Abstract
A wide spectrum of clinical entities can lead to pre and postmenopausal hyperandrogenism, which is characterized by slow or more rapid onset of virilizing symptoms (menstrual irregularities, hirsutism, androgenetic alopecia). Functional hyperandrogenism in the context of polycystic ovary syndrome (PCOS) remains the most prevalent cause for hyperandrogenism both in pre and postmenopausal females; however, other clinical entities such as ovarian hyperthecosis and benign or malignant neoplasms (e.g., adrenal androgen-secreting adenomas and ovarian tumors of androgen-secreting cells) are often challenging to diagnose. Laboratory testing should include measurement of testosterone, sex hormone binding globulin (SHBG), gonadotropins, estradiol, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and 17-OH-progesterone values, as well as markers of other endocrine disorders leading to secondary hyperandrogenism, especially Cushing's syndrome. Testosterone values of more than 150 ng/dL generally require further investigation, and increased DHEA-S (more than 700 μg/dL) is suggestive of adrenal androgen-secreting tumors. Androgen suppression during prolonged dexamethasone test can facilitate differential diagnosis between adrenal and ovarian androgen excess production and point to autonomous production in case of tumors. In case of smaller ovarian tumors (e.g., Leydig cell), imaging might not be diagnostic, so that in case of high clinical suspicion, selective ovarian catheterization can be a valuable tool, when available. In this paper, we highlight four rare conditions of hyperandrogenism beyond PCOS, each reflecting specific stages or challenges across the female lifespan. We suggest that detailed biochemical testing and high clinical suspicion should promptly lead to valuable invasive diagnostic tools (ovarian catheterization/laparoscopy) in case imaging is not diagnostic.