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