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

immediate fertility not desired: pain without endometrioma or suspected severe/deep disease

1st line – analgesia

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
1st line – 

analgesia

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

1st line – combined oral contraceptive pill (OCP)

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
1st line – 

combined oral contraceptive pill (OCP)

OCPs suppress the hypothalamic-pituitary-ovarian axis and subsequent oestrogen/progesterone secretion, thereby inducing atrophy of ectopic implants.

If pain is strictly related to the menstrual cycle, then continuous use of the OCP can be recommended as women may become amenorrhoeic and will experience less cyclic pain.[66] Women should be made aware that irregular spotting is common with continuous use.

Side effects are generally mild and time-limited. Life-threatening cardiovascular adverse events are more likely to occur in women aged over 35 years, who are heavy smokers, have acquired/inherited thrombophilia, or have experienced a prior cardiovascular event. Therefore, OCPs are not recommended for these women.

There is an increasing debate on the use of OCPs as first-line therapy because of concern over oestrogenic side effects and progression of more advanced stage disease.

Consult product literature for guidance on dosage for individual preparations.

Consider – analgesia

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

May be used in combination with an oral contraceptive pill.

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

1st line – progestogen

Back
ONGOING
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immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
1st line – 

progestogen

Progesterone induces decidualisation and eventual atrophy of implants. Certain formulations also suppress the hypothalamic-pituitary-ovarian axis, resulting in decreased steroid hormone stimulation of implants. Many such women will become amenorrhoeic.[61] Continuous administration significantly reduces pain, whereas prescribing a luteal phase-only regimen is ineffective.

The levonorgestrel IUD is approved for long-term use, with individual devices approved for up to 5 to 6 years of use prior to exchange. The levonorgestrel IUD significantly reduces pelvic pain (up to 6 months of therapy) and the recurrence of painful periods after surgery. This effect is more dramatic in women with advanced-stage disease.[62] Serum progestin levels remain low, allowing the device to provide effective therapy without promoting a hypo-oestrogenic state. The etonogestrel-releasing subdermal implant can also be considered for long-term therapy because it lasts for 3 years.[76]

Dienogest, an oral progestin, reduces endometriotic implants while providing similar symptomatic relief to gonadotrophin-releasing hormone (GnRH) agonists, with better quality-of-life scores.[77] Three to 4 months of treatment may be required to see the full effect. It is not currently available in the US and some other countries, except in combination with estradiol valerate. However, this combination is sometimes used off-label for endometriosis.

Serious adverse events that occur with progestogens include decreased bone mineral density, especially with prolonged use. This effect may be more marked in adolescents, when the rate of bone mineralisation peaks. The subcutaneous form of medroxyprogesterone acetate and IUD levonorgestrel may reduce this risk.[55][75] IUD levonorgestrel should be placed during the early proliferative phase of the menstrual cycle. Other bothersome side effects include weight gain, irregular uterine bleeding, and mood changes.

Use caution with medroxyprogesterone. Doses of subcutaneous and intramuscular formulations are different.

Primary options

medroxyprogesterone: 150 mg intramuscularly every 3 months; 104 mg subcutaneously every 3 months

OR

levonorgestrel intrauterine device: 52 mg/unit every 5 years

OR

etonogestrel subdermal implant: 68 mg/unit every 3 years

OR

estradiol valerate/dienogest: 1 tablet once daily according to product literature

OR

dienogest: 2 mg orally once daily

Consider – analgesia

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

2nd line – gonadotrophin-releasing hormone (GnRH) antagonist

Back
ONGOING
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immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
2nd line – 

gonadotrophin-releasing hormone (GnRH) antagonist

Elagolix is an oral GnRH antagonist that suppresses ovarian oestrogen production in a dose-dependent manner.[78] In the US, it is licensed for the treatment of moderate to severe endometriosis-related pain.

Two 6-month placebo-controlled phase 3 trials reported significant reductions in dysmenorrhoea and non-menstrual pelvic pain among women with endometriosis-associated pain who were randomised to elagolix.[79]

Hypo-oestrogenic adverse effects were similar to those of injectable GnRH agonists, and included hot flushes, increased serum lipids, and decreased bone mineral density.[79]

The maximum recommended duration of elagolix use is 6 to 24 months (depending on dose) to reduce the extent of bone loss.

A lower initial dose and longer treatment course (up to 24 months) is recommended in women without coexisting dyspareunia. A higher initial dose can be considered in women with coexisting dyspareunia; however, women on the higher dose should receive a shorter treatment course (up to 6 months). The dose should be adjusted to the lowest effective dose guided by the severity of symptoms.

Elagolix is contraindicated in women with severe hepatic impairment. Women with moderate hepatic impairment should only be prescribed the lower dose for up to 6 months. Women with mild impairment do not require any modifications to the recommended dose regimen.

Relugolix, another GnRH antagonist, is available in combination with estradiol and norethisterone, which are thought to reduce hypo-oestrogenic adverse effects.[80]​ In the US, it is approved for the management of moderate to severe endometriosis-related pain.

In two 6-month phase 3 trials, significantly more women who received relugolix combination therapy experienced improvements in dysmenorrhoea and non-menstrual pelvic pain compared with those who received placebo.[80]​ The least squares mean percentage loss in lumbar spine and total hip bone mineral density was less than 1% after 24 weeks. Headache, nasopharyngitis, and hot flushes were the most common adverse effects.[80]

The maximum recommended treatment duration for relugolix combination therapy is 24 months due to the risk for continued bone loss.

Relugolix/estradiol/norethisterone is contraindicated in patients with hepatic impairment of any severity.

Primary options

elagolix: 150 mg orally once daily for up to 24 months; women with dyspareunia: consider initiating treatment at the higher dose of 200 mg twice daily for up to 6 months; moderate hepatic impairment: 150 mg once daily for up to 6 months

OR

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

Consider – analgesia

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

Consider – laparoscopy

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

laparoscopy

Additional treatment recommended for SOME patients in selected patient group

When to offer surgery is debatable and varies among specialists. It is usually determined by the individual clinician and woman. The patient’s symptoms, preferences and priorities regarding pain and fertility are elements that should be considered.[36]​ The side effects of hormonal therapy may influence the decision to proceed to surgery. For example, gonadotrophin-releasing hormone agonists and progestogens are not ideal options in adolescents due to the potential impact on bone mineral density at such a critical point in development. Therefore, laparoscopy may be preferred. Furthermore, both progestogens and androgens have bothersome side effects that may result in a preference for surgery.

Conservative surgical management with laparoscopic excision or ablation of visible implants provides effective treatment of pain-related complaints.[Figure caption and citation for the preceding image starts]: Laparoscopic image of endometriotic noduleFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@68c421f6 Diagnostic laparoscopy alone may impart a therapeutic response in up to 30% of women.[98] Several studies have established a clear relationship between surgical intervention and reduction of pain in women with endometriosis.

Rectal, bladder, and ureteral injury may occur because of the alterations in normal anatomy. These risks should be discussed prior to surgery. Bowel preparation facilitates these difficult procedures and should be administered to any woman undergoing operative laparoscopy.

Appendectomy should be considered in women undergoing laparoscopic surgery for suspected endometriosis if there is a complaint of right-sided pain and the appendix appears abnormal. Up to 50% of appendiceal specimens will yield abnormal pathology, but the effect on pain and future adverse outcomes is difficult to assess.[101]

2nd line – gonadotrophin-releasing hormone (GnRH) agonist

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
2nd line – 

gonadotrophin-releasing hormone (GnRH) agonist

Rapidly induce a hypo-oestrogenic state by down-regulating the hypothalamic-pituitary-ovarian axis. An initial rise in gonadotrophins and oestrogen (flare) occurs after administration, but chronic exposure provides the desired response.

Approximately 85% of women with confirmed endometriosis will experience significant reduction in pain complaints.[82] Empirical use in women with chronic pelvic pain may also be considered, regardless of the diagnosis.[83] One systematic review found no difference in the positive therapeutic effect of GnRH agonists when compared with other hormonal regimens.[64] However results of one trial suggest that GnRH agonists have similar efficacy to that of continuous oral contraceptive pills in treating endometriosis-associated pain.[86]

Prolonged exposure (>6 months) can lead to an irreversible decrease in bone mineral density (BMD).[115] GnRH agonists may not be an ideal choice in adolescents because of the potential impact on BMD at such a critical point in development. To reduce menopausal symptoms and the effect on BMD without reducing the efficacy of pain relief, GnRH agonists should be administered with hormonal add-back therapy (e.g., norethisterone or conjugated oestrogens plus medroxyprogesterone), which should be offered from the beginning of treatment. Non-hormonal forms of add-back therapy to alleviate vasomotor symptoms include selective serotonin reuptake inhibitors, serotonin-noradrenaline (norepinephrine) reuptake inhibitors, and various herbal remedies.

GnRH agonists lack the bothersome side effects of progestogens (weight gain, irregular uterine bleeding, mood changes) and androgens (darkening facial hair, acne, oily skin, deepening of the voice, and male-pattern hair loss) and are therefore usually recommended prior to initiating these other hormonal therapies. However, they are typically less well tolerated than progestogens.

Primary options

leuprorelin: 3.75 mg intramuscularly once monthly; or 11.25 mg intramuscularly every 3 months

or

nafarelin: 200 micrograms (1 spray) in one nostril in the morning and 200 micrograms (1 spray) in the other nostril in the evening; start between days 2-4 of menstrual cycle

or

goserelin: 3.6 mg subcutaneously every 28 days

-- AND --

norethisterone: 5 mg orally once daily

or

oestrogens, conjugated/medroxyprogesterone: 0.3 mg/1.5 mg orally once daily initially, increase according to response

Consider – analgesia

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

Consider – laparoscopy

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

laparoscopy

Additional treatment recommended for SOME patients in selected patient group

When to offer surgery is debatable and varies among specialists. It is usually determined by the individual clinician and woman. The patient’s symptoms, preferences and priorities regarding pain and fertility are elements that should be considered.[36]​ The side effects of hormonal therapy may influence the decision to proceed to surgery. For example, gonadotrophin-releasing hormone agonists and progestogens are not ideal options in adolescents due to the potential impact on bone mineral density at such a critical point in development. Therefore, laparoscopy may be preferred. Furthermore, both progestogens and androgens have bothersome side effects which may result in a preference for surgery.

Conservative surgical management with laparoscopic excision or ablation of visible implants provides effective treatment of pain-related complaints.[Figure caption and citation for the preceding image starts]: Laparoscopic image of endometriotic noduleFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@41f8a52b Diagnostic laparoscopy alone may impart a therapeutic response in up to 30% of women.[98] Several studies have established a clear relationship between surgical intervention and reduction of pain in women with endometriosis.

Rectal, bladder, and ureteral injury may occur because of the alterations in normal anatomy. These risks should be discussed prior to surgery. Bowel preparation facilitates these difficult procedures and should be administered to any woman undergoing operative laparoscopy.

Appendectomy should be considered in women undergoing laparoscopic surgery for suspected endometriosis if there is a complaint of right-sided pain and the appendix appears abnormal. Up to 50% of appendiceal specimens will yield abnormal pathology, but the effect on pain and future adverse outcomes is difficult to assess.[101]

3rd line – androgen

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
3rd line – 

androgen

Produce a hypo-oestrogenic state by directly suppressing the hypothalamic-pituitary-ovarian axis. Onset of amenorrhoea seems to correlate with therapeutic effect.

Clinical trials have shown that androgens (e.g., danazol) effectively reduce pain related to endometriosis when compared with placebo.[63] They may also be effective post-surgical adjuncts. Improved revised American Society for Reproductive Medicine scores were noted at laparoscopy.[63] However, their use is limited by adverse effects that include darkening facial hair, acne, oily skin, deepening of the voice, and male-pattern hair loss.[63][87] Furthermore, reports have linked danazol to ovarian cancer.[88]

Initial dosing schedule depends on severity of disease. Maintenance dose is achieved when women experience amenorrhoea or a reduction in pain.

Primary options

danazol: 200-800 mg/day orally given in 2 divided doses

Consider – analgesia

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

Consider – laparoscopy

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

laparoscopy

Additional treatment recommended for SOME patients in selected patient group

When to offer surgery is debatable and varies among specialists. It is usually determined by the individual clinician and woman. The patient’s symptoms, preferences and priorities regarding pain and fertility are elements that should be considered.[36]​ The side effects of hormonal therapy may influence the decision to proceed to surgery. For example, gonadotrophin-releasing hormone agonists and progestogens are not ideal options in adolescents due to the potential impact on bone mineral density at such a critical point in development. Therefore, laparoscopy may be preferred. Furthermore, both progestogens and androgens have bothersome side effects which may result in a preference for surgery.

Conservative surgical management with laparoscopic excision or ablation of visible implants provides effective treatment of pain-related complaints.[Figure caption and citation for the preceding image starts]: Laparoscopic image of endometriotic noduleFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@74790292 Diagnostic laparoscopy alone may impart a therapeutic response in up to 30% of women.[98] Several studies have established a clear relationship between surgical intervention and reduction of pain in women with endometriosis.

Rectal, bladder, and ureteral injury may occur because of the alterations in normal anatomy. These risks should be discussed prior to surgery. Bowel preparation facilitates these difficult procedures and should be administered to any woman undergoing operative laparoscopy.

Appendectomy should be considered in women undergoing laparoscopic surgery for suspected endometriosis if there is a complaint of right-sided pain and the appendix appears abnormal. Up to 50% of appendiceal specimens will yield abnormal pathology, but the effect on pain and future adverse outcomes is difficult to assess.[101]

4th line – hysterectomy

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
4th line – 

hysterectomy

Considered the definitive treatment for symptomatic women who have persistent pain despite conservative measures, and no longer desire childbearing potential.

Consider – bilateral salpingo-oophorectomy and excision of visible peritoneal disease

Back
ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

bilateral salpingo-oophorectomy and excision of visible peritoneal disease

Additional treatment recommended for SOME patients in selected patient group

For the best chance of cure, hysterectomy with bilateral salpingo-oophorectomy and excision of visible peritoneal disease should be offered, focusing on excising deep infiltrating lesions.[106] The principle is based on removal of common areas of implantation along with the primary source of endogenous oestrogen production, and with a focus on excising deep infiltrating lesions. However, there is little distinction in the literature as to whether this is an effective treatment modality specifically for cyclical pain.[107]

Consider – hormone replacement therapy (HRT)

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ONGOING
|
immediate fertility not desired: pain without endometrioma or suspected severe/deep disease
Consider – 

hormone replacement therapy (HRT)

Additional treatment recommended for SOME patients in selected patient group

Oestrogen replacement is generally warranted after hysterectomy with bilateral salpingo-oophorectomy to reduce vasomotor symptoms and risk of bone loss, especially in pre-menopausal and symptomatic post-menopausal women. HRT reduces the incidence of fracture and the risk of coronary artery disease in pre-menopausal women who undergo surgical menopause. However, there are increases in risk of breast cancer, venous thrombosis, and stroke in post-menopausal women. Therefore, risks versus benefits of HRT should be discussed with the woman before initiating treatment.

immediate fertility not desired: pain with endometrioma or suspected severe/deep disease

1st line – surgery

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ONGOING
|
immediate fertility not desired: pain with endometrioma or suspected severe/deep disease
1st line – 

surgery

Ovarian endometriomas do not resolve in response to hormonal suppression and, if symptomatic, should be addressed surgically.[Figure caption and citation for the preceding image starts]: Laparoscopic image of ovarian endometriomaFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@1a4007a

Radical excision of affected areas with restoration of normal anatomy is the preferred method of treating symptomatic women with deep peritoneal disease.[96][97]

NICE advises that 3 months of pre-operative gonadotrophin-releasing hormone (GnRH) agonist treatment should be considered as an adjunct to surgery for deep endometriosis involving the bowel, bladder or ureter.[36]

Improvement in pain may last up to 5 years after surgery, but the risk of re-intervention approaches 50% in women with moderate to severe disease.[98] Less aggressive surgical measures and younger age are predictive of recurrence.[95][99]

For this reason, prolonged hormonal suppression is recommended after surgery for endometriosis.[6]

Consider – post-surgery hormonal therapy

Back
ONGOING
|
immediate fertility not desired: pain with endometrioma or suspected severe/deep disease
Consider – 

post-surgery hormonal therapy

Additional treatment recommended for SOME patients in selected patient group

If surgery does not result in complete removal of implants, postoperative medical therapy using a gonadotrophin-releasing hormone agonist, progestogen, or androgen may be indicated to increase the duration of pain relief and delay recurrence of symptoms. Some reports indicate a reduction in anatomical relapse, and in the frequency and intensity of dysmenorrhoea recurrence with postoperative use of oral contraceptive pills.[67][68][69] There is insufficient evidence to determine whether hormonal suppression, either before or after surgery, is associated with any significant benefit compared with surgery alone.[91][92][93]

immediate fertility desired

1st line – controlled ovarian hyper-stimulation

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ONGOING
|
immediate fertility desired
1st line – 

controlled ovarian hyper-stimulation

May be achieved with ovulation induction medications including a selective oestrogen receptor modulator (i.e., clomifene), an aromatase inhibitor (e.g., letrozole), highly purified gonadotrophins (also known as menotrophin), or recombinant follicle-stimulating hormone (FSH).

Clomifene (a competitive antagonist of estradiol) disrupts negative feedback and augments gonadotrophin-releasing hormone production.

Letrozole (a competitive reversible inhibitor of testosterone aromatisation) decreases circulating oestrogen, affects the hypothalamic feedback, and induces greater levels of FSH.

A typical starting dose of any gonadotrophin is dependent on the woman's age, diagnosis, and prior stimulation history. The length of the stimulation is dependent on the response to medications.

These medications should only be utilised by experienced infertility practitioners because of the high risk of ovarian hyper-stimulation syndrome and higher-order multiple gestations.

Primary options

clomifene: 50-200 mg orally once daily for 5 days

OR

letrozole: 5 to 7.5mg orally once daily for 5 days, starting on day 3 of cycle

Secondary options

menotrophin: consult product literature for guidance on dose

OR

follitropin alfa: 75-225 international units subcutaneously once daily

Consider – analgesia

Back
ONGOING
|
immediate fertility desired
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

Consider – therapeutic laparoscopy

Back
ONGOING
|
immediate fertility desired
Consider – 

therapeutic laparoscopy

Additional treatment recommended for SOME patients in selected patient group

The role of surgery is controversial since advanced reproductive technologies successfully treat infertility despite most disease state considerations. However, if symptomatic women without endometrioma or severe deep disease desire fertility, surgery should be offered regardless of age. Women with endometrioma or severe deep disease usually require surgery if pain or large endometrioma (>3 cm) present. Women who fail fertility treatment can be offered surgery, and there is some evidence in support of fertility treatments soon after corrective surgery. One meta-analysis of data from cohort studies found that women who had surgery for deep infiltrating endometriosis before IVF were 2.2 times more likely to have a live birth, compared with unoperated women with deep infiltrating endometriosis who underwent IVF.[109][Figure caption and citation for the preceding image starts]: Laparoscopic image of ovarian endometriomaFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@4abeb0c6[Figure caption and citation for the preceding image starts]: Laparoscopic image of endometriotic noduleFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@6f4071dc

Risk of ovarian failure (reduced number of primordial follicles) after excising endometriomas is approximately 2.4%.[95]

2nd line – IVF

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immediate fertility desired
2nd line – 

IVF

Although there is no consensus among experts, there has been a recent shift in the paradigm for those with sub-fertility and endometriosis. Many agree that IVF may be a more viable option for older women and those with multiple contributing factors (such as endometriosis) when compared with surgery. Although IVF is costly it may be the most viable option for women with advanced endometriosis and sub-fertility; however, there are no validating, large randomised trials. Sub-fertility in the setting of advanced endometriosis is controversial, but it remains a viable option for women with advanced disease who are symptomatic or have failed previous IVF cycles.[110]

Sub-fertile women with endometrioma may show a diminished response to gonadotrophin stimulation, but the IVF success rates match those who defer surgery.[114]

Consider – analgesia

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immediate fertility desired
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

In clinical trials, non-steroidal anti-inflammatory drug (NSAIDs) effectively treat primary dysmenorrhoea and provide adequate analgesia, but their use remains inconclusive for endometriosis-associated pain.[58][59]

There appears to be positive feedback between prostaglandin (PG) synthesis, aromatase activity, and oestrogen production, mediated by abnormally high COX-2 activity in the setting of endometriosis.[57] Superficial, often atypical implants (seen more commonly in adolescents) are active PG producers.

Since endometriosis is a chronic inflammatory condition, NSAIDs may improve symptoms of PG-associated inflammation and pain by interrupting receptor-mediated signalling pathways.

Variable responses may be seen with different medicines in each woman.

Ketorolac is only indicated for acute, moderate to severe pain or during the postoperative period; do not use for chronic conditions.

If dysmenorrhoea is the primary complaint, pre-emptively administer oral NSAIDs prior to onset of menses.

In the UK, the National Institute for Health and Care Excellence recommends paracetamol (alone or in combination with an NSAID) as an alternative first-line analgesic for women with endometriosis-related pain.[36]​​

Primary options

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

OR

celecoxib: 200 mg orally once or twice daily

OR

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

ketorolac: consult specialist for guidance on dose

Consider – therapeutic laparoscopy

Back
ONGOING
|
immediate fertility desired
Consider – 

therapeutic laparoscopy

Additional treatment recommended for SOME patients in selected patient group

The role of surgery is controversial since advanced reproductive technologies successfully treat infertility despite most disease state considerations. However, if symptomatic women without endometrioma or severe deep disease desire fertility, surgery should be offered regardless of age. Women with endometrioma or severe deep disease usually require surgery if pain or large endometrioma (>3 cm) present. Women who fail fertility treatment can be offered surgery, and there is some evidence in support of fertility treatments soon after corrective surgery. One meta-analysis of data from cohort studies found that women who had surgery for deep infiltrating endometriosis before IVF were 2.2 times more likely to have a live birth, compared with unoperated women with deep infiltrating endometriosis who underwent IVF.[109][Figure caption and citation for the preceding image starts]: Laparoscopic image of ovarian endometriomaFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@79dfbec3[Figure caption and citation for the preceding image starts]: Laparoscopic image of endometriotic noduleFrom the collection of Dr Jonathon Solnik; used with permission [Citation ends].com.bmj.content.model.Caption@22945681

Risk of ovarian failure (reduced number of primordial follicles) after excising endometriomas is approximately 2.4%.[95]

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