Steroidogenesis-Related Genes
Genes such as CYP21, CYP11a, CYP17, and CYP19 are integral to ovarian and adrenal steroid hormone production. Variants in these genes can disrupt hormone synthesis, contributing to the hormonal imbalances typical of PCOS⁸ ¹².

Genes Influencing Hormone Sensitivity
AR (Androgen Receptor) and SHBG (Sex Hormone Binding Globulin) play a key role in how the body responds to circulating hormones. Genetic changes here can enhance androgen effects, leading to symptoms like acne and excess hair growth⁸ ¹².

Gonadotropin Regulation Genes
LH, AMH, and FSHR are involved in regulating follicle development and ovulation. Mutations or dysregulation in these genes may impair reproductive function and contribute to infertility in individuals with PCOS⁸ ¹².

Genes Involved in Insulin Dynamics
PCOS is closely linked to insulin resistance, often influenced by genes such as INS, CAPN10, and IRS-1/2. These genes affect insulin secretion and action, and their alteration can exacerbate metabolic symptoms⁶ ¹².

Epigenetic Regulators of PCOS
Genes like NCOR1 and PPARG1 are associated with epigenetic regulation, impacting how other genes are expressed. These regulators may influence PCOS development without changing the underlying DNA sequence⁸ ¹². 

Additional Genetic Contributors
Other genes, including FTO, PCOS1, and SRD5A1/2, have also been linked to PCOS. These genes may affect diverse traits such as metabolism, fat distribution, and androgen activity, further illustrating the multifaceted genetic nature of the condition¹².

Recent studies highlight clear racial and ethnic differences in the prevalence and metabolic impact of PCOS. Hispanic women with PCOS are more likely to experience severe metabolic complications, including higher rates of insulin resistance, elevated fasting glucose, and an increased risk of type 2 diabetes. One study reported a 42.2% prevalence of metabolic syndrome in Hispanic women with PCOS, significantly higher than that of non-Hispanic Black (24.5%) and non-Hispanic White women (33.8)⁷ ¹⁶. 

Non-Hispanic Black women, while showing a lower rate of certain metabolic syndrome components such as hypertriglyceridemia, still demonstrate elevated insulin resistance and a heightened risk for type 2 diabetes⁵ ⁷. Additionally, qualitative research has shown that American Indian women with PCOS often face culturally specific barriers in diagnosis and care—such as limited access to specialists and a lack of culturally responsive education—highlighting how PCOS may be underdiagnosed or undertreated in Indigenous communities³. These findings suggest that both Hispanic and Black women—and other marginalized groups—are disproportionately affected by the metabolic burden of PCOS, though the clinical presentation and risk factors may vary between groups.

Insulin, a hormone produced by the pancreas, plays a critical role in helping cells absorb glucose from the bloodstream to use for energy. In many individuals with PCOS, the body’s cells become resistant to insulin’s effects—a condition known as insulin resistance. This means glucose is less efficiently absorbed, leading to elevated blood sugar levels¹⁴ ⁴.

In response, the pancreas compensates by producing more insulin, resulting in hyperinsulinemia (excess insulin in the blood). While this helps to control blood sugar temporarily, it triggers other hormonal consequences—particularly in the ovaries¹⁶. 

Elevated insulin levels stimulate the theca cells in the ovaries to produce more androgens, such as testosterone. This overproduction of male hormones contributes to many hallmark symptoms of PCOS, including acne, irregular periods, and excess hair growth⁶ ¹⁴. 

Moreover, high insulin can reduce levels of sex hormone-binding globulin (SHBG), a protein that normally binds to excess androgens in the bloodstream. Lower SHBG levels mean more free, active androgens, which intensifies the hormonal imbalance⁴ ⁶.

Chronic low-grade inflammation plays a central role in the development and progression of PCOS. Unlike acute inflammation caused by injury or infection, this inflammation is persistent and systemic, often driven by abnormal immune activity. In women with PCOS, white blood cells release elevated levels of pro-inflammatory cytokines like interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), even without any infection—suggesting the immune system itself contributes to the disorder’s pathology⁵ ¹⁵.

This inflammation directly influences hormone production in the ovaries. Cytokines stimulate theca cells to increase androgen synthesis, such as testosterone. Studies show that exposure to inflammatory signals like IL-1β and lipopolysaccharide (LPS) increases the expression of key steroidogenic enzymes in ovarian cells, leading to hormonal imbalances typical of PCOS⁵ ¹³. 

Low-grade inflammation also interacts with insulin resistance, another core feature of PCOS. Inflammatory cytokines impair insulin signalling, while excess insulin further activates inflammatory pathways. This creates a cycle: inflammation raises androgens, which worsen insulin resistance, which in turn fuels more inflammation⁵ ¹¹. This feedback loop contributes to both the reproductive and metabolic complications of PCOS, including irregular periods, obesity, and type 2 diabetes⁵ ¹⁸. 

Overall, low-grade inflammation is not merely a byproduct of PCOS—it is a driver. By promoting both androgen excess and insulin resistance, it plays a key role in the disorder’s progression. Targeting inflammation could lead to better outcomes for both reproductive health and metabolic function in women with PCOS⁵ ⁹.

In a healthy menstrual cycle, follicles within the ovaries develop under the influence of hormones like follicle-stimulating hormone (FSH). One of these follicles typically matures into a dominant follicle, which then releases an egg during ovulation. However, in individuals with PCOS, the ovaries often produce abnormally high levels of androgens, such as testosterone⁴ ⁸. 

This excess of androgens disrupts the delicate hormonal balance required for normal follicle development. As a result, many follicles begin to grow but fail to mature fully. These underdeveloped follicles stall in their growth phase and do not release an egg—a process known as anovulation⁶ ¹². Without ovulation, the menstrual cycle becomes irregular or may even stop entirely, which is a hallmark symptom of PCOS⁴ ¹⁴. 

Additionally, the accumulation of these immature follicles in the ovaries gives rise to the "polycystic" appearance often seen in ultrasound imaging. Despite the name, these are not true cysts, but rather fluid-filled sacs containing undeveloped eggs that never completed the ovulatory process⁴ ⁸.

This androgen-driven disruption in follicle maturation not only impairs fertility but also contributes to broader hormonal imbalances, including elevated luteinizing hormone (LH) levels and reduced progesterone, further exacerbating cycle irregularity and associated symptoms⁴ ¹³.