Lactational Amenorrhea: Neuroendocrine Pathways Controlling Fertility and Bone Turnover.

Lactation is a physiological state of hyperprolactinemia and associated amenorrhea. Despite the fact that exact mechanisms standing behind the hypothalamus-pituitary-ovarian axis during lactation are still not clear, a general overview of events leading to amenorrhea may be suggested. Suckling remains the most important stimulus maintaining suppressive effect on ovaries after pregnancy. Breastfeeding is accompanied by high levels of prolactin, which remain higher than normal until the frequency and duration of daily suckling decreases and allows normal menstrual function resumption. Hyperprolactinemia induces the suppression of hypothalamic Kiss1 neurons that directly control the pulsatile release of GnRH. Disruption in the pulsatile manner of GnRH secretion results in a strongly decreased frequency of corresponding LH pulses. Inadequate LH secretion and lack of pre-ovulatory surge inhibit the progression of the follicular phase of a menstrual cycle and result in anovulation and amenorrhea. The main consequences of lactational amenorrhea are connected with fertility issues and increased bone turnover. Provided the fulfillment of all the established conditions of its use, the lactational amenorrhea method (LAM) efficiently protects against pregnancy. Because of its accessibility and lack of additional associated costs, LAM might be especially beneficial in low-income, developing countries, where modern contraception is hard to obtain. Breastfeeding alone is not equal to the LAM method, and therefore, it is not enough to successfully protect against conception. That is why LAM promotion should primarily focus on conditions under which its use is safe and effective. More studies on larger study groups should be conducted to determine and confirm the impact of behavioral factors, like suckling parameters, on the LAM efficacy. Lactational bone loss is a physiologic mechanism that enables providing a sufficient amount of calcium to the newborn. Despite the decline in bone mass during breastfeeding, it rebuilds after weaning and is not associated with a postmenopausal decrease in BMD and osteoporosis risk. Therefore, it should be a matter of concern only for lactating women with additional risk factors or with low BMD before pregnancy. The review summarizes the effect that breastfeeding exerts on the hypothalamus-pituitary axis as well as fertility and bone turnover aspects of lactational amenorrhea. We discuss the possibility of the use of lactation as contraception, along with this method's prevalence, efficacy, and influencing factors. We also review the literature on the topic of lactational bone loss: its mechanism, severity, and persistence throughout life.

Oxytocin and Bone: Review and Perspectives.

Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.

Eating behaviours related to psychological stress are associated with functional hypothalamic amenorrhoea in exercising women.

Functional hypothalamic amenorrhoea (FHA) can occur due to the independent or combined effects of psychogenic and energetic stressors. In exercising women, research has primarily focused on energy deficiency as the cause of FHA while psychological stressors have been ignored. To assess both psychological and metabolic factors associated with FHA in exercising women, we performed across-sectional comparison of 61 exercising women (≥2 hours/week, age 18-35 years, BMI 16-25kg/m2), who were eumenorrheic or amenorrhoeic confirmed by daily urine samples assayed for reproductive hormone metabolites. Psychological factors and eating behaviours were assessed by self-report questionnaires. Exercising women with FHA had lower resting metabolic rate (p=0.023), T3 (p<0.001), T4 (p=0.013), leptin (p=0.002), higher peptide YY (p<0.001), greater drive for thinness (p=0.017), greater dietary cognitive restraint (p<0.001), and displayed dysfunctional attitudes, i.e., need for social approval (p=0.047) compared to eumenorrheic women. Amenorrhoeic women displayed asignificant positive correlation between the need for social approval and drive for thinness with indicators of stress, depression, and mood, which was not apparent in eumenorrheic women. In exercising women with FHA, eating behaviours are positively related to indicators of psychological stress and depression.

Can improvement in hormonal and energy balance reverse cardiovascular risk factors in athletes with amenorrhea?

Female athletes display a high prevalence of hypothalamic amenorrhea as a result of energy imbalance. In these athletes with amenorrhea, decreased luteinizing hormone/follicule-stimulating hormone secretion leads to deficiency in endogenous estrogen. The severe estrogen deficiency in these athletes may increase cardiovascular risk similar to that in postmenopausal women. This review discusses the potential cardiovascular risk factors in athletes with amenorrhea as a result of hypoestrogenism, which include endothelial dysfunction and unfavorable lipid profiles. We also consider the potential to reverse the cardiovascular risk by restoring energy or hormonal imbalance along the reproductive axis in athletes with amenorrhea.

Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer.

PURPOSE: Ovarian function is important for optimizing endocrine treatment in patients with hormone receptor-positive (HR+) early breast cancer (eBC). The aim of the study was to determine whether patients' pretreatment levels of anti-Mullerian hormone (AMH) were associated with menses status after chemotherapy and to build a predictive nomogram model for amenorrhea in women with HR+ eBC. METHODS: Between August 2013 and December 2014, 120 premenopausal patients with HR+ eBC were included retrospectively. The associations among age, prechemotherapy levels of AMH, follicle-stimulating hormone (FSH),and estradiol (E2) and the 2-year postchemotherapy menses status were analyzed. We determined the cutoff values of hormone levels by using the biostatistical tool (Cutoff Finder). A novel nomogram was established to predict the 2-year amenorrhea status based on the logistic analysis. Concordance index (C-index) was used to validate the capacity. RESULTS: One hundred nine women (90.8%) experienced amenorrhea after chemotherapy. AMH < 0.965 ng/ml predicted amenorrhea at 2 years (AUC 0.84, sensitivity 74% and specificity 81.8%), independent of age. The predictive nomogram based on age and pretreatment AMH and FSH levels was developed to predict the probability of 2-year postchemotherapy amenorrhea with a C-index of 0.88 (95% CI 0.84-0.91). CONCLUSIONS: In premenopausal patients with HR+ eBC, prechemotherapy AMH concentration was associated with the patient's 2-year amenorrhea status, independent of age. The nomogram model based on age and pretreatment AMH and FSH levels accurately predicted the 2-year amenorrhea status.

Bone metabolism in patients with anorexia nervosa and amenorrhoea.

PURPOSE: Aim of this study is focusing on bone metabolism in AN patients with amenorrhoea and related estrogen deficiency effects. METHODS: AN patients were compared both with healthy females and with postmenopausal women (reference model for estrogen deficiency). The study sample included 81 females with AN. Laboratory tests [25-OH vitamin D, bone turnover markers, intact parathyroid hormone, sclerostin (SOST) and dickkopf-related protein (DKK1)] and dual energy X-ray absorptiometry (DXA) were taken into account. RESULTS: AN patients had higher levels of C-terminal telopeptide of type I collagen (CTX) than both control groups. AN adolescents had CTX higher than AN young adults. In postmenopausal women, intact N-propeptide of type I collagen was higher if compared with each other group. In AN groups, Dickkopf-related protein 1 was significantly lower than the two control groups. No differences were found in sclerostin except in adolescents. In AN adolescents, DXA values at femoral sites were higher than in AN young adults and a positive correlation was found with body weight (p < 0.01) and with fat mass evaluated using DXA (p < 0.01). CONCLUSIONS: AN women with amenorrhoea have an increased bone resorption like postmenopausal women but bone formation is depressed. The consequent remodeling uncoupling is considerably more severe than that occurring after menopause.

The role of total body fat mass and trunk fat mass, combined with other endocrine factors, in menstrual recovery and psychopathology of adolescents with Anorexia Nervosa.

OBJECTIVE: To determine the threshold of total body and trunk fat mass required for menstrual recovery and to assess the impact of body composition in psychopathology of adolescents with Anorexia Nervosa (AN). METHODS: Prospective study of 60 adolescents presented with secondary amenorrhea and diagnosed with AN. Anthropometrics, body composition by dual-energy X-ray absorptiometry, hormonal studies and responses to mental health screens (EAT-26), were obtained at the beginning and at complete weight restoration, in all adolescents, independently of menstrual recovery (Group A) or not (Group B). RESULTS: At weight restoration, Group A total body fat mass, trunk fat mass, and trunk/extremities fat ratio were significantly higher (p < .001) than Group B. Menstruation was expected in 20% of total body fat mass and 20% of trunk fat mass (% of total trunk tissue). At time of menstrual recovery, total body fat mass (%) and trunk fat mass (%) were significantly negatively correlated with EAT-26 (r = -0.363, p = .032) and (r = -0.416, p = .013), respectively, while an increase of 0.40% of trunk fat mass (%) lowers EAT-26 by one unit. DISCUSSION: Trunk fat mass distribution can positively influence psychopathology of adolescents with AN.

Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments.

Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 ± 31 vs. 1,327 ± 18 kcal/day, P < 0.001) but not in OV (1,284 ± 24 vs. 1,252 ± 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 ± 2%) vs. OV (103 ± 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (ρ = 0.38, P < 0.001) and leptin (ρ = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation.

Hypogonadotropic hypogonadism in a trisomy X carrier: phenotype description and genotype correlation.

We report on a 31-year old female who presented at genetic counseling for a small uterus, secondary amenorrhea and sterility. Gonadotropic hormone levels were low, suggesting a Hypogonadotropic Hypogonadism (HH) condition. Cytogenetic analysis demonstrated the presence of Trisomy X associated to an interstitial deletion of chromosome 4q13.2, resulting in the complete loss of a copy of the GNRHR gene. As GNRHR is known to be responsible for an autosomal recessive form of HH, we checked the status of the undeleted allele and we found the Q106R substitution. In conclusion, the results of our cytogenetic and molecular analyses have allowed us to clarify the etiology of the patient's condition.

Reductions in urinary collection frequency for assessment of reproductive hormones provide physiologically representative exposure and mean concentrations when compared with daily collection.

OBJECTIVE: To determine if reducing the frequency of urinary sample collection from daily to 5, 3, or 2 days per week during a menstrual cycle or 28-day amenorrheic monitoring period provide accurate representations of the reproductive hormone metabolites estrone-1-glucuronide (E1G) and pregnanediol glucuronide (PdG) exposure and mean concentrations. METHODS: Exercising women presenting with eumenorrhea or exercise-associated menstrual disturbances collected daily urine samples for the assessment of E1G and PdG concentrations. After enzyme immunoassay analysis of the daily samples, E1G and PdG data were systematically removed from each menstrual cycle or amenorrheic monitoring period to mimic three reduced collection frequencies, representing 5, 3, and 2 days per week. Exposure and mean concentration were calculated for both hormones and all four urinary collection frequencies. RESULTS: E1G and PdG exposure and mean cycle concentrations derived from reduced collection frequencies were not different from daily collection (P > 0.05), independent of whether menstrual cycles and monitoring periods were analyzed together or separately. Bland-Altman analysis indicated acceptable agreement between each reduced collection frequency and daily collection. CONCLUSIONS: Compared with daily urinary collection, a reduced collection frequency of 5, 3, or 2 days each week provides accurate E1G and PdG profiles of collection periods of various lengths and types of menstrual function. Reduction of urinary sample collection frequency may enable researchers to reduce participant burden and costs, increase compliance, and study a wider range of study populations.

[Central female hypogonadism as a model of premature aging].

Central (hypogonadotropic) hypogonadism in women could also be a cause of persistent amenorrhea and hypoestrogenemia. The aim of this study was to evaluate symptoms of premature aging in women of young age with central hypogonadism. 88 young women (25 [21; 30] y.o.) with central hypogonadism (with isolated hypogonadotropic hypogonadism n=42, and associated with the other types of pituitary insufficiencies n=46), 53 healthy young women (24 [23; 28] y.o.) and 50 healthy postmenopausal women (56 [53; 58] y.o.) were examined. In young women with central hypogonadism frequency of psychoemotional, neurovegetative and urogenital disorders, peripheral sex steroid concentrations, lipid and mineral homeostasis parameters differed significantly from the healthy young women of similar age and were comparable with postmenopausal women of middle/older age. Thus, according to clinical, hormonal and biochemical abnormalities biological age of female patients with central hypogonadism advanced significantly chronological young age and corresponded to middle/older age. The central female hypogonadism is a model of premature aging.

Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea.

A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5 days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly higher in HSR than SS animals (p<0.04). There was no change in either group after 5 days of moderate stress. The ratio of serotonin/TH correlates with ovarian estrogen production with a sensitivity×stress interaction. Therefore, it appears that the serotonin system determines stress sensitivity and the NE system responds to stress. We hypothesize that elevated NE with low serotonin functionality ultimately leads to stress-induced infertility. In contrast, high serotonin functionality maintains ovulation in the presence of stress even with elevated NE.

Cortisol secretory parameters in young exercisers in relation to LH secretion and bone parameters.

OBJECTIVE: Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers (AE) from eumenorrhoeic exercisers (EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and nonexercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. DESIGN: Cross-sectional. SUBJECTS: We studied 21 AE, 18 EE and 20 nonexercisers aged 14-21 years (BMI 10th-90th%iles). MEASUREMENTS: Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation (P1NP) and bone resorption (CTX) marker were measured. RESULTS: BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve (AUC) were highest in AE (P = 0.04, 0.007, 0.04 and 0.003) and were associated inversely with fat mass (r = -0.29, -0.28 and -0.35, P = 0.03, 0.04 and 0.007). We observed inverse associations between cortisol and LH AUC (r = -0.36, P = 0.008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1NP in nonexercisers. CONCLUSIONS: Higher cortisol secretion in AE compared with EE and nonexercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol.

Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

BACKGROUND: Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. AIM: To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. MATERIALS AND METHODS: Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 µg GnRH challenge was tested every three months. RESULTS: Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. CONCLUSIONS: Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

Clinical, hormonal and metabolic characteristics of polycystic ovary syndrome among obese and nonobese women in the Croatian population.

Obesity has a deteriorating impact on women with PCOS, although prevalence and the impact of specific traits of PCOS remain inconstant in different populations. Therefore, the aim of this study was to explore the differences in clinical, hormonal and metabolic features between obese and nonobese Croatian women diagnosed as having PCOS according to Rotterdam consensus criteria. The study included 74 obese and 208 nonobese women with PCOS. Clinical, biochemical and metabolic variables were compared among those PCOS subgroups. Obese subjects with PCOS had a higher risk of developing oligo-amenorrhea (OR 3.7; 95% CI, 1.1-12.5) and lower risk for developing hirsutism and acne (OR 0.2; 95% CI, 0.1-0.3 and OR 0.8; 95% CI 0.5-1.4, respectively). Obese PCOS subjects also had a higher risk of developing hyperandrogenemia (OR 2.5; CI 95% 0.9-6.7), insulin resistance (OR 4.5; CI 95%, 2.6-7.9), hypercholesterolemia (OR 5.0, CI 95% 2.5-10.2), hypertriglyceridemia (OR 5.2; 95% CI, 2.9-9.2) as well as elevated serum CRP levels (OR 4.1; 95% CI 1.4-12.2) compared to nonobese PCOS women. In conclusion, nonobese Croatian women with PCOS are more inclined to cosmetic problems associated with PCOS then metabolic ones. This is the first study to report the impact of obesity on acne and irregular menses as a study outcome. Obesity deteriorates menstrual regularity, insulin sensitivity and lipid profile in Croatian women with PCOS; therefore one of the fundamental treatment strategies of PCOS should be obesity prevention.

Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls.

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.

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

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

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

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

Anti-Mullerian hormone as a predictor of follicular reserve in ovarian insufficiency: special emphasis on FSH-resistant ovaries.

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by ovarian granulosa cells and its serum levels reflect ovarian follicle reserve. The main objective of this study was to test the use of AMH assay in identifying women with primary amenorrhea (PA) and existing follicles and to study follicle phase dependent AMH secretion. METHODS: Serum levels of AMH were measured in subjects with FSH-resistant ovaries (FSHRO, n= 12), primary ovarian insufficiency (POI) with PA (n= 11) or secondary amenorrhea (SA n= 20) of unknown etiology, and controls (n= 23), and in Turner syndrome (TS) [45,X (n= 18), mosaicism (n= 7), structural X chromosome abnormalities (SCA, n= 10)], and healthy controls (n= 34). RESULTS: Serum levels of AMH in women with FSHRO were comparable with those in control women (2.76 ± 2.37 versus 3.77 ± 2.36 ng/ml) and significantly higher than in women with PA (0.05 ± 0.04 ng/ml; P < 0.001) or SA of unknown origin (0.12 ± 0.20 ng/ml; P < 0.001). TS girls/women with 45,X or SCA had low serum AMH levels (0.13 ± 0.09 and 0.27 ± 0.19 ng/ml) compared with their controls (3.34 ± 2.23 ng/ml) or subjects with mosaicism (2.33 ± 2.81 ng/ml). AMH expression was detected in granulosa cells of women with FSHRO but not in any of the 45,X fetal ovarian specimens. CONCLUSIONS: A serum AMH assay could be used to identify patients with decreasing ovarian reserves and POI. Moreover, our results support the notion that AMH is secreted mainly by small non-selected follicles, since follicular granulosa cells were AMH-positive and serum AMH levels were normal/low normal in women with FSHRO, who lack follicle development beyond the small antral stage.

Adiponectin and bone metabolism markers in female rowers: eumenorrheic and oral contraceptive users.

This study investigated whether adiponectin, bone formation (osteocalcin) and bone resorption [type I carboxyterminal telopeptide (ICTP)] values are influenced by menstrual cycle phase and oral contraceptive use in female rowers. Twenty-four rowers divided into normally cycling athletes (NOC; no.=15) and athletes taking oral contraceptive pills (OC; no.=9) participated in this study. Fasting blood samples, body composition and aerobic capacity measurements were taken during the follicular (FP) and the luteal (LP) phases of the menstrual cycle. Adiponectin, insulin, glucose, insulin resistance, body composition and aerobic capacity did not fluctuate significantly during menstrual cycle in both groups. Osteocalcin and ICTP were lower (p<0.05) in OC compared with NOC, but did not change significantly across menstrual cycle phases in both groups. Estradiol and progesterone were not related to adiponectin, osteocalcin or ICTP (r<0.147; p>0.05). Adiponectin was correlated (p<0.05) with osteocalcin (r=0.452) and fat free mass (r=0.428), and osteocalcin was related (p<0.05) to insulin (r=-0.413), glucose (r=-0.486) and insulin resistance (r=-0.528). In conclusion, adiponectin was not affected by menstrual cycle phase and OC use in female rowers, while bone metabolism markers were lower in OC compared to NOC groups. Adiponectin and osteocalcin were interrelated and may characterise energy homeostasis in female athletes.