Relative importance of AMH and androgens changes with aging among non-obese women with polycystic ovary syndrome

BACKGROUND To assess the changes in phenotypes and endocrine profiles of women with polycystic ovary syndrome (PCOS) with advancing age. METHODS In a cross-sectional study conducted at a private tertiary fertility clinical and research center we identified anonymized electronic records of 37 women who had presented with a prior diagnosis of PCOS. They were stratified as younger (<35 years) and older (≥40 years). As controls, we identified 43 women with age-specific low functional ovarian reserve and 14 young women with normal functional ovarian reserve. Endocrine profiles for each group were evaluated based on total (TT) and free testosterone (FT), anti-Müllerian hormone (AMH) and sex hormone binding globulin (SHBG). RESULTS Patients including those with PCOS were mostly non-obese, evidenced by normal BMIs (21.6 ± 6.0) with no differences between study groups. Young PCOS patients presented with a typical pattern of significant hyperandrogenemia and elevated AMH in comparison to young women with normal functional ovarian reserve [TT 44.0 (32.9-58.7) vs. 23.9 (20.3-28.1) ng/dL, (P<0.05); and AMH 7.7 (6.2-9.1) vs. 2.5 (2.0-3.0) ng/mL, (P<0.05)]. With advancing age, hyperandrogenemia in PCOS diminished in comparison to young women with normal functional ovarian reserve, resulting in similar TT levels [28.6 (19.7-37.5) vs. 23.9 (20.3-28.1) ng/dL]. Though also declining, AMH remained significantly elevated in older PCOS women in comparison to young women with normal functional ovarian reserve [4.0 (2.7-5.2) vs. 2.5 (2.0-3.0) ng/mL, (P<0.05)]. Patients with low functional ovarian reserve demonstrated significantly lower AMH at both young and older ages compared to women with normal functional ovarian reserve (P<0.05 for both). However, among patients with low functional ovarian reserve no differences were observed at young compared to older ages in TT [17.6 (12.9-24.1) vs. 18.1 (13.6-24.1) ng/dL)] and AMH [0.4 (0.3-0.6) vs. 0.3 (0.2-0.5) ng/mL]. SHBG did not differ significantly between groups but trended opposite to testosterone. CONCLUSIONS The PCOS population predominantly consisted of non-obese phenotype at both young and advanced ages. This suggests that patients with "classical" obese PCOS phenotype rarely reach tertiary infertility care, while non-obese PCOS patients may be more resistant to lower levels of infertility treatments. PCOS patients also demonstrate more precipitous declines in testosterone then AMH with advancing age. These data support incorporation of AMH as diagnostic criterion for PCOS regardless of age, and imply that testosterone should not be relied upon in the diagnosis of PCOS in older women.