Determining an optimal cut-off value for follicle-stimulating hormone to predict microsurgical testicular sperm extraction outcome in patients with non-obstructive azoospermia

ABSTRACT Objective To determine the optimal cut-off value for follicle stimulating hormone (FSH) to predict the outcome of microsurgical testicular sperm extraction (micro-TESE) in patients with nonobstructive azoospermia (NOA). Subjects and methods We included a total number of 180 patients with NOA. The serum level of FSH was determined and all the subjects underwent micro-TESE. We determined the optimal cut-off value for FSH and assessed whether the test could be effectively used as a successful predictor of sperm retrieval by calculating the Receiver Operating Characteristic (ROC) area under the curve. Results Overall we included a total number of 171 patients with mean age of 34.3 ± 8.6 years. The micro-TESE was considered to be successful in 79 (43.8%) while it failed in 92 (56.2%) patients. We found that the mean level of serum FSH was significantly higher in group those with failed micro-TEST compared to successful group (p < 0.001). The cut-off value for FSH was calculated to be 14.6 mIU/mL to predictive the outcome of micro-TESE with a sensitivity of 83.5% [73.5%-90.9%] and a specificity of 80.3% [69.5%-88.5%]. At this value, the other parameters were calculated to be PPV, 81.5%; NPV, 82.4; LR+, 4.23; and LR-, 0.21. Conclusions The results of the current study indicate that FSH plasma levels above 14.6 mIU/mL can be considered to be the failure predictor of the micro-TESE in NOA patients.

Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin

ABSTRACT Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10

Increased sympathetic cardiac autonomic modulation after two consecutive tilt tests in women with polycystic ovary syndrome / Aumento da modulação autonômica cardíaca simpática após dois testes de inclinação consecutivos em mulheres com síndrome dos ovários policísticos

Abstract Objective The present study aimed to analyze cardiac autonomic modulation via spectral and symbolic analysis of heart rate variability (HRV) in women with polycystic ovary syndrome (PCOS) who were subjected to two consecutive tilt tests. Methods A total of 64 women were selected and divided into 2 groups: control (without PCOS), and PCOS. Concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, homocysteine, sex hormone-binding globulin, thyroid stimulating hormone, fasting insulin, testosterone, androstenedione, and 17-hydroxyprogesterone levels, triglycerides, free androgen index (FAI), and homeostasis assessment model (HOMA-IR) were assessed. Cardiac autonomic modulation was evaluated by spectral and symbolic analyses during two consecutive tilt tests (two moments) and supine moments before, between and after (three moments) the tilt tests. Results Women with PCOS had higher fasting insulin, HOMA-IR indexes, testosterone and FAI. Additionally, we observed that the PCOS group had greater sympathetic autonomic cardiac modulation in supine 2, tilt 1, and supine 3 moments compared with controls. Conclusion Women with PCOS had higher autonomic sympathetic cardiac modulation even after a second tilt test. No adaptation to this provocative test was observed. Spectral analysis was more sensitive for identifying differences between groups than the symbolic analysis.

Resumo Objetivo O presente estudo teve como objetivo analisar a modulação autonômica cardíaca por análise espectral e simbólica da variabilidade da frequência cardíaca (VFC) em mulheres com síndrome dos ovários policísticos (SOP) que foram submetidas a dois testes consecutivos de inclinação. Métodos Um total de 64 mulheres foram selecionadas e divididas em 2 grupos: controle (sem SOP) e SOP. Concentrações de hormônio folículo-estimulante, hormônio luteinizante, prolactina, estradiol, homocisteína, globulina de ligação a hormônios sexuais, hormônio estimulante da tireóide, insulina em jejum, testosterona e androstenediona e níveis de 17-hidroxiprogesterona, triglicerídeos, índice de andrógeno livre (FAI) e homeostase modelo de avaliação (HOMA-IR) foram avaliados. A modulação autonômica cardíaca foi avaliada por análises espectrais e simbólicas durante dois testes de inclinação consecutivos (dois momentos) e momentos supinos antes, entre e após (três momentos) os testes de inclinação. Resultados Mulheres com SOP apresentaram insulina em jejuM, índices HOMA-IR, testosterona e FAI mais altos. Além disso, observamos que o grupo PCOS apresentou maior modulação cardíaca autonômica simpática nos momentos supino 2, inclinado 1 e supino 3 em comparação aos controles. Conclusão Mulheres com SOP apresentaram modulação cardíaca simpática autonômica mais alta mesmo após um segundo teste de inclinação. Nenhuma adaptação a esse teste provocativo foi observada. A análise espectral foi mais sensível para identificar diferenças entre os grupos do que a análise simbólica.

Effect of Wubi Shanyao pills on sexual function in mice with kidney-yang-deficiency induced by hydrocortisone / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of Chinese medicine Wubi Shanyao pills on sexual function of kidney-yang-deficiency mice induced by hydrocortisone.@*METHODS@#Male Kunming mice were injected with hydrocortisone for 10 days to prepare the kidney-yang-deficiency model, and administrated with Wubi Shanyao pills (0.91, 1.82, 2.73 g/kg) for 9 weeks. The general behaviors of mice (autonomous activity, grasping power) were observed; sexual behaviors (capture, straddle, ejaculation frequency and incubation period) of mice were detected by mating experiment. The serum levels of cortisol, adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E@*RESULTS@#Wubi Shanyao pills increased the number of independent activities, grasping power, capture frequency of model mice and shortened the capture latency (all @*CONCLUSIONS@#Wubi Shanyao pills can improve the sexual function of mice with kidney-yang-deficiency induced by hydrocortisone, which may be related to regulating the hypothalamus-pituitary-adrenal axis (HPA axis), promoting the proliferation of testicular cells, and inhibiting cell apoptosis.

Improvement of fertility parameters with tribulus terrestris and anacyclus pyrethrum treatment in male rats

ABSTRACT Objective Anacyclus Pyrethrum (AP) and Tribulus Terrestris (TT) have been reported as male infertility treatment in several studies; however, in Iranian traditional medicine these two plants are prescribed simultaneously. In this study, we aimed to determine the effects of AP and TT extracts both separately and simultaneously on the male Wistar rat fertility parameters. Materials and Methods 32 male Wistar rats were divided into 4 groups: Control, TT, AP, and AT treated groups. Treatment continued for 25 days and rats were weighed daily. Their testes were dissected for histological studies. Sperm analysis including sperm count, viability and motility were performed. Serum was obtained to evaluate testosterone, LH and FSH levels. Histological studies were conducted to study Leydig, and Sertoli cells, spermatogonia and spermatid cell numbers, and to measure seminiferous diameter and epithelium thickness. Results Sperm count increased in all the treatment groups. Sperm viability and motility in AT and AP groups were elevated. TT and AT groups showed significantly increased testosterone level compared to control group (P=004, P=0.000, respectively) and TT, AP and AT treatment groups showed increased LH level (P=0.002, P=0.03 and P=0.000, respectively) compared to control, while only AT group showed increased FSH (p=0.006) compared to control. Histological studies showed significant increase of spermatogonia, Leydig and Sertoli cell numbers and epithelial thickness in AT group compared to other groups. All the treatment groups had higher number of Leydig, spermatogonia and spermatid cells. Conclusion TT and AP improved sexual parameters; however, their simultaneous administration had higher improving effects on studied parameters.

Supposed pituitary-production of human chorionic Gonadotropin induced by androgen deprivation therapy

ABSTRACT Introduction: The main cause of slightly elevated human chorionic gonadotropin (HCG) after successful treatment of male germ cell tumors is considered to be pituitary-derived HCG. It is well known that pituitary-derived HCG is frequently detected in postmenopausal women. We evaluated the status of serum HCG in men with elevated gonadotropins, which were induced by androgen deprivation therapy, using commercially available assays. Materials and Methods: We enrolled 44 patients with prostate cancer, who underwent luteinizing-hormone releasing hormone agonist treatment. We measured serum follicle-stimulating hormone (FSH), serum luteinizing hormone (LH), serum total HCG, serum free HCG-β subunit, and urine total HCG 3 times per patient, on the day of treatment initiation, the next day, and 3 months after. Results: On the day after treatment initiation, serum and urine HCG was detected in 61% and 73% of patients, respectively. Markedly strong correlations were observed between serum/urine HCG and FSH/LH. In particular, receiver operating characteristic curve analysis indicated excellent area under the curve (0.977, 95% confidence interval 0.951-1.003)) for serum HCG-detectable LH. At the cutoff value of 21.07 mIU/mL for serum HCG-detectable LH, the sensitivity and specificity were 96.7% and 95.3%, respectively. Serum HCG-β was not detectable at any times in any patients. Conclusions: Suggested pituitary-derived HCG can be frequently detected in patients with elevated gonadotropins, and there is a firm association between HCG detection and gonadotropin levels.

Clinical and laboratory parameters of gonadotropin-releasing hormone analog treatment effectiveness in children with precocious puberty

OBJECTIVE: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression. METHODS: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA. RESULTS: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h. CONCLUSION: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.

Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency / 亚洲男科学杂志(英文版)

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.

Heavy cigarette smoking and alcohol consumption are associated with impaired sperm parameters in primary infertile men / 亚洲男科学杂志(英文版)

We assessed the concomitant impact of cigarette smoking and alcohol consumption in men presenting for primary couple's infertility. Data from 189 infertile men were analyzed. Semen analysis, serum hormones, and sperm DNA fragmentation (SDF) were obtained. Smoking status was categorized as follows: current nonsmoker (-S), moderate smoker (+MS), and heavy smoker (+HS). Alcohol consumption was categorized as follows: abstainer (-D), moderate drinker (+MD), and heavy drinker (+HD). Descriptive statistics and logistic regression models were applied. Among all the participants, 132 (69.8%), 30 (15.9%), and 27 (14.3%) patients were -S, +MS, and +HS, respectively. In addition, 67 (35.4%), 77 (40.7%) and 45 (23.8%) men were -D, +MD and +HD, respectively. Regarding concomitant habits, 52 (27.5%) patients were nonsmokers and abstainers (-S/-D: Group 1), 91 (48.1%) had at least one recreational habit (-S/+D or +S/-D: Group 2), and 46 (24.3%) were both smokers and drinkers (+S/+D: Group 3). Sperm concentration and progressive motility were lower in +HS and +HD, compared with -S and -D (all P < 0.05), respectively. Similarly, both parameters were significantly lower in Group 3 than Groups 1 and 2 (all P < 0.05). SDF values were higher in Group 3 than Groups 1 and 2 (both P < 0.05). In multivariate analysis, follicle-stimulating hormone (FSH) levels and concomitant +S/+D status were independent predictors of impaired sperm concentration and progressive motility (all P < 0.05). Heavy smoking and heavy drinking were associated with worse seminal parameters than moderate smoking/drinking and nonsmoking/abstaining. When concomitant, +S/+D status has an even greater detrimental effect on semen parameters.

Testosterone undecanoate supplementation together with human chorionic gonadotropin does not impair spermatogenesis in males with isolated hypogonadotropic hypogonadism: a retrospective study / 亚洲男科学杂志(英文版)

Gonadotropin therapy is commonly used to induce virilization and spermatogenesis in male isolated hypogonadotropic hypogonadism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment; therefore, testosterone (T) supplementation can serve as an alternative therapy to normalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undecanoate (TU) supplementation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) months in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.

Predictive significance of serum inhibin B on testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men / 亚洲男科学杂志(英文版)

The purpose of this study was to determine the diagnostic accuracy of serum inhibin B (INHB) as a predictor of the retrieval outcome of testicular haploid gametes (spermatids and testicular spermatozoa) in nonobstructive azoospermic men. Serum hormone levels, testicular volume, and histological evaluation were performed in 403 Chinese nonobstructive azoospermic men. Testicular haploid gamete was successfully retrieved in 213 of 403 patients (52.85%). The haploid gamete group always had higher INHB levels than the non-haploid gamete group. According to the receiver operating characteristic (ROC) curve analysis, INHB was a good predictor of testicular haploid gamete retrieval outcome in all patients (sensitivity: 77.93% and specificity: 91.58%) and patients with normal follicle-stimulating hormone (FSH; sensitivity: 88.52% and specificity: 70.83%). The area under the ROC curve (AUC) of INHB was similar to that of FSH in all patients or patients with normal FSH. In patients with elevated FSH, INHB was superior to FSH in predicting the presence of haploid gamete (AUC: 0.73 vs 0.55, P < 0.05), with a sensitivity of 60.00% and a specificity of 80.28%. It concluded that serum INHB as an effective marker for spermatogenesis was a significant predictor of testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men. Especially, INHB is superior to FSH in predicting the presence of haploid gamete in the patients with elevated FSH.

Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility / 亚洲男科学杂志(英文版)

Anti-Müllerian hormone (AMH) is a functional marker of fetal Sertoli cells. The germ cell number in adults depends on the number of Sertoli cells produced during perinatal development. Recently, AMH has received increasing attention in research of disorders related to male fertility. This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders. We have determined that follicle-stimulating hormone (FSH) promotes AMH transcription in the absence of androgen signaling. Testosterone inhibits the transcriptional activation of AMH. The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue, for example, that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis. The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Müllerian duct syndrome (PMDS), combined with clinical manifestations. The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development (DSD). Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells. Serum AMH levels are varying in patients with male fertility-related disorders, including pubertal delay, severe congenital hypogonadotropic hypogonadism, nonobstructive azoospermia, Klinefelter syndrome, varicocele, McCune-Albright syndrome, and male senescence.

Advanced bone age as an indicator facilitates the diagnosis of precocious puberty / Idade óssea avançada como um indicador de facilitação do diagnóstico de puberdade precoce

Abstract Objective: Diagnosis of central precocious puberty has always been challenging in clinical practice. As an important method in the diagnosis of central precocious puberty, luteinizing hormone-releasing hormone stimulation test is complex and time-consuming. In many cases, clinical traits are inconsistent with luteinizing hormone-releasing hormone stimulation test results, therefore not reliable for diagnosis. In this study, the authors intended to find an indicator that predicts the results of the luteinizing hormone-releasing hormone stimulation test among subjects with early pubertal signs. Methods: Cases of 382 girls with early breast development before 8 years old and luteinizing hormone-releasing hormone stimulation test before 9 years old were included and underwent follow-up tests. Patients with peak luteinizing hormone level ≥5 IU/L were considered positive in the luteinizing hormone-releasing hormone stimulation test. Anthropometric data, body mass index, bone age evaluation, blood hormones levels of luteinizing hormone, estradiol, follicle-stimulating hormone, and uterine and ovarian volumes were analyzed. Results: Subjects with positive results in the initial test demonstrated early bone maturation, accelerated growth, and elevated basal blood luteinizing hormone, estradiol, and follicle-stimulating hormone levels, when compared with subjects with negative results in the initial test. Subjects with positive results in the follow-up test presented a more advanced bone age and more accelerated linear growth, when compared with subjects with negative results in the follow-up test. Conclusions: According to the statistical analysis, advanced bone age is the most effective predictor of the result of luteinizing hormone-releasing hormone stimulation test.

Resumo Objetivo: O diagnóstico da puberdade precoce central sempre foi complicado na prática clínica. Como um importante método no diagnóstico de puberdade precoce central, o teste de estimulação do hormônio liberador do hormônio luteinizante é complexo e demorado. Em muitos casos, as características clínicas são incompatíveis com os resultados do teste de estimulação do hormônio liberador do hormônio luteinizante e, assim, não são confiáveis para o diagnóstico. Neste estudo, visamos constatar um indicador que previsse os resultados do teste de estimulação do hormônio liberador do hormônio luteinizante entre indivíduos com sinais puberais precoces. Métodos: Foram incluídos casos de 382 meninas com desenvolvimento precoce das mamas antes dos 8 anos de idade e teste de estimulação do hormônio liberador do hormônio luteinizanteantes dos 9 anos e elas foram submetidas a testes de acompanhamento. Os resultados das pacientes com nível máximo de hormônio luteinizante ≥ 5 IU/L foram consideradas positivos no teste de estimulação do hormônio liberador do hormônio luteinizante. Foi feita uma análise dos dados antropométricos, do índice de massa corporal, da avaliação da idade óssea, dos níveis sanguíneos de hormônio luteinizante, volumes uterinos e ovarianos de estradiol (E2) e do hormônio folículo-estimulante. Resultados: Os indivíduos com resultado positive no teste inicial demonstraram maturação precoce do osso, crescimento acelerado e níveis sanguíneos elevados de hormônio luteinizante, estradiol e hormônio folículo-estimulante, em comparação aos indivíduos com resultados negativos no teste inicial. Os indivíduos com resultados positivos no teste de acompanhamento apresentaram um maior avanço na idade óssea e crescimento linear mais acelerado, em comparação aos indivíduos com resultados negativos no teste de acompanhamento. Conclusões: De acordo com a análise estatística, a idade óssea avançada é o indicador mais efetivo do resultado do teste de estimulação do hormônio liberador do hormônio luteinizante.

Low estrogen doses normalize testosterone and estradiol levels to the female range in transgender women

OBJECTIVE: The ideal dosage of cross-sex hormones remains unknown. The aim of this study was to evaluate the luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin levels after low-dose estrogen therapy with or without cyproterone acetate in transgender women. METHODS: The serum hormone and biochemical profiles of 51 transgender women were evaluated before gonadectomy. Hormone therapy consisted of conjugated equine estrogen alone or combined with cyproterone acetate. The daily dose of conjugated equine estrogen was 0.625 mg in 41 subjects and 1.25 mg in 10 subjects, and the daily dose of cyproterone acetate was 50 mg in 42 subjects and 100 mg in one subject. RESULTS: Estrogen-only therapy reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 731.5 to 18 ng/dL, 6.3 to 1.1 U/L and 9.6 to 1.5 U/L, respectively. Estrogen plus cyproterone acetate reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 750 to 21 ng/dL, 6.8 to 0.6 U/L and 10 to 1.0 U/L, respectively. The serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin in the patients treated with estrogen alone and estrogen plus cyproterone acetate were not significantly different. The group receiving estrogen plus cyproterone acetate had significantly higher levels of gamma-glutamyltransferase than the group receiving estrogen alone. No significant differences in the other biochemical parameters were evident between the patients receiving estrogen alone and estrogen plus cyproterone acetate. CONCLUSION: In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone and estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects.

Predictive factors for pituitary response to pulsatile GnRH therapy in patients with congenital hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Pulsatile gonadotropin-releasing hormone (GnRH) may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism (CHH) by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile GnRH therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile GnRH therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile GnRH therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone (LH) response subgroups according to their LH level (LH <2 IU l-1 or LH ≥2 IU l-1) 1 month into pulsatile GnRH therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after GnRH therapy. Among all patients, LH increased from 0.4 ± 0.5 IU l-1 to 7.5 ± 4.4 IU l-1 and follicle-stimulating hormone (FSH) increased from 1.1 ± 0.9 IU l-1 to 8.8 ± 5.3 IU l-1. A Cox regression analysis showed that basal testosterone level (β = 0.252, P = 0.029) and triptorelin-stimulated FSH60min(β = 0.518, P = 0.01) were two favorable predictors for pituitary response to GnRH therapy. Nine patients (9/82, 11.0%) with low LH response to GnRH therapy were classified into the poor LH response subgroup. After pulsatile GnRH therapy, total serum testosterone level was 39 ± 28 ng dl-1 versus 248 ± 158 ng dl-1 (P = 0.001), and testicular size was 4.0 ± 3.1 ml versus 7.9 ± 4.5 ml (P = 0.005) in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH60minand basal total serum testosterone are favorable predictors of pituitary LH response to GnRH therapy.

Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: a meta-analysis / 亚洲男科学杂志(英文版)

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

The role of moderate-to-vigorous physical activity in mediating the relationship between central adiposity and immunometabolic profile in postmenopausal women

ABSTRACT Objectives To analyze the role of moderate-to-vigorous physical activity (MVPA) in mediating the relationship between central adiposity and immune and metabolic profile in postmenopausal women. Materials and methods Cross-sectional study comprising 49 postmenopausal women (aged 59.26 ± 8.32 years) without regular physical exercise practice. Body composition was measured by dual-energy X-ray absorptiometry. Fasting blood samples were collected for assessment of nonesterified fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, insulin and estimation of insulin resistance (HOMA-IR). Physical activity level was assessed with an accelerometer (Actigraph GTX3x) and reported as a percentage of time spent in sedentary behavior and MVPA. All analyses were performed using the software SPSS 17.0, with a significance level set at 5%. Results Sedentary women had a positive relationship between trunk fat and IL-6 (rho = 0.471; p = 0.020), and trunk fat and HOMA-IR (rho = 0.418; p = 0.042). Adiponectin and fat mass (%) were only positively correlated in physically active women (rho = 0.441; p = 0.027). Physically active women with normal trunk fat values presented a 14.7% lower chance of having increased HOMA-IR levels (β [95%CI] = 0.147 [0.027; 0.811]). Conclusions The practice of sufficient levels of MVPA was a protective factor against immunometabolic disorders in postmenopausal women.

Mammographic density among indigenous women in forested areas in the state of Amapá, Brazil: a cross-sectional study / Densidade mamográfica em mulheres indígenas de áreas da floresta do estado do Amapá, Brasil: estudo transversal

ABSTRACT CONTEXT AND OBJECTIVE: There is no register of breast cancer cases among indigenous populations in Brazil. The objective here was to evaluate the association of clinical and demographic characteristics with mammographic density among indigenous women. DESIGN AND SETTING: Cross-sectional analytical study conducted in indigenous territories in the state of Amapá, Brazil. METHODS: Women were recruited from three indigenous territories and underwent bilateral mammography and blood collection for hormonal analysis. They were interviewed with the aid of an interpreter. Mammographic density was calculated using computer assistance, and was expressed as dense or non-dense. RESULTS: A total of 137 indigenous women were included in this study, with an average age of 50.4 years, and an average age at the menarche of 12.8 years. Half (50.3%) of the 137 participants had not reached the menopause at the time of this study. The women had had an average of 8.7 children, and only two had never breastfed. The average body mass index of the population as a whole was 25.1 kg/m2. The mammographic evaluation showed that 82% of women had non-dense breasts. The clinical characteristics associated with mammographic density were age (P = 0.0001), follicle-stimulating hormone (FSH) (P < 0.001) and estrogen levels (P < 0.01). CONCLUSIONS: The majority of the indigenous women had non-dense breasts. Age, menopausal status and FSH and estrogen levels were associated with mammographic density.

RESUMO CONTEXTO E OBJETIVO: Não há registro de casos de câncer de mama em populações indígenas no Brasil. O objetivo foi avaliar a associação de características clínicas e demográficas com a densidade mamográfica em mulheres indígenas. TIPO DE ESTUDO E LOCAL: Estudo transversal, analítico, realizado em territórios indígenas no estado do Amapá, Brasil. MÉTODOS: Mulheres foram recrutadas de três territórios indígenas e submetidas a mamografia bilateral e a coleta de sangue para análise hormonal. As participantes foram entrevistadas com a ajuda de um intérprete. A densidade mamográfica foi calculada com assistência de computador, e expressa como densa ou não densa. RESULTADOS: 137 mulheres foram incluídas no estudo, com média de 50,4 anos e média de idade à menarca de 12,8 anos. Metade (50,3%) das 137 participantes não havia entrado na menopausa no momento do estudo. As mulheres tinham em média 8,7 filhos, e duas nunca haviam amamentado. O índice de massa corpórea médio da população como um todo foi de 25,1 kg/m2. A análise mamográfica mostrou que 82% das mulheres tinham mamas não densas. As características clínicas associadas com a densidade mamográfica foram idade (P = 0.0001), hormônio folículo-estimulante (FSH, P < 0,001) e níveis de estrogênio (P < 0,01). CONCLUSÕES: A maioria das indígenas tinha mamas não densas. Idade, status menopausal e níveis de estrógeno e FSH foram associados com a densidade mamográfica.

Clomiphene citrate treatment for late onset hypogonadism: rise and fall

ABSTRACT Objective: Previous series have demonstrated that Clomiphene Citrate (CC) is an effective treatment to increase Total Testosterone (TT) in Late Onset Hypogonadism (LOH) patients. However, what happens to TT levels after ending CC treatment is still debatable. The objective of this study is to evaluate TT levels 3 months after the discontinuation of CC in patients with LOH who were previously successfully treated with the same drug. Materials and Methods: Twenty-seven patients with LOH that were successfully treated (achieved TT levels >11nmol/l) with CC 50mgs daily for 50 days were prospectively recruited in our Andrological outpatient clinic. CC was then stopped for 3 months and TT levels were measured at the end of this period. Results: Mean TT level before discontinuation of CC was 22.7±8.1nmol/L (mean±SD). Three months after discontinuation, mean TT level significantly decreased in all patients, 10.2±3.9nmol/l (p<0.01). Twenty-one patients (78%) decreased TT levels under 11nmol/L. Six patients (22%) had TT levels that remained within the normal recommended range (≥11nmol/l). No statistical significant differences were observed between both groups. Conclusion: In the short term LOH does not seem to be a reversible condition in most patients after CC treatment. More studies with longer follow-up are needed to evaluate the kinetics of TT in LOH.

Tear osmolarity and tear function assessment in patients with polycystic ovary syndrome / Avaliação da osmolaridade lacrimal e da função lacrimal em pacientes com síndrome dos ovários policísticos

ABSTRACT Purpose: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by chronic anovulation and hyperandrogenism. Hormonal changes can affect tear function. This study evaluates tear function and impact of hyperandrogenism on it in PCOS patients. Methods: Fifty patients with PCOS and thirty control volunteers were examined for tear break-up time, Schirmer-I and tear osmolarity. Also, serum levels of total testosterone, FSH, LH and AMH were determined in venous blood samples in the early follicular phase. PCOS patients were divided into two groups by plasma total testosterone level: Group A with normal (≤0.513 ng/ml;n=27), Group B with higher hormone level (>0.513 ng/ml;n=23). Healthy control group indicated as Group C (n=30). Results: LH, total testosterone levels were higher in the PCOS group than in the control group (p=0.012; p=0.025). Mean values of tear break-up time and Schirmer-I were different between groups and especially Group A and C were near to each other differing from B (p>0.05). Tear osmolarity results were higher in Group B, compared to A and C (p=0.049; p=0.033). No significant difference detected in tear osmolarity value means of Group A and C (p=0.107). AMH levels were higher in Group B, compared to A and C (p=0.002; p=0.001). AMH levels in Group A were higher than that of C (p=0.002). Positive correlation between levels of total testosterone and AMH was detected in all PCOS patients (n=50;Pearson's r=0.579; p<0.001). Conclusion: Tear function can be affected in PCOS patients with hyperandrogenism. Tear osmolarity is the most sensitive and objective assessment method for ocular surface changes in PCOS.

RESUMO Objetivo: A síndrome do ovário policístico (SOP) é uma doença endócrina caracterizada por anovulação crônica e hiperandrogenismo. As alterações hormonais podem afetar a função cardíaca. Este estudo avalia a função lacrimal e o impacto do hiperandrogenismo sobre ela em pacientes com SOP. Métodos: Cinquenta pacientes com SOP e trinta voluntárias de controle foram examinadas para tempo de ruptura lacrimal, Schirmer-I e osmolaridade lacrimal. Além disso, os níveis séricos de testosterona total, FSH, LH e HAM foram determinados em amostras de sangue venoso na fase folicular precoce.As pacientes com SOP foram divididas em dois grupos por nível de testosterona plasmática total: Grupo A com nível normal (≤0.513 ng/ml; n = 27), Grupo B com nível superior de hormônio (> 0,513 ng/ml; n = 23). Grupo de controle saudável indicado como Grupo C (n = 30). Resultados: Os níveis de LH e testosterona total foram maiores no grupo com SOP do que no grupo controle (p = 0,012; p = 0,025). Os valores médios de tempo de ruptura lacrimal e Schirmer-I foram diferentes entre os grupos, e especialmente os Grupos A e C estavam próximos um do outro, diferente do B (p > 0,05). Os resultados de osmolaridade lacrimal foram maiores no Grupo B, em comparação com A e C (p = 0,049; p = 0,033). Não houve diferença significativa detectada em valor médio de osmolaridade lacrimal nos Grupos A e C (p = 0,107). Os níveis de HAM foram maiores no Grupo B, em comparação com A e C (p = 0,002; p = 0,001). Os níveis de AMH no Grupo A foram superiores aos de C (p = 0,002). Uma correlação positiva entre os níveis de testosterona total e AMH foi detectada em todas as pacientes com SOP (n = 50; Pearson's r = 0,579; p < 0,001). Conclusão: a função lacrimal pode ser afetada em pacientes com SOP com hiperandrogenismo. A osmolaridade lacrimal é o método de avaliação mais sensível e objetivo para alterações da superfície ocular em SOP.