Novas perspectivas no diagnóstico do hipogonadismo pediátrico masculino: a importância do AMH como marcador de células de Sertoli

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHb mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.b mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.As células de Sertoli são a população de células mais ativa nos testículos durante a primeira e segunda infância. Neste período, o hipogonadismo só pode ser evidenciado sem o uso de testes estimulatórios se a função das células de Sertoli for avaliada. O AMH é um marcador útil do número e da atividade das células de Sertoli no período pré-puberal. A concentração sérica de AMH é alta da metade da vida fetal até a metade da puberdade. A produção de AMH pelos testículos aumenta em resposta ao FSH e é potencialmente inibida por androgênios. O AMH sérico não é detectável em pacientes anorquídicos. No hipogonadismo central ou primário afetando a gônada inteira, ou estabelecido na vida fetal ou infância, a concentração de AMH sérica é baixa. Por outro lado, quando o hipogonadismo afeta apenas as células de Leydig (por exemplo, nas mutações, LHb, defeitos do receptor de LH/CG ou das enzimas esteroidogênicas), a concentração de AMH sérico é normal ou alta. Em meninos púberes com hipogonadismo central, a concentração de AMH é baixa para o estágio na escala de Tanner (refletindo a falta de estímulo pelo FSH), mas alta para a idade (indicando a falta do efeito inibidor da testosterona). O tratamento com FSH provoca um aumento do AMH sérico, enquanto a administração de hCG aumenta os níveis de testosterona, que fazem a downregulation do AMH. Em conclusão, a concentração sérica de AMH é útil na avaliação da função gonadal, excluindo a necessidade de testes estimulatórios, e direciona o diagnóstico etiológico do hipogonadismo pediátrico masculino. Além disso, o AMH sérico é um marcador excelente da ação do FSH e dos androgênios nos testículosFil: Grinspon, Romina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rey, Rodolfo Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentin

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Anti-Müllerian hormone and lifestyle, reproductive, and environmental factors among women in rural South Africa

BACKGROUND : Few data exist regarding anti-Müllerian hormone, a marker of ovarian reserve, in relation to environmental factors with potential ovarian toxicity. METHODS : This analysis included 420 women from Limpopo, South Africa studied in 2010-2011. Women were administered comprehensive questionnaires, and plasma concentrations of anti-Müllerian hormone and dichlorodiphenyltrichloroethane were determined. We used separate multivariable models to examine the associations between natural log-transformed anti-Müllerian hormone concentration (ng/ml) and each of the lifestyle, reproductive, and environmental factors of interest, adjusted for age, body mass index, education, and parity. RESULTS : The median age of women was 24 years (interquartile range [IQR] = 22 to 26); the median anti-Müllerian hormone concentration was 3.1 ng/ml (IQR = 2.0 to 6.0). Women who reported indoor residual spraying in homes with painted walls (indicative of exposure to pyrethroids) had 25% lower (95% confidence interval [CI] = -39%, -8%) anti-Müllerian hormone concentrations compared with women who reported no spraying. Little evidence of decreased anti-Müllerian hormone concentrations was observed among women with the highest dichlorodiphenyltrichloroethane levels. Compared with women who used an electric stove, no association was observed among women who cooked indoors over open wood fires. The findings also suggested lower anti-Müllerian hormone concentrations among women who drank coffee (-19% [95% CI = -31%, -5%]) or alcohol (-21% [95% CI = -36%, -3%]). CONCLUSIONS : These are among the first data regarding anti-Müllerian hormone concentrations relative to pesticides and indoor air pollution. Our results are suggestive of decreased ovarian reserve associated with exposure to pyrethroid pesticides, which is consistent with laboratory animal data.http://journals.lww.com/epidem/pages/default.aspx2016-05-31hb201

Predictive factors for ovarian response in a corifollitropin alfa/GnRH antagonist protocol for controlled ovarian stimulation in IVF/ICSI cycles

Background This secondary analysis aimed to identify predictors of low (&#60;6 oocytes retrieved) and high ovarian response (&#62;18 oocytes retrieved) in IVF patients undergoing controlled ovarian stimulation with corifollitropin alfa in a gonadotropin-releasing hormone (GnRH) antagonist protocol. Methods Statistical model building for high and low ovarian response was based on the 150 μg corifollitropin alfa treatment group of the Pursue trial in infertile women aged 35–42 years (n = 694). Results Multivariable logistic regression models were constructed in a stepwise fashion (P &#60;0.05 for entry). 14.1 % of subjects were high ovarian responders and 23.2 % were low ovarian responders. The regression model for high ovarian response included four independent predictors: higher anti-Müllerian hormone (AMH) and antral follicle count (AFC) increased the risk, and higher follicle-stimulating hormone (FSH) levels and advancing age decreased the risk of high ovarian response. The regression model for low ovarian response also included four independent predictors: advancing age increased the risk, and higher AMH, higher AFC and longer menstrual cycle length decreased the risk of low ovarian response. Conclusions AMH, AFC and age predicted both high and low ovarian responses, FSH predicted high ovarian response, and menstrual cycle length predicted low ovarian response in a corifollitropin alfa/GnRH antagonist protocol

The impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve: a systematic review

Background Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. Objective The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti-Müllerian hormone level. Data Sources MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. Study Design All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Müllerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. Data Extraction Two reviewers performed the data extraction independently. Results A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Müllerian hormone concentration after ovarian cystectomy (weighted mean difference, –1.14 ng/mL; 95% confidence interval, –1.36 to –0.92; I2 = 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti-Müllerian hormone assay and studies using IOT anti-Müllerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti-Müllerian hormone (weighted mean difference, –1.44 [95% confidence interval, –1.71 to –1.1; I2 = 0%], –0.88 [95% confidence interval, –1.71 to –0.04; I2 = 0%], and –1.56 [95% confidence interval, –2.44 to –0.69; I2 = 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Müllerian hormone. Conclusion Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Müllerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve

Antimüllerian hormone in relation to tobacco and marijuana use and sources of indoor heating/cooking

To evaluate exposure to tobacco, marijuana and indoor heating/cooking sources in relation to anti-Müllerian hormone (AMH) levels

Anti-Mullerian hormone and Insulin-like growth factor-1 are predictive markers for ovarian reserve

Background: Ovarian reserve is defined as the existent quantitative and qualitative supply of follicles which are found in the ovaries that can potentially develop into mature follicles which in effect determines a woman’s reproductive potential. Many tests of ovarian reserve are employed including clinical, endocrine static, endocrine dynamic and  ultrasonographic markers. Aims of study: To determine the age-related changes in AMH and IGF-1 levels that occurs in Iraqi women as markers of ovarian reserve and to determine the specificity and sensitivity of IGF-1 and FSH for ovarian reserve. Subjects, material and methods: One hindered cases were collected dividing into two groups; first group includes fifty cases of child bearing age, healthy, fertile females with regular menstrual cycle while second group includes fifty cases of postmenopausal aging group, healthy with normal fertility history. Serum levels of Follicle stimulating hormone, Luteinizing hormone, Prolactin, Anti Müllerian Hormone and Insulin like Growth Factor-1 were estimated for all cases. Results: The overall mean age of the respondents was 45.06 ± 16.68 years old with significant statistical difference between the mean age of pre and post-menopausal women. Results of Anti Müllerian Hormone showing a significant statistical difference between means of Anti Müllerian Hormone hormone for pre-menopausal women (2.89± 2.07 ng/ml) and post-menopausal women (0.0± 0.0 ng/ml). Measuring of Insulin like Growth Factor-1 showing significant statistical difference between pre-menopausal women (211.04± 63.81 ng/ml) and post-menopausal groups' women (120.70± 39.69 ng/ml). Similarly results of Follicle stimulating hormone reveal significant differences between means of Follicle stimulating hormone for pre-menopausal women (6.03± 1.53 ml U/ ml) and post-menopausal women (56.06± 17.07 ml U/ ml). There was no significant association between AMH and IGF1 hormones and IGF1 hormone has been failed to detect ovarian reserve and still the AMH is the gold standard test. Conclusion: Significant changes occur in Anti Müllerian Hormone, I Insulin like Growth Factor-1  and Follicle stimulating hormone with progression of the age and Anti Müllerian Hormone still the stander ovarian reserve test in compare with Insulin like Growth Factor-1 and Follicle stimulating hormone. Key words: Ovarian reserve, AMH, IGF-1

Changes in serum anti-Müllerian hormone levels may predict damage to residual normal ovarian tissue after laparoscopic surgery for women with ovarian endometrioma.

We measured serum anti-Müllerian hormone levels before and after surgery in women undergoing unilateral and monolocular cystectomy for benign ovarian diseases. Comparing to control benign cysts, we found a significant decline in serum anti-Müllerian hormone levels with consequent depletion of follicles in tissue specimens after surgery for women with ovarian endometrioma

Genome-wide association study identifies common and low-frequency variants at the AMHgene locus that strongly predict serum AMH levels in males

Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adolescents aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ∼9 M ‘1000 Genomes Reference Panel’ imputed genetic variants. Genetic variants at the AMH protein-coding gene showed considerable allelic heterogeneity, with both common variants [rs4807216 (PMale = 2 × 10−49, Beta: ∼0.9 SDs per allele), rs8112524 (PMale = 3 × 10−8, Beta: ∼0.25)] and low-frequency variants [rs2385821 (PMale = 6 × 10−31, Beta: ∼1.2, frequency 3.6%)] independently associated with apparently large effect sizes in males, but not females. For all three SNPs, we highlight mechanistic links to AMH gene function and demonstrate highly significant sex interactions (PHet 0.0003–6.3 × 10−12), culminating in contrasting estimates of trait variance explained (24.5% in males versus 0.8% in females). Using these SNPs as a genetic proxy for AMH levels, we found no evidence in additional datasets to support a biological role for AMH in complex traits and diseases in men

Hormona antimülleriana (AMH) como herramienta diagnóstica en la mujer

La hormona antimülleriana (AMH) es producida por el testículo fetal e infantil en altas cantidades y por el testículo adulto y el ovario, en cantidades más moderadas. En el ovario, la expresión de la AMH se limita a las células de la granulosa de los folículos primarios, secundarios y antrales; los folículos preantrales y antrales pequeños son los principales productores. Los niveles de AMH persisten relativamente estables durante la infancia y la pubertad, y disminuyen progresivamente en la cuarta y quinta décadas de la vida hasta hacerse indetectables aproximadamente 5 años antes del último ciclo menstrual. Así, la determinación de AMH sérica es una herramienta útil para valorar la masa de células foliculares: los niveles bajos o indetectables de AMH reflejan una escasa o nula reserva folicular (por ejemplo: insuficiencia ovárica primaria congénita o adquirida), en tanto que los niveles elevados indican un exceso de folículos pequeños (por ejemplo: síndrome de ovario poliquístico y tumores de la granulosa). La determinación de la AMH se ha transformado en un marcador esencial en la evaluación de pacientes que recurren a técnicas de reproducción asistida, ya que permite estimar las probabilidades de éxito y también decidir el protocolo de estimulación por utilizar de modo de evitar el riesgo de una hiperestimulación ovárica.Anti-müllerian hormone (AMH) is synthesized by the fetal and prepubertal testis in high levels, and by the adult testis and the ovary in lower levels. In the ovary, AMH expression is limited to granulosa cells of primary, secondary and antral follicles; preantral and small antral follicles are the main AMH source. In the female, serum AMH levels are relatively stable during childhood and puberty, and subsequently decrease in the fourth and fifth decades of life to become undetectable approximately 5 years prior to the last menstrual cycle. Serum AMH is a useful tool to assess the amount of granulosa cells present in the gonads: low or undetectable AMH indicates a poor or absent ovarian reserve (for instance, in primary ovarian insufficiency), whereas high AMH levels are indicative of excessive follicles (for instance, in the polycystic ovary syndrome and granulosa cell tumors). Serum AMH determination has thus become an essential marker in the assessment of patients undergoing assisted reproduction technology treatments, since it allows to estimate the success rate as well as to decide the most adequate stimulation protocol in order to avoid an ovary hyperstimulation syndrome. Key words: anti-müllerian hormone, granulose cells, folicular reserve, primary ovarian insufficiency, polycystic ovary syndromeFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Bedecarraz, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Brugo Olmedo, Santiago. Centro Médico Seremas; ArgentinaFil: de Vincentiis, Sabrina. Centro Médico Seremas; ArgentinaFil: Calamera, Patricio. Centro Médico Seremas; ArgentinaFil: Blanco, Ana María. Centro de Estudios Bioquímicos, Andrológicos y Ginecológicos; ArgentinaFil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Freire, Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Centro Médico Seremas; Argentin