Medical Therapy of Endometriosis

It is essential to know that medical treatment never cures endometriosis : the lesions only become inactive. This therapy is based upon the knowledge that endometriosis is an hormone responsive tissue.

Types of Medical Therapy

Medical menopause : LHRH agonists (or antagonists)

LHRH agonists (eg Lupron Depot, Synarel, Zoladex, Decapeptyl) will suppress ovarian function, resulting in an artificial menopause with all its consequences such as hot flushes, night sweats, insomnia, vaginal dryness, loss of sexual interest, and depression.
According to the FDA LHRH agonists should not be taken for longer than six months in a lifetime because of the risk of osteoporosis.
Can give excellent pain relief but the symptoms will come back after treatment has been stopped.
Can be associated with add back therapy (small doses of estrogens) enough to prevent the worst menopause symptoms

Progestagens only and oral contraception

Higher doses of progestagens (eg orgametril, lutenyl, danazol) decidualise and growth of the endometrium and endometriosis as occurs during pregnancy
Can give pain relief but the symptoms will come back after treatment has been stopped.
Higher doses of these progestagens with some androgenic side effects, invariably are associated with weight gain and symptoms of androgenisation
Oral contraception probably remains the best choice. When given continuously, the recurrence of cystic ovarian endometriosis is less

Experimental drugs

Anti-progestins primate experiments suggest they might be as effective as GNRH agonist without the side effects. Today no drugs are approved for endometriosis.
Aromatase inhibitors : since endometriosis lesions produce estrogens within the lesions it might be useful to suppress this activity. Today there is no evidence of clinical superiority.
Anti-angiogenic products. Since endometriosis is associated with local angiogenesis, something we demonstrated back in 1994, this might be a logic approach in the future.
Anti TNFa drugs This therapy has been hyped following preliminary evidence of decreasing implantation in primates. It is a typical example how research data were overemphasized by their authors. We recently demonstrated that in women anti TNFa is not effective for pain.

Indications of medical therapy

after Surgery if surgery was too difficult or too dangerous. Incomplete surgery is not an indication although too often medical therapy is given for this reason.
Prevention of recurrences Although few solid data exist we believe that oral contraception might reduce recurrences.
Prevention of progression : no data.

Side effects of medical therapy

LHRH agonists and antagonists :menopause with all the symptoms of menopause.
Progestagens only :

Orgametril, danazol en gestrinone have androgenic side effects such as weight gain, acne and sometimes hirsutism . Lutenyl is newer with less side effects.
oral contraception Today oral contraception is often given continuously without any scientific evidence or superiority. In a high percentage this is associated with spotting.

Common mistakes

Prolonged medical treatment without a positive diagnosis of endometriosis
medical therapy as an alibi for incomplete surgery.
unawareness of the anabolic side effects of progestagen only therapy

unawareness of the important placebo effect for any type of medical therapy , as demonstrated for TNFa . In this article we asked the question whether medical therapy indeed does reduce pain. We wrote in the discussion “We have scrutinized the literature on the medical treatment of endometriosis associated pain. The evidence of efficacy maybe weak as the blinding in most studies appears inadequate.Researchers and patients were able to guess whether individuals were randomized to placebo or active treatment if menstruation was prevented or if there were major side-effects such as hot flushes, or recognizable physical signs such as vaginal atrophy. In addition, conclusions are usually based abolish menstruation will thus by definition be effective in reducing dysmenorrhea. Given the strong correlation between pain symptoms it remains uncertain whether these treatments are effective for all pain symptoms associated with endometriosis or simply dysmenorrhea alone.”