Emerging drugs for endometriosis.
Medical treatment of endometriosis relies on drugs that suppress ovarian steroids and induce an hypoestrogenic state that causes atrophy of ectopic endometrium. Gonadotrophin-releasing hormone (GnRH) analogues, danazol, progestogens and oestrogen-progestin combinations have all proven effective in relieving pain and reducing the extent of endometriotic implants. However, symptoms often recur after discontinuation of therapy and hypoestrogenism-related side effects limit the long-term use of most medications. Furthermore, these therapies are of limited value in patients with a desire to become pregnant because they inhibit ovulation. An important target for current research is to identify effective therapies that can be safely administered in the long term. GnRH analogues with add-back therapy, progestogens and continuous oral contraceptive are options available for a medium or long-term systemic treatment. Mifepristone, an antiprogestogen, may constitute an alternative if encouraging preliminary data on its effectiveness and tolerability are confirmed. A very appealing area of interest is the possibility of treating endometriosis without suppressing ovarian function. Aromatase inhibitors might have such characteristics as they have been shown to inhibit oestrogen production selectively in endometriotic lesions, without affecting ovarian function; the clinical role of these drugs in the treatment of endometriosis is under evaluation. Levonorgestrel medicated intrauterine device has proven effective in relieving dysmenorrhoea associated with endometriosis, as well as pain associated with rectovaginal endometriosis. Although a systemic absorption is present determining side effects, this approach is promising in the long-term management of this condition. A fundamental objective of research in endometriosis treatment is to develop new therapeutic approaches based on the findings from experimental studies on the aetiopathogenesis of the disease; current research is focusing on anti-inflammatory drugs and modulators of the immune system. TNF-binding protein-1 and IL-12 have proved effective in reducing endometriotic lesions in animal models, while pentoxifylline and INF-alpha 2b have shown encouraging results in clinical studies. This area may be of paramount importance in the near future in order to develop a therapy that could prevent or eradicate endometriosis rather than merely relieving the symptoms.
Fedele
Luigi
L
Deaprtment of Obstetrics and Gynaecology, San Paolo Hospital, University of Milan, Italy.
Berlanda
Nicola
N
D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D003278:Contraceptives, Oral, Hormonal / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects / Q000502:physiology; D003613:Danazol / Q000009:adverse effects / Q000627:therapeutic use; D004715:Endometriosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D004958:Estradiol / Q000097:blood; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D005867:Gestrinone / Q000009:adverse effects / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D016912:Levonorgestrel / Q000627:therapeutic use; D015735:Mifepristone / Q000627:therapeutic use; D010053:Ovary / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D011372:Progestins / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000893:Anti-Inflammatory Agents; D047072:Aromatase Inhibitors; D003278:Contraceptives, Oral, Hormonal; D016207:Cytokines; D020847:Estrogen Receptor Modulators; D006727:Hormone Antagonists; D011372:Progestins; D005867:Gestrinone; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016912:Levonorgestrel; D003613:Danazol