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Tumor Discovery Cancer progression in PCOS

mechanism behind PCOS pathogenesis is still largely quality of life in terms of their health. This article might also
unknown, there is a vast amount of evidence indicating aid in the efforts of identifying novel therapeutic targets to
that hyperandrogenism is crucial to the progression and counteract shared dysregulation in PCOS and cancer.
consequences of PCOS . Whether PCOS is a single clinical
[4]
entity or a conglomerate of many diseases with a common 2. Pathophysiology of PCOS
clinical appearance is unclear as of yet. Researchers have PCOS is a multifaceted syndrome and its complex
reported heightened risks of insulin resistance, diabetic pathophysiology is yet to be fully understood. The two most
mellitus, cardiovascular disease, metabolic syndrome, notable phenotypes of PCOS are hyperandrogenism and
endometrial dysfunction, and pregnancy complications in ovarian dysfunction. Increased blood levels of free (unbound)
PCOS patients [5-7] . testosterone, a crucial hormone involved in the pathogenesis
The risk of cancer among PCOS-affected women has of PCOS, are indicative of hyperandrogenism [26-28] . Figure 1
been a topic of debate over the years . Given the high illustrates the pathophysiology of PCOS.
[8]
incidence of PCOS, any link to cancer would be crucial from Androgens, including dehydroepiandrosterone,
the standpoint of public health. Identifying the component dehydroepiandrosterone sulfate, testosterone,
that significantly increases the risk of developing cancer is dihydrotestosterone, and androstenedione, are found
extremely challenging due to the multifactorial nature of in serum in decreasing order of concentration [29,30] .
the syndrome, along with its heterogeneous presentation . The hypothalamic-pituitary-ovarian axis is thought to
[9]
In more developed countries, endometrial cancer is one of be imbalanced in PCOS as a result of neuroendocrine
the most common reproductive cancers, but it is ranked as dysregulation. This leads to increased frequency of
the second most common in less developed countries . gonadotropin-releasing hormone pulses. The increase
[10]
Stein and Leventhal initially described PCOS in 1935, but in frequency of GnRH pulses promotes luteinizing
the first study of PCOS and the risk of endometrial cancer hormone (LH) rather than follicle-stimulating hormone
was only published after 14 years later [11,12] . Although (FSH) production, leading to an increase in LH: FSH
the direct association of PCOS with breast cancer and ratio in PCOS, which causes hyperandrogenism [31,32] . The
ovarian cancer has yet to be established, the incidence of anti-Müllerian hormone (AMH) produced by ovarian
these cancers in PCOS patients has been observed over granulosa cells is a regulatory factor of GnRH release.
the years in several studies [13-15] . Androgens are believed In PCOS patients, high AMH stimulates LH production
to be involved in the pathogenesis of ovarian cancer in through AMH receptor on the hypothalamus and pituitary,
PCOS patients, while the level of estrogen is related to the increasing the secretion of androgen by ovarian theca cells.
progression of endometrial cancer [16-18] . One of the key At the same time, high AMH suppresses FSH receptor and
drugs used in PCOS management is oral contraceptives. aromatase production in granulosa cells; a low level of FSH
Studies have suggested that oral contraceptives interfere prevents testosterone from being converted to estrogen,
with cancer-associated regulations and reduce the risk of thus resulting in androgen excess. Elevated testosterone,
developing cancer in PCOS women [19,20] . The association of in turn, promotes the direct and indirect release of AMH
breast cancer with PCOS is unclear, but incessant research from granulosa cells [33,34] .
efforts have been made to find a strong link between
them. Although the effects of androgen on breast cancer In PCOS, there are disruptions in the interactions
development in PCOS have not been fully understood, and coordination between LH, FSH, insulin-like growth
studies have shown evidence of the role of estrogen in factor 1 (IGF-1), AMH, androgen conversion enzymes,
breast cancer development [21-23] . Several studies are also and additional variables, resulting in arrested ovarian
underway to identify the genes responsible for cancer follicular development. Ovarian hyperandrogenism,
pathogenesis in PCOS [24,25] . hyperinsulinemia from insulin resistance, and intra-ovarian
paracrine signaling are all factors in PCOS that disrupt
We reviewed the current state of knowledge in a
comprehensive manner, specifically the overall potential follicle growth. The reduced FSH level inhibits ovarian
follicular development, which may cause amenorrhea,
of hazardous cancers that could occur in patients with anovulation, and polycystic morphology [33,35-36] .
PCOS, along with the underlying factors and mechanism.
The information provided in this article would help Although insulin receptor gene alterations are
create awareness among the younger generation, thus uncommon, hyperinsulinemia, and insulin resistance are
ameliorating these problems. Early detection and proper two prominent clinical conditions of PCOS in women.
treatment can lessen the burden of clinical symptoms and Insulin resistance, a disordered physiological state caused
concomitant psychological anguish, thus reducing the by impaired glucose transport and utilization, is a result
risk of developing cancer and the effect on PCOS patients’ of the biological effects of insulin being reduced when it is

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