Polycystic ovary syndrome (PCOS) is a challenging diagnosis for physicians to make. Its classification as a “syndrome” indicates that a constellation of symptoms may be observed, including acne, hirsutism, other signs of hyperandrogenism, amenorrhea, and infertility. Additionally, there is no single diagnostic test or algorithm that physicians use to assess patients. Recent consensus has formed around using the Rotterdam criteria to diagnose women with PCOS. The Rotterdam criteria require women to have two of the following symptoms to be diagnosed with PCOS: clinical or biochemical signs of androgen excess, ovulatory dysfunction, or polycystic ovaries. In addition, PCOS is a diagnosis of exclusion, which requires physicians to rule out common diseases that could present with similar symptoms. This list includes hypothyroidism, hyperprolactinemia, and non-classic congenital adrenal hyperplasia, and could extend to include Cushing’s syndrome, hypogonadotropic hypogonadism, or androgen-secreting tumors depending on the patient’s presentation.
The diagnosis can be especially complicated in adolescents or peri-menopausal/menopausal women. For adolescents, many PCOS symptoms may be routine during puberty (e.g. acne or irregular menstrual cycles), which makes distinguishing between pathological and normal processes complicated. This problem is further exacerbated by the fact that ovaries often display PCO morphology during pubertal development; therefore, ovarian imaging is not recommended for PCOS diagnosis in adolescents. Exceptions to the standard diagnostic criteria are also proposed for women nearing or after menopause. The 2018 International Evidence-based Guideline (https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline) recommends considering historical, rather than current, oligo-ovulation status due to menstrual cycles becoming less regular in peri-menopausal women. The Guideline also suggests evaluating a woman’s history of PCO morphology or assessing ovarian morphology using age-specific criteria due to ovarian follicle numbers decreasing as women age.
Given these challenges, research efforts have recently focused on determining whether there are biomarkers that could be useful in the diagnosis of PCOS. Anti-Müllerian hormone (AMH) has received considerable attention as a potential biomarker of PCOS since its concentrations are highly correlated with the number of ovarian follicles and may even be a suitable substitute for ovarian imaging. However, there are a number of limitations associated with the use of AMH for PCOS diagnosis. First, assays from different manufacturers have variable reactivity with the multiple forms of AMH present in circulation. Second, overlap exists between AMH concentrations measured in women with and without PCOS. Third, lack of a certified reference material, and therefore assay standardization, complicates selection of cut-off values. Finally, studies across broader cohorts of women, spanning both age and different ethnic groups, are critical if AMH is to be useful for PCOS diagnosis.
Early research has also identified several regulatory microRNAs that are elevated in women with PCOS. While many studies have employed follicular fluid, some have assessed microRNAs in serum, which would make them more useful for routine diagnosis. Some identified microRNAs are predicted to have effects on insulin or testosterone concentrations, which are dysregulated in women with PCOS. However, there is no consensus on potential diagnostic microRNAs at this point. Overall, further studies are required if either AMH or selected microRNAs would be added to the recommended diagnostic criteria for PCOS.
- Karakas, Sidika E. “New biomarkers for diagnosis and management of polycystic ovary syndrome,” Clinica Chimica Acta, 2017.
- Sørensen et al. “MicroRNAs related to androgen metabolism and polycystic ovary syndrome,” Chemico-Biological Interactions, 2016.