Serum Inhibin Research Articles

Serum Insulin-Like Factor 3 Levels Are Reduced in Former Users of Anabolic Androgenic Steroids Suggesting Persistent Impaired Leydig Cell Function

Background: Illicit use of anabolic androgenic steroids (AAS) has emerged as a public health concern among men, but the long-term effect on gonadal function is still unresolved. Serum insulin-like factor 3 (INSL3) has emerged as a novel and potentially superior marker of Leydig cell function than serum testosterone per se. INSL3 synthesis and secretion exhibit far less daily variation than testosterone. Further, serum INSL3 levels are not related to body composition. The objective of this study was to investigate INSL3 as a marker of Leydig cell function in former AAS users. Methods: Community-based cross-sectional study including men aged 18 - 50 years, involved in recreational strength training and allocated to one of three groups: current (n = 46) or former AAS users (n = 42) or controls (n = 44). Mean age (SD) of all participants were 32 (7) years and the elapsed duration since AAS cessation, geometric mean (95% CI), was 32 (23; 45) months in former AAS users. All procedures were performed during one visit in the morning hours following overnight fasting. We drew blood through a cannula placed in an antecubital vein following 30 minutes of supine rest. Medical records, testicular size, questionaries, and detailed history of strength training and AAS use were obtained in a structured interview. Serum INSL3 and testosterone were measured using liquid chromatography mass spectrometry. Results: Serum INSL3 was markedly suppressed among current AAS users compared with former AAS users and controls, P < 0.001. Additionally, former AAS users also displayed lower serum INSL3 concentrations than controls, mean (SD), 0.43 (0.31) versus 0.60 (0.22) µg/L, P = 0.006 and the difference remained significant in a multivariate linear regression, (B) (95%CI), -0.17 (-0.28;-0.55) µg/L, P=0.004, adjusted for plasma LH, plasma sexual hormone-binding globulin, age, body fat %, smoking and use of other illicit drugs. Longer accumulated duration of AAS use (log2) was associated with reduced serum INSL3 levels in former AAS users, (B) (95%CI), -0.08 (-0.14;-0.01), P=0.022, suggesting a dose-response relation between AAS use and suppression of serum INSL3. We evaluated the association between INSL3 and total testosterone levels and they were not associated among former users and controls in a multivariate linear regression, P=0.821. We noted recovery of serum inhibin B levels among former AAS users reaching the mean plasma level of controls after elapsed duration since AAS cessation of ≈ 21 months; (B) (95%CI), 2.2 (0.7; 3.7) months, P = 0.006. In contrast, we did not note any recovery of serum INSL3, P = 0.541, or total testosterone, P = 0.861, among former AAS users. Conclusions: Serum INSL3 is decreased years following AAS cessation in former AAS users, independently of plasma testosterone, suggesting persistent impaired Leydig cell function, which should be investigated further.

Role of inhibin B in detecting recurrence of granulosa cell tumors of the ovary in postmenopausal patients

IntroductionSeveral biomarkers have been proposed for the detection of recurrences in adult-type granulosa cell tumors of the ovary. Here we validate the value of inhibin B in detecting recurrences and...

Prediction of Fetal Growth Restriction Using Combined Fetal Biometry and Maternal Serum( Inhibin A) in Pregnant Women with Type 1 Diabetes.

Prediction of Fetal Growth Restriction using Combined Fetal Biometry and Maternal Serum [Inhibin A] in Pregnant Women with Type 1 DiabetesAbstractBackground: FGR is a major determinant of perinatal and childhood morbidity and mortality and is associated with the risk of chronic diseases in later life.Objective: to assess the diagnostic value of early detection of fetal growth restriction using combined fetal biometry and maternal serum biomarker inhibin A in type 1 diabetic patients.Patients and Methods: A prospective study on 100 diabetic pregnant women. Maternal Serum Inhibin A, Hemoglobin AIC, fasting glucose serum levels, all done for each patient once in second trimester. Serial fetal ultrasound biometry done as one assessment in second trimester and two assessments in third trimester. Ultrasonic markers for fetal growth restriction were performed. Follow-up was done for 3 antenatal care visits.Results: The IUGR was [66%] and non-IUGR was [34%]. Mean serum inhibin A level in IUGR cases 673.83± 470.43, mean serum inhibin A in NON- IUGR cases 102.06 ± 106.29) P value

Ovarian Reserve Biomarkers and Menstrual Cycle Length in a Prospective Cohort Study.

While age-related changes in menstrual cycle length are well known, it is unclear whether anti-Müllerian (AMH) or other ovarian reserve biomarkers have a direct association with cycle length. To determine the association between biomarkers of ovarian reserve and menstrual cycle length. Secondary analysis using data from time to conceive (TTC), a prospective time to pregnancy cohort study. The age-independent association between cycle length and biomarkers of ovarian reserve was analyzed using linear mixed and marginal models. Study participants were TTC-enrolled women aged 30-44 years with no history of infertility who were attempting to conceive for <3 months were enrolled. Serum AMH, follicle-stimulating hormone, and inhibin B levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. The primary outcome was menstrual cycle length; follicular and luteal phase lengths were secondary outcomes. Multivariable analysis included 1880 cycles from 632 women. Compared with AMH levels of 1.6 to 3.4 ng/mL, women with AMH <1.6 ng/mL had cycles and follicular phases that were 0.98 (95% CI -1.46, -0.50) and 1.58 days shorter (95% CI -2.53, -0.63), respectively, while women with AMH >8 ng/mL had cycles that were 2.15 days longer (95% CI 1.46, 2.83), follicular phases that were 2 days longer (95% CI 0.77, 3.24), and luteal phases that were 1.80 days longer (95% CI 0.71, 2.88). Increasing AMH levels are associated with longer menstrual cycles due to both a lengthening of the follicular and the luteal phase independent of age.

Dynamic Changes in Serum Inhibin B Levels in 6- to 24-Month-Old Children Receiving Cryptorchidism Surgery.

ObjectiveCryptorchidism is the most common congenital disability and is defined as the absence of one or both testicles in the scrotum during fetal development. In patients with cryptorchidism, lowered serum inhibin B levels suggest testicular dysfunction. The practical application of serum inhibin B levels in childhood remains controversial. The purpose of this study was to observe the post-operational changes of serum inhibin B levels in patients with cryptorchidism and provide evidence that serum inhibin B is a potential marker for the efficacy of testicular surgery.MethodsA total of 83 male children with cryptorchidism were enrolled in this study. All the children had blood samples taken by venipuncture on the day of surgery. The serum inhibin B levels in the blood samples were measured using an ELISA kit. Paired t-tests were used to assess differences between the groups.ResultsThe results show that, compared with the preoperative values, there was a statistically significant increase in serum inhibin B values one month after the operation in each group (P < 0.05). Compared with the one-month post-operation results, there were no significant changes six months after operation in each group (P>0.05). However, serum inhibin B values decreased significantly in all groups at 12 months post-operation (P < 0.05), suggesting that serum inhibin B values are significantly correlated with age. Correlation analysis showed that serum inhibin B was negatively correlated with age from 6 to 36 months, and the correlation coefficient was −0.488.ConclusionSerum inhibin B can be used as a short-term evaluation index of cryptorchidism surgery rather than as a long-term indicator.

Serum inhibin B for differentiating between congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty: a systematic review and meta-analysis

PurposeThe distinction between congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) in patients with delayed puberty is difficult to distinguish, but important for timely treatment. The aim of this study is to perform a systematic review and meta-analysis to determine the diagnostic performance of serum inhibin B (INHB) levels for differentiating CHH and CDGP.MethodsPubMed, EMBASE, and Cochrane Library databases were systematically searched from the date of database inception to November 10, 2019 for studies examining the use of serum INHB to discriminate between CHH and CDGP. Pooled odds ratios (OR), sensitivity, specificity, and 95% confidence intervals (CI) were calculated. The Quality Assessment of Diagnostic Studies-2 (QUADAS-2) was used to assess the quality of the included studies. Sub-analyses were performed including that based on testicular volume (TV) and study design.ResultsSeven studies, comprising of 349 patients (96 CHH and 253 CDGP), were included in the meta-analysis. For differentiating between CHH and CDGP, INHB level exhibited good diagnostic accuracy with a pooled sensitivity of 92% (95% confidence interval [CI]: 0.86–0.96, I2 = 0.4%, p = 0.4343), specificity of 92% (95% CI: 0.88–0.94, I2 = 68.1%, p = 0.0009), and pooled area under the receiver operating characteristic curve (AUC) of 0.9619. The cut-off values of INHB for boys were 56, 66, 80, 96, 94.7, 111, and 113 pg/ml (assay method standardized to Gen II ELISA). Sub-analyses showed that testicular volume and study design could be a source of statistically significant heterogeneity in specificity. In boys with a testicular volume of ≤3 ml, INHB performed well with a sensitivity of 92%, specificity of 98%, and AUC of 0.9956.ConclusionINHB exhibits excellent diagnostic efficiency in distinguishing CHH from CDGP, especially in boys with severe puberty deficiency (TV ≤ 3 ml).

Randomized, assessor-blind, antimüllerian hormone–stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with follitropin delta

To establish the relationship between follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing invitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimüllerian hormone (AMH) levels. Randomized, controlled, assessor-blind, AMH-stratified (low 5.0-14.9 pmol/L; high 15.0-44.9 pmol/L) dose-response trial. Reproductive medicine clinics. A total of 158 Japanese women (20-39 years of age). Controlled ovarian stimulation with 6, 9, or 12 μg/d of follitropin delta or 150 IU/d follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle. Number of oocytes retrieved. Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with follitropin delta. The vital pregnancy rate per started cycle with follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum. This trial establishes the dose-response relationship between follitropin delta and ovarian response in Japanese women. NCT02309671.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among boys in Mexico City

BackgroundEndocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.MethodsOur analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8–14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8–14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10–18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.ResultsIn utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.ConclusionThese findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.

P.673 Serum testosterone, inhibin b, anti-mullerian hormone, dehydroepiandrosterone-sulfate levels and 2d:4d digit ratio in boys with specific learning disorder

The impact of testosterone (T) on the exogenous (Experiment 1) and endogenous (Experiment 2) orienting of visual attention in males was examined. Sixteen male participants completed both an exogenous and an endogenous cuing task on two separate days. About 2–3 h prior to testing, either a placebo or a dose of T was administered. The inhibition of return (IOR) phenomenon was observed during the exogenous cuing task, but IOR was not influenced by T. During the endogenous task, participants demonstrated the expected cuing effects on both days. However, longer reaction time to invalid target locations was observed following T-administration. The manipulation of T-levels in males provides converging evidence of dissociation between reflexive and volitional orienting of attention.

Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

PurposeHigher grade aneuploidies (HGAs) of the male sex chromosomes are a rare genetic group of pathologies caused by nondisjunction meiotic events. The aim of this study was to evaluate the impact of early androgenic therapy on the testicular secretory hormone profile, and the pathophysiological implications.Patients and methodsIn this cross-sectional study, 18 HGA subjects aged 6–8 years were recruited. They were divided into two groups, based on whether or not they had previously undergone testosterone therapy (group 1: 11 untreated subjects; group 2: 7 treated subjects). Serum FSH, LH, testosterone (T), inhibin B (INHB) and anti-Müllerian hormone (AMH) were determined, and auxological parameters were assessed. Five group 1 patients and four group 2 patients were treated with hCG (human chorionic gonadotropin) for inguinal cryptorchidism; their hormone profile and auxological parameters were assessed both pre- and post-hCG treatment.ResultsGroup 1 subjects showed significantly higher testicular volume and higher levels of AMH and INHB (p < 0.0001). Subjects who had undergone hCG therapy showed a significantly higher testicular volume, penis length (respectively, p = 0.008 and p = 0.0005 for group 1 and p = 0.04 and p = 0.001 for group 2) and T (p = 0.005 for group 1 and p = 0.004 for group 2).ConclusionsHGA patients undergoing early testosterone therapy show an earlier and persistent suppression of testicular secretory function. At this age, the testes are still responsive to stimulation with hCG. The selection of patients to be treated must be accompanied by a thorough clinical and hormonal evaluation.

Total Motile Sperm Count in Adolescent Boys with Varicocele is Associated with Hormone Levels and Total Testicular Volume.

The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count. We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as <9 million sperm per ejaculate. A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p <0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count. Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.

GnRH stimulation testing and serum inhibin B in males: insufficient specificity for discriminating between congenital hypogonadotropic hypogonadism from constitutional delay of growth and puberty.

Are GnRH tests and serum inhibin B levels sufficiently discriminating to distinguish transient constitutional delay of growth and puberty (CDGP) from congenital hypogonadotropic hypogonadism (CHH) that affects reproductive health for life? Both parameters lack the specificity to discriminate CDGP from CHH. GnRH tests and inhibin B levels have been proposed to differentiate CDGP from CHH. However, their diagnostic accuracies have been hampered by the small numbers of CHH included and enrichment of CHH patients with more severe forms. The aim of this study was to assess the diagnostic performance of GnRH tests and inhibin B measurements in a large cohort of CHH male patients with the whole reproductive spectrum. From 2008 to 2018, 232 males were assessed: 127 with CHH, 74 with CDGP and 31 healthy controls. The participants were enrolled in two French academic referral centres. The following measurements were taken: testicular volume (TV), serum testosterone, inhibin B, LH and FSH, both at baseline and following the GnRH test. Among CHH patients, the LH response to the GnRH test was very variable and correlated with TV. Among CDGP patients, the LH peak was also variable and 47% of CHH patients had peak LH levels overlapping with the CDGP group. However, no patients with CDGP had an LH peak below 4.0 IU/l, while 53% CHH patients had LH peak below this threshold. Among CHH patients, inhibin B levels were also variable and correlated with TV and peak LH. Inhibin B was significantly lower in CHH patients than in CDGP patients but 50% of CHH values overlapped with CDGP values. Interestingly, all patients with CDGP had inhibin B levels above 35 pg/ml but 50% of CHH patients also had levels above this threshold. As CHH is very rare, an international study would be necessary to recruit a larger CHH cohort and consolidate the conclusion reached here. Peak LH and basal inhibin B levels are variable in both CHH and CDGP with significant overlap. Both parameters lack specificity and sensitivity to efficiently discriminate CHH from CDGP. This reflects the varying degree of gonadotropin deficiency inherent to CHH. These two diagnostic procedures may misdiagnose partial forms of isolated (non-syndromic) CHH, allowing them to be erroneously considered as CDGP. This study was funded by Agence Française de Lutte contre le Dopage: Grant Hypoproteo AFLD-10 (to J.Y.); Agence Nationale de la Recherche (ANR): Grant ANR-09-GENO-017-01 (to J.Y.); European Cooperation in Science and Technology, COST Action BM1105; Programme Hospitalier de Recherche Clinique (PHRC), French Ministry of Health: PHRC-2009 HYPO-PROTEO (to J.Y.); and Programme Hospitalier de Recherche Clinique (PHRC) "Variété", French Ministry of Health, N° P081216/IDRCB 2009-A00892-55 (to P.C.). There are no competing interests. N/A.

Interactions between serum FSH, inhibin B and antral follicle count in the decline of serum AMH during the menstrual cycle in late reproductive age.

ObjectiveTo investigate the hormonal interrelationships during the menstrual cycle in women of late reproductive age with suppressed serum AMH and antral follicle count (AFC).MethodsSerum hormones (AMH, FSH, LH, estradiol, progesterone, inhibin A, inhibin B), AFC (2‐10 mm) and AMH/AFC ratio (an estimate of AMH/follicle) were assessed every 2‐3 days across the menstrual cycle in 26 healthy ovulatory women aged 18‐50 years.ResultsAn 11‐fold fall in AMH/AFC was observed in women aged ≥45 years compared to those 18‐45 years (P < .001). Although women ≥45 years exhibited normal menstrual cycle patterns of serum estradiol, progesterone, LH and inhibin A, FSH was elevated (P < .001) and inhibin B suppressed (P < .001) compared to the younger group. Overall FSH was inversely correlated (r = .55, P < .05) and AMH directly correlated (r = .88, P < .01) with AFC; however, these relationships were curvilinear and more pronounced when AFC was low. Inhibin B was directly linearly correlated (r = .70, P < .01) with AFC across both high and low AMH/follicle groups.ConclusionsIt is hypothesized that the marked fall in AMH/follicle in late reproductive age is attributed to the change in the hormonal interplay between the pituitary and ovary. The fall in AFC leads to a decrease in inhibin B and a concomitant increase in FSH by a recognized feedback mechanism. It is postulated the elevated FSH suppresses AMH either directly or indirectly through oocyte‐specific growth factors leading to a marked fall in AMH/follicle. We propose that pituitary‐ovarian and intra‐ovarian regulatory systems underpin the accelerated fall in AMH/follicle during the transition to menopause.

Study of a Hormonal Assay in PCOS Patients with Type 2 DM and their Correlation with Inhibin B

Background: inhibin B considered a sensitive marker for follicles numbers of the ovary. Inhibin B levels increased with overnighted, lipedema and PCOS women. PCOS affects women in menstrual age. Obesity and insulin resistance have an association with PCOS. This syndrome increases LH, FSH, Prolactin. and testosterone hormonal levels. Aim: examine the role of inhibin B in polycystic ovary syndrome (PCOS) with type 2DM patients, and to investigate the correlation between these quantities with serum inhibin B for women on the 12th day of their ovulation developments and correlation of inhibin with other biochemical parameters in those patients. Patient and Method: sixty women included in this study divided into two groups of 30 subjects. The first group is for women who had PCOS with type 2DM, and the second for control subjects. PCOS with type 2DM patients diagnosed according to Rotterdam ESHRE/ASRAM. The biomedical test is done for FBS, Cholesterol, TG, LDL, HDL, HbA1c for all subjects included in this study. Results: BMI, weight, prolactin and testosterone, FBS, cholesterol, TG, LDL, HDL, HbA1c had significantly higher levels in PCOS women with type 2DM. while inhibin B level showed to be significantly lower in PCOS with type 2DM. when this study attempted to find the correlation between the inhibin B with the biochemical tests, only the TG and HbA1c show a significant correlation in PCOS with type 2DM women. Discussion: The high levels of biochemical parameters for diabetic female patients’ groups with PCOS are due to the association of PCOS with insulin resistance and obesity. So, the low inhibin B levels in PCOS with type 2DM and its correlation with HbA1c and TG in the PCOS group could be an indication for using inhibin B as a type 2 DM marker. This study supported by Katrine et al 2017 when found out that when they diagnosed type 2DM at a younger age the levels of event rate (HbA1c and FBS) was higher in PCOS compared with controls Conclusion: There is a significant correlation in inhibin-B levels with HbA1c and TG levels in PCOS women with type 2 DM.

Association between acrylamide exposure and sex hormones in males: NHANES, 2003-2004.

IntroductionAcrylamide is widely present in heat-processed food, cigarette smoke and environment. Reproductive toxicity was reported in animals treated with acrylamide, particularly in males. The reproductive toxicity of acrylamide and its active metabolite, glycidamide, was reported to be mainly mediated through DNA damage in spermatocytes. However, the effect of acrylamide on sex hormones in men is unknown.MethodsThere were 468 male subjects (age ≧ 12 years) enrolled to determine the relationships between hemoglobin adducts of acrylamide (HbAA) and hemoglobin adducts of glycidamide (HbGA) with several sex hormones using the National Health and Nutrition Examination Survey (NHANES), 2003 to 2004. All potential confounding variables in the data set were properly adjusted.ResultsWe found that one unit increase in the natural log-transformed HbAA level was associated with an increase in natural log transformed serum inhibin B level by 0.10 (SE = 0.05; P = 0.046), and natural log transformed serum sex hormone binding globulin (SHBG) by 0.15 (SE = 0.15; P = 0.036). With respect to HbGA, one unit increase in the natural log-transformed HbGA level was associated with an increase in natural log transformed serum anti-Müllerian Hormone (AMH) level by 0.31 (SE = 0.00; P = 0.003).ConclusionIn this representative cohort, we identified positive associations between acrylamide exposure and several sex hormones in men. The HbAA is positively associated with inhibin B and SHBG, and HbGA is positively associated with AMH. Other than genotoxicity, our findings suggested that altered sex hormones might also play a role in acrylamide-related reproductive toxicity in males.

Puberty and Inhibin B in 35 Adolescents With Pituitary Stalk Interruption Syndrome.

Background: In patients with pituitary stalk interruption syndrome (PSIS), long-term follow-up is necessary to address their gonadotrophic status. The objectives of this study were (1) to describe pubertal features of and (2) to assess the ability of serum inhibin B concentration to predict hypogonadotropic hypogonadism (HH) in patients with PSIS.Methods: This retrospective single-center study included 35 patients with PSIS and known gonadotrophic status for whom a serum sample preserved at −22°C (collected at initial evaluation or later) was available for measuring inhibin B by the same hormonal immunoassay method.Results: Among the 21 boys, 15 had normal puberty (early in two), and six had partial (n = 2) or complete (n = 4) HH. Among the 14 girls, five had normal puberty (early in one)—four with regular menses and one in the process of puberty—, four had complete HH, and five had amenorrhea (primary in three and secondary in two) after normal pubertal development, despite a normal pubertal gonadotropin response to gonadotropin-releasing hormone test. These were considered as having partial HH. Only three boys had values over the normal lower range for serum inhibin B concentrations despite partial (n = 2) or complete (n = 1) HH. Inhibin B concentrations were low in all girls with complete HH, normal in all those with partial HH except in one and in those with normal puberty except in two. Considering boys and girls together, the occurrence of under-range inhibin B was significantly higher in those with HH than in those without (47 vs. 10%, p = 0.02). All 15 patients with HH had associated thyroid-stimulating hormone and adrenocorticotropic hormone deficiency except for 3 girls with partial HH.Conclusions: Under-range inhibin B concentrations in patients with PSIS might be suggestive of HH. These concentrations provide a simple first-line predictive test, especially in boys.

Relationship between Serum Inhibin A and Pregnancy Outcomes

Relationship between Serum Inhibin A and Pregnancy Outcomes

Are serum levels of inhibin A in second trimester predictors of adverse pregnancy outcome?

ObjectiveDuring pregnancy, inhibin A is mainly derived from the placenta and regulates the implantation and differentiation of embryos. Our aim was to assess whether second trimester serum inhibin A was associated with an increased risk of adverse pregnancy outcomes.MethodsWe investigated the serum levels of Inhibin A during the second trimester in pregnancy, and analyzed associations between the Inhibin A and the risk of adverse pregnancy outcome. 12,124 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Multivariate logistic regression analysis was conducted to estimate the relative risk between Inhibin A and adverse pregnancy outcome.ResultsCompared with the group without adverse pregnancy outcome, during the second trimester of pregnancy, age and Inhibin A were risk factors for pre-eclampsia, gestational diabetes mellitus and preterm delivery; Inhibin A was risk factors for low birth weight. Gravidity and Inhibin A were risk factors for macrosomia; while parity was a protective factor against pre-eclampsia, gestational hypertension and low birth weight.ConclusionElevated Inhibin A levels in pregnancy are significantly associated with pre-eclampsia, GDM, macrosomia, low birth weight and preterm delivery.

Inhibin A-A Promising Predictive Parameter for Determination of Final Oocyte Maturation in Ovarian Stimulation for IVF/ICSI.

The number of mature oocytes is a key factor in the success of Assisted Reproductive Techniques (ART). Exogenous gonadotropins are administered during ovarian stimulation in order to maximize the number of oocytes available for fertilization. During stimulation, monitoring is mandatory to evaluate individual response, to avoid treatment complications and assist in the determination of the optimal day for final oocyte maturation and oocyte retrieval. Routine monitoring during stimulation includes transvaginal ultrasound examinations and measurement of serum estradiol (E2). Due to multifollicular growth of follicles of varying size, serum E2 levels are commonly supraphysiological and often variable, rendering E2-measurement during ovarian stimulation unreliable as a determinant of oocyte maturity. In contrast to serum E2, serum Inhibin A levels increase once a minimum follicle size of 12–15 mm is achieved. Due to this fact, serum Inhibin A levels could present in combination with ultrasound monitoring a more reliable parameter to determine the optimal follicle size for final oocyte maturation, as only follicles with a size of 12 mm and beyond will contribute to the serum Inhibin A level. This prospective observational, cross-sectional study demonstrates, that on the day of final oocyte maturation serum Inhibin A is strongly correlated to the number of follicles ≥15 mm (0.72) and to the number of retrieved and mature oocytes (ρ 0.82/0.77, respectively), whereas serum E2 is moderately correlated to the parameters mentioned above (ρ 0.64/0.69/0.69, respectively). With an area under the curve (AUC) of 0.91 for Inhibin A, compared to an AUC of 0.84 for E2, Inhibin A can be regarded as a better predictor for the optimal timing of trigger medication with a threshold number of ≥10 mature oocytes. It can be concluded from this data that serum Inhibin A in combination with transvaginal ultrasound monitoring may be a more powerful tool in the decision making process on trigger timing as compared to E2.

SUN-002 Hormonal Profile of Ovarian Sertoli-Leydig Cell Tumor

Background: Sertoli-Leydig cell tumors account for less than 1% of ovarian tumors, and information about their biochemical markers has been lacking. Objective: The objective was to characterize the hormonal profile of Sertoli-Leydig cell tumor, which should be helpful in recognizing this rare condition in the future. Methods: We reviewed test results including serum total and free testosterone, steroid hormone precursors, and inhibin B levels in a 17-year-old adolescent girl with ovarian Sertoli-Leydig cell tumor who developed secondary amenorrhea for 6 months, deepening of the voice, acne, and severe hirsutism. Results: Our patient had serum testosterone 641 ng/dL (expected 20 - 38), dihydrotestosterone 42.5 ng/dL (expected 3 - 18), 17-OH progesterone 659 ng/dL (expected 20 - 265), androstenedione 869 ng/dL (expected 50 - 224), 17-OH pregnenolone 760 ng/dL (expected 53 - 357), DHEA 1250 ng/dL (expected 4 - 491), and DHEA-S of 366 mcg/dL (expected 44 - 248). Inhibin B level was 321 pg/mL (expected <136); inhibin A was normal. Anti-mullerian hormone, a-fetoprotein, carcinoembryonic antigen, and CA-125 tumor markers were not elevated. Karyotype was female 46,XX. Dexamethasone 0.5 mg QID PO for 4 days resulted in plasma ACTH <5.0 pg/mL and serum cortisol <1.0 mcg/dL, total testosterone 611 ng/dL, free testosterone 25.1 ng/dL (expected <0.04 - 1.09 ng/dL), and 17-OH progesterone 887 ng/dL. Abdomen and pelvis MRI demonstrated a right ovarian mass primarily solid with high cellularity, measured 4.4 x 3.9 cm; there was at least moderate diffuse enhancement of the mass after contrast administration; adrenal glands were normal. Surgical pathology of the resected right ovary revealed moderately to poorly differentiated Sertoli-Leydig cell tumor. Single antibody immunostain procedures with appropriate controls showed a staining pattern supportive of this rare diagnosis: WT-1 showed moderate nuclear staining, calretinin showed a strong positive stain, and CK showed a patchy moderate staining pattern; immunostains for myogenin, desmin, and EMA were negative. Genetic testing revealed a germline heterozygous mutation in DICER1 gene, c3737del, p.Asn1246Metfs*12, establishing the diagnosis of DICER1 syndrome, an autosomal dominant disorder predisposing to cancer. Menses resumed one month after tumor resection. Conclusions: High serum 17-OH progesterone, androstenedione, 17-OH pregnenolone, and DHEA levels used as indicators of adrenocortical function could be markers of an ovarian tumor. If serum 17-OH progesterone and testosterone remain high when cortisol and plasma ACTH are suppressed on Dexamethasone test, a source of 17-OH progesterone and testosterone is other than ACTH-dependent adrenal one. High serum inhibin B level may be sign of an ovarian tumor. Patients with Sertoli-Leydig cell tumor should be screened for DICER1 gene syndrome to assess risk for other rare neoplasms.