Synonyms: uterine leiomyomas; myomas
Fibroids are extremely common benign monoclonal tumours of the smooth muscle cells of the uterine myometrium, containing a large amount of extracellular matrix with disordered collagen. They start as multiple, single-cell seedlings distributed throughout the uterine wall. These then increase in size very slowly over many years, stimulated by oestrogens and progestogens. As the fibroid grows, the central areas may not receive an adequate blood supply and undergo benign degeneration often followed by calcification. The cause of fibroids is debated but it is thought to be a combination of acquired genetic change plus the effects of hormones and growth factors, possibly related to a response to ischaemic injury at the time of menses.
Fibroids, which are often multiple, are classified according to their position within the uterine wall:
- Intramural (the majority).
- Submucosal: growing into the uterine cavity. They may be pedunculated and may protrude through the cervical os.
- Subserosal: growing outwards from the uterus - can be:
- Pedunculated subserous (abdominal)
Most uterine fibroids are asymptomatic but they can cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure or pain and also occasionally they may contribute to reproductive dysfunction.Fibroids don't undergo malignant change to a sarcoma except in very rare circumstances but tumours assumed to be benign fibroids may occasionally later be identified as uterine sarcomas.Most women with sarcoma have symptoms of a suspected gynaecological malignancy: abdominal pain and abnormal bleeding.
It should be noted that there is a lack of studies regarding predisposing risk factors and fibroid research has been underfunded compared to that for other non-malignant diseases.
- Uterine fibroids are the most common non-cancerous tumours in women of childbearing age, occurring in 77% of women.
- Uterine fibroids are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women.
- Fibroids are more common in obese women and women with an early menarche - factors which increase lifetime exposure to oestrogen.
- Exercise and increased parity are protective factors. Smoking may also be protective
- Fibroids are three times more common in African-American women than in white Americans. Black women tend to be younger at the time of diagnosis and have more numerous, larger and more symptomatic fibroids. Interestingly, fibroids and keloid, both more common in African-American women, have similar genetics.
- Although they have been reported occasionally in adolescents, most women are in their 30s or 40s when the myomas become symptomatic. The incidence increases with age up to the menopause.
- First-degree relatives of a woman with fibroids have a 2.5 times increased risk of developing fibroids themselves
- There is no definite relationship between the use of oral contraceptives and the presence or growth of fibroids. In the majority of menopausal women with fibroids hormone replacement therapy (HRT) will not have any affect but in those where the fibroids do grow, this appears to be proportional to the dose of progestogen.
- Up to half of women with fibroids have no symptoms. The presence of symptoms depends on their size, position and condition.
- They usually present between the ages of 30 and 50 years.
- They may cause excessive or prolonged heavy periods, leading to iron-deficiency anaemia and therefore lethargy and pallor. Larger fibroids, no matter their position, appear to be more likely to cause menorrhagia, possibly due to a variety of growth factors promoting angiogenesis.
- Pedunculated submucosal fibroids may cause persistent intermenstrual bleeding.
- Women with fibroids are slightly more likely than women without, to experience pelvic pain but this is unrelated to the size or number of myomas.
- 5% of pregnant women noted to have fibroids experience acute pain during the pregnancy, due to fibroid degeneration.
- An enlarging uterus may cause lower abdominal discomfort and heaviness due to pressure effects. Pressure on the bowel may cause constipation and pressure on the bladder may cause urinary symptoms.
- Fibroids may present with recurrent miscarriage or infertility. However, only submucous fibroids decrease fertility but their removal restores fertility to baseline rates.
- Palpable abdominal mass arising from the pelvis.
- Enlarged, often irregular, firm, non-tender uterus palpable on bimanual pelvic examination.
- Signs of anaemia due to menorrhagia.
Fibroids are so common that other more serious causes of abnormal bleeding or pelvic mass can often co-exist and need to be excluded. The differential diagnosis for fibroids depends on the symptoms they are causing but includes:
- Dysfunctional uterine bleeding.
- Endometrial polyps, endometrial cancer.
- Chronic pelvic inflammatory disease.
- Tubo-ovarian abscess.
- Uterine sarcoma.
- Ovarian tumour.
- Pelvic masses (other causes of a pelvic mass include tumour of the large bowel, appendix abscess, and diverticular abscess).
- Pregnancy test may be indicated.
- FBC (anaemia), iron studies.
- Pelvic ultrasound may be indicated to exclude other causes of a pelvic mass, to confirm the presence and size of a fibroid and to exclude possible complications such as urinary tract obstruction causing hydronephrosis. Transvaginal ultrasound (TVUS) is more accurate.
- Saline infusion ultrasound is superior to TVUS and hysteroscopy, in detecting submucous fibroids
- MRI is highly sensitive and specific and is occasionally required if ultrasound is not definitive in assessing the fibroid(s) when myomectomy is being considered.
- Endometrial sampling (Pipelle®): for histology in the assessment of abnormal uterine bleeding.
- Hysteroscopy: with biopsies.
- The combination of lactic acid dehydrogenase (LDH), LDH isoenzyme 3 and gadolinium-enhanced MRI is highly accurate in diagnosing leiomyosarcoma pre-operatively, if sarcoma is suspected clinically.
Treatment is only required if symptomatic, as long as other causes of pelvic masses and abnormal bleeding have been excluded. Expectant management is a valid option, especially in the peri-menopause.
- Non-steroidal anti-inflammatory agents (eg, ibuprofen) may be tried. They reduce menstrual blood loss when the cause is unknown but there is little evidence for their effectiveness in fibroid-related bleeding.
- Antifibrinolytic agents (eg, tranexamic acid) may also also reduce menorrhagia.
- Combined hormonal contraception (CHC): despite the 'pill' previously being considered a risk factor for fibroid growth, CHC is helpful if the patient requires contraception, although it is not as effective as a levonorgestrel-releasing intrauterine system (LNG-IUS).
- LNG-IUS (Mirena®):
- A prospective comparative study of 54 women with fibroid-related menorrhagia showed that not only does the LNG-IUS reduce the amount of menstrual loss but also reduces the uterine size in women with fibroids, although women with uterine distortion were excluded.In this study fibroids were associated with a higher expulsion rate, especially if submucous.
- A Cochrane review states that LNG-IUS appears to reduce fibroid-related bleeding but the studies were small and of poor quality.
- Danazol: a Cochrane review could not find any evidence regarding the use of danazol in the management of fibroids.
- Gonadotrophin-releasing hormone (GnRH) agonists:
- Produce reduction in the size of fibroids, in the region of 50% within three months but, once discontinued, fibroids regrow to their former size within about two months; therefore, they are mainly useful pre-hysterectomy. A Cochrane review concluded that their use leads to shorter operation times and shorter hospital stays, and increases the likelihood of a vaginal hysterectomy.
- They are associated with significant side-effects, including significant menopausal symptoms and also bone loss, which can lead to osteoporosis in long-term use.
- Mifepristone is a progesterone receptor inhibitor which is effective at reducing fibroid-related bleeding but, as it results in exposure of the endometrium to unopposed oestrogen, it may cause endometrial hyperplasia.It does not reduce uterine volume and hence has no role pre-surgery.
- Ulipristal acetate:
- A selective progesterone receptor modulator (SPRM), with predominantly inhibitory action. It acts by inhibiting cell proliferation and inducing apoptosis. It has been shown to be superior to placebo and non-inferior to GnRH agonists.[9, 10]
- Like mifepristone however, long term endometrial safety data are still required before SPRMs can be used other than pre-surgery. The licensed indication is for pre-operative treatment and duration of treatment should not exceed two three-month courses of 5 mg daily.
- A recent study showed no endometrial hyperplasia in 107 women treated with four, three-month courses of ulipristal acetate (10 mg daily) followed by either 10 days of norethisterone acetate (10 mg daily) or placebo. It effectively controlled bleeding and pain and reduced fibroid size.
- Aromatase inhibitors, such as letrozole: a Cochrane review concluded that there is insufficient evidence to support their use in the treatment of uterine fibroids.
February 2018 - Dr Hayley Willacy recently read a safety note from MHRA regarding ulipristal acetate. Five reports of serious liver injury, including four cases of hepatic failure needing liver transplantation, have been reported worldwide in women using ulipristal for uterine fibroids.The following temporary safety measures have been introduced while an EU-wide review of the evidence is ongoing:
- Do not initiate new treatment courses, including in women who have completed one or more treatment courses previously.
- Perform liver function tests at least once a month in all women currently taking ulipristal acetate. Stop treatment in any woman who develops transaminase levels more than 2 times the upper limit of normal, closely monitor and refer for specialist hepatology evaluation as clinically indicated. Liver function tests should be repeated in all women 2 to 4 weeks after stopping treatment.
- Check transaminase levels immediately in current or recent users who present with signs or symptoms suggestive of liver injury (such as nausea, vomiting, malaise, right hypochondrial pain, anorexia, asthenia or jaundice). If transaminase levels are more than 2 times the upper limit of normal, stop treatment, closely monitor and refer for specialist hepatology evaluation as clinically indicated.
- Advise women on the signs and symptoms of liver injury.
Surgery is indicated when:
- There is excessively enlarged uterine size.
- Pressure symptoms are present.
- Medical management is not sufficient to control symptoms.
- The fibroid is submucous and fertility is reduced.
Surgical options include:
- Myomectomy - this is used in patients who wish to maintain their reproductive potential or keep their uterus:
- Abdominal myomectomy is a safe alternative to a hysterectomy. However, there is a risk of excessive bleeding and a risk of requiring hysterectomy at the time of the operation. Therefore, blood should be cross-matched pre-operatively and the patient needs to give their consent to hysterectomy should the need arise. Also 4-17% of women will later go on to have a hysterectomy.
- Laparoscopic myomectomy is associated with less pain, shorter hospital stay and reduced recovery time. It is the best treatment option for symptomatic women with symptomatic subserous fibroids, who wish to maintain their fertility.
- Hysteroscopic myomectomy is an established surgical procedure for women with submucosal fibroids and excessive uterine bleeding, infertility or repeated miscarriages.When performed for treatment of abnormal bleeding, this resolves in 74-94% at two years. 12% subsequently require hysterectomy.
- Laparoscopic laser myomectomy is not recommended by the National Institute for Health and Care Excellence (NICE), other than for research, due to lack of evidence for its safety and efficacy.
- Myomectomy carries an annual recurrence rate of 2-3%.
- Pedunculated vaginal fibroids may be removed vaginally but histology is essential to exclude a sarcoma in women aged over 60 years.
- Hysteroscopic endometrial ablation - for women presenting with menorrhagia.
- Total hysterectomy:
- This has been the mainstay of treatment for many years, eliminating both symptoms and the possibility of recurrence, and fibroids are the indication for approximately one third of hysterectomies in the USA.
- In women who have completed their family, hysterectomy remains the most effective treatment for excessive uterine bleeding.
- It is also indicated when there are many fibroids.
- If these are small then the vaginal route is appropriate but if they are large (especially if intraligamentous) then laparotomy is indicated with preservation of ovaries if possible.
- The risk of blood loss is directly related to the uterine size. This may be reduced by pre-treatment with GnRH agonists.
- NICE recommends that laparoscopic techniques for hysterectomy (eg, laparoscopically assisted vaginal hysterectomy, laparoscopic hysterectomy, laparoscopic supracervical hysterectomy and total laparoscopic hysterectomy) appear to be sufficiently safe and effective to support their use. There is, however, a higher risk of urinary tract injury and of severe bleeding in comparison with open surgery.
- Uterine artery embolisation (UAE):
- This procedure has been shown to be both effective (for short- and medium-term symptom relief) and safe for women who wish to keep their uterus, although the effects on fertility and pregnancy are uncertain.[19, 20]
- If patients are considering pregnancy, there is a theoretical risk of placental insufficiency leading to small-for-gestational-age babies, increased caesarean section and prematurity.
- Ensuring the tumour is a benign fibroid and not a malignant sarcoma is essential prior to UAE.
- Women should be informed during consenting that symptom relief may not be achieved for some women and that symptoms may return.
- Although complications are rare, they may necessitate life-saving hysterectomy, consent for which is required prior to the procedure.
- The REST trial was a randomised controlled trial (RCT) comparing UAE with surgery in 157 women followed for five years. There was no difference in reduction in symptoms or patient satisfaction but a third of women having UAE required re-intervention.
- UAE is a cost-effective option compared with hysterectomy at one year, saving £1,000 per patient but this gain is lost by five years due to greater rates of secondary intervention. The faster, shorter recovery time needs to be weighed against the need for further treatment in a third of patients.
- MRI-guided transcutaneous focused ultrasound:
- This procedure has low morbidity and very rapid recovery. High-power pulses of ultrasound are used to ablate the fibroid - there may be skin burns as a result. Long-term outcome (fertility and the need for further treatments) is as yet uncertain.
- NICE now advises that short-term safety and efficacy evidence is now adequate to support the use of MRI-guided transcutaneous focused ultrasound, although notes that further treatment may be required and effects on subsequent pregnancy are uncertain.
- Iron-deficiency anaemia.
- Bladder frequency, constipation (due to increased pelvic pressure).
- Hyaline degeneration (asymptomatic).
- Torsion of pedunculated fibroid.
- Ureteral obstruction causing hydronephrosis.
- Infertility: this may occur as a result of narrowing of the isthmic portion of the Fallopian tube or as a consequence of interference with implantation (submucosal fibroids).
- In pregnancy:
Typically, fibroids regress with the menopause and symptoms resolve.
Further reading and references
; NICE Clinical Guideline (January 2007)
; NICE CKS, February 2013 (UK access only)
; Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril. 2007 Apr87(4):725-36.
; Sarcoma post-embolization for presumed uterine fibroids. Gynecol Oncol. 2008 Jan108(1):244-7. Epub 2007 Oct 22.
; Uterine fibroids: the elephant in the room. Science. 2005 Jun 10308(5728):1589-92.
; Pharmacological treatment of uterine fibroids. Ann Med Health Sci Res. 2014 Sep4(Suppl 3):S185-92. doi: 10.4103/2141-9248.141955.
; Efficacy of the levonorgestrel-releasing intrauterine system in uterine leiomyoma. Int J Gynaecol Obstet. 2012 Jan116(1):35-8. doi: 10.1016/j.ijgo.2011.07.031. Epub 2011 Sep 28.
; Progestogens or progestogen-releasing intrauterine systems for uterine fibroids. Cochrane Database Syst Rev. 2013 Feb 282:CD008994. doi: 10.1002/14651858.CD008994.pub2.
; Danazol for uterine fibroids. Cochrane Database Syst Rev. 2009 Jul 8(3):CD007692. doi: 10.1002/14651858.CD007692.pub2.
; Mifepristone for uterine fibroids. Cochrane Database Syst Rev. 2012 Aug 158:CD007687. doi: 10.1002/14651858.CD007687.pub2.
; Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012 Feb 2366(5):409-20. doi: 10.1056/NEJMoa1103182.
; Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med. 2012 Feb 2366(5):421-32. doi: 10.1056/NEJMoa1103180.
; Long-term treatment of uterine fibroids with ulipristal acetate . Fertil Steril. 2014 Jun101(6):1565-73.e1-18. doi: 10.1016/j.fertnstert.2014.02.008. Epub 2014 Mar 12.
; Aromatase inhibitors for uterine fibroids. Cochrane Database Syst Rev. 2013 Oct 2310:CD009505. doi: 10.1002/14651858.CD009505.pub2.
; Endoscopic management of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 2008 Mar 4.
; NICE Interventional Procedures Guidance, November 2003
; Are the anticipated benefits of myomectomy achieved in women of reproductive age? A 5-year review of the results at a UK tertiary hospital. J Obstet Gynaecol. 2004 Jun
; Treatment of uterine fibroids for abnormal uterine bleeding: myomectomy and uterine artery embolization. Best Pract Res Clin Obstet Gynaecol. 2007 Dec21(6):995-1005. Epub 2007 May 2.
; Severe complications of hysterectomy: the VALUE study. BJOG. 2004 Jul111(7):688-94.
; NICE Interventional Procedures Guidance, November 2007
; NICE Interventional Procedures Guidance, November 2010
; Royal College of Obstetricians and Gynaecologists. Third edition (2013)
; Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results. BJOG. 2011 Jul118(8):936-44. doi: 10.1111/j.1471-0528.2011.02952.x. Epub 2011 Apr 12.
; NICE Interventional Procedures Guidance, November 2011
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