Defining Hyperandrogenism in Women With Polycystic Ovary Syndrome: A Challenging Perspective

Abstract

This study provides evidence that, by including a steroid profile in the definition of hyperandrogenemia, the majority of women with PCOS are hyperandrogenic, although a clinical and biochemical heterogeneity exists. In addition, these data demonstrate that hirsutism and high androgen levels cannot be used indifferently to define hyperandrogenism.

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

“…As expected, an androgen profile rather than testosterone alone should be used, as documented by several recent studies (12,13,14,15,16,18). A fundamental prerequisite is represented by the fact that if different androgens are needed to fully define hyperandrogenemia in these women, it could be that different mechanisms may be involved in regulating the enzyme activity involved in the androgen production rate or in their metabolic clearance rate (18). In addition, although there is a consensus that increased androgen production in PCOS women is mainly dependent on hyperactivity of the ovarian theca cells, some uncertainty still remains regarding the role of adrenals and extraglandular sites (8), such as the adipose tissue and the liver and possibly the skin cell, as they express the most crucial genes of steroidogenesis and also utilize sex steroid precursors of potent androgens (19,20).…”

“…In fact, it is well know that insulin excess is able to stimulate theca cell steroidogenesis and reduces hepatic SHBG synthesis, thereby leading to hyperandrogenemia (8). This has been confirmed by a long list of studies showing a significant association between insulin and androgens, particularly testosterone and androstenedione (13,14,18). In addition, there is a general consensus that in most women with PCOS, a mild-tomoderate insulin resistance may be responsible for the high prevalence of the metabolic syndrome (39) and that insulin sensitizers, such as metformin, may improve total and free testosterone in these women (1,8).…”

“…In fact, increasing evidence supports that androgen excess represents a constitutive biomarker of PCOS. As expected, an androgen profile rather than testosterone alone should be used, as documented by several recent studies (12,13,14,15,16,18). A fundamental prerequisite is represented by the fact that if different androgens are needed to fully define hyperandrogenemia in these women, it could be that different mechanisms may be involved in regulating the enzyme activity involved in the androgen production rate or in their metabolic clearance rate (18).…”

“…Several recent studies have shown that extremely accurate and sensitive technologies in the detection and analysis of steroids, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) (8), have significantly improved the definition of the androgenemic blood pattern in women with PCOS (11,12,13,14,15,16,17,18). These studies have clearly shown that a steroid profile, including not only testosterone blood levels but also androstenedione and the free androgen index (FAI), may optimize the diagnosis of hyperandrogemia in women with PCOS, therefore improving our understanding on the heterogeneity of its phenotypes.…”

“…Circulating blood concentrations of androstenedione may be high or relatively normal in women with PCOS, often independent of testosterone values, which may reflect a different origin, production rate or metabolic processes (18). They may also refer to a subset of PCOS women with a primary ovarian functional hyperandrogenism, since overproduction of androstenedione from both the ovaries and the adrenals has been demonstrated (53).…”