Antimullerian hormone levels alone are insufficient and nonspecific for PCOM diagnosis: Study

In the 2003 Rotterdam criteria, polycystic ovarian morphology (PCOM) was included as a criterion for the diagnosis of PCOS. In 2018, the Rotterdam criteria evolved into the universally accepted international guideline diagnostic criteria for PCOS. These criteria consist of any two of three key features: oligo- or anovulation, clinical and/or biochemical hyperandrogenism, and/or PCOM on ultrasound in adults, although other relevant disorders are excluded. The definition of PCOM, including ovarian volume and/or the number of follicles per ovary (FNPO), using ultrasound examination is challenging.

In addition the guideline acknowledged the controversy and challenges associated with this diagnostic criterion, particularly in the adolescent population, where ultrasound is no longer recommended for diagnosis. The accuracy and reproducibility of FNPO measurements depend on the skills of the ultrasound operator as well as the instrument used.

Given these ultrasound challenges, antimullerian hormone (AMH) levels have been proposed as an alternative marker for PCOM as well as for diagnosing PCOS. Antimullerian hormone is a dimeric glycoprotein and predominantly secreted by granulosa cells of the preantral and small antral ovarian follicles. AMH inhibits the recruitment of follicles from the primordial follicle pool. It also seems to inhibit aromatase activity, which is responsible for the conversion of androgens into estrogens. Finally, it has an inhibitory effect on follicle-stimulating hormone-dependent follicle growth. Therefore, increased AMH levels can contribute to ovulatory dysfunction because of the accumulation of antral follicles and to hyperandrogenism because of aromatase inhibition, which are both often observed in women with PCOS. Convincingly, it has been shown that women with PCOS have higher levels of AMH compared with ovulatory women without PCOS. In addition, strong correlations have been observed between follicle number on ultrasound and circulating AMH levels in PCOS. However, significant heterogeneity exists between studies addressing the role of AMH levels as a diagnostic marker in PCOS, leaving the diagnostic role of this hormone unclear. The aim of this study by Kim van der Ham et al was to assess the diagnostic accuracy of AMH for PCOS as well as the accuracy for the detection of PCOM. This work was used to update the international evidence-based PCOS guideline.

Eligible studies were those conducted in humans, published in English, and reporting sensitivity, specificity, and/or area under the curve values. Extracted data included study population, age, body mass index, AMH assay, cut-off value of AMH levels, sensitivity, specificity, and area under the curve values. The risk of bias was assessed using the quality assessment of diagnostic accuracy studies tool. A random effects model was used to test diagnostic accuracy.

Eighty-two studies were included. The adult AMH-PCOS meta-analyses (n = 68) showed a pooled sensitivity and specificity of 0.79 (95% confidence interval [CI], 0.76–0.82; I2 = 86%) and 0.87 (95% CI, 0.84–0.89; I2 = 91%). The adolescent AMH-PCOS metaanalysis (n = 11) showed a pooled sensitivity and specificity of 0.66 (95% CI, 0.58–0.73; I2 = 74%) and 0.78 (95% CI, 0.71–0.83; I2 = 45%). The adult AMH-PCOM meta-analysis (n = 7) showed a pooled sensitivity and specificity of 0.79 (95% CI, 0.72–0.85; I2 = 94%) and 0.87 (95% CI, 0.78–0.93; I2 = 94%).

Authors found a significant heterogeneity among the studies. Multiple factors contributed to this high heterogeneity. Two of these factors include differences in age and BMI. It is well known that AMH levels decrease with increasing age. Even in women with PCOS, who seem to have a prolonged reproductive lifespan and a delayed menopause, AMH levels still decline over time. Similarly, women with a higher BMI appear to have lower AMH levels in the general population as well as in PCOS. There were differences in BMI and age among the included study populations, and not all studies matched their cases and controls for these variables. The use of hormonal contraceptives may also influence AMH levels, just as it does with other sex steroid levels.

In conclusion, this meta-analysis demonstrated that AMH level is a reasonably sensitive and specific marker for detecting PCOM in adults, although it lacks accuracy for PCOM in adolescents. Moreover, the AMH level is unsuitable as a single diagnostic test for a heterogeneous and multicomponent diagnosis, such as PCOS. Heterogeneity among the studies was observed, mainly because of different AMH threshold levels, assay types, and variations in age, BMI, and control group characteristics, with the need for further research to strengthen the current evidence. On the basis of these results, AMH levels alone are not recommended for the diagnosis of PCOS in the 2023 international evidence-based guidelines for the assessment and management of PCOS. However, it could be considered an endocrine substitute for the ultrasound assessment of PCOM. Therefore, AMH is incorporated into the guideline diagnostic algorithm, where it is indicated in those with either (but not both) irregular cycles or hyperandrogenism. This substantive change in diagnostic criteria for such a common condition is expected to reduce inconvenience and the cost of diagnosis. This work has also identified research priority areas moving forward.

Source: Kim van der Ham, M.D.,a Joop S. E. Laven, Ph.D.,a Chau Thien Tay, Fertil Steril® Vol. 122, No. 4, October 2024

https://doi.org/10.1016/j.fertnstert.2024.05.163