Hormone treatments aim to induce atrophy of ectopic endometrium, either by altering the effect of oestrogen on endometriotic tissue or by reducing circulating oestrogen levels.

Androgens

• Androgens (danazol and gestrinone) inhibit secretion of pituitary gonadotrophins. They have androgenic, anti-oestrogenic, and anti-progestogenic activity, and usually cause amenorrhoea and induce a reversible postmenopausal state. Their use is limited by androgenic adverse effects.
• Evidence is limited due to lack of data, but gestrinone appears to be effective for the treatment of pain associated with endometriosis.
• There is limited evidence from a Cochrane systematic review (of two randomized, double-blind, placebo-controlled trials) that danazol is effective at treating the symptoms of endometriosis when compared with placebo, but its use is limited by the occurrence of androgenic adverse effects.

GnRH analogues

• The GnRH analogues (buserelin, goserelin, nafarelin, leuprorelin, and triptorelin) initially stimulate pituitary secretion and then rapidly inhibit secretion due to pituitary down-regulation. This is followed by anovulation, markedly reduced oestrogen levels, and amenorrhoea, inducing a reversible postmenopausal state and regression of endometriotic deposits.
• There is limited evidence, due to poor quality data, that GnRH analogues are as effective as other medical treatments in relieving the pain associated with endometriosis.
• There is evidence from one prospective, double-blind, randomized controlled trial (n = 179) [Hornstein et al, 1995] that 3 months of treatment with nafarelin may be as effective as 6 months of treatment, for pain relief [RCOG, 2006].

Add-back therapy

• GnRH analogues reduce bone mineral density, typically by 4–6% during 6 months of treatment [DTB, 1999]; this bone loss may not be entirely reversible [RCOG, 2006]. They can also cause postmenopausal symptoms. These adverse effects may be reduced by the use of additional add-back therapy.
• Tibolone, or combined progestogen plus oestrogen can be used as add-back therapy for women taking GnRH analogues.
• There is good evidence that both combined progestogen plus oestrogen add-back therapy or danazol add-back therapy are protective of bone mineral density in women treated with GnRH analogues. Progestogen alone is not effective. However, danazol has significant adverse effects that limit its use.
• We have recommended tibolone because most CKS expert reviewers agree that tibolone (2.5 mg daily) is the preferred treatment. There is evidence from a small trial that tibolone is more effective than placebo.