What are fibroids?     

     Uterine leiomyomas (also referred to as fibroids or myomas) are the most common pelvic neoplasm in females. Fibroids are noncancerous monoclonal tumors arising from the smooth muscle cells and fibroblasts of the myometrium. They arise in reproductive-age females and, when symptomatic, typically present with symptoms of abnormal uterine bleeding and/or pelvic pain/pressure. Uterine fibroids may also have reproductive effects (eg, infertility, adverse pregnancy outcomes).

Uterine fibroids are benign, hormone-dependent neoplasms (benign tumors) of the myometrium, which mainly consist of smooth muscle cells and are therefore classified as leiomyomas (from Greek leíos = “smooth” and mys = “muscle”). The leiomyoma is usually a nodular, encapsulated, round tumor. Fibroids can occur individually (solitary fibroids), but they are often distributed in large numbers in the uterus, which are then referred to as myomatosus uterus/fibroid uterus.

     Fibroids were first described in 1973 by the British pathologist Matthew Bailey, and at the present time, uterine fibroids are one of the most common gynecological diseases.

 

 

Types of Fibroids

The size of a fibroid can vary, some grow up to 20 centimeters and in individual cases can grow to simulate a pregnancy in the 5th month.

The fibroids are mainly classified according to their location. There are three types of fibroids classified by their location:

  • Intramural Fibroids: the most common are intramural fibroids. These grow in the uterine wall. If they are small, they do not change the shape of the uterus; if they increase in size, they may become ovoid-shaped.
  • Subserosal Fibroids: the subserosal fibroids grow towards the serosa (outer margin of the uterus). When they increase in size, they can grow outward to such an extent that they are only connected to the uterus via a stalk and are then referred to as  pedunculated myoma extending outside of the uterus.
  • Submucosal Fibroids: Submucosal fibroids grow towards the internal uterine cavity. They are rare (5% of fibroids), but cause symptoms early on. Submucosal fibroids can also appear as pedunculated myomas and thus penetrate into the cervix uteri.

In some clinical settings Uterine fibroids are further described using the International Federation of Gynecology and Obstetrics (FIGO) classification system for fibroid location is the most commonly used classification system and is  as follows:

  • Intramural myomas (FIGO type 3, 4, 5) – These fibroids are located within the uterine wall. They may enlarge sufficiently to distort the uterine cavity or serosal surface. Some fibroids may be transmural and extend from the serosal to the mucosal surface.
  • Submucosal myomas (FIGO type 0, 1, 2) – These leiomyomas derive from myometrial cells just below the endometrium (lining of the uterine cavity). These neoplasms protrude into the uterine cavity. The extent of this protrusion is described by the FIGO/European Society of Hysteroscopy classification system and is clinically relevant for predicting outcomes of hysteroscopic myomectomy
  • Type 0 – Completely within the endometrial cavity
  • Type 1 – Extend less than 50 percent into the myometrium
  • Type 2 – Extend 50 percent or more within the myometrium
  • Subserosal myomas (FIGO type 6, 7) – These fibroids originate from the myometrium at the serosal surface of the uterus. They may have a broad or pedunculated base and may be intraligamentary (ie, extending between the folds of the broad ligament).
  • Cervical myomas (FIGO type 8) – These leiomyomas are located in the cervix rather than the uterine corpus.

 

Causes and risk factors for the development of uterine fibroids

causes

Although the exact cause is not yet fully understood, it has been established that both estrogen and progesterone play a key role in the development of fibroids. Some studies suggest that estrogen inhibits the tumor suppressor gene p53 in myoma tissue. This leads to an unchecked proliferation of the cells with an increase in the size of the myoma.

Presumably there is also a genetic predisposition for the development of uterine fibroids. It is believed that there are at least 145 different genes that influence the development of fibroids. Among other things, these genetic factors regulate the effect of hormones in the formation of myoma.

 

Some associated risk factors include:

  • Early menarche  – which refers to mensuration/menarche before 12 years of age.  This is thought to be the result of increases the number of cell divisions, which increases the risk of mutations in the genes that control myometrium proliferation.
  • Reproductive dysfunction (absence of childbirth) . Anovulation – with infertility allows for the continuous effect of estrogens on the myometrium which is unopposed.  while pregnancy reduces the time of free exposure of estrogens to the myometrium as these hormonal effects are reduced during pregnancy.
  • Obesity, leading to insulin resistance  – increases the fraction of free estrogens. At the same time, the conversion of androgens to estrogens increases in adipose tissue – this mechanism is more important in postmenopausal women.

The growth of fibroids is multifactoral and along with hormonal factors which effect fibroid growth a certain role is played by hereditary predisposition. There is also an immune theory for the growth of fibroids: the rapid growth of fibroids is observed with pronounced immune disorders that contribute to increased cell growth, angiogenesis and inflammation. Various growth factors play an important role. Damage to the structure of the uterus: curettage, inflammation, mutations – lead to the expression of growth factors and increase the risk of uterine fibroids and endometrial pathology. Myoma of the uterus can proceed for a long time without pronounced clinical manifestations.

 

Epidemiology

Myoma is one of the most common benign tumors in women. Postmortem, fibroids can be detected in 25% of women over the age of 30. The frequency peak is between the ages of 35 and 45.

The prevalence increases with age up to menopause. Fibroids are also known to be more common in African Americans and do not occur in postmenopausal women. In addition, fibroids are more common in nulliparous women (women who have never given birth) than in women with children.

 

In the Nurses’ Health Study II, a large prospective study in the United States, over 95,000 females ages 25 to 44 were followed from 1989 to 1993. The age-standardized incidence rates of fibroids confirmed by ultrasound or hysterectomy were 9.2 per 1000 woman-years overall, 30.6 for Black females, and 8.9 for White females. Overall incidences by age group were: 25 to 29 (3.3 per 1000 woman-years), 30 to 34 (6.8), 35 to 39 (10.3), and 40 to 44 (16.0).

  • In a population-based study of an urban health plan in Washington, DC, 1364 females ages 35 to 49 years were randomly selected and assessed by survey and/or ultrasound. Newly detected fibroids were present in 59 percent of Black females and 43 percent of White females; for females in their late 40s, the estimated frequency of fibroids was >80 percent and near 70 percent for Black and White females, respectively.
  • A cross-sectional study in Europe of 1756 patients with fibroid-related symptoms found myomas in 12 to 24 percent. Myomas are clinically apparent in approximately 12 to 25 percent of reproductive-age females and noted on pathologic examination in approximately 80 percent of surgically excised uteri.
  • A detailed pathologic study of 100 hysterectomy specimens found myomas in 77 percent of uterine specimens. Most patients had multiple myomas, with an average of 7.6 fibroids.
  • An ultrasound screening study of asymptomatic females aged 18 to 30 found a prevalence of 26 percent in Black females and 7 percent in White females.

The prevalence of leiomyomas increases with age during the reproductive years . Leiomyomas have not been described in prepubertal girls, but they are occasionally noted in adolescents. Most, but not all, patients have shrinkage of leiomyomas after menopause.