Think of a hormone as a key and the cells of its target tissue, such as an organ or fat tissue, as specially shaped locks. Scientists have identified over 50 hormones in the human body so far. Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, skin, muscles and other tissues. In some individuals, yes—but improvements are more closely tied to insulin sensitivity than weight alone. First, women with hyperandrogenemia exhibit either higher basal insulin secretion and decreased post-prandial insulin secretion (O’Meara et al., 1993), or exaggerated acute insulin response to glucose (Dunaif and Finegood, 1996). In syndromes of extreme insulin resistance, and in obese women with PCOS, insulin resistance is the driver of the ovarian production of androgens (Spiegelman and Flier, 1996); however, in the most common form of PCOS, androgen excess is instrumental in promoting hyperglycemia. Moderate androgen deficiency during aging predisposes men to increased adiposity and insulin resistance leading to metabolic syndrome. Therefore, we propose that moderate androgen deficiency in men promotes adiposity and insulin resistance, but with moderate β-cell dysfunction and the incidence of T2D is mild. Therefore, the integration of androgenic and metabolic signals could be an evolutionary strategy to enhance muscle anabolism and glycogen storage in males when food is available. The evolutionary and biological basis for testosterone stimulation of insulin secretion in males is likely to promote anabolism, since both testosterone and insulin are anabolic hormones. Surprisingly, male rats with castration-induced testosterone deficiency exhibit a decrease in β cell mass due to increased apoptosis and decreased proliferation, but this is not observed in castrated male mice (Harada et al., 2018). Testosterone action on an extranuclear AR in β cell amplifies the insulinotropic action of islet-derived GLP-1 via increasing cAMP production and PKA activation. We reasoned that because GLP-1 is secreted by α-cells (Liu et al., 2011, Marchetti et al., 2012), testosterone would enhance GSIS in cultured islets but not in cultured INS-1 cells (which do not secrete GLP-1). Together, these observations suggest that testosterone is necessary for normal GSIS in men, and that men with androgen deficiency (e.g., those undergoing ADT) develop β-cell dysfunction that predisposes them to T2D. This suggests that the hyperglycemia observed in patients treated by ADT is at least partially due to β cell dysfunction leading to insulin deficiency. These improve insulin sensitivity and reduce inflammation. Inflammation also feeds back into insulin resistance, creating a reinforcing loop. PCOS is characterized, in many cases, by elevated or dysregulated androgens (e.g., testosterone). In reality, they are outward expressions of deeper metabolic and hormonal dysregulation. Its primary role is in glucose metabolism and androgen reduction. D-chiro-inositol is produced from myo-inositol via an enzyme called epimerase, which converts myo to d-chiro in insulin-sensitive tissues. Women with PCOS show reduced inositol availability in ovarian follicular fluid — a deficit that impairs FSH sensitivity and contributes to poor oocyte quality even when FSH levels are adequate. It functions as a second messenger in FSH signaling within ovarian granulosa cells.
