Serum anti-Müllerian Hormone Concentrations Research Articles

Model of Anti-Mullerian Hormone Over Age to Predict Menopause in Polycystic Ovary Syndrome and Eumenorrheic Women: A Study on Southern Indian Population.

Introduction Anti-mullerian hormone (AMH) is a member of the transforming growth factor β family and is a marker of ovarian reserve; it is produced by the granulosa cells of developing preantral and early antral ovarian follicles. AMH concentration decreases with increasing age. Its concentration is increased relatively in those with polycystic ovary syndrome (PCOS) than eumenorrheic women. Objectives In this research, using a model of AMH over age, the age of menopause is predicted in PCOS and eumenorrheic women. Study design The study subjects were classified into two groups. Group 1 included PCOS subjects. Group 2 included eumenorrheic women. General profiles such as age, BMI, and hormonal parameters such as AMH were measured. Based on the exponential functional dependence of AMH over age, a model was proposed, and the value of exponential constants such as log βo and β1 were calculated using least square approximation. An arbitrary value of 0.2 ng/mL for AMH was taken as a cut-off value to predict the age of menopause in both groups. Outcome measures We predicted the age of menopause using a model of AMH over age by the least square approximation technique. Results The age prediction for menopause using the least squares model of AMH over age showed that in group 1 patients with PCOS, menopause is projected to occur at around 54.7 years, while in group 2 with eumenorrheic women, it is expected to happen at approximately 45.2 years. Conclusion Data demonstrates that serum AMH concentration declines over time, and predicting the age of menopause reflects sustained reproductive life span in PCOS subjects.

The role of anti-Mullerian hormone and other correlates in patients with polycystic ovary syndrome

ABSTRACT Background Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. Methods A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. Results Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. Conclusion Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.

Effect of a GnRH Antagonist on Anti-Müllerian Hormone and Follicular Population in Anestrous Bitches.

The objective of this study was to describe the effect of the third-generation GnRH antagonist, acyline, on ovarian follicular population and serum anti-Müllerian hormone (AMH) concentrations in female dogs. Four late anestrous bitches were administered 330 μg/kg SC acyline every 10 days for 60 days and followed up for 45 days. Blood samples were drawn on days -1, 15, 30, 45, 60, 75, 90 and 105 for AMH determination. Then, the females were ovariectomized and the excised ovaries were gross and histologically evaluated. The total ovarian follicles were counted. None of the female dogs presented estrus during treatment. Only one bitch presented an ovulatory estrus 20 days after treatment. The total number of ovarian follicles in these bitches was 96,200.10 ± 26,125.12, with 84.13%, 11.36%, 7.8% and 0.01% corresponding to primordial, primary, secondary and antral structures, respectively. Pretreatment AMH concentrations were 0.62 ± 0.17 ng/mL. This hormone varied throughout the study period (p < 0.01), diminishing to nadir values during treatment to then rapidly recover after its effect (0.2 ± 0.05 vs. 0.67 ± 0.22 ng/mL; p < 0.01). Acyline rapidly and reversibly prevented the initiation of cycling without affecting follicle count but diminishing serum AMH concentrations.

The Value of Anti-Müllerian Hormone in Predicting Ovulation Induced by Aromatase Inhibitors in Women With Polycystic Ovary Syndrome

ObjectivesThis study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS). MethodsFrom January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes. ResultsIn total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284–0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561–0.910) with P = 0.104. ConclusionsIn women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles.

Long-term exposure to air pollution and anti-mullerian hormone rate of decline: a population-based cohort study in Tehran, Iran.

Anti-mullerian hormone (AMH) concentration is a marker of ovarian reserve that decreases with age. However, a decrease in AMH may occur more rapidly under the influence of environmental factors. The present study investigated the association between long-term exposure to ambient air pollutants with serum concentrations of AMH and the AMH rate of decline. This study included 806 women with median age of 43years (interquartile range: 38-48) participating in the Tehran Lipid and Glucose Study (TLGS) that were followed from 2005 to 2017. The AMH concentration and the demographic, anthropometric, and personal health parameters of the study participants were obtained from the TLGS cohort database. Air pollutant data were collected from the monitoring stations and the individual exposures were estimated by previously developed land use regression (LUR) models. Multiple linear regression analysis was used to estimate linear relationships between the air pollutant exposures and serum concentration of AMH and with the AMH declination rate. The results show no statistically significant associations between exposures to any of the air pollutants (including PM10, PM2.5, SO2, NO, NO2, NOX, and benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX) with serum concentration of AMH. Compared to the first tertile, no statistically significant associations were observed between the second or third tertiles of air pollutants, with the AMH rate of decline. In this study, we did not find significant association between air pollution and AMH in middle age women in Tehran, Iran. Future work may study such associations in younger women.

Contemporary Anti-Retroviral Drugs (ARVDs) Disrupt Follicular Development in Female Wistar Rats.

There are genuine concerns that long-term use of anti-retroviral drugs may be associated with reproductive complications in females. This study aimed to ascertain the effect of highly active anti-retroviral drugs on the ovarian reserve and reproductive potential of female Wistar rats and by extension to HIV-positive human females. A total of 25 female Wistar rats, weighing between 140g and 162g, were randomly allotted into non-intervention and intervention groups, receiving the anti-retroviral drugs, Efavirenz (EFV), Tenofovir Disoproxil Fumarate (TDF), Lamivudine (3TC), and a fixed-dose combination (FDC). The dosage was administered orally at 8 am daily for 4 weeks. Serum concentrations of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and estradiol were measured using standard biochemical techniques (ELISA). Follicular counts were made on fixed ovarian tissue from the sacrificed rats. The mean AMH level for the control group and the EFV, TDF, 3TC, and FDC groups were 11.20, 6.75, 7.30, 8.27, and 6.60 pmol/L, respectively. The EFV and FDC groups had the lowest AMH, compared to the other groups, but there was no statistically significant difference in AMH across the groups. The mean count of antral follicles was significantly lower in the group that received EFV when compared to the other groups. The corpus luteal count was significantly higher in the control group than in the intervention groups. The study demonstrated a disruption in the reproductive hormones of female Wistar rats receiving anti-retroviral regimens containing EFV. Clinical studies are required to determine if these changes are seen in women receiving EFV-based treatment, as this may compromise reproductive function and predispose them to early menopause.

Anti-Müllerian hormone levels in serum and testes of male dogs: relations with neuter status and bilateral abdominal cryptorchidism

Anti-Müllerian hormone (AMH) analysis has contributed to new information in the reproductive endocrinology of domestic animals, due to clinically available diagnostic tools. An accurate and rapid diagnostic method to distinguish between neutered and bilateral abdominal cryptorchid dogs is needed in veterinary practice. Therefore, this study uses an enzyme-linked immunosorbent assay to evaluate the clinical relevance of AMH analysis in peripheral blood as a diagnostic tool for dogs with suspected bilateral abdominal cryptorchidism. The possible alteration of the AMH localization in testicular tissue caused by this pathologic condition was also investigated using immunohistochemistry. Male dogs were divided into three groups of healthy intact (n = 14), healthy castrated (n = 14), and bilateral abdominal cryptorchid (n = 14) dogs. The results demonstrated a higher level of serum AMH in the cryptorchid group compared to the intact group (P < 0.01), while serum AMH levels of all castrated dogs were below the limit of detection (<0.05 ng/mL). Moreover, the percentage of positive AMH immunostaining of the intact group was less than that of the cryptorchid group (P < 0.01). A significantly positive correlation was found between serum AMH concentration and localization in testicular tissues (r = 0.93, P < 0.01). Our findings suggest that AMH levels in the peripheral blood could be used as an alternative and rapid screening method for detecting dogs with abdominal cryptorchidism.

Determining the age group-based cut-off values of serum anti-Mullerian hormone concentrations to diagnose polycystic ovary syndrome

Objective To determine the cut-off values of the serum anti-Müllerian hormone (AMH) concentration for different age groups (21–25, 26–30, 31–35 years) to diagnose polycystic ovary syndrome (PCOS). Methods In total, 187 women aged 21–35 years were included in this descriptive study. Patients diagnosed with PCOS according to the Rotterdam Criteria formed the PCOS group (n = 93), whereas those without symptoms related to PCOS formed the control group (n = 94). Follicular phase serum hormone concentrations were evaluated during the endocrinological assessment of patients with PCOS. Serum levels of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, androstenedione, and AMH were measured. The free androgen index and LH/FSH ratio were calculated. Cut-off values of serum AMH concentrations for the age groups were measured using receiver operating characteristic curve analysis. Results The prevalence rates of frank, ovulatory, normoandrogenic, and non-polycystic ovary PCOS were 69.9, 10.8, 10.8, and 8.6%, respectively. Serum AMH concentrations >5.56 ng/mL were associated with PCOS in the 21–25-year-old group. The cut-off value was 4.01 ng/mL in the 26–30-year-old group, whereas it was 3.42 ng/mL in the oldest age group. The correlation between the antral follicle count (AFC) and serum AMH level was strong for each age group. Conclusions The serum AMH concentration is a valuable parameter for assessing patients with symptoms indicative of PCOS. We recommend measuring serum AMH levels to support the diagnosis or to use them instead of the AFC for the Rotterdam criteria.

Factors affecting the distribution of serum anti-müllerian hormone levels among infertile Asian women: a multi-nation, multi-centre, and multi-ethnicity prospective cohort study.

How do age, ethnicity, and other characteristics affect serum anti-mullerian hormone (AMH) levels in Asian women undergoing fertility treatment? Age, ethnicity, obesity (BMI ≥ 30 kg/m2), and polycystic ovarian syndrome (PCOS) significantly impacted serum AMH levels, with the rate of decrease accelerating as age increased; a concentration of 4.0 ng/ml was the optimal cut-off for diagnosis of PCOS. There are significant differences in ovarian reserve among women from different races and ethnicities, and Asian women often have poorer reproductive outcomes during assisted reproductive treatment cycles. A population-based multi-nation, multi-centre, multi-ethnicity prospective cohort study of 4613 women was conducted from January 2020 to May 2021. Infertile women of 20-43 years of age were enrolled. The exclusion criteria included: age <20 or >43, non-Asian ethnicity, and missing critical data. Participants were Asian women of Chinese, Japanese, Korean, Thai, Vietnamese, Malay, Indian, and Indonesian ethnicities from 12 IVF centres across Asia. These women were all naïve to ovarian stimulation cycles and attended IVF centres for fertility assessment. The AMH measurement was performed using an AMH automated assay on a clinically validated platform. A total of 4556 infertile Asian women were included in the final analyses. The mean ± SD for serum AMH concentrations (ng/ml) across specific age groups were: overall, 3.44 ± 2.93; age <30, 4.58 ± 3.16; 30-31, 4.23 ± 3.23; 32-33, 3.90 ± 3.06; 34-35, 3.21 ± 2.65; 36-37, 2.74 ± 2.44; 38-39, 2.30 ± 1.91; 40 and above, 1.67 ± 2.00. The rate of AMH decrease was ∼0.13 ng/ml/year in patients aged 25-33 and 0.31 ng/ml/year in women aged 33-43. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%). Age (P < 0.001), ethnicity (P < 0.001), obesity (P = 0.007), PCOS (P < 0.001), and a history of endometrioma cystectomy (P = 0.01) were significantly associated with serum AMH values. Smoking status, pretreatment with GnRH agonist (GnRHa) or the oral contraceptive pill (OCP), freezing-thawing of blood samples, and sampling on Day 2 to Day 5 of the menstrual cycle or randomly did not appear to affect serum AMH levels. An AMH concentration of 4.0 ng/ml was the optimal cut-off for PCOS diagnosis with a sensitivity of 71.7% and specificity of 75.8% (AUC = 0.81, CI 95%: 0.79-0.83; P < 0.001). The incidence of PCOS was supposedly high in this cohort as some IVF clinics were tertiary referral centres for managing specific fertility issues encountered by women with PCOS. Treatment with GnRHa or OCP before AMH testing was regionally and ethnically confined, mostly in Hong Kong SAR and Japan. Moreover, this reference for serum AMH value is limited to Asian women of the ethnicities examined and may not apply to other ethnicities not included in the study. This is the first study to collate and construct age-specific reference ranges for serum AMH levels using the same bioassay on Asian women of different ethnicities. The findings of this investigation can assist clinicians to counsel and prognosticate about Asian women's ovarian reserve and reproductive potential, thus providing better strategies for personalized fertility interventions. This study was technically supported by Ferring Pharmaceuticals and received no specific grant from any funding agency. All authors have no competing interests to disclose. NCT04203355.

Anti-Mullerian Hormone Is a Significant Marker for Male Infertility

To evaluate serum anti-Mullerian hormone (AMH) in men with normal, reduced sperm concentration and in azoospermic men as a possible clinical marker of male factor infertility. Prospective study Private clinic of Dr. Yasir Al-Wattar and Al-Batool Teaching Hospital in Mosul. This study was conducted on one hundred male subjects aged less than 50 years for the period from July to November 2011, infertile men were classified according to their sperm count into oligospermics (n=28) and azoospermics(n=47), twenty five men were normal (n=25).Serum concentrations of FSH and Testosterone were measured using ELISA, serum Anti-Mullerian hormone concentrations were measured using AMH/MIS enzyme linked immunosorbant assay kit. Significant differences in serum AMH, FSH and Testosterone concentrations were found between normal, oligospermic &amp; azoospermic men. AMH negatively correlated with FSH in oligospermic and azoospermic men and positively with testosterone in azoospermics and negatively with testosterone in oligospermics. Anti-Mullerian hormone should be evaluated in patients with oligospermia and azoospermia, it may serve as a marker of male infertility.

Anti-Müllerian hormone and pregnancy after autologous hematopoietic stem cell transplantation for multiple sclerosis.

Autologous hematopoietic stem cell transplantation (AHSCT) has been approved for multiple sclerosis (MS) in many European countries. A large proportion of patients are women of child-bearing age. For them, AHSCT may have negative consequences for reproductive health, since the ovaries are particularly susceptible to alkylating agents. Anti-Müllerian hormone (AMH) reflects the ovarian reserve and has been suggested as a potential biomarker of fertility in women. The aim of this study was to investigate AMH levels in relation to age and reproductive potential in MS patients treated with AHSCT. The study cohort comprised 38 female patients, aged 20-44 years, who underwent AHSCT for MS using a cyclophosphamide (200 mg/kg)/rabbit-anti-thymocyte globulin (6 mg/kg) conditioning regimen between 2013-2020. Clinal follow-up visits were made 3 months after AHSCT and then yearly. AMH was analysed in blood samples. The median age at transplantation was 28 years (interquartile range, IQR 25-33). The median AMH concentration was 23 pmol/l at baseline (IQR 6.0-30), 0.5 pmol/l at 3 months (IQR 0-1.5) and 1.1 pmol/l at 2 years (IQR 0-2.9). A multiple linear regression model was used to determine if age and/or AHSCT influenced AMH values; both significantly did (age, -0.21 per year, p = 0.018; AHSCT -19, p <0.0001). Seven women became pregnant, six spontaneously and one both spontaneously and with IVF. One patient underwent an abortion, all other pregnancies led to live births. Six of the women became pregnant despite low or very low post-AHSCT serum concentrations of AMH, suggesting that low serum AMH concentrations do not necessarily reflect impaired fertility in patients treated with high-dose cyclophosphamide.

Serum anti-müllerian hormone (AMH) concentration during pregnancy: a longitudinal study.

A prospective longitudinal cohort study aimed to longitudinally examine the kinetics of Anti-müllerian hormone (AMH) during the first two trimesters of pregnancy. Pregnant women with stored 1st trimester serum samples were recruited at 24-28 weeks gestation during their gestational diabetes testing, where they provided an additional serum sample. The samples were analysed for AMH, oestradiol and progesterone concentrations. A decrease in serum AMH was observed in 40 out of 45 (88.9%) (95% CI 75.9% to 96.3%) of the participants in this study. The median serum AMH concentration was 10.9 pmol/L in the 1st trimester and 6.5 pmol/L during the 2nd trimester, with a significantly different distribution of the values between the 1st and the 2nd trimester AMH samples (p<0.001). The median percentage of AMH difference of -39.8%. This study demonstrated a significant decrease in serum AMH levels from the 1st to the 2nd trimester of pregnancy. The absolute decrease in AMH levels seems to be positively associated with 1st trimester AMH levels, whereas the percentage of AMH difference is not. Further studies are required to elucidate the potential physiological mechanisms of this finding.

Ovarian reserve of infertile women in Libreville: A retrospective analysis of 124 cases at the University Mother and Child Hospital in Libreville, Gabon.

There has been an increasing number of sub-fertile women in Gabon during the last 20 years. Antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) are known as the most accurate markers of ovarian reserve in women and are related to age and weight. Therefore, the current study examines the relationship between AFC and serum AMH with age and weight among sub fertile Gabonese women. This is a retrospective study carried out in the assisted reproduction department of the Mother and Child University Hospital of Libreville. Over a period of 2 years, from 1st June 2019 to 30th May 2021. From the patient records we collected the following data, age, weight CFA and AMH of 124 women who had consulted for infertility. We excluded incomplete files. The average age and weight of women participating in the current study were 38 (±5.74) years and 76.3 (±14.59) kg. The average serum AMH concentration was 2.33 (±2.17) ng/mL) while the average AFC was 14.63 (±11.37). Significant negative correlation between the age and the serum AMH (r2= -0.368; p <0.0001) and between the age and the CFA (r2=-0.560; p <0.0001) were observed in the current study. This study suggests that sub-infertile women residing in Gabon generally have normal serum AMH concentration and AFC levels. Age significantly impact serum AMH and AFC levels.

High anti-Müllerian hormone (AMH) is associated with increased risks of ectopic pregnancy in women undergoing fresh embryo transfer cycle, a cohort study

BackgroundEctopic pregnancy is more common amongst assisted reproduction cycles and is a cause of significant maternal morbidity. Few predictive markers exist to help identify and modify risk of ectopic pregnancy in preparing for embryo transfer. The relationship between serum and AMH and ectopic pregnancy rate is unknown.MethodsThis was a retrospective cohort study investigating women who underwent fresh embryo transfer cycles from January 2017 to December 2019 in Peking University Third Hospital. The primary outcome was ectopic pregnancy. Restricted cubic splines with four knots for AMH concentration (0-3, 3-6, 6-12, 12-max) were used to map out the non-linear relationship between the predicted ectopic pregnancy rate and the serum AMH concentration. Log binomial regression was used to test the crude risk ratio (cRR) and the adjusted risk ratio (aRR) after adjustment for confounders with 95% confidence intervals (CI) to determine the difference across various groups.ResultsA total of 13,718 cycles in women undergoing fresh embryo transfer were eligible for analysis. The ectopic pregnancy rate was 1.3% per embryo transfer cycle initiated and 3.3% per pregnancy. Serum AMH concentrations were higher amongst women with ectopic pregnancy than in women with a confirmed intrauterine pregnancy or heterotopic pregnancy or who did not become pregnant (Mean levels: 4.0 ng/ml vs 3.2 ng/ml, 1.7 ng/ml, and 2.8 ng/ml). An AMH concentration of 7 ng/ml represented the best cut-off value to predict ectopic pregnancy. The ectopic pregnancy rate was 3.4% per cycle and 7.5% per pregnancy in women with AMH levels ≥ 7 ng/ml; and 1.2% per cycle and 2.9% per pregnancy in women with AMH levels < 7 ng/ml. Serum AMH concentration ≥ 7 ng/ml was associated with an increased risk of ectopic pregnancy in all fresh embryo transfer cycles started (aRR = 2.35 (1.45, 3.58)) as well in women who became pregnant (aRR = 2.23 (1.49, 3.33).ConclusionsBaseline AMH concentration ≥ 7 ng/ml is associated with an increased risk of ectopic pregnancy in fresh embryo transfer cycles.

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause.

Phthalates, ubiquitous endocrine-disrupting chemicals, may affect ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1189 multiracial/multiethnic women aged 45 to 56 years without hormone therapy from the Study of Women's Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999 to 2000 and 2002 to 2003, resulting in a total of 2111 observations. Linear mixed-effect models were used to calculate percentage differences (%D) and 95% CIs in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed statistically significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%; 95% CI, -3.66 to -0.47) and MnBP with testosterone (%D: -1.99%; 95% CI, -3.82 to -0.13), after adjusting for multiple comparisons with false discovery rates less than 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%; 95% CI, -24.10 to -3.14), MEHHP (%D: -15.58%; 95% CI, -24.59 to -5.50), and MEOHP (%D: -13.50%; 95% CI, -22.93 to -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.

Does the addition of serum antimüllerian hormone concentrations to the Framingham Risk Score and Pooled Cohort Equations improve the prediction of cardiovascular disease?

Abstract The present study revealed that the addition of serum antimüllerian hormone concentrations to Framingham Risk Score and Pooled Cohort Equations could potentially improve the risk prediction of cardiovascular disease. Objective The current study aimed to examine the added value of serum antimüllerian hormone (AMH) concentration to the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) in predicting the risk of cardiovascular disease (CVD) in women of reproductive age. Methods Women 30 years and older were considered eligible for this population-based prospective study. The univariate and multivariate Cox proportional hazard models were used to evaluate the association between the serum concentrations of AMH and the risk of CVD. Results In the enhanced model, which integrated AMH into FRS and PCE and was adjusted for family history of premature CVD, AMH showed a significant association with the risk of CVD during a 19-year follow-up of 800 women (hazard ratio, 0.77 [95% CI, 0.60-0.99] and hazard ratio, 0.64 [95% CI, 0.48-0.84], respectively). According to the likelihood-ratio test, the addition of AMH measurements to FRS and PCE could significantly improve the risk prediction of CVD (P = 0.02 and P &lt; 0.001, respectively); however, the integration of this biomarker did not improve the classification of risk categories. Conclusions The present findings revealed that the addition of serum AMH concentrations to FRS and PCE could potentially improve the risk prediction of CVD.

AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence: A long-term longitudinal study of healthy girls.

Anti-Müllerian hormone (AMH) is produced by granulosa cells in small growing ovarian follicles. In adult women, serum concentrations of AMH reflect the ovarian reserve of resting primordial follicles, and low AMH is associated with risk of early menopause. In contrast, patients with polycystic ovary syndrome (PCOS) have elevated AMH. The primary aim of this study was to evaluate the individual tracking of serum AMH concentrations, as well as whether AMH in early childhood reflects ovarian activity in adolescence. In this large longitudinal study of healthy girls were examined from infancy to adolescence (1997-2019) including physical examination, assessment of serum concentrations of reproductive hormones (in infancy, median age 0.3yrs; mid-childhood, 7.2yrs; puberty, 11.3yrs; and adolescence, 15.9yrs), transabdominal ultrasound (TAUS, puberty and adolescence) and magnetic resonance imaging (MRI, puberty) of the ovaries. Each girl maintained her relative AMH concentration (expressed as standard deviation (SD) scores) over time; mean variation of individual age adjusted AMH concentrations was 0.56±0.31 SD.Serum concentrations of AMH in adolescence correlated with AMH in infancy and childhood; infancy: r=0.347; mid-childhood: r=0.637; puberty: r=0.675, all p<0.001.AMH correlated negatively with FSH concentrations in all age groups (infancy: r=-0.645, p<0.001; mid-childhood: r=-0.222, p<0.001; puberty: r=-0.354, p<0.001; adolescence: n=275, r=-0.175, p=0.004).Serum AMH concentrations in mid-childhood correlated with the number of follicles in puberty (TAUS and MRI) as well as in adolescence (TAUS); e.g. total number of follicles: TAUS puberty (r=0.607), MRI puberty (r=0.379), TAUS adolescence (r=0.414), all p<0.001.AMH concentration in infancy as well as in mid-childhood predicted low AMH (<10pmol/L) in adolescence; AMH infancy <7.5pmol/L as predictor of low AMH in adolescence: sensitivity 0.71, specificity 0.70, AUC 0.759; AMH mid-childhood < 8.4pmol/L as predictor of low AMH in adolescence: sensitivity 0.88, specificity 0.87, AUC 0.949.Girls with high serum AMH concentration in mid-childhood (AMH >30.0pmol/L vs. other girls) had higher adolescent LH (median 4.53 vs. 3.29 U/L p=0.041), LH/FSH ratio (1.00 vs 0.67, p=0.019), testosterone (1.05 vs 0.81nmol/L, p=0.005), total number of follicles (23 vs. 19, p=0.004), and higher prevalence of irregular cycles (10/15=67% vs. 28/113=25%, p=0.002). The present findings suggest remarkably stable ovarian activity from small growing follicles in healthy girls, supporting AMH in early life as a useful clinical tool to predict future ovarian activity. The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065), the EU (QLK4-CT1999-01422; QLK4-2001-00269), the Novo Nordisk Foundation and The Danish Ministry of Science Technology and Innovation (2107-05-0006). A.S.B. is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 464240267. KM receives honoraria from Novo Nordisk A/S for teaching at the Danish annual postgraduate course of pituitary diseases.

Двусторонний крипторхизм как клинический маркер ранней диагностики врожденного дефицита гонадотропных гормонов: клинические наблюдения

Bilateral cryptorchidism is a common symptom of congenital gonadotropin deficiency. Detection of congenital hypogonadotropic hypogonadism (CHH) at an early age is important for preventing the long delayed puberty and timely initiation of therapy. The purpose — to identify СHH in boys with bilateral cryptorchidism based on hormonal examinations during mini-puberty. Material and methods. We present five clinical cases of patients with bilateral cryptorchidism, with CHH diagnosed in mini-puberty. The examination of 1–6 months old boys included tests of serum LH, FSH, testosterone, anti-Müllerian hormone (AMH), and inhibin B. To assess the pituitary gonadotropic function, a test with a Gn-RH analogue was performed. Patients with established CHH underwent molecular genetic testing. Results. The basis for СHH identification were the low serum concentrations of gonadotropins, AMH, testosterone, and inhibin B in boys with bilateral cryptorchidism during mini-puberty. Mutations in the FGF8 and SPRY4 genes associated with CHH were detected in 2 patients. CHH as part of hypopituitarism was revealed in 2 boys. Conclusions. Hormonal examination of boys with bilateral cryptorchidism during mini-puberty allows establishing gonadotropin deficiency at an early age, to carry out a long-term control for patients, and to begin treatment timely. Hormonal examination during mini-puberty can be the basis for diagnosing both isolated CHH and congenital hypopituitarism.

Evaluation of serum anti-Müllerian hormone (AMH) and equine chorionic gonadotrophin (eCG) concentrations in pregnant mares in relation to foetal sex

The aim of this study was to investigate the foetal sex related difference and progression in maternal serum anti-Müllerian hormone (AMH) and equine chorionic gonadotrophin (eCG) concentrations during different points of time in pregnant Arabian mares. The study groups formed by 12 healthy male offspring- and 12 healthy female offspring-foaling mares, designated as group MFM and group FFM, respectively. Peripheral blood samples were collected on the day of natural mating and then monthly until the 6thmonth (mo) of gestation. Serum AMH was measured in all serum samples; eCG was measured in samples collected from 2 to 5 months Of gestation. Serum AMH concentrations of group FFM at mo 4 and mo 5 (3.89 ± 0.49 ng/ml; 2.89 ± 0.32 ng/ml), were significantly higher than in group MFM (2.11 ± 0.46 ng/ml; 1.87 ± 0.32 ng/ml), (P&lt; 0.05). The mo of gestation (mo 1–6) had no effect on serum AMH concentrations of either group MMF or FFM (P&gt; 0.05). Serum eCG concentrations of group FFM at mo 2 (359.73 ± 41.51 mIU/ml), were significantly higher than in group MFM (255 ± 21.18 mIU/ml) (P&lt; 0.05). Group-time interaction for eCG concentrations at mo 2–4 was non-significant (P&gt; 0.05). Concentrations of serum AMH showed no relationship with corresponding eCG levels at mo 2–4 (P&gt; 0.05). Individual variations in AMH and eCG concentrations and the inability to determine a cut-off point for determination of foetal sex make these hormones unlikely candidates for determining foetal sex in the mare.

Clinical Utilities of Anti-Müllerian Hormone

The anti-Müllerian hormone (AMH) plays an essential role in sex determination in early embryonic development. Through a series of sequential steps that follows inheriting an XY chromosome, Sertoli cell differentiation upregulates the expression of AMH-suppressing Müllerian duct development and maintains the AMH at a high level until puberty. In females, the AMH is produced by granulosa cells of follicles beginning in the second half of fetal life and continues through adulthood, with a steady decline through the reproductive years and severe decline at menopause, until levels eventually become undetectable. The AMH is essential for the regulation of follicular maturation via the recruitment of primordial follicles throughout folliculogenesis. AMH serum concentration in women strongly correlates with ovarian reserve quantity and reflects ovulation potential. Because the AMH is expressed almost exclusively by growing follicles before FSH-dependent selection, it commonly serves as a marker for ovarian function in various clinical situations, including in the diagnosis and pathogenesis of polycystic ovarian syndrome, artificial reproductive technology, and predictions of menopause or premature ovarian failure.