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Tumor Discovery Cancer progression in PCOS

Figure 1. Pathophysiology of PCOS. Hyperandrogenism and ovarian dysfunction are the main phenotypes of PCOS. Neuroendocrine dysregulation
disrupts the balance of the hypothalamic-pituitary-ovarian axis, resulting in an increase in frequency of GnRH release. The increased GnRH pulse frequency
causes an elevated LH: FSH ratio, leading to hyperandrogenism. Several factors such as elevated AMH level, insulin resistance, hyperinsulinemia, low
SHBG level, and increased ROS generation contribute to hyperandrogenism in PCOS. Clinical features of hyperandrogenism include hirsutism, acne, and
androgenic alopecia, while decreased FSH level causes amenorrhea, anovulation, and polycystic morphology. Low progesterone, along with unopposed
estrogen, leads to endometrial hyperplasia.
AMH: Anti-Müllerian hormone; DHEAS: Dehydroepiandrosterone sulfate; FSHR: Follicle-stimulating hormone receptor; GnRH: Gonadotropin-
releasing hormone; LH: Luteinizing hormone; NF-κB: Nuclear factor kappa B; PCOS: Polycystic ovary syndrome; ROS: Reactive oxygen species;
SHBG: Sex hormone-binding globulin.
present at high amounts [35,37] . Insulin resistance is higher testosterone in the blood is unbound, while the remaining
in peripheral tissues, particularly in skeletal muscles. 98% is predominantly bound to sex hormone-binding
Burghen et al., who noted that hyperinsulinemia is related globulin (SHBG). Growing levels of testosterone are
to insulin resistance, made the initial argument that considered a characteristic of puberty in teenage females.
insulin plays a role in ovarian function in women with PCOS may develop if this condition worsens and there is an
hyperandrogenemia [38,39] . In particular, it has been shown overproduction of testosterone [46,47] . In addition to directly
that insulin secreted from pancreatic beta cells acts directly increasing ovarian androgen production, hyperinsulinemia
through its own receptor at physiological concentrations also increases the fraction of free testosterone in PCOS by
on cultivated polycystic ovary theca cells and stimulates lowering the synthesis of liver SHBG . Hence, low serum
[48]
androgen production, which is noticeably higher than SHBG level in PCOS patients leads to hyperandrogenism.
in ovarian theca cells from normal women. Importantly, The production of a large amount of ROS can be
insulin can work in synergy with LH to boost androgen considered a contributing factor in the pathophysiology
biosynthesis, while increasing androstenedione production of PCOS. The imbalance between free radicals and
on its own [38,40,41] . antioxidants in the body occurs from the overproduction
Hirsutism, acne, and androgenic alopecia are clinical of ROS, leading to oxidative stress . Oxidative stress
[45]
signs and symptoms of hyperandrogenism caused is more frequent in obese PCOS patients who develop
by hyperinsulinemia . The majority of women with early insulin resistance . The vast amount of ROS causes
[49]
[42]
PCOS, in fact, have insulin resistance and compensatory increased production of pro-inflammatory cytokines .
[50]
hyperinsulinemia, which is partially attributed to an The pro-inflammatory cytokines that are produced inside
innate insulin resistance mechanism, especially in those the endometrium can easily hinder the mechanism of
who are overweight or obese, or have diabetes [8,43,44] . In action of insulin in PCOS, resulting in insulin resistance
PCOS women, the hypersecretion of adrenocorticotropic and eventually causing hyperandrogenism [51,52] .
hormone causes the overproduction of androgens from the The detailed mechanism of the entire process of
adrenal glands . oxidative stress causing inflammation and eventually
[45]
Hyperandrogenism is mainly manifested by free or leading to hyperandrogenism is still under investigation,
unbound testosterone in the blood. Only 1–2% of the with several pathways and factors considered to be potential

Volume 2 Issue 1 (2023) 3 https://doi.org/10.36922/td.328