Introduction

Uterine fibroids (leiomyomas or myomas) are benign growths in or around the uterus. They are quite common and occur in up to 89% of women of reproductive age.¹

Fibroids are mostly symptomless and are discovered by chance on routine tests or scans. Even though the fibroids are harmless by themselves, they could lead to complications in rare cases of pregnancy or result in infertility. When the fibroids are large, they can lead to severe symptoms like heavy bleeding and pelvic pain.² 

Knowing the cause of uterine fibroids will be useful in early intervention. This article discusses the various causes and risk factors.

Hormonal influences

Female sex hormones, particularly oestrogen and progesterone, have a distinct role to play in the development and growth of uterine fibroids.³ These hormones stimulate the fibroid tissue, causing it to enlarge. 

Fibroids are most common during reproductive years when hormone levels are highest; They frequently grow during pregnancy when hormone production increases dramatically, and typically shrink after menopause when hormone levels naturally decline. 

Oestrogen was considered the main hormone causing fibroids to grow. However, recent studies show that progesterone plays a big part too.⁴ Progesterone works by attaching to special receptors in the fibroid cells, which can trigger signals that help the fibroids grow and survive. It also helps increase blood flow to the fibroids so that they grow.

Genetic factors

Both genes and how they are controlled can increase the risk of getting uterine fibroids.
Recent research shows that changes in certain genes and other genetic factors play a big role in the formation of uterine myomas.⁵ Some of these changes include mutations in the MED12 gene, imbalance in other gene levels, problems with an enzyme called fumarate hydratase, and alterations in the chromosomes.

Besides genes, changes in how genes are turned on or off, called epigenetic changes, also contribute to the problem. For example, the way DNA is packaged in fibroid stem cells is different from normal cells, which may help fibroids grow.

Studies have also found certain genetic markers in cases of both early periods and a higher chance of getting fibroids.⁵ 

Racial and ethnic disparities

Uterine fibroids, though affecting a majority of women worldwide, are more prevalent among Black women than other races. The incidence can be as high as 3-4 times more than that of other women.⁶

When compared with the general population, the growth of fibroids in Black women is distinctly different. Black women develop larger uterine fibroids at an earlier age. Their symptoms are more frequent, severe and debilitating, including pelvic pain, bladder issues, and heavy and/or abnormal menstrual bleeding. For Black women in perimenopause or menopause, uterine fibroids continue growing rather than slow or cease, contrary to the general population. Genetic differences may also be the reason why fibroids are more common in this group.⁷

Obesity and lifestyle factors

Women who are obese have a higher risk of developing uterine fibroids compared to women of normal weight. Those with the highest body mass index (BMI) had a 19% higher risk. Gaining more weight after the age of 18 also increases the risk by 26% compared to those whose weight stayed the same. However, the risk doesn’t increase evenly at all weight levels. Obesity may increase the risk of having uterine fibroids, but the relationship is not completely linear.⁸

There is also a connection between diet, lifestyle, and the risk of developing uterine fibroids (myomas), but it is complex and not always clear.⁹

• High glycemic index foods: A diet high in foods that raise blood sugar (high glycemic index and glycemic load) quickly may increase the risk of fibroids. This could be because these foods increase the levels of certain hormones and growth factors that help fibroids grow
• Alcohol: drinking alcohol, especially beer, over many years, may increase the risk of fibroids, though not all studies agree
• Caffeine (coffee and tea): Most studies do not show a strong link between caffeine and fibroid risk, but some suggest a possible increased risk for younger women
• Soy products: The effect of soy is not determined, with conflicting views across studies
• Fats, meat, and fish: The evidence is mixed. Some types of fats and fatty acids may slightly raise or lower risk, but overall, total fat intake doesn’t seem to have a major effect. The impact of eating meat or fish also varies between populations and may depend on other factors, like pollutants in food
• Fruits and vegetables: Eating more fruits and vegetables, especially citrus fruits and green vegetables, is linked to a lower risk of fibroids. These foods contain natural compounds (phytochemicals) that may help prevent fibroid growth

A diet high in fruits and vegetables and low in high-sugar foods may reduce the risk of uterine fibroids. The effects of soy, meat, fish, fats, and alcohol are less clear and may vary between individuals and populations. Healthy lifestyle choices, especially a balanced diet rich in plant foods, could help avoid fibroids.

Environmental exposures

Exposure to endocrine-disrupting chemicals (EDCs) may increase the risk and severity of uterine fibroids by disrupting hormones and affecting how uterine cells grow and repair themselves.¹⁰

EDCs are chemicals found in everyday items like plastics, personal care products, and even some foods. These chemicals enter our bodies through eating, breathing, or the skin. EDCs can interfere with the body’s natural hormones by either mimicking them or blocking their normal actions.

Recent research shows that women exposed to higher levels of EDCs, such as phthalates and parabens, may have a higher risk of developing uterine fibroids. These chemicals can affect how cells grow and die, and cause changes in gene regulation, which can aid the growth of fibroids.

Studies have shown that exposure to EDCs during childhood or before birth can increase the likelihood of fibroids later in life by damaging the DNA repair process in uterine cells. Some groups, like Black women, may be exposed to higher levels of certain EDCs, which explains differences in fibroid rates among different populations.

Reproductive history

• Early menarche (early periods): Getting your period at a young age seems to slightly increase the risk of developing fibroids later in life. Starting periods early may mean a longer lifetime exposure to oestrogen, which can cause fibroids
• Nulliparity (never having children): Women who have never given birth have a higher chance of developing fibroids compared to women who have had children. Pregnancy and childbirth seem to have a protective effect. It could be due to the hormonal changes during pregnancy or the changes in the uterus after birth¹¹

Vitamin D deficiency

Having low levels of vitamin D may increase the risk of developing uterine fibroids. Women with vitamin D deficiency are more likely to develop fibroids. They also tend to be larger. Vitamin D can affect cell growth and cell death.¹² Research is on to see if vitamin D can effectively treat or prevent fibroids in humans.

Gut microbiota and oestrogen metabolism

An unhealthy gut microbiome may contribute to fibroid growth by affecting hormones and inflammation.

• Gut microbiome imbalance: Studies show women with fibroids tend to have less diverse gut bacteria and altered bacterial communities¹³
• Oestrogen connection: Certain gut bacteria help regulate oestrogen levels. An unhealthy gut microbiome can lead to higher oestrogen levels, which may trigger fibroid growth¹⁴
• Inflammation & immune effects: Gut bacteria influence inflammation and immune responses. Imbalances might create an environment that promotes fibroid development¹⁵ 

Extracellular matrix (ECM) and tissue environment

Extracellular matrix (ECM) is like a scaffold that holds tissues together.¹⁶

In uterine fibroids, there's too much ECM, making the fibroids tough and rigid.¹⁷

• Too much ECM: Fibroids have a lot of extra ECM made of proteins like collagen and fibronectin. This excess ECM is what makes fibroids firm
• Role of hormones: oestrogen and progesterone, the female hormones, encourage cells to produce even more ECM
• Growth factors: Substances called growth factors, such as TGF-β and PDGF, also promote ECM buildup in fibroids
• Cytokines: Certain proteins that affect inflammation and immunity also contribute to the development of fibroids

Summary

Uterine fibroids develop due to a complex interplay between diverse factors, like hormonal influences (oestrogen and progesterone), genetic factors, racial predispositions, lifestyle, environment, reproductive history, vitamin D deficiency, gut microbiome imbalances, and extracellular matrix abnormalities, to name a few.

Understanding these can help women to recognise personal risk factors and seek timely medical help. While fibroids affect up to 89% of reproductive-age women and are often symptomless, early detection can prevent complications like heavy bleeding, pelvic pain, or fertility issues.
Some research suggests dietary interventions, maintaining a healthy weight and ensuring adequate vitamin D levels may help reduce fibroid risk. These approaches give women practical tools for potential prevention. As more research takes place, particularly regarding genetic markers, gut microbiome influences, and environmental factors, more prevention and treatment strategies will emerge.