Uterine fibroids, also referred to as leiomyomas or myomas, are growths that develop in or on the uterus (also known as a womb).¹ Fibroids are very common, and according to the NHS, it is estimated that 2 in 3 women will develop a fibroid at some point in their lives.² Although symptoms are not always present, fibroids can sometimes cause symptoms such as heavy menstrual bleeding, painful periods, bloating and abdominal pain. Whilst the exact cause of fibroids is unknown, researchers have observed a link between the hormones estrogen & progesterone, and fibroid growth.¹ Continue reading to learn more about fibroids and the role of estrogen and progesterone on fibroid growth. 

Understanding Uterine Fibroids

Uterine fibroids are benign tumours (non-cancerous) and are made up of smooth muscle and fibrous tissue. They can present as multiple fibroids, in the form of a cluster, or as a singular fibroid. They often vary by size, which can range from approximately 1 mm to 20 cm, which could influence the severity of symptoms.¹

Classification of Fibroids 

The classification of uterine fibroids is based on the location of the growth, and there are three main areas in which fibroids develop in the uterus. These classifications include:²

• Subserosal: This type of fibroid growth develops on the outside of the uterus, along the wall of the womb, and into the pelvis
• Intramural: This is the fibroid type with the highest prevalence. They develop within the muscle wall of the uterus
• Submucosal: A Submucosal fibroid is a growth that develops in the muscle right under the inner lining of the uterus and into the cavity of the uterus

Risk factors

A few factors have been associated with an increased risk for fibroid growth, including: 

• Age: Age is one of the main risk factors for developing fibroids, mostly affecting women in their 30s and 40s. Additionally, fibroid growth tends to decline in postmenopausal women³ 
• Race: Whilst all females of reproductive age can develop uterine fibroids, black women are at higher risk for developing fibroids in comparison to women from other racial groups. Additionally, black women are more likely to develop larger fibroids and tend to present with more severe symptoms^4,5 
• Weight: A high BMI or obesity could increase the risk of developing fibroids.^6,7
• Hypertension: Hypertension, or high blood pressure, has been associated with a higher risk for developing uterine fibroids⁸ 

Symptoms 

Symptoms of uterine fibroids include:²

• Heavy bleeding during menstruation 
• Painful periods 
• Stomach, or abdominal pain 
• Frequent urination 
• Pain or discomfort during sex 
• Constipation 

It is important to note that often, people with fibroids may not experience any symptoms, especially when the fibroids are relatively small. The presence of these symptoms, as well as their severity, will vary from individual to individual. 

Hormonal regulation in the female reproductive system

Estrogen and Progesterone are two of the main hormones involved in the female reproductive system. They are important for regulating the function of the reproductive system and reproductive processes such as growth, puberty, and the menstrual cycle. 

• Puberty: During puberty, estrogen levels rise, which leads to the development of secondary sexual characteristics. It is the main driver of the ‘growth spurt’ and it results in the maturation of breasts and body composition changes⁹ 
• Menstrual Cycle: Estrogen and progesterone work together to regulate your menstrual cycle. Estrogen mainly plays a role in ovulation, as it rises during the mid-follicular phase and then drops after ovulation is done. It helps thicken the line of the uterus in order to get it ready for pregnancy. Progesterone, on the other hand, maintains the thickening of the uterine lining after ovulation. If pregnancy does not happen, progesterone levels drop, which results in menstruation. This happens because when progesterone levels go down, the uterine lining gets thinner, which results in its shedding (this is what causes a period)¹⁰ 
• Menopause: Estrogen levels start to drop before menopause, and with menopause, the lower levels of estrogen will stop the body from ovulating. Similarly, progesterone levels will also start to go down before menopause, during the ‘perimenopause’ state¹¹ 

The link between estrogen and progesterone and fibroid growth

Estrogen and fibroid growth 

Estrogen could play a role in promoting fibroid growth. Fibroid tissues produce more local estrogen, which further promotes growth. In addition, fibroid tissues contain more estrogen receptors than normal tissue, which makes them more sensitive to the estrogen hormone. Estrogen also encourages progesterone receptors, which can further encourage fibroid growth. Estrogen was also found to slow down or prevent the production of certain tumour-suppressing genes, such as p53, which encourages cell growth and survival. This group of effects could ultimately lead to the development of fibroids and their growth.¹² 

Progesterone and fibroid growth 

Some studies have found that progesterone plays a role in fibroid growth through activating certain signalling pathways. The activation of these pathways promotes fibroid cell survival and growth. Similarly to estrogen, fibroid tissues also have many progesterone receptors, which cause them to be more responsive to progesterone and susceptible to its effects (fibroid cell survival and growth).^13,14 

Treatment options for targeting hormones

Some medical treatments for uterine fibroids are used to target the reproductive hormones, estrogen and progesterone, to manage symptoms and shrink fibroids. The main treatments for fibroids that target hormones include: 

• Gonadotropin-releasing hormone (GnRH) agonists: GnRH agonists are hormones that slow down or prevent the production of estrogen. They are used for uterine fibroids because fibroid growth thrives when estrogen levels are high. Preventing estrogen from being produced even further can slow down fibroid growth and could even allow the fibroids to shrink. This treatment option is more commonly used before surgery, to shrink the fibroids before having them removed surgically and is typically used as a short-term treatment. It is not recommended for long term use due to its side effects, such as menopausal symptoms (e.g hot flashes, muscle stiffness, vaginal dryness, etc…) and the thinning of the bones, which is referred to as osteoporosis¹⁵ 
• Gonadotropin-releasing hormone (GnRH) antagonists: These work similarly to GnRH agonists; however, they are faster-acting. They are primarily used to treat and stop heavy menstrual bleeding and will not have an effect on the shrinking of fibroids.¹⁶ These can be taken for a longer period of time than the agonists, due to the fewer and less severe side effects
• Selective progesterone receptor modulators (SPRMs): This is a treatment option that is not widely used for the treatment of fibroids, and further studies are required before it can be widely used for the treatment of fibroids. Thus far, some studies have shown that SPRMs can be effective for shrinking fibroids and treating heavy menstrual bleeding.https://pubmed.ncbi.nlm.nih.gov/28444736/ They work as antagonists, by binding to progesterone receptors and limiting the effects of progesterone in the body.¹⁷ One form of SPRM that may be used for fibroids is Ulipristal Acetate (UPA), however, dosages need to be managed, and it should be used occasionally. There are concerns with the use of UPA, particularly surrounding its effect on liver damage and toxicity, so it is crucial that your doctor and your liver function are being monitored throughout treatment¹⁸ 

Non-hormonal treatments can include over-the-counter pain medication, birth control, oral therapies (e.g tranexamic acid, elagolix) and non-steroidal anti-inflammatory drugs (NSAIDs). Surgery can also be a possible treatment option, particularly in more advanced cases, but the surgical procedure used can vary depending on fibroid size and location, as well as the number of fibroids present in the uterus. 

Summary 

To summarise, uterine fibroids can be a serious condition that could lead to symptoms which significantly impact your quality of life. Although there is still no specific known cause for uterine fibroids, clinical evidence supports a link between the hormones estrogen and progesterone and the development of these fibroids. Understanding the role of estrogen and progesterone in the reproductive system and their role in fibroid growth will allow for early detection and effective treatment options. Moreover, if you are experiencing symptoms of uterine fibroids, you must speak to your doctor to discuss these symptoms and decide on the best course of treatment.