Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

fertility desired

1st line – medical therapy

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ONGOING
|
fertility desired
1st line – 

medical therapy

A number of treatments cause bone loss with prolonged use, such as gonadotrophin-releasing hormone (GnRH) agonists (e.g., leuprorelin) and antiprogestogens (e.g., mifepristone). Mifepristone has also been noted to cause endometrial hyperplasia in 28% of women and transient transaminase elevations in 4%. [ Cochrane Clinical Answers logo ]

Both GnRH agonists and antiprogestogens cause vasomotor symptoms and selective oestrogen receptor modulators are only effective in post-menopausal women. The use of 'add-back therapy' with hormone replacement therapy may avoid the vasomotor side effects and bone effects of GnRH analogue therapy.[89][90]

These adverse effects limit the role of medical therapies to the short term (3 to 6 months). Consequently, medical treatment is usually provided as a preoperative adjunct in selected cases, such as in patients with heavy bleeding and significant anaemia requiring a period of stabilisation and haemoglobin-enhancement pending surgery.[88]

In some countries, mifepristone is only commercially available as 200 mg/dose tablets, which makes giving the lower doses used for this indication difficult. Consult with a pharmacist, as special compounding of this drug may be required.

The levonorgestrel intrauterine contraceptive device significantly decreases bleeding in women with fibroid-associated heavy menstrual bleeding.

GnRH antagonists (e.g., elagolix, relugolix) in combination with estradiol and norethisterone are approved for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Non-steroidal anti-inflammatory drugs have been tried empirically in the medical management of excessive bleeding, dysmenorrhoea, and pelvic pain.

Tranexamic acid reduces heavy menstrual bleeding and causes necrosis of fibroids, especially larger fibroids.[102][103]

Primary options

leuprorelin: 3.75 mg intramuscularly once monthly for up to 3 months; or 11.25 mg intramuscularly as a single dose

OR

mifepristone (gynaecologic): 5-50 mg orally once daily for 3-6 months

OR

levonorgestrel intrauterine device: insert 52 mg device into uterine cavity, remove and replace (if necessary) after 6 years

OR

elagolix/estradiol/norethisterone acetate and elagolix: 300 mg (elagolix)/1 mg (estradiol)/0.5 mg norethisterone once daily in the morning, and 300 mg (elagolix) once daily in the evening for up to 24 months

OR

relugolix/estradiol/norethisterone acetate: 40 mg (relugolix)/1 mg (estradiol)/0.5 mg norethisterone once daily for up to 24 months

Secondary options

naproxen: 500 mg orally twice daily when required

OR

tranexamic acid: 1300 mg orally three times daily for a maximum of 5 days during monthly menstruation

1st line – myomectomy

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ONGOING
|
fertility desired
1st line – 

myomectomy

The only surgical procedure that preserves fertility and effectively ameliorates fibroid-related symptoms is myomectomy. For women with poor prior reproductive outcome or infertility in whom the only finding is a distorted uterine cavity from the presence of one or more uterine fibroids (most commonly submucous fibroids), myomectomy can promote both fertility and successful pregnancy outcome. Currently, there is no evidence that a laparoscopic approach is any more efficacious than myomectomy through an abdominal incision, although the former is associated with less postoperative febrile illness.[142]

Major complications of myomectomy include recurrence of fibroid growth and haemorrhage. Recurrence rates following myomectomy are higher in laparoscopic myomectomy, particularly in cases with multiple fibroids.[110][111] It is important to recognise that fibroid recurrence does not indicate symptom recurrence or the need for re-intervention. Significant haemorrhage can result in emergent hysterectomy in a small number of cases.[106][107] Hysteroscopic resection can be complicated by fluid overload, coma, and even death.[108]

Patients may also receive medical therapy prior to myomectomy.

The US Food and Drug Administration issued a safety communication cautioning against the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids. This is because power morcellation carries a risk of spreading undetected uterine sarcoma, with resultant worsening prognosis.[83][84]​ Uterine sarcoma is a rare medical condition, particularly in the setting of long-standing uterine fibroids as present in the majority of patients.

fertility not desired

1st line – uterine artery embolisation or myomectomy

Back
ONGOING
|
fertility not desired
|
uterine preservation desired
1st line – 

uterine artery embolisation or myomectomy

Among symptomatic patients who opt for uterine-preserving surgery, alternatives include myomectomy and uterine artery embolisation (UAE).

UAE should be considered only in women not desiring any future fertility. However, pregnancies have been known to occur following UAE, with significant adverse obstetric outcomes, in particular significantly higher miscarriage rates, as well as other adverse events including postpartum haemorrhage and increased risk for caesarean delivery.[127] Therefore, it is important to ensure that women are aware of this and given contraception if required.

Long-term studies of UAE are lacking; however, in one study comparing outcomes of UAE and abdominal myomectomy, the former resulted in a 29% rate of further invasive therapy during the 3 to 5 years of follow-up, as compared with 3% in the myomectomy group.[73]

If haemorrhage becomes significant, myomectomy may need to be converted to hysterectomy intra-operatively.[106][107]

The US Food and Drug Administration issued a safety communication cautioning against the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids. This is because power morcellation carries a risk of spreading undetected uterine sarcoma, with resultant worsening prognosis.[83][84]​ Uterine sarcoma is a rare medical condition, particularly in the setting of long-standing uterine fibroids as present in the majority of patients.

Consider – preoperative medical therapy

Back
ONGOING
|
fertility not desired
|
uterine preservation desired
Consider – 

preoperative medical therapy

Additional treatment recommended for SOME patients in selected patient group

Medical treatment is usually provided as a preoperative adjunct in selected cases, such as in patients with heavy bleeding and significant anaemia requiring a period of stabilisation and haemoglobin enhancement pending surgery.[88]

A number of treatments cause bone loss with prolonged use such as gonadotrophin-releasing hormone (GnRH) agonists (e.g., leuprorelin) and some antiprogestogens (e.g., mifepristone), which have been noted to cause endometrial hyperplasia in 28% of women and transient transaminase elevations in 4%. [ Cochrane Clinical Answers logo ]

Both GnRH agonists and antiprogestogens cause vasomotor symptoms. [ Cochrane Clinical Answers logo ] The use of 'add-back therapy' with hormone replacement therapy may avoid the vasomotor side effects and bone effects of GnRH analogue therapy.[89][90]

In some countries, mifepristone is only commercially available as 200 mg/dose tablets, which makes giving the lower doses used for this indication difficult. Consult with a pharmacist, as special compounding of this drug may be required.

The levonorgestrel intrauterine contraceptive device significantly decreases bleeding in women with fibroid-associated heavy menstrual bleeding.

GnRH antagonists (e.g., elagolix, relugolix) in combination with estradiol and norethisterone are approved for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Non-steroidal anti-inflammatory drugs have been tried empirically in the medical management of excessive bleeding, dysmenorrhoea, and pelvic pain.

Tranexamic acid reduces heavy menstrual bleeding and causes necrosis of fibroids, especially larger fibroids.[102][103]

Primary options

leuprorelin: 3.75 mg intramuscularly once monthly for up to 3 months; or 11.25 mg intramuscularly as a single dose

OR

mifepristone (gynaecologic): 5-50 mg orally once daily for 3-6 months

OR

levonorgestrel intrauterine device: insert 52 mg device into uterine cavity, remove and replace (if necessary) after 6 years

OR

elagolix/estradiol/norethisterone acetate and elagolix: 300 mg (elagolix)/1 mg (estradiol)/0.5 mg norethisterone once daily in the morning, and 300 mg (elagolix) once daily in the evening for up to 24 months

OR

relugolix/estradiol/norethisterone acetate: 40 mg (relugolix)/1 mg (estradiol)/0.5 mg norethisterone once daily for up to 24 months

Secondary options

naproxen: 500 mg orally twice daily when required

OR

tranexamic acid: 1300 mg orally three times daily for a maximum of 5 days during monthly menstruation

1st line – hysterectomy

Back
ONGOING
|
fertility not desired
|
uterine preservation not desired: surgical candidate
1st line – 

hysterectomy

Hysterectomy remains an excellent treatment option for patients with symptomatic fibroids in whom fertility preservation is unimportant.[72]

There are four generally recognised surgical approaches to hysterectomy for benign conditions of the uterus such as leiomyomata uteri: abdominal hysterectomy, vaginal hysterectomy, laparoscopic hysterectomy, and robotic hysterectomy.[143]

The US Food and Drug Administration issued a safety communication cautioning against the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids. This is because power morcellation carries a risk of spreading undetected uterine sarcoma, with resultant worsening prognosis.[83][84]​ Uterine sarcoma is a rare medical condition, particularly in the setting of long-standing uterine fibroids as present in the majority of patients.

Consider – preoperative medical therapy

Back
ONGOING
|
fertility not desired
|
uterine preservation not desired: surgical candidate
Consider – 

preoperative medical therapy

Additional treatment recommended for SOME patients in selected patient group

A number of treatments cause bone loss with prolonged use, such as gonadotrophin-releasing hormone (GnRH) agonists (e.g., leuprorelin) and antiprogestogens (e.g., mifepristone), which have been noted to cause endometrial hyperplasia in 28% of women and transient transaminase elevations in 4%. [ Cochrane Clinical Answers logo ]

Both GnRH agonists and antiprogestogens cause vasomotor symptoms. [ Cochrane Clinical Answers logo ] The use of 'add-back therapy' with hormone replacement therapy may avoid the vasomotor side effects and bone effects of GnRH analogue therapy.[89][90]

Consequently, medical treatment is usually provided as a preoperative adjunct in selected cases, such as in patients with heavy bleeding and significant anaemia requiring a period of stabilisation and haemoglobin enhancement pending surgery.[88]

In some countries, mifepristone is only commercially available as 200 mg/dose tablets, which makes giving the lower doses used for this indication difficult. Consult with a pharmacist, as special compounding of this drug may be required.

The levonorgestrel intrauterine contraceptive device significantly decreases bleeding in women with fibroid-associated heavy menstrual bleeding.

GnRH antagonists (e.g., elagolix, relugolix) in combination with estradiol and norethisterone are approved for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Non-steroidal anti-inflammatory drugs have been tried empirically in the medical management of excessive bleeding, dysmenorrhoea, and pelvic pain.

Tranexamic acid reduces heavy menstrual bleeding and causes necrosis of fibroids, especially larger fibroids.[102][103]

Primary options

leuprorelin: 3.75 mg intramuscularly once monthly for up to 3 months; or 11.25 mg intramuscularly as a single dose

OR

mifepristone (gynaecologic): 5-50 mg orally once daily for 3-6 months

OR

levonorgestrel intrauterine device: insert 52 mg device into uterine cavity, remove and replace (if necessary) after 6 years

OR

elagolix/estradiol/norethisterone acetate and elagolix: 300 mg (elagolix)/1 mg (estradiol)/0.5 mg norethisterone once daily in the morning, and 300 mg (elagolix) once daily in the evening for up to 24 months

OR

relugolix/estradiol/norethisterone acetate: 40 mg (relugolix)/1 mg (estradiol)/0.5 mg norethisterone once daily for up to 24 months

Secondary options

naproxen: 500 mg orally twice daily when required

OR

tranexamic acid: 1300 mg orally three times daily for a maximum of 5 days during monthly menstruation

1st line – uterine artery embolisation

Back
ONGOING
|
fertility not desired
|
uterine preservation not desired: non surgical candidate
1st line – 

uterine artery embolisation

Patients with significant obesity, diabetes, or hypertension, and those with serious cardiac or pulmonary dysfunction represent a high-risk group for major surgery and would therefore fall into this category.[48]

Uterine artery embolisation (UAE) is an alternative for symptomatic patients who may not be medical candidates for hysterectomy.

UAE should be considered only in women not desiring any future fertility. However, pregnancies have been known to occur following UAE. with significant adverse obstetric outcomes, in particular significantly higher miscarriage rates, as well as other adverse events including postpartum haemorrhage and increased risk for caesarean delivery.[127] Therefore, it is important to ensure that women are aware of this and given contraception if required.

Long-term studies of UAE are lacking; however, in one study comparing outcomes of UAE and abdominal myomectomy, the former resulted in a 29% rate of further invasive therapy during the 3 to 5 years of follow-up as compared with 3% in the myomectomy group.[73] If haemorrhage becomes significant, myomectomy may need to be converted to hysterectomy intra-operatively.[106][107]

Consider – preoperative medical therapy

Back
ONGOING
|
fertility not desired
|
uterine preservation not desired: non surgical candidate
Consider – 

preoperative medical therapy

Additional treatment recommended for SOME patients in selected patient group

A number of treatments cause bone loss with prolonged use, such as gonadotrophin-releasing hormone (GnRH) agonists and antiprogestogens, which have been noted to cause endometrial hyperplasia in 28% of women and transient transaminase elevations in 4%. [ Cochrane Clinical Answers logo ]

Both GnRH agonists and antiprogestogens cause vasomotor symptoms. [ Cochrane Clinical Answers logo ] The use of 'add-back therapy' with hormone replacement therapy may avoid the vasomotor side effects and bone effects of GnRH analogue therapy.[89][90]

Consequently, medical treatment is usually provided as a preoperative adjunct in selected cases, such as in patients with heavy bleeding and significant anaemia requiring a period of stabilisation and haemoglobin enhancement pending surgery.[88]

In some countries, mifepristone is only commercially available as 200 mg/dose tablets, which makes giving the lower doses used for this indication difficult. Consult with a pharmacist, as special compounding of this drug may be required.

The levonorgestrel intrauterine contraceptive device significantly decreases bleeding in women with fibroid-associated heavy menstrual bleeding.

GnRH antagonists (e.g., elagolix, relugolix) in combination with estradiol and norethisterone are approved for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Non-steroidal anti-inflammatory drugs have been tried empirically in the medical management of excessive bleeding, dysmenorrhoea, and pelvic pain.

Tranexamic acid reduces heavy menstrual bleeding and causes necrosis of fibroids, especially larger fibroids.[102][103]

Primary options

leuprorelin: 3.75 mg intramuscularly once monthly for up to 3 months; or 11.25 mg intramuscularly as a single dose

OR

mifepristone (gynaecologic): 5-50 mg orally once daily for 3-6 months

OR

levonorgestrel intrauterine device: insert 52 mg device into uterine cavity, remove and replace (if necessary) after 6 years

OR

elagolix/estradiol/norethisterone acetate and elagolix: 300 mg (elagolix)/1 mg (estradiol)/0.5 mg norethisterone once daily in the morning, and 300 mg (elagolix) once daily in the evening for up to 24 months

OR

relugolix/estradiol/norethisterone acetate: 40 mg (relugolix)/1 mg (estradiol)/0.5 mg norethisterone once daily for up to 24 months

Secondary options

naproxen: 500 mg orally twice daily when required

OR

tranexamic acid: 1300 mg orally three times daily for a maximum of 5 days during monthly menstruation

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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