What do you know about Uterine Fibroids?

Uterine fibroids are the most common benign pelvic tumours in women.

They are present in up to 8 out of 10 women by the age of 50.

Heavy menstrual bleeding (HMB), the most common symptom, occurs in about 30% of patients and can result in life threatening anaemia (1,2).

Painful and excessive uterine bleeding, interferes with all aspects of everyday life and self-image, resulting in symptoms of distress, feeling helpless, anxiety, depression and lack of support. (1). Women of colour are affected more severely(1). For many women, lack of awareness regarding Uterine fibroids may lead to them living with the condition chronically without seeking care (1).

Uterine fibroids (also known as uterine myomas or leiomyomas) affect a wide cross-section of the population, with prevalence, symptom severity, and overall disease burden generally higher among women of colour (1,2). Uterine fibroids (UF) are benign, monoclonal, uterine smooth muscle tumours believed to arise from a single fibroid stem cell within the myometrium

Symptoms of uterine fibroids – Bleeding and pain

The majority of women affected by uterine fibroids (UF) are asymptomatic, but many women experience symptoms such as heavy and irregular menstrual bleeding.

Heavy menstrual bleeding (HMB), the most common symptom, occurs in about one-third of patients and can result in life threatening anaemia (1,2).

With regard to heavy menstrual bleeding, fibroids significantly alter the production of vasoconstrictors in the endometrium, leading to increased menstrual blood loss. Fibroids also increase the production of angiogenic factors such as basic fibroblast growth factor and reduce the production of coagulation factors resulting in heavy menses (3).

Abnormal uterine bleeding is one of the most common symptoms in women with uterine fibroids. Normal menses occurs every 24 to 35 days. The American Congress of Obstetrics and Gynecology (ACOG) defines heavy menstrual bleeding as diagnosed when bleeding exceeds 80 mL, however for clinical purposes, any level of menstrual bleeding which causes distress to the patient is managed as heavy menstrual bleeding (3).

Submucosal and intramural fibroids both exert significant effects on endometrial gene expression and function. The TGF-β3 downstream effects of excessive TGF-secretion from uterine fibroids influence the entire endometrium. This leads to decreased production of transcription factors necessary for implantation during the window of implantation and aberrant production of coagulation factors during menses. Fibroids also exert their effect on the endometrium through altered gene expression and changes to the immune environment and vasoconstrictive factors(3).

Diagram summarizing the effects of submucosal and intra mural fibroids on bleeding.

Adapted from Ikhena DE et al. 3 AB p640

Pain associated with fibroids

Along with HMB, UF-associated pain is another frequent problem reported by patients .The size and location of UF impacts pain during menstruation but not during pre-menstruation or during sexual intercourse. In addition, fibroid size, often exceeding 10 cm in diameter, can lead to “direct” or bulk” symptoms such as abdominal protrusion; pelvic pressure; urinary urgency, frequency, or incontinence; and constipation and/or tenesmus (1).

The other symptoms associated with fibroids are heterogenous, including pelvic pressure, dyspareunia, bloating, constipation, congestion, heaviness, urinary frequency, and reproductive dysfunction. Uterine fibroids are associated to infertility and adverse pregnancy outcomes, such as miscarriage, abortion, complicated labour and post-partum haemorrhage (2).

It has been suggested that approximately 60% of women with symptomatic fibroids present with multiple symptoms (2).

EFFECT OF SYMPTOMS ON QUALITY OF LIFE

Potential symptoms of uterine fibroids include painful and excessive uterine bleeding, interference with everyday life and self-image, as well as impaired fertility (1). Symptoms associated with UF can negatively impact daily living and quality of life (QoL) (1).

The chronic nature of UF symptoms can ultimately have a severe impact on patients’ day-to-day activities, making it challenging for patients to maintain emotional and psychological well-being (1).

A common emotional response to UF is the concern of self-image and worth, which can contribute to difficulties in relationships. Fatigue and missing work due to UF are reported by many women (1).

More than half of the women in one survey, were disturbed (some, most, or all of the time) by the fear of soiling outer or underclothes and feeling inconvenienced about always carrying extra pads, tampons, and clothing to avoid accidents (4).

Frequent urination caused important to very important distress in 24% of women during the daytime hours and 17% during the nigh (4).

Effects of Uterine Fibroids on a woman’s mental health

Adapted from Herve F et al. 4 A p37

There are numerous studies that highlight the association between fibroids and emotional distress and depression (5).

For example, studies have reported these values for their participants (5):

· 100% reported some type of psychological distress

· 50% reported feeling helpless

· 50% had scores concerning for clinical levels of anxiety

· 22% had scores consistent with clinical depression

· About 25% reported a lack of support

Risk factors for Uterine Fibroids

Several risk factors have been identified, ranging from genetic predisposition to variable lifestyle behaviours (1).

· Modifiable lifestyle factors that may significantly impact UF incidence include vitamin D deficiency, exercise and diet, smoking, obesity, contraceptive use and dyslipidaemia (1).

A positive family history is a significant risk factor for developing uterine fibroids furthermore

women of colour often have severe or very severe work-related symptoms (1).

The burden of disease attributable to UF is substantially higher for women of African descent than for other racial or ethnic groups. Black women develop UF at a younger age, on average around 5.3 years younger than white women. They also have larger and greater numbers of UFs and are more likely to report severe disease than others of similar socioeconomic status, which contributes to a higher risk of complications with surgical treatment. Tumours from women of colour over 45 years of age demonstrated grow fast and did not show a significant decline in growth rate with age (1).

Clinical Fertility Outcomes in the Presence of Uterine Fibroids

One in every ten women seeking fertility treatment has uterine fibroids. The effect of uterine fibroids on infertility is largely dependent on the location of the fibroid, with submucosal and intramural fibroids having the most significant impact (3).

Uterine fibroids are also associated with several pregnancy-related complications, spontaneous abortion, preterm delivery and caesarean delivery (1).

Treatment of Uterine Fibroids

For decades, hysterectomy has been the preferred surgical treatment option for symptomatic uterine fibroids. However, as more women delay maternity beyond the age of 30 years, there is a growing demand for alternatives to hysterectomy. In fact, a more recent national survey revealed that a majority of affected women seeking treatments for symptomatic uterine fibroids prefer treatments that: do not involve invasive surgery (79%), preserve the uterus (51%), and preserve fertility (43% of women aged <40 years) (7).

Uterine fibroids affect a large segment of the population and can negatively impact daily living and QoL of those affected, resulting in severe occupational and economic costs (1).

More recently, several new uterus-sparing therapies, including endometrial ablation, uterine artery embolization, and MRI-guided focused ultrasound, have been introduced, which contributed to a substantial decline in hysterectomy (7).

The medical management of uterine myomas aims to provide relief from clinical symptoms (2).

This is usually performed in order to ameliorate uterine bleeding and haemoglobin levels in patients wishing to avoid or postpone the surgical approach; it has also the purpose of theoretically making possible less invasive surgical treatments by reducing myoma and uterine size. 2 Barra D p2 Heavy menstrual bleeding related to the presence of uterine fibroids is hormonally treated by administering three classes of drugs: oral contraceptives (combined estroprogestin and/or progestins), progesterone receptors (SPRMs) and gonadotropin-releasing hormone (GnRH) agonists in depot formulations. Additionally, tranexamic acid can be employed to limit blood. GnRH-antagonists may overcome the burden of injectable GnRH-agonists (2).

Enhanced patient education and empowerment

For many women, lack of awareness regarding Uterine fibroids and normal menstruation may lead to living with the condition chronically without seeking care(1).Patients need to feel that they understand the disease, have been presented with all of the treatment options, understand which option(s) best meet their needs, and what the risks and benefits of those options are (5).

References

1. Al-Hendy A, Myers E, Stewart E. Uterine Fibroids: Burden and Unmet Medical Need. Semin Reprod Med. 2017;35(06):473–480.

2. Barra F, Vitale SG, Seca M, Scala C, Leone Roberti Maggiore U, Cianci A, et al. The potential role of elagolix for treating uterine bleeding associated to uterine myomas. Expert Opin Pharmacother. 2020;21(12):1419–1430.

3. Ikhena DE, Bulun SE. Literature Review on the Role of Uterine Fibroids in Endometrial Function. Reprod Sci. 2018;25(5):635–643.

4. Hervé F, Katty A, Isabelle Q, Céline S. Impact of uterine fibroids on quality of life: a national cross-sectional survey. Eur J Obstet Gynecol Reprod Biol. 2018;229:32–37.

5. Marsh E, Chibber S, Saad W. Patient-Centered Care and Uterine Fibroids. Semin Reprod Med. 2017;35(06):560–564.

6. Hapangama DK, Bulmer JN. Pathophysiology of Heavy Menstrual Bleeding. Womens Health. 2016;12(1):3–13.

7. Chwalisz K, Taylor H. Current and Emerging Medical Treatments for Uterine Fibroids. Semin Reprod Med. 2017;35(06):510–522.