Drugs for Endometriosis

Drugs for endometriosis relieve pain and slow lesion growth by suppressing ovulation and oestrogen or by blocking inflammation. They do not cure the disease and do not improve fertility. Treatment follows a step plan: analgesics, hormonal suppression, then second-line options and surgery. Choice depends on pain pattern, wish for pregnancy, side effects and cost.

Classification. NSAIDs and other analgesics; combined hormonal contraception; progestogens (dienogest, norethisterone acetate, medroxyprogesterone acetate, levonorgestrel intrauterine system, implant); GnRH agonists and antagonists with add-back; danazol; aromatase inhibitors; neuromodulators.

Mechanism. Hormonal drugs stop ovulation and reduce oestrogen-driven growth and bleeding of endometriotic tissue. Dienogest is a progestogen with direct anti-proliferative and anti-inflammatory effects. NSAIDs inhibit prostaglandin synthesis.

Neuropathic and central pain. Amitriptyline 10 to 50 mg at night, gabapentin 300 to 900 mg three times daily, or duloxetine 30 to 60 mg daily can help when pain persists; pelvic physiotherapy and psychological support add benefit.

Treatment plan. Start empirical treatment without surgery when history and examination fit. Review at 3 months. Switch if pain persists, rather than waiting longer.

• First-line. NSAIDs plus a hormonal option: continuous combined pill or progestogen (dienogest or norethisterone acetate), or the levonorgestrel intrauterine system.
• Alternative. DMPA or implant when oestrogen is unsuitable; switching between progestogens.
• Specialist. GnRH agonists or antagonists with add-back for refractory pain; aromatase inhibitors; surgery to excise lesions; fertility treatment (surgery and IVF, not suppression).
• Emergency. Acute pain or rupture of an endometrioma (analgesia, admission).

Selection. For women wanting pregnancy, hormonal suppression does not improve fertility and may delay conception; use analgesia, then surgery or assisted reproduction. After surgery, long-term hormonal suppression lowers recurrence.

Contraindications. Pregnancy; undiagnosed vaginal bleeding; active venous thromboembolism; severe liver disease; breast cancer; contraindications of combined contraception for combined products; osteoporosis (GnRH analogues without add-back); NSAID contraindications such as peptic ulcer and renal disease.

Serious adverse effects.

• Progestogens: irregular bleeding, weight gain, mood change, acne, headache, bone loss with DMPA.
• GnRH analogues: hot flushes, bone loss, vaginal dryness, mood change.
• Danazol: androgenic effects (acne, hirsutism, voice deepening), liver injury, thrombosis, teratogenicity.
• NSAIDs: gastrointestinal bleeding, renal injury, cardiovascular risk.

Major interactions. Enzyme inducers lower hormonal levels; NSAIDs with anticoagulants and ACE inhibitors; danazol with warfarin and statins; combined pills with lamotrigine.

Common prescribing errors.

• Delaying treatment until surgery confirms the diagnosis.
• Prolonged GnRH agonist treatment without add-back.
• Using hormonal suppression to treat infertility.
• Not reviewing at 3 months.
• Prescribing danazol without counselling on virilisation and contraception.

Special groups.

• Pregnancy: stop all treatment; symptoms often improve in pregnancy.
• Breastfeeding: progestogen-only methods are compatible.
• Adolescents: start with NSAIDs and hormonal options; early treatment prevents years of pain.
• Older adults: lesions regress after menopause; avoid unopposed oestrogen therapy.
• Kidney: avoid NSAIDs in impairment.
• Liver: avoid danazol and oral progestogens in severe disease.
• East Africa: diagnosis is often delayed and confused with pelvic inflammatory disease or tuberculosis; combined pills, norethisterone, medroxyprogesterone and NSAIDs are widely available; the levonorgestrel system and dienogest may not be; take a careful history before assuming infection.

Monitoring. Pain score and bleeding at 3 months and 6 months; blood pressure; weight; bone density with prolonged GnRH or DMPA use; liver tests with danazol.

Referral and escalation. Persistent pain after 2 treatments; endometrioma over 4 cm or growing; bowel or bladder symptoms; infertility; suspected deep disease.

Comparison with alternative classes. Hormonal suppression and surgery are about equally effective for pain, but recurrence follows stopping drugs. NSAIDs act at once but do not treat the disease.