Variation in circulating antimüllerian hormone precursor during the periovulatory and acute postovulatory phases of the human ovarian cycle

Pankhurst, Michael W.; Chong, Yih Harng

doi:10.1016/j.fertnstert.2016.06.010

Cited by 19 publications

(18 citation statements)

References 35 publications

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“…To date, few studies have studied longitudinal decline and short-term variation of AMH. Two recent reports found AMH levels to remain stable throughout the menstrual cycle, 38,39 whereas others reported absolute differences ≤0.5 ng/mL 40 and 0.8 ng/mL. 41 The average yearly decline of AMH, also measured with an AnshLabs assay, was estimated to be 6% to 8%.…”

Section: Discussionmentioning

confidence: 98%

Anti-Müllerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women

et al. 2017

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BACKGROUND:Earlier age at menopause is widely considered to be associated with an increased risk of cardiovascular disease. However, the underlying mechanisms of this relationship remain undetermined. Indications suggest that anti-Müllerian hormone (AMH), an ovarian reserve marker, plays a physiological role outside of the reproductive system. Therefore, we investigated whether longitudinal AMH decline trajectories are associated with an increased risk of cardiovascular disease (CVD) occurrence. METHODS:This study included 3108 female participants between 20 and 60 years of age at baseline of the population-based Doetinchem Cohort. Participants completed ≥1 of 5 consecutive quinquennial visits between 1987 and 2010, resulting in a total follow-up time of 20 years. AMH was measured in 8507 stored plasma samples. Information on total CVD, stroke, and coronary heart disease was obtained through a hospital discharge registry linkage. The association of AMH trajectories with CVD was quantified with joint modeling, with adjustment for age, smoking, oral contraceptive use, body mass index, menopausal status, postmenopausal hormone therapy use, diastolic blood pressure, total cholesterol, highdensity lipoprotein cholesterol, and glucose levels. RESULTS:By the end of follow-up, 8.2% of the women had suffered from CVD, 4.9% had suffered from coronary heart disease, and 2.6% had experienced a stroke. After adjustment, each ng/mL lower log AMH level was associated with a 21% higher risk of CVD (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and a 26% higher risk of coronary heart disease (hazard ratio, 1.25; 95% confidence interval, 1.08-1.46). Each additional ng/mL/year decrease of log AMH was associated with a significantly higher risk of CVD (hazard ratio, 1.46; 95% confidence interval, 1.14-1.87) and coronary heart disease (hazard ratio, 1.56; 95% confidence interval, 1.15-2.12). No association between AMH and stroke was found. CONCLUSIONS:These results indicate that AMH trajectories in women are independently associated with CVD risk. Therefore, we postulate that the decline of circulating AMH levels may be part of the pathophysiology of the increased cardiovascular risk of earlier menopause. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.

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Section: Discussionmentioning

confidence: 98%

Anti-Müllerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women

et al. 2017

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“…Similarly, in this study, the marked decline in total AMH levels during pregnancy was not matched by a concordant change in the cleavage-state of AMH, although a slight increase in the cleavage of circulating AMH was observed during the middle period of pregnancy. The extent of cleavage of AMH varies in other physiological circumstances [ 7 , 40 ], with the regulation of this being currently unknown. The concentrations of ovarian steroid hormones change markedly during pregnancy [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in Circulating ProAMH and Total AMH during Healthy Pregnancy and Post-Partum: A Longitudinal Study

et al. 2016

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Circulating Anti-Müllerian hormone (AMH) is derived from the gonads, and is a mixture of the prohormone (proAMH), which does not bind to AMH receptors, and receptor-competent AMH. The functions of a hormone are partially defined by the factors that control its levels. Ovarian reserve accounts for 55~75% of the woman-to-woman variation in AMH level, leaving over 25% of the biological variation to be explained. Pregnancy has been reported to decrease circulating AMH levels, but the observations are inconsistent, with the effect of pregnancy on the bioactivity of AMH being unknown. We have therefore undertaken a longitudinal study of circulating proAMH and total AMH during pregnancy. Serum samples were drawn at 6–8 gestational time-points (first trimester to post-partum) from 25 healthy women with prior uneventful pregnancies. The total AMH and proAMH levels were measured at each time-point using ELISA. The level of circulating total AMH progressively decreased during pregnancy, in all women (p<0.001). On average, the percentage decline between the first trimester and 36–39 weeks’ gestation was 61.5%, with a standard deviation of 13.0% (range 30.4–81.2%). The percentage decline in total AMH levels associated with maternal age (R = -0.53, p = 0.024), but not with the women’s first trimester AMH level. The postpartum total AMH levels showed no consistent relationship to the woman’s first trimester values (range 31–273%). This raises the possibility that a fundamental determinant of circulating AMH levels is reset during pregnancy. The ratio of proAMH to total AMH levels exhibited little or no variation during pregnancy, indicating that the control of the cleavage/activation of AMH is distinct from the mechanisms that control the total level of AMH.

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“…The proteolytic processing of AMH takes place at different sites in the molecule (i.e., amino acid at position 229 and 451 [13][14][15]) and introduces conformational changes which expose new antigenic determinants and change its affinity to antibodies. The mechanisms that govern AMH processing in circulation is known to only a limited extent and is illustrated by the presence of different molecular forms of AMH across the menstrual cycle (16); in addition it is likely that individual variations exist. The samples were analyzed with the use of ELISA assays targeting three different compositions of AMH according to the localization of the epitope (Supplemental Fig.…”

Section: Amh Assaysmentioning

confidence: 99%

Associations of different molecular forms of antimüllerian hormone and biomarkers of polycystic ovary syndrome and normal women

Wissing

Mikkelsen

Kumar³

et al. 2019

Fertility and Sterility

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Objective: To study different antim€ ullerian hormone (AMH) isoforms in women with polycystic ovary syndrome (PCOS) and healthy regularly cycling women and to investigate whether levels of AMH isoforms combined with baseline characteristics can predict PCOS. Design: Cross-sectional study. Setting: Fertility clinic. Patient(s): Eighty-eight women with PCOS and 24 age-and body mass index (BMI)-matched normal control subject women recruited from April 2010 to February 2013. AMH isoforms were analyzed in biobanked serum samples collected at Holbaek Fertility Clinic, Denmark. All study participants went through a baseline examination including gynecologic history, objective examination, transvaginal ultrasound, and blood sampling. Each woman was characterized by measurement of total T, free T, SHBG, A, DHEAS, FSH, LH, E 2 , PRL, TSH, serum insulin, plasma glucose, and C-peptide. Interventions(s): None. Main Outcome Measure(s): Serum levels of three different AMH isoforms. Result(s): Levels of AMH measured with each of three AMH ELISAs were significantly higher in women with PCOS compared with control women. The ratio between AMH isoforms showed significant associations with metabolic parameters (BMI, SHBG, C-peptide, cholesterols, triglycerides, and the modified homeostasis-model assessment). Prediction of PCOS showed a high precision with areas under the receiver operating characteristic curve of 97% when AMH measurements were combined with androgens and BMI. Conclusion(s): Three ELISAs detecting different parts of the AMH molecule all detected significantly higher levels in women with PCOS compared with control women. The relative distribution of AMH isoforms did not differ between women with PCOS and control women. AMH isoforms alone and in combination with baseline characteristics predicted PCOS with close to 100% area under the receiver operating characteristic curve. (Fertil Steril Ò 2019;112:149-55. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

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Variation in circulating antimüllerian hormone precursor during the periovulatory and acute postovulatory phases of the human ovarian cycle

Cited by 19 publications

References 35 publications

Anti-Müllerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women

Anti-Müllerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women

Changes in Circulating ProAMH and Total AMH during Healthy Pregnancy and Post-Partum: A Longitudinal Study

Associations of different molecular forms of antimüllerian hormone and biomarkers of polycystic ovary syndrome and normal women

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