding, but nowadays are not usually used for the induction of withdrawal bleeding in women with amenorrhoea. Heavy or "severe" bleeding appears to be very uncommon and figures of 1-2% were frequently mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral oestrogen, including the combined pill, are more likely to successfully stop an episode of bleeding than short courses. However, there are no hard data to show that a course of oestrogen treatment has any beneficial effect on long-term bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be very little risk associated with the short-term oestrogen regimens currently used. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. It is clear that the bleeding disturbances associated with DMPA and NET-EN use are poorly understood and that urgent research is necessary to clarify pathophysiological mechanisms and improve management.This report summarizes a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience with these contraceptives. A wide range of approaches are described. The most frequently emphasized aspect of management is thorough pretreatment counseling with further support and counseling at follow-up visits. Estrogens in various forms are widely used for the treatment of prolonged, frequent, or heavy bleeding episodes, but now are not usually used for induction of withdrawal bleeding episodes in women with amenorrhea. Heavy or severe bleeding appears very uncommon and figures of 1-2% are mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral estrogen, including the combined pill, are more likely to successfully stop an episode of heavy bleeding than short courses. However, there are no hard data to show that a course of estrogen treatment has any beneficial effect on longterm bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be little risk associated with short-term estrogen regimens currently in use. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. Clearly, bleeding connected with DMPA and NET--EN use are poorly understood and research is necessary to clarify pathophysiological mechanisms and improve management.

The effects of endurance running on body composition, menstrual cycles, and gonadotropins were studied in 19 healthy, young, regularly menstruating women. Midfollicular plasma concentrations of unstimulated and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone and follicle-stimulating hormone were examined at baseline and after each subject's weekly mileage had increased 30 miles (delta 30) and 50 miles (delta 50) above baseline. Mean +/- standard error of the mean unstimulated luteinizing hormone and follicle-stimulating hormone did not change significantly. GnRH-stimulated luteinizing hormone was 76.3 +/- 22.0 micrograms/min/ml at baseline and declined to 20.2 +/- 4.5 micrograms/min/ml at delta 50 (P less than 0.02). GnRH-stimulated follicle-stimulating hormone was 28.4 +/- 7.0 micrograms/min/ml at baseline and declined to 9.6 +/- 2.1 micrograms/min/ml at delta 50 (P less than 0.02). There were no significant correlations between changes in body composition and changes in gonadotropin responses. Eighteen subjects developed oligomenorrhea.

Random blood samples were obtained from a group of patients having oligomenorrhea or secondary amenorrhea, who responded to progesterone with uterine withdrawal bleeding, associated with hirsutism (N = 35) or not associated with hirsutism (N = 9). A few blood samples were obtained during the midfollicular phase of normal cycles in age-matched normal females (N = 10) as controls for comparison. Plasma gonadotropins (follicle-stimulating hormone and luteinizing hormone [LH]) and steroid hormones including testosterone (T), androstenedione (A), estradiol (E 2 ), estrone (E 1 ), and progesterone (P) were quantitated by radioimmunoassay. The percentage of free fraction of E 2 and T was determined by equilibrium dialysis at 37° C, and the percentage of T-E 2 -binding globulin (TeBG)-bound fraction of E 2 and T was estimated by the specific steroid displacement-charcoal adsorption technique. The binding capacity of plasma TeBG was measured by the modified Scatchard plot technique. The E 2 :T ratios of concentrations and the binding parameters were also evaluated. The weight (but not height) of hirsute females was significantly higher than that of normal females. Plasma LH, T, A, and E 1 levels were significantly elevated in hirsute females. Plasma T concentrations, including free, index, and total, correlated positively with degree of hirsutism. E 2 :T ratios of concentration also suggested a similar, but negative, correlation. The percentage of free E 2 increased more than the percentage of free T when the percentage of TeBG-bound E 2 decreased more than the percentage of TeBG-bound T in hirsute females. The E 2 :T ratios of the percentage of free and TeBG-bound fractions did not show any correlation with degree of hirsutism. The T-binding capacity of plasma TeBG decreased in hirsute females and was also correlated significantly with degree of hirsutism. The elevated plasma T concentrations (including free, index, and total concentrations) in hirsute females overlapped significantly with that of normal females, thus they failed to discriminate each other.