Japanese Translation

Treatment of pain

Empirical treatment of pain symptoms without a definitive diagnosis

GPP

Empirical treatment for pain symptoms presumed to be due to endometriosis without a definitive diagnosis includes counselling, adequate analgesia, progestagens, the combined oral contraceptive (COC) and nutritional therapy. It is unclear whether the COC should be taken conventionally, continuously or in tricycle regimen. A GnRH agonist may be taken but this class of drug is more expensive, and associated with more side-effects and concerns about bone density.

 

Treatment of endometriosis-associated pain in confirmed disease

Non-steroidal anti-inflammatory drugs

A

There is inconclusive evidence to show whether NSAIDs (specifically naproxen) are effective in managing pain caused by endometriosis (Allen et al., 2005).

Evidence Level 1a

Hormonal treatment

A

Suppression of ovarian function for 6 months reduces endometriosis associated pain. The hormonal drugs investigated - COCs, danazol, gestrinone, medroxyprogesterone, acetate and GnRH agonists - are equally effective but their side-effect and cost profiles differ (Davis et al., 2007 ; Prentice et al., 1999; Prentice et al., 2000; Selak et al., 2007).

Evidence Level 1a

 

A

The levonorgestrel intra-uterine system (LNG IUS) reduces endomestriosis associated pain.

Evidence Level 1a

Duration of GnRH agonist treatment

A

Treatment for 3 months with a GnRH agonist may be as effective as 6 months in terms of pain relief (Hornstein et al., 1995).

Evidence Level 1b

GnRH agonist treatment with 'add-back'

A

Treatment for up to 2 years with combined oestrogen and progestagen 'add-back' appears to be effective and safe in terms of pain relief and bone density protection; progestagen only 'add-back' is not protective (Sagsveen et al., 2003). However, careful consideration should be given to the use of GnRH agonists in women who may not have reached their maximum bone density.

Evidence Level 1a

Surgical treatment

GPP	Depending upon the severity of disease found, ideal practice is to diagnose and remove endometriosis surgically at the same time, provided that pre-operative adequate consent has been obtained (Abbott et al., 2003; Chapron et al., 2003b; Fedele et al., 2004a; Redwine and Wright, 2001).

 

A

Ablation of endometriotic lesions plus laparoscopic uterine nerve ablation (LUNA) in minimal-moderate disease reduces endometriosis associated pain at 6 months compared to diagnostic laparoscopy; the smallest effect is seen in patients with minimal disease (Jacobson et al., 2001). However, there is no evidence that LUNA is a necessary component (Sutton et al., 2001), and LUNA by itself has no effect on dysmenorrhoea associated with endometriosis (Vercellini et al., 2003a).

Evidence Level 1b

There are no data supporting the use of uterine suspension but, in certain cases, there may be a role for pre-sacral neurectomy especially in severe dysmenorrhoea (Soysal et al., 2003).

GPP

Endometriosis associated pain can be reduced by removing the entire lesions in severe and deeply infiltrating disease. If a hysterectomy is performed, all visible endometriotic tissue should be removed at the same time (Lefebvre et al., 2002). Bilateral salpingo-oophorectomy may result in improved pain relief and a reduced chance of future surgery (Namnoum et al., 1995).

Pre-operative treatment

A

Although hormonal therapy prior to surgery improves rAFS scores, there is insufficient evidence of any effect on outcome measures such as pain relief (Yap et al., 2004).

Evidence Level 1a

Post-operative treatment

A

Compared to surgery alone or surgery plus placebo, post-operative hormonal treatment does not produce a significant reduction in pain recurrence at 12 or 24 months, and has no effect on disease recurrence (Yap et al., 2004).

Evidence Level 1a

The above quoted Cochrane review is based on two studies of 6 months post-operative GnRHa treatment, indicating that more research is obviously needed. As endometriosis is a chronic oestrogen-dependent disease, further hormonal treatment is often needed in many women.

In a small RCT, the LNG IUS, inserted after laparoscopic surgery for endometriosis associated pain, significantly reduced the risk of recurrent moderate-severe dysmenorrhoea at 1 year follow-up (Vercellini et al., 2003c).

Hormone replacement therapy

C

Hormone replacement therapy (HRT) is recommended after bilateral oophorectomy in young women given the overall health benefits and small risk of recurrent disease while taking HRT (Matorras et al., 2002). The ideal regimen is unclear: adding a progestagen after hysterectomy is unnecessary but should protect against the unopposed action of oestrogen on any residual disease. However, the theoretical benefit of avoiding disease reactivation and malignant transformation should be balanced against the increase in breast cancer risk reported to be associated with combined oestrogen and progestagen HRT and tibolone (Beral and Million Women Study Collaborators, 2003).

Evidence Level 4

Supporting Documentation