Use of the serum anti-Müllerian hormone assay as a surrogate for polycystic ovarian morphology: impact on diagnosis and phenotypic classification of polycystic ovary syndrome

Fraissinet, Alice; Robin, Geoffroy; Pigny, Pascal; Lefebvre, Tiphaine; Catteau-Jonard, Sophie; Dewailly, Didier

doi:10.1093/humrep/dex239

Cited by 65 publications

(55 citation statements)

References 31 publications

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“…A limitation of this approach was that the diagnosis of PCOS did not include PCOM, and it is possible that some HA-EM women with normal AMH levels did have PCOM. Nevertheless, our AMH threshold for PCOM was similar to those established in women with ultrasonographically determined PCOM (32,33,43). Second, waist measurements to assess body fat topography were missing in a substantial number of women.…”

Section: Discussionsupporting

confidence: 79%

Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk

Torchen

Tsai

Jasti

et al. 2019

Obesity

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Objective Women with metabolic syndrome (MetS) have higher endogenous testosterone (T) levels than unaffected women. This study investigated whether hyperandrogenemia (HA) was a marker for increased cardiometabolic risk in reproductively normal premenopausal women. Methods Reproductive hormones and metabolic parameters were assessed in 198 women with regular menses and no clinical hyperandrogenism (eumenorrheic [EM]). Hyperandrogenic EM women were compared with 110 women with NIH criteria polycystic ovary syndrome. Results Twenty‐two percent of EM women had HA. Levels of non–sex hormone–binding globulin (SHBG)‐bound T were elevated in 68% of women, total T levels were elevated in 43% of women, and dehydroepiandrosterone sulfate levels were elevated in 30% of women. The prevalence of HA increased with BMI category (P = 0.01): 12% for BMI < 25 kg/m2, 22% for BMI of 25 to 30 kg/m2, and 31% for BMI ≥ 30 kg/m2. MetS (adjusted odds ratio 2.9; 95% CI: 1.2‐6.9) and dysglycemia risks (adjusted odds ratio 2.7; 95% CI: 1.2‐5.8) were increased in hyperandrogenic EM women compared with normoandrogenic EM women, with adjustment for BMI. SHBG levels were independently associated with these metabolic end points (P < 0.001), whereas androgen levels were not. A cluster analysis confirmed that there was a discrete subset of EM women with HA and metabolic abnormalities. Conclusions HA is common in EM women and is associated with increased risks for MetS and dysglycemia. However, low SHBG levels rather than elevated androgen levels may be the primary predictor of this relationship with metabolic dysfunction.

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Section: Discussionsupporting

confidence: 79%

Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk

Torchen

Tsai

Jasti

et al. 2019

Obesity

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“…The higher AMH levels in phenotype A than in phenotype C or D partly explain the unusually high AMH levels found in the PCOS group in its whole, compared with other studies. This difference is probably not related to the type of assay used because it has been shown that the results obtained with this assay can be superimposed on those of other manual assays .…”

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confidence: 46%

Age‐stratified thresholds of anti‐Müllerian hormone improve prediction of polycystic ovary syndrome over a population‐based threshold

Dewailly¹

2017

Clinical Endocrinology

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In this issue, Quinn et al report their experience on the diagnostic value of the anti-Müllerian hormone (AMH) assay for the recognition of polycystic ovary syndrome (PCOS). This subject remains very much debated and, in particular, there is no consensus on a specific threshold discriminating PCOS from normal women. One of the reasons, but certainly not the only one, is the heterogeneity of the control groups between the various studies reported to date. In their work, Quinn et al have benefited from the formation of a cohort of women from the general population, which is undeniably a strength compared with other studies that used female controls recruited mainly through infertility not related to an ovarian problem. However, the recruitment of patients with PCOS also differs between the various studies, mostly because of selection bias. The Quinn et al's study does not escape this bias, having used a PCOS population including a majority of patients with the phenotype A of the Rotterdam classification ("fullblown" phenotype), whereas the so-called mild phenotypes (C and D) were hardly represented (supplemental Table 1). Therefore, if their control group confirm this fact in their control group. On the other hand, it is interesting to note that the median AMH levels in the PCOS group are much less affected by age, which should make the AMH assay particularly effective in older women, as claimed by the authors. But actually, we would have expected better results from the ROC analysis in this group, which is not so evident in Figure 2. To understand this, we must look at the values of the IQR. In Table 2, it can be seen in the control group that these values decrease parallel to the median values along with advancing age. On the other hand, in the PCOS group, the IQR increases with age, which in my opinion is quite interesting. Indeed, this suggests that AMH levels are much more dispersed among older women. This may suggest that PCOS patients are not all equal to the effect of ovarian ageing, which some studies have found to alleviate PCOS symptoms. 6 Therefore, one can ask the question of the interest of diagnosing a fading PCOS. Would a higher threshold for women over 35 years be more relevant in order to diagnose only those with still active PCOS?Other factors besides age may also influence the AMH threshold for PCOM. The authors mention the effect of weight, but the literature is quite controversial on this point. However, recent studies seem to show that the influence of weight is minimal and that there is no need to stratify the threshold for diagnosis of AMH as a function of weight. 7,8 On the other hand, the authors emphasize the value of a diagnostic threshold in younger women and, in particular, in adolescents in whom ultrasound is often noncontributory. I fully agree with them in their desire to have solid studies, exploring the diagnostic value of the AMH assay for the diagnosis of PCOM, and subsequently PCOS, in adolescents.The study of Quinn et al strengthens us in the belief that the AMH assay will ev...

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“…Rotterdam criteria recognize four PCOS phenotypes: classic PCOS with (type A) and without (type B) polycystic ovaries, ovulatory PCOS (type C) without intermittent or absent cycles, and "non-hyperandrogenic" PCOS (type D) without high T or excessive body hair [1,3]. Phenotype B, however, will likely be subsumed within Type A when three-dimensional ovarian ultrasonography and standardized AMH immunoassays become widely available enabling accurate characterization of polycystic ovaries [9]. So, in essence, PCOS comprises three distinct phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

et al. 2019

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Indian rhesus macaque nonhuman primate models for polycystic ovary syndrome (PCOS) implicate both female hyperandrogenism and developmental molecular origins as core components of PCOS etiopathogenesis. Establishing and exploiting macaque models for translational impact into the clinic, however, has required multi-year, integrated basic-clinical science collaborations. Paradigm shifting insight has accrued from such concerted investment, leading to novel mechanistic understanding of PCOS, including hyperandrogenic fetal and peripubertal origins, epigenetic programming, altered neural function, defective oocytes and embryos, adipogenic constraint enhancing progression to insulin resistance, pancreatic decompensation and type 2 diabetes, together with placental compromise, all contributing to transgenerational transmission of traits likely to manifest in adult PCOS phenotypes. Our recent demonstration of PCOS-related traits in naturally hyperandrogenic (High T) female macaques additionally creates opportunities to employ whole genome sequencing to enable exploration of gene variants within human PCOS candidate genes contributing to PCOS-related traits in macaque models. This review will therefore consider Indian macaque model contributions to various aspects of PCOS-related pathophysiology, as well as the benefits of using macaque models with compellingly close homologies to the human genome, phenotype, development and aging.

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Use of the serum anti-Müllerian hormone assay as a surrogate for polycystic ovarian morphology: impact on diagnosis and phenotypic classification of polycystic ovary syndrome

Abstract: No external funding. The authors have no conflict of interest to declare.

Cited by 65 publications

References 31 publications

Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk

Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk

Age‐stratified thresholds of anti‐Müllerian hormone improve prediction of polycystic ovary syndrome over a population‐based threshold

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

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