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Understanding Uterine Fibroids

Uterine fibroids are also called myoma or leiomyoma

Understanding Uterine Fibroids

Uterine fibroids (uterine leiomyoma) are benign, monoclonal, hormone-sensitive, smooth muscle tumours of the uterus2, 8. They are the most common benign tumours of the female reproductive tract in pre-menopausal women.

While literature-reported incidence rates for uterine fibroids vary, in part due to the large proportion of women who go undiagnosed, uterine fibroids are estimated to affect between 20% and 40% of women of reproductive age2. Uterine fibroids are reported to be more frequent in the mature age group (40% to 70% of women between 35 years and 50 years) 9,10.

Although a number of risk factors have been linked to the development of uterine fibroids, the causes of uterine fibroids are not fully understood11. Factors such as African or Black-American ethnicity, older age, family history of uterine fibroids, nulliparity (the condition of never having given birth) or lower parity (number of times a woman has given birth), and obesity have all been associated with a higher risk of developing uterine fibroids 11, 12.

Uterine fibroids are often asymptomatic, but when symptomatic, the primary symptoms are heavy (uterine) bleeding, anaemia, abdominal pressure, abdominal pain, increased urinary frequency and infertility2. In particular, heavy menstrual blood loss is one of the most frequently disabling symptoms of uterine fibroids8.

References

  • 126 Reference 2 - Wallach EE, et al. Uterine Myomas: An overview of development, clinical features and management. Obstet Gynecol 2004;104(2):393-406.
  • 481 Reference 8 - Evans P., et al. “Uterine fibroid tumors: diagnosis and treatment.” American Family Physician 2007; 75(10):1503-1508.
  • 482 Reference 9 - Baird DD, et al. High cumulative incidence of uterine leioyomyoma in black and white women : Ultrasound evidence. Am J Obstet Gynecol 2003;188(1):100-107.
  • 484 Reference 10 - Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. 725-36. Fertil Steril. 2007 Apr;87(4).
  • 485 Reference 11- Divakar H. Asymptomatic uterine fibroids. Best Pract & Research Clinical Obstetrics and Gynaecology. 2008. 22: (4), pp. 643–654.
  • 486 Reference 12 - Flake GP, Andersen J, Dixon D. Etiology and Pathogenesis of Uterine Leiomyomas: A Review. 2003. Environmental Health Perspectives.111(8).

Pathogenesis

The pathophysiology of uterine fibroids (also called leiomyoma, fibroma, fibromyoma, myoma or leiomyofibroma) is not well understood. There is, however, some epidemiological evidence to suggest a genetic predisposition for non-syndromic uterine fibroids, although no specific gene has yet been identified.

Oestrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental oestrogens has only recently been explored. Growth factors with mitogenic activity, such as TGF-β3, bFGF, EGF, and IGF-I, are elevated in fibroids and may be the effectors of oestrogen and progesterone promotion12.

Several predisposing factors have been identified as being associated with uterine fibroids, including black race, heredity, nulliparity (the condition of never having given birth), obesity, polycystic ovary syndrome (PCOS), diabetes, and hypertension, and there is emerging evidence that familial predisposition to uterine fibroids is associated with a distinct pattern of clinical and molecular features compared with uterine fibroids in families without this prevalence13.

References

  • 486 Reference 12 - Flake GP, Andersen J, Dixon D. Etiology and Pathogenesis of Uterine Leiomyomas: A Review. 2003. Environmental Health Perspectives.111(8).
  • 487 Reference 13 - Okolo, S.,2008. Incidence, aetiology and epidemiology of uterine fibroids. Best Practice and Research Clinical Obstetrics and Gynaecology. Vol 22:4. Pp 571-588.

Classification of Uterine Fibroids

Uterine fibroids are traditionally classified according to their anatomical location as intramural, submucosal or subserosal. In addition, fibroids may be pedunculated (attached to the uterus by a stalk). Some larger fibroids may have characteristics of each type. Fibroids are not always isolated as there are often several coexistent lesions; in cases of multiple fibroids, a detailed ‘mapping’ of each lesion is valuable from a surgical point of view, although this may not always define a precise clinical situation14.

Fibroids can vary in size from millimetres to over 10 centimetres, and this can have a considerable clinical impact on the patient, with larger fibroids tending to respond less to pharmaceutical interventions, requiring more invasive surgical treatment options15.

Classification of Uterine Fibroids14, 16

  • Intramural fibroids: are fibroids which normally do not distort the uterine cavity and have <50% protruding into the serosal surface of the uterus and are the most common type. They typically develop within the wall of the uterus, beginning as small nodules in the muscular wall of the uterus. With time, intramural fibroids may expand inwards, causing distortion and elongation of the uterine cavity. They typically give the uterus a globular feeling on examination (like early pregnancy). They increase overall blood flow to the uterus and if large can distort and enlarge the internal cavity, even if they do not encroach onto it.
  • Subserosal fibroids: are those were >50% of the fibroid protrudes out of the serosal surface of the uterus. A subserosal fibroid may be sessile or pedunculated. They can grow quite large, but do not typically affect the size of the uterine cavity. They are more likely to produce pressure symptoms than heavy menstrual bleeding or infertility.
  • Submucosal fibroids: are defined as fibroids, which distort the uterine cavity according to the classification by the European Society of Hysteroscopy. The classification of these fibroids is then further divided into three subtypes: pedunculated fibroids without intramural extension (type 0), sessile (fixed in one location) with intramural extension of fibroid <50% (type I), and sessile with an intramural extension of >50% (type II). The degree of intramural extension can be assessed by ultrasonography or by hysteroscopy by observing the angle between the fibroid and the endometrium at the attachment to the uterine wall.

Submucosal fibroids are the fibroid type most likely to interfere with fertility14.

Other types of less frequent fibroids are:

  • Cervical fibroids: are found in the ‘neck’ (cervix) of the uterus and are difficult to remove without damaging the surrounding area.
  • Intraligamentous fibroids: are fibroids which may grow from a subserosal location into the peritoneal folds of the broad ligaments.

 

Illustration shows different types of uterine fibroids

References

  • 488 Reference 14 - Somigliana E, Vercellini P, Daguati R, Pasin R, De Giorgi O, Crosignani PG. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update. 2007 Sep-Oct;13(5):465-76.
  • 490 Reference 15 - National Collaborating Centre for Women’s and Children’s Health. Heavy Menstrual Bleeding – Clinical Guideline. 2007.
  • 492 Reference 16 - Bajekal N, Li TC. Fibroids, infertility and pregnancy wastage. Hum Reprod Update. 2000 Nov-Dec;6(6):614-20.

Fibroids and fertility

Uterine fibroids, and in particular those which distort uterine anatomy and interfere with normal uterine physiology, can have adverse effect on reproductive function, leading to sub-fertility, later pregnancy complications, and miscarriage16. The incidence of fibroids in infertile women without any other obvious cause of infertility is estimated to be between 1% and 2.4%, however, there is a lack of prospective studies available to clearly determine the burden of fibroids in terms of their impact on fertility17.

A number of factors may influence fertility and pregnancy outcomes, including the size, location, and number of fibroids. Available evidence suggests that submucosal, intramural, and subserosal fibroids interfere with fertility in decreasing order of importance. Indeed, submucosal fibroids are linked to a 70% reduction in delivery rate17. There is some data suggesting an impact of the number and dimension of the lesions on fertility; in particular, fibroids over 5 cm in diameter, and located close to the cervix, are more likely to pose a problem16.

References

  • 492 Reference 16 - Bajekal N, Li TC. Fibroids, infertility and pregnancy wastage. Hum Reprod Update. 2000 Nov-Dec;6(6):614-20.
  • 493 Reference 17 - Ezzati M, Norian J, Segars J. Management of uterine fibroids in the patient pursuing assisted reproductive technologies. Womens Health. 2009. 5(4): 413-421.

Uterine Fibroids Economic Impact

Women with uterine fibroids experience significantly worse Health-Related Quality of Life (HRQoL) than women without fibroids3. Heavy menstrual bleeding (HMB) is common in women with symptomatic fibroids, and is associated with a considerable QoL burden, including psychological and social factors, and disruption to a normal routine39. Uterine fibroids impair productivity, increase absenteeism, and are associated with increased disability claims for symptomatic women40. In the CHASM study4 which was carried out in five European countries (France, Germany, Italy, Spain and UK) and used WPAI-SHP to measure absenteeism scores, employed women with uterine fibroids reported an absenteeism rate of 32.7%. Furthermore productivity was impaired by 36.1% and activity was impaired by 37.9%4.

Surgical treatment for uterine fibroids place a significant demand on health care resources. A further economic burden may be associated with the complications resulting from surgery, or the need for re-surgery, particularly in cases where the women have undergone UAE or myomectomy.

References

  • 127 Reference 3 - Spies JB., et al. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002; 99(2): 290-300.
  • 477 Reference 4 - Downes E., et al. The burden of uterine fibroids in five European countries. Eur J Obstet Gynecol Reprod Biol 2010; 152(1): 96-102.
  • 2903 Reference 39 - Clinical Guideline on Heavy Menstrual Bleeding. January 2007. National Collaborating Centre for Women’s and Children’s Health/ NICE
  • 2905 Reference 40 - Stewart EA. Uterine Fibroids. The Lancet. 2001. Vol 357.
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