Telomere length is not altered in girls with idiopathic central precocious puberty treated with a GnRH analog - leuprolide acetate.

BACKGROUND: Idiopathic central precocious puberty (iCPP) presents a disproportionate advancement of bone age and maturation, as well as metabolic and endocrinological changes that may be related to effects on telomere biology. OBJECTIVE: To investigate the telomere length in iCPP girls treated with GnRHa. STUDY DESIGN: Observational case-control study with 85 girls, including 45 iCPP treated with GnRHa and 40 controls. It was analyzed age, height, weight and body mass index (BMI), insulin, triglycerides, testosterone, insulin resistance by HOMA, and telomere length by real-time PCR. Statistical analyses were determined by Wilcoxon test and Spearman correlation was carried out. RESULTS: Weight, BMI, insulin level and HOMA index were higher in the iCPP than in the control group (p < .01); without difference between mean ages. The telomere length did not differ between iCPP and control group. However, a negative correlation was observed between the telomere length and age in iCPP (p = .0009) and control group (p = .014), and weight in the iCPP (p = .017). CONCLUSIONS: We did not observe any difference in the telomere length in the iCPP and control group. Even though, some characteristics of the disease, such as increased weight and body fat, negatively influence the telomere biology.

Dataset on lipid profile of bovine oocytes exposed to Lα-phosphatidylcholine during in vitro maturation investigated by MALDI mass spectrometry and gas chromatography-flame ionization detection.

Data presented in this article are related with the research article entitled "Effect of soybean phosphatidylcholine on lipid profile of bovine oocytes matured in vitro" [1]. This article describes the differences in the relative abundance of the lipid ions detected by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in control and Lα-phosphatidylcholine-treated oocytes. In addition, the fatty acids (FA) content in pure Lα-phosphatidylcholine supplement and oocytes was analyzed by gas chromatography-flame ionization detection (GC-FID). The dataset provides information and inputs for further studies aiming to optimize in vitro maturation conditions and cryotolerance of mammalian oocytes.

Effect of soybean phosphatidylcholine on lipid profile of bovine oocytes matured in vitro.

The phospholipid (PL) composition of embryo and oocyte membranes affects thermal phase behavior and several physicochemical properties such as fluidity and permeability. The characterization of PL profiles and the development of suitable in vitro maturation (IVM) protocols, that are able to modify membrane's composition, may result in significant improvements in oocyte developmental potential and cryotolerance. Using soybean phosphatidylcholine (PC) as a model supplement, we evaluated the effect of PL supplementation during IVM on bovine cumulus-oocyte-complex (COC). Substantial changes in the lipid profiles of oocyte membrane were observed and associated with pre-implantation data. The propensity of the PC supplement to become soluble in the maturation medium and/or diffuse into mineral oil was also assessed. Oocytes were matured in TCM without supplementation, i.e. control, (n=922) or supplemented with 50 or 100µM PC (n=994). The maturation media and mineral oil pre- and post- IVM, along with control and PC-treated oocytes were then analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and the lipid profiles were compared via principal component analysis (PCA). Soybean PCs are bioavailable and stable in IVM medium; further, PCs did not diffuse to the mineral oil, which also remained unaltered by the metabolism of treated oocytes. PC supplementation at 100µM resulted in substantially greater relative abundances of polyunsatured PL, namely PC (32:1), PC (34:2), PC (36:6), PC (36:4), and PC (38:6), in oocyte membrane. These differences indicated that short-term exposure to the PC supplement could indeed modify the lipid composition of IVM-oocytes in a dose-dependent manner. Membrane incorporation of polyunsaturated molecular species of PC was favored, and does so without compromising the viability of the subsequent embryo in regards to cleavage, blastocyst development and hatching rate. The reported approach will allow for the development of novel strategies to modulate oocyte membrane dynamics and structure.

Gonadotropin and Estradiol Levels after Leuprolide Stimulation Tests in Brazilian Girls with Precocious Puberty.

STUDY OBJECTIVE: To determine the best cutoff value on the leuprolide stimulation test for the diagnosis of central precocious puberty (CPP) in a Brazilian population. DESIGN, SETTING, AND PARTICIPANTS: This observational study included 60 girls with CPP, as shown on the basis of serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and 3 hours after subcutaneous administration of 500 µg leuprolide acetate and by measuring serum estradiol concentrations 24 hours later. Six months later, each subject was clinically evaluated to determine whether she had experienced progressive or nonprogressive puberty. MAIN OUTCOME MEASURES: Analyzing the best cutoff for LH after subcutaneous administration of 500 µg leuprolide acetate. RESULTS: The best cutoff was a 3-hour LH level of greater than 4.0 mIU/mL, providing the highest sensitivity (73%) and specificity (83.1%), whereas a 3-hour LH level greater than 8.4 mIU/mL had a specificity of 100%. A 24-hour E2 concentration greater than 52.9 pg/mL had a sensitivity of 68% and a specificity of 74%. There was no association between pubertal development and disease progression. Signs such as thelarche and pubarche did not determine the evolution of the disease (P = .17). Clinical condition was associated with bone age/chronological age (P = .01), basal LH (P < .01), 3-hour LH (P = .02), baseline LH/FSH indices (P < .01) and after 3 hours (P < .01), and E2 at 24 hours (P = .02). CONCLUSION: The optimal parameter indicating hypothalamic-pituitary-gonadal axis activation in our sample was a 3-hour LH level greater than 4.0 mIU/mL. A diagnosis of CPP, however, should be based on a set of criteria and not on an isolated measurement, because typical laboratory findings associated with CPP may not be present in all patients.

Use of a Gonadotropin-releasing Hormone Analog to Treat Idiopathic Central Precocious Puberty Is Not Associated with Changes in Bone Structure in Postmenarchal Adolescents.

STUDY OBJECTIVES: To evaluate bone quantity and quality in postmenarchal adolescents treated for idiopathic central precocious puberty (CPP) in childhood with a gonadotropin-releasing hormone analog (GnRHa) and to determine the serum concentrations of bone remodeling markers. DESIGN AND PARTICIPANTS: This cross-sectional study included 53 postmenarchal adolescent girls who were divided into 2 groups: 27 adolescents who were treated with GnRHa in childhood for idiopathic CPP (the CPP group) and 26 women who presented with physiological development of secondary sex traits (the control group). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Weight, height, body mass index, age at menarche, time since menarche, body composition, bone mineral density (BMD), bone quality, and serum insulin, glucose, osteocalcin, and carboxyl-terminal telopeptide of type I collagen concentrations were compared in the 2 groups. BMD data were analyzed by using both dual-energy x-ray absorptiometry (DXA) and osteosonography, and body composition was measure with the use of DXA and electrical bioimpedance. RESULTS: BMD and bone quality did not differ significantly between the CPP and control groups when analyzed by using DXA or osteosonography. Serum osteocalcin concentration was significantly lower (P = .02) in the CPP than in the control group. Insulin was higher in the CPP group, and hyperinsulinemia was an independent predictor of bone quantity and quality assessed by using osteosonography. Body mass index and percent fat were determined by using DXA, and the duration of use of GnRHa treatment and the time since GnRHa discontinuation were not independent predictors of bone quantity and quality. CONCLUSION: Postmenarchal adolescents treated with GnRHa for CPP in childhood did not show a reduction in bone quantity or quality.

Effect of infertility on the sexual function of couples: state of the art.

OBJECTIVE: Assess the state of the art on the relationship between infertility and the sexual function of couples. DATA SOURCES: The PubMed, Lilacs, and Google Scholar databases were searched for articles that assessed the sexual function of infertile couples (IC). Recent patents on this subject were assessed. STUDY SELECTION: Quantitative studies published in the English language (case-control, cross-sectional, cohort, multicenter, observational studies, randomized controlled trials, meta-analyses, systematic reviews) that used structured and semi-structured questionnaires for quantitative assessment of the sexual function of infertile couples were identified using the search terms: "infertile couple" and "sexuality", "sexual dysfunction", "sexual function", "sexual disorder", "hypoactive sexual desire". DATA EXTRACTION: One researcher identified 12 studies, and extracted data on 1871 IC. Five studies used different instruments to assess different aspects of sexual function and 7 studies assessed sexual function based on sub-domains of instruments used to evaluate marital relationships. DATA SYNTHESIS: Incongruent results due to different objectives and methodologies, the lack of specific questionnaires to assess sexual function, and uncontrolled social and relationship variables that could have interfered with sexual function were evident in most studies. CONCLUSION: The lack of standardized methodology or validated tools in most studies prevents to establish the impact of infertility on the sexual function of IC.

Hormone therapy for sexual function in perimenopausal and postmenopausal women.

BACKGROUND: The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. OBJECTIVES: To assess the effect of hormone therapy (HT) on sexual function in perimenopausal and postmenopausal women. SEARCH METHODS: We searched for articles in the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform, ISI Web of Knowledge and OpenGrey. The last search was performed in December 2012. SELECTION CRITERIA: We included randomised controlled trials comparing HT to either placebo or no intervention (control). We considered as HT estrogens alone; estrogens in combination with progestogens; synthetic steroids (for example tibolone); or selective estrogen receptor modulators (SERMs) (for example raloxifene, bazedoxifene). Studies of other drugs possibly used in the relief of menopausal symptoms were excluded. We included studies that evaluated sexual function using any validated assessment tool. The primary outcome was a composite score for sexual function and the scores for individual domains (arousal and sexual interest, orgasm, and pain) were secondary outcomes. Studies were selected by two authors independently. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors and checked by a third. Risk of bias assessment was performed independently by two authors. We contacted study investigators as required. Data were analysed using standardized mean difference (SMD) and relative risk (RR). We stratified the analysis by participant characteristics with regard to menopausal symptoms. The overall quality of the evidence for the primary outcome was evaluated using the GRADE criteria. MAIN RESULTS: The search retrieved 2351 records from which 27 studies (16,393 women) were included. The 'symptomatic or early post-menopausal' subgroup included nine studies: perimenopausal women (one study), up to 36 months postmenopause (one study), up to five years postmenopause (one study), experiencing vasomotor or other menopausal symptoms (five studies), or experiencing hot flushes and sexual dysfunction (one study). The 'unselected postmenopausal women' subgroup included 18 studies, which included women regardless of menopausal symptoms and permitted the inclusion of women with more than five years since the final menstrual period. No studies were restricted to women with sexual dysfunction. Only five studies evaluated sexual function as a primary outcome. Eighteen studies were deemed at high risk of bias, and the other nine studies were at unclear risk of bias. Twenty studies received commercial funding.Findings for sexual function (measured by composite score):For estrogens alone versus control, in symptomatic or early postmenopausal women the SMD and 95% CI were compatible with a small to moderate benefit in sexual function for the HT group (SMD 0.38, 95% CI 0.23 to 0.54, P < 0.00001, 3 studies, 699 women, I² = 55%, high-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a small benefit (SMD 0.16, 95% CI -0.02 to 0.34, P = 0.08, 2 studies, 478 women, I² = 44%, low-quality evidence). The subgroups were not pooled because of considerable heterogeneity.For estrogens combined with progestogens versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with a small to moderate benefit for sexual function in the HT group (SMD 0.42, 95% CI 0.19 to 0.64, P = 0.0003, 1 study, 335 women, moderate-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a small benefit (SMD 0.09, 95% CI -0.02 to 0.20, P = 0.10, 3 studies, 1314 women, I² = 0%, moderate-quality evidence). The subgroups were not pooled because of considerable heterogeneity.For tibolone versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with no effect to a small benefit for sexual function in the HT group (SMD 0.13, 95% CI 0.00 to 0.26, P = 0.05, 1 study, 883 women, low-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with no effect to a moderate benefit (SMD 0.38, 95% CI 0.04 to 0.71, P = 0.03, 2 studies, 142 women, I² = 0%, low-quality evidence). In the combined analysis, the 95% CI was compatible with no effect to a small benefit (SMD 0.17, 95% CI 0.04 to 0.29, P = 0.008, 3 studies, 1025 women, I² = 20%).For SERMs versus control, in symptomatic or early postmenopausal women the 95% CI was compatible with no effect to a moderate benefit for sexual function in the HT group (SMD 0.23, 95% CI -0.04 to 0.50, P = 0.09, 1 study, 215 women, low-quality evidence). In unselected postmenopausal women, the 95% CI was compatible with small harm to a small benefit (SMD 0.04, 95% CI -0.20 to 0.29, P = 0.72, 1 study, 283 women, low-quality evidence). In the combined analysis, the 95% CI was compatible with no effect to a small benefit (SMD 0.13, 95% CI -0.05 to 0.31, P = 0.16, 2 studies, 498 women, I² = 2%).A comparison of SERMs combined with estrogens versus control was only evaluated in symptomatic or early postmenopausal women. The 95% CI was compatible with no effect to a small benefit for sexual function in the HT group (SMD 0.21, 95% CI 0.00 to 0.43, P = 0.05, 1 study, 542 women, moderate-quality evidence). AUTHORS' CONCLUSIONS: HT treatment with estrogens alone or in combination with progestogens was associated with a small to moderate improvement in sexual function, particularly in pain, when used in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), but not in unselected postmenopausal women. Evidence regarding other HTs (synthetic steroids and SERMs) is of low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest an important effect of tibolone or of SERMs alone or combined with estrogens on sexual function. More studies evaluating the effect of synthetic steroids, SERMS and the association of SERM + estrogens would improve the quality of the evidence for the effect of these treatments on sexual function in peri and postmenopausal women. Future studies should also evaluate the effect of HT solely among women with sexual complaints.

Brief cognitive behavioral intervention in groups in a Brazilian assisted reproduction program.

The study's objective was to assess the effect of a cognitive behavioral group intervention on the pregnancy rates of patients submitted to in vitro fertilization (IVF) techniques or to intracytoplasmic sperm injection (ICSI). The study was conducted on 188 patients, 93 who participated in a group of psychological intervention before the IVF and ICSI procedures and 95 patients submitted to IVF and ICSI during the same period of time, who did not participate in the intervention (control group). Clinical pregnancy was the outcome measure. Demographic and clinical variables were compared between groups in order to assess the group's homogeneity. Participants in the psychological intervention obtained a pregnancy rate of 39.8%, significantly higher than the 23.2% rate of nonparticipants (χ(2) = 6.03, p = .01, odds ratio of 22 (CI: 1.16-4.13). The data suggest that group psychological intervention before IVF and ICSI in order to control stress seems to increase the rate of success of these procedures.

Leuprolide acetate reduces both in vivo and in vitro ovarian steroidogenesis in infertile women undergoing assisted reproduction.

Despite the probable inhibitory effects of GnRH analogues on ovarian steroidogenesis in vitro, their association with assisted reproduction protocols shows favorable results. This suggests that there are important differences in the behaviors of these drugs when administered in vivo versus in vitro. To clarify these differences, this study was designed to analyze the effect of leuprolide acetate (LA) on ovarian steroidogenesis in women undergoing In Vitro Fertilization (IVF). A prospective, randomized open label study was conducted on 14 women (26-35 years): seven receiving only gonadotrophins (Group 1) and seven receiving gonadotrophin plus LA at 1mg/day (Group 2). The LA in vivo effect was determined with serum and follicular fluid (FF) samples and via luteinized granulosa cell cultivation (GCC), where cells were obtained during oocyte retrieval after ovarian hyperstimulation. In vitro analysis was performed via addition of LA to GCC only for Group 1 (without LA) at progressively higher concentrations (0, 10(-12), 10(-9) and 10(-6)M). In vivo, the main observation was a reduction in androgen production in Group 2, represented by lower androstenedione production in FF (G1=6479+/-3458; G2=3021+/-1119 ng/ml; p=0.04) and a lower testosterone peak in GC at 96h (G1=0.64+/-0.12 ng/ml; G2=0.50+/-0.19 ng/ml; P=0.02), but a higher fertilization rate (G1=67%; G2=83%; p=0.009). In vitro, testosterone, estradiol and progesterone were also reduced by LA, even though this reduction occurred for progesterone only at the highest LA dosage (10(-6)M; 606.0+/-114.3 ng/ml versus 1524.0+/-246.5 ng/ml; p=0.02). Results show that LA reduces ovarian steroidogenesis in vivo by essentially inhibiting androgen synthesis; whereas, in vitro, ovarian steroidogenesis is reduced overall.

Gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period.

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.

Efeitos dos esteróides sexuais sobre o humor e a cognição / Effect of sexual steroids on mood and cognition

Estudos experimentais e observacionais sugerem que os esteróides sexuais apresentam uma série de efeitos sobre o cérebro e que, potencialmente, afetam a cognição e o humor. O uso dos estrogênios na peri e pós-menopausa está associado à melhora da concentração, humor, memória e sono. Está também associado a retardo no declínio da função cognitiva, característico do envelhecimento, e os dados sugerem também um papel dos estrogênios no retardo do início da doença de Alzheimer. Vários estudos observacionais indicam, ainda, que os estrogênios atuam melhorando o humor e têm ação antidepressiva. Já a progesterona e seus derivados têm mostrado efeitos opostos aos dos estrogênios. Por outro lado, dados de estudos randomizados e controlados mostraram que a associação de estrogênios mais progestagênios utilizados em mulheres na pós-menopausa não só falhou em melhorar a memória, cognição e qualidade de vida, mas também aumentou o risco de demência, portanto contradisse os estudos observacionais e experimentais. Novas pesquisas serão necessárias para esclarecer essas controvérsias. Os dados disponíveis até o momento indicam que não se deve prescrever primariamente a estrogenioterapia para prevenir depressão, doença de Alzheimer ou piora da função cognitiva.

The results of several experimental and observational studies suggest that sexual steroids present effects on central nervous system and potentially may affect mood and cognition. The use of estrogens in pre and postmenopausal period is associated to improvement of concentration, mood, memory and sleep pattern. Estrogens are also is associated to a delay in cognitive function decline characteristic of aging process or to the onset of Alzheimer disease. The observational studies indicate that estrogens may improve the mood and act as antidpressive but progesterone and its derivatives have opposite effect. However, randomized controlled trials suggest that the estrogen or estrogen plus progestins not only failed to improove mood, cognition na quality of life but also increase the risk of dementia. Therefore, there is a contradiction between observational and controlled randomized studies. Further investigations must to be done in order to clarify this controversy. However, up to now the data indicate that estrogen therapy is not to be primarily indicated to prevent depression, Alzheimer disease or cognition impairment.