OBJECTIVE: In male congenital hypogonadotropic hypogonadism (CHH), it was observed that lower dose human gonadotropic hormone (hCG) can maintain normal intratesticular testosterone levels. We propose this study to compare the low-dose hCG, follicle stimulating hormone (FSH), and Testosterone (T) [LFT Regimen] to conventional treatment to induce virilization and fertility.
METHODS: This open-label randomized pilot study was conducted from June 2020 to December 2021.
METHODS: CHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH (150U thrice per week), and T(100 mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce anti-mullerian hormone (AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups.
RESULTS: Out of 30 patients, 23 (76·7%) subjects achieved spermatogenesis, and the median time was 12 (9-14·9) months. There was no difference in achieving spermatogenesis between the two groups (64·3% vs 7·5%,P = 0·204), and even the median time for spermatogenesis was similar (15months vs 12months,P = 0·248). Both groups had nonsignificant median plasma AMH at spermatogenesis, [6·6 ng/ml (3·3-9·76) vs4·41 ng/ml (2·3-6·47), P = 0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable [152·4 pg/ml (101·7-198·0) vs49·1 pg/ml (128·7-237·3), P = 0·488].
CONCLUSIONS: A reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

OBJECTIVE: To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development.
METHODS: Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs). Also, measurements from 42 patients with Klinefelter syndrome were included.
RESULTS: In both sexes, inhibin B concentrations were high during minipuberty, decreased in childhood, and increased significantly from Tanner stages B1 to B3 (peak: B4) in females and from G1 to G3 (peak: G3) in males. Despite variations in menstruating females, inhibin B concentrations remained relatively constant after puberty, until becoming unmeasurable at menopause. Despite a modest decrease, the inhibin B concentration in males remained relatively high from puberty onwards. At any age, males had highest concentrations. Inhibin B standard deviation (SD) scores were lower in OC-users (median SD score = -0.88) than in non-users (SD score = 0.35), p < 0.001. In patients with Klinefelter syndrome, inhibin B concentrations spanned the reference range until around 15 years of age, where they decreased to subnormal or unmeasurable levels.
CONCLUSIONS: Valuable sex- and age-specific reference data for inhibin B concentrations were provided. In OC-users, decreased concentrations of inhibin B underlined the ovaries as the only place of inhibin B production. In patients with Klinefelter syndrome, the decline in inhibin B concentrations at puberty underlined the shift in regulation of inhibin B production at pubertal onset.

UNASSIGNED: This study aimed to distinguish isolated hypogonadotropic hypogonadism (IHH) from constitutional delay in growth and puberty (CDGP) by various hormonal tests in both sexes.
UNASSIGNED: Boys with testicular volume (TV) <4 ml (14-18 years) and girls with breast B1 stage (13-18 years) were enrolled in this study. A detailed history, clinical examination and hormonal analysis including basal luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin B, anti-Mullerian hormone (AMH), testosterone (boys), oestradiol (girls), triptorelin stimulation test and 3-day human chorionic gonadotropin (HCG) stimulation test (boys) were performed. All patients were followed for 1.5 years or till 18 years of age. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-offs with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for various hormones to distinguish IHH from CDGP.
UNASSIGNED: Of 34 children (male: 22 and female: 12), CDGP and IHH were diagnosed in 21 and 13 children, respectively. 4 hours post-triptorelin LH had the highest sensitivity (100%) and specificity (100%) for identifying IHH in both sexes. Basal inhibin B had good sensitivity (male: 85.7% and female: 83.8%) and specificity (male: 93.3% and female: 100%) for diagnosing IHH. 24 hours post-triptorelin testosterone (<34.5 ng/dl), day 4 post-HCG testosterone (<99.7 ng/dl) and 24 hours post-triptorelin oestradiol (<31.63 pg/ml) had reasonable sensitivity and specificity for identifying IHH. Basal LH, FSH and AMH were poor discriminators for IHH in both sexes.
UNASSIGNED: The best indicator was post-triptorelin 4-hour LH followed by inhibin B, which had a reasonable diagnostic utility to distinguish IHH from CDGP in both boys and girls.

UNASSIGNED: There is a significant, but poorly understood, male preponderance in prevalence of autism spectrum disorder (ASD). The aim of this study was to examine the relationship between male preponderance in ASD and Inhibin B (InhB) and Anti-Müllerian hormone (AMH) levels and the 2D/4D finger ratio associated with fetal androgen exposure.
UNASSIGNED: 42 patients with ASD and 42 neurotypical controls between the ages of 5 and 10 were included. ASD diagnosis and severity were determined using K-SADS PL (Kiddie-SADS - Present and Life Time) Version 2016 and the Childhood Autism Rating Scale (CARS). Serum InhB and AMH were measured. The 2D/4D finger length ratio was also calculated for hand anthropometric measurements.
UNASSIGNED: Serum InhB levels were higher in children diagnosed with ASD compared to the neurotypical controls (p=0.003). Serum AMH levels were similar in both groups. Positive correlation was determined between AMH and CARS scores (r=0.315, p=0.05). 2D/4D finger ratios in the ASD group were significantly lower than in the control group (p<0.001).
UNASSIGNED: The study findings suggest that InhB, AMH, and fetal testosterone may be associated with male preponderance in ASD. More research is now required for a better understanding of this subject.

OBJECTIVE: To investigate the diagnostic value of anti-Mullerian hormone (AMH) and Inhibin B (InhB) in menopausal women with osteoporosis from the Chinese Daur ethnic group.
METHODS: A total of 175 menopausal women were selected and divided into the osteoporosis group (N = 90) and the control group (N = 85). BMD was measured by dual-energy X-ray absorptiometry, and laboratory indicators of osteoporosis, for example, serum osteocalcin (OC), β-collagen special sequence (β-CTX), and procollagen type I amino-terminal propeptide (PINP), bone alkaline phosphatase (BALP), AMH, and InhB were measured by commercial kits. The relationship between osteoporosis and AMH or InhB was analyzed. The predictive values of AMH and InhB were reflected by the ROC curve and logistic regression.
RESULTS: The level of BMD was decreased and the levels of OC, β-CTX, PINP, and BALP of the menopausal osteoporosis group were increased. The concentration of AMH and InhB in the menopausal osteoporosis group was decreased and they had connections with each other. AMH and InhB could be used as independent indicators for the occurrence of osteoporosis in menopausal women and their combination had a higher diagnostic value.
CONCLUSIONS: AMH and InhB measurements in menopausal women had a certain clinical significance in the detection of osteoporosis. The occurrence of osteoporosis was related to BMD, OC, β-CTX, BALP, AMH, and InhB.

OBJECTIVE: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB).
METHODS: Data from 1,230 consecutive men presenting for primary couple\'s infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values.
RESULTS: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34-41 years] vs. 36.0 years [31-40 years]); had smaller testicular volume (TV) (12 mL [10-15 mL] vs. 15 mL [12-20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9-11.0 million/mL] vs. 13.8 million/mL [3.1-36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%-25.3%] vs. 20.0% [7.0%-36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values.
CONCLUSIONS: More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Klinefelter syndrome (KS) is a male genetic disease caused by the presence of an extra X chromosome, causing endocrine disorders mainly responsible for a high rate of infertility and metabolic disorders in adulthood. Scientific research is interested in identifying new biomarkers that can be predictive or prognostic of alterations strictly connected to KS. Lipocalin-2 (LCN-2, also known as NGAL) is a small protein initially identified within neutrophils as a protein related to innate immunity. Serum LCN-2 estimation seems to be a useful tool in predicting the metabolic complications caused by several pathological conditions. However, little is known about its potential role in infertility conditions. The present pilot study aims to investigate the presence of LCN-2 in the serum of a group of pre-pubertal and post-pubertal children affected by KS, compared to healthy controls. We demonstrated for the first time the presence of elevated levels of LCN-2 in the serum of KS patients, compared to controls. This increase was accompanied, in pre-pubertal KS patients, by the loss of correlation with LH and HDL, which instead was present in the healthy individuals. Moreover, in all KS individuals, a positive correlation between LCN-2 and inhibin B serum concentration was found. Despite the limited size of the sample analyzed, our preliminary data encourage further studies to confirm the findings and to extend the study to KS adult patients, to verify the predictive/prognostic value of LCN-2 as new biomarker for metabolic diseases and infertility associated with the pathology.

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OBJECTIVE: Management of cryptorchidism is typically recommended within the first 18 months of life to maximize fertility potential. However, there is a paucity of longitudinal postoperative data for Chinese infants. We aim to evaluate the Testicular function change when the procedure is done within the first year of life.
METHODS: We prospectively enrolled 51 children diagnosed with unilateral inguinal cryptorchidism into the surgical group between January 2021 and January 2022. Orchidopexy was carried out through a single transverse scrotal incision. Assessments of anti-Mullerian hormone (AMH), inhibin B (InhB), testosterone (T) levels, testicular volume and testicular atrophy index (TAI) were conducted at baseline, 6 months, and 1 year following surgery. Concurrently, clinical data from 42 healthy age-matched controls were collected during their routine physical examinations.
RESULTS: At 6- and 12-months post-surgery, testicular volume increased significantly to 0.98 ± 0.12 mL and 1.01 ± 0.12ml. AMH levels also rose from 76.40 ± 15.77 ng/mL to 81.52 ± 15.32 ng/mL and 87.50 ± 15.36 ng/mL. However, these parameters are significantly lower than age-matched healthy controls (both P < 0.001). InhB levels significantly increased after surgery and even surpassed those of healthy controls after 6 months (both P < 0.001). The TAI was 16.7% and 8.6% at 6- and 12-months following surgery.
CONCLUSIONS: Although orchiopexy can improve testicular growth and function, the restoration of testicular function to the level of healthy peers might take longer. To expedite the recovery of testicular function and bring it in line with that of peers, we recommend addressing cryptorchidism at the earliest opportunity.

BACKGROUND: Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent.
OBJECTIVE: The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls.
METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model.
RESULTS: A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH.
CONCLUSIONS: Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.