research The Search for the Causes of Common Hyperandrogenism, 1965 to Circa 2015
From 1965 to 2015, significant progress was made in understanding androgen excess disorders like premature adrenarche and polycystic ovary syndrome (PCOS). Key discoveries include the identification of unique plasma androgen patterns and the role of 11-oxytestosterones as major adrenal androgens. Research into PCOS pathogenesis highlighted areas such as neuroendocrinology, insulin resistance, and genetics, with genome-wide studies revealing the steroidogenic regulator DENND1A as a key factor. The DENND1A.V2 splice variant is overexpressed in PCOS theca cells, contributing to the PCOS phenotype. Obesity worsens PCOS symptoms through insulin resistance and increased testosterone production. Despite these advances, much remains to be understood about these disorders.