Anti-Müllerian hormone receptor could help determine PCOS phenotype, severity
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Levels of anti-Müllerian hormone and the soluble anti-Müllerian hormone receptor 2 could indicate the severity of glucose metabolism impairment associated with remaining ovarian function among women with polycystic ovary syndrome, according to findings from a cross-sectional study published in Clinical Endocrinology.
“By determining biomarkers, it is possible to classify PCOS patients into subgroups that correlate with different PCOS phenotypes and the clinical severity,” Josef van Helden, MD, director of the Laboratory Diagnostic Center at RWTH University Hospital Aachen and assistant professor at the University of Technology in Aachen, Germany, and colleagues wrote. “Regardless of the BMI, low adiponectin and soluble anti-Müllerian hormone receptor 2 levels in patients indicate the PCOS phenotype A, which is correlated with oligomenorrhea or amenorrhea.”
In a cross-sectional study, van Helden and colleagues analyzed data from 130 reproductive-aged women with PCOS recruited from gynecological practices and fertility centers in northern Germany (mean age, 30 years). Researchers assessed weight, height, cycle day and cycle length, as well as levels of fasting glucose, insulin before and after a 75 g oral glucose tolerance test, intact proinsulin, C-peptide and anti-Müllerian hormone (AMH) and the soluble AMH receptor 2. Researchers stratified participants by glucose status: those with normal insulin sensitivity (n = 33; mean BMI, 24.82 kg/m²), those with insulin overstimulation at 60 minutes after the OGTT (n = 22; mean BMI, 25.77 kg/m²) and those with insulin resistance (n = 75; mean BMI, 31.03 kg/m²).
“In these three subgroups, the different PCOS phenotypes were distributed differently,” the researchers wrote. “The insulin resistance group showed the highest proportion of patients with chronic anovulation (88%). In the insulin overstimulation group, 72.7% were still ovulating and showed normal ovarian cyclic activity. In the group with normal glucose metabolism, the proportion of anovulatory patients was 45.5%. A similar distribution was found with hyperandrogenemia.”
Researchers observed strong between-group differences for levels of soluble AMH receptor 2, adiponectin levels, and soluble AMH receptor 2 to AMH ratio. Within the cohort, mean AMH level was 5.88 ng/mL, 5.32 ng/mL and 7.3 ng/mL for women with normal insulin sensitivity, insulin overstimulation and insulin resistance, respectively. The mean soluble AMH receptor 2 to AMH ratio across the three groups was 0.34, 0.51 and 0.24, respectively; mean adiponectin levels across groups were 9.71 ng/mL, 12.78 ng/mL and 7.84 ng/mL, respectively.
Researchers observed a strong correlation between soluble AMH receptor 2 and adiponectin (r = 0.818; P < .0001), indicating a relationship between the degree of glucose metabolic impairment and ovarian function.
“Taken together, these results provide clear evidence that there is a link between glucose metabolism, PCOS phenotype and clinical severity,” the researchers wrote. “Therefore, it is worth looking for biomarkers that can be used to classify and stratify patients.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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Andrea Dunaif, MD
It has been clearly established using the gold standard method, the hyperinsulinemic glucose clamp technique, that the three main Rotterdam phenotypes are associated significant differences in insulin sensitivity. The NIH phenotype, characterized by hyperandrogenism and ovulatory dysfunction, is associated with profound severe insulin resistance and increased risk for type 2 diabetes. The non-NIH Rotterdam phenotypes of ovulatory dysfunction and hyperandrogenism, and ovulatory dysfunction and polycystic ovarian morphology, are associated with minimal, if any, insulin resistance. The study by Van Helden and colleagues confirms these phenotype-associated differences in insulin sensitivity using surrogate markers of insulin resistance; the most insulin-resistant women were those with PCOS with ovulatory dysfunction and hyperandrogenism, the NIH phenotype. The positive correlation between soluble AMH receptor and markers of insulin sensitivity is intriguing, but this finding is constrained by the potential confounding effect of unmeasured factors that could account for the observed association. In summary, classifying PCOS according to Rotterdam criteria is a straightforward and well-validated approach to predicting metabolic risk in affected women, with the NIH phenotype identifying those PCOS who are at greatest risk.
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