Comparison of structural and hormonal changes in the ovary betweenwomen with polycystic ovary syndrome and healthy controls: A prospective follow-up study of over 10 years

The aim of the study is to assess hormonal and structural changes in the ovary differ between women with polycystic ovary syndrome (PCOS) and healthy controls over a 10-year period of aging. This study designed as a prospective nested-cohort study was conducted within a previously established prevalence study of female staff in the Mineral Research and Exploration (MTA) institution. Of the initial study population, 68 were diagnosed with PCOS at ≥35 years-old, based on the Rotterdam criteria. Among the 68 PCOS patients contacted for the current study, 41 (60.3%) agreed to participate, forming the "study group". Additionally, a total of 43 age and body-mass index (BMI)-matched women were included from the initial study population of 183 healthy controls ≥35 years-old to serve as the "control group". Transvaginal/pelvic ultrasonography was performed to measure antral follicle count (AFC) and ovarian volume (OV) between March 2022 and March 2023. Morning blood samples were collected to assess hormones [anti- Mullerian-hormone (AMH), Total-testosterone (TT), sex-hormone binding globulin (SHBG), free-androgen-index (FAI), dehydroepiandrosterone-sulfate (DHEAS)]. Changes in ovary structure and hormones were evaluated by calculating the "Delta" over a period of ~12-13 years. According to results of current study the mean±SD age (44.1±6.5 vs. 46.4±4.2 years, respectively) and the median [interquartile range (IQR)] of the BMI [24.7(IQR: 21.9-27.8) vs. 25.2(IQR: 23.2-28.9) kg/m2, respectively] were comparable between PCOS and control groups. Regarding the comparison of the structure of the ovaries, OV and AFC were significantly higher in both ovaries of the PCOS group compared to controls. Over the follow-up period, a significantly higher decrease in AFC in the right ovary [Delta-AFC-right: -7.8(±4.7) vs. -3.5(±3.2), respectively, p=0.008] and in the left ovary [Delta-AFC-left: -7.9(±6.2) vs. -4.2(±3.1), respectively, p=0.022] was found in PCOS group. Regarding the hormonal profile, AMH, TT, FAI, and DHEAS were significantly higher in PCOS compared to controls. When comparing the delta values of the hormonal changes over the 10 years, v significantly higher decreases in serum TT [Delta-TT: -11.5(±12.8) vs. -5.2(±9) ng/dL, respectively, p=0.01], and serum AMH [Delta-AMH: -2.5(IQR;-3.35;-1.19) vs. - 1.15(IQR:-1.87;-0.69), respectively, p=0.007] were observed in PCOS group. No significant differences were found in delta-SHBG, delta-FAI and delta-DHEAS. When serum AMH levels were tested as a marker for diagnosis of PCOS in perimenopausal women (mean age of 44), receiver operator characteristics curve analysis revealed an area under the curve (AUC) of 0.72 (95% CI, 0.60–0.83) with a cut-off value of 0.295 ng/mL (specificity of 0.81 and sensitivity of 0.61). In conclusion, in aging PCOS women compared to healthy controls, significantly higher decreases in AFC, OV, AMH and TT were observed. Despite the higher decrease in those parameters, aging PCOS women still exhibit high AMH, OV, AFC and androgen levels. AMH could have a moderate value as a marker for the diagnosis of PCOS in perimenopausal women, with an AUC of ~0.70. Further follow-up trials in unselected populations, stratifying by age, are warranted to identify a reliable diagnostic marker for PCOS in aging women.