Menstrual and Uterine Disorders Current and Future Medical Treatments for Endometriosis
Valentina Ciani, Claudia Tosti, MD, Serena Pinzauti, MD, Stefano Luisi, MD, PhD and Felice Petraglia, MD Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena
Abstract
Endometriosis is a chronic condition characterized by dysmenorrhea, dyspareunia, pelvic pain, and infertility. Endometriosis is often treated surgically upon diagnosis, but a high rate of recurrence suggests that a combination of surgical and medical management might provide better outcomes. The primary goal of medical treatment is to interrupt the growth and activity of endometriotic lesions. Due to the chronic nature of this disease, long-term or repeated courses of medication may be required to control symptoms. Medical treatments now recognize the use of gonadotropin-releasing hormone agonists, oral contraceptives, danazol, and progestins. Increasing knowledge about the pathogenesis of endometriosis is providing the opportunity to use new agents for treatment, including anti-inflammatory and antiangiogenesis compounds, to prevent or inhibit the development of endometriosis. The future outlook is to use a multiple approach for treating women with endometriosis with the goal of eradicating the disease and eliminating the symptoms.
Keywords
Endometriosis, gonadotropin-releasing hormone analogs, progestins, oral contraceptive, selective progesterone receptor modulators, aromatase inhibitors, thiazolidinediones, omega-3, antiangiogenetic agents
Disclosure: The authors have no conflicts of interest to declare. Received: August 4, 2011 Accepted: August 24, 2011 Citation: US Obstetrics & Gynecology, 2011;6(2):84–8 Correspondence: Felice Petraglia, MD, Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy. E:
petraglia@unisi.it
Endometriosis is a chronic condition characterized by growth of endometrial tissue in sites other than the uterine cavity, most commonly in the pelvic cavity, including the ovaries, the uterosacral ligaments, and pouch of Douglas. Common symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. The etiology recognizes a number of theories on how endometrial tissue occurs outside the uterus, including retrograde menstruation through the fallopian tubes, transportation of tissue in the blood or lymph, and the local differentiation of mesothelial or blood cells into endometrium-like tissue.1
disease is not correlated with frequency and severity of symptoms or with long-term prognosis in terms of conceptions and recurrences. Accordingly, a more pragmatic approach to the treatment of endometriosis has developed, centred more on the woman’s needs than on the extent of lesions. In other words, the problems of patients with endometriosis are disease-related symptoms and not the tissue growth per se and treatments should be focused on resolution of complaints, rather than a priori excision of lesions.4
The clinical presentation is variable, with some women experiencing several severe symptoms and others having no symptoms at all. The prevalence in women without symptoms is two to 50 %, depending on the diagnostic criteria and the populations studied. The incidence is 40–60 % in women with dysmenorrhea and 20–30 % in women with subfertility.2
The pathogenesis of the disease is
multifactorial and includes an hormonal rearrangement (estrogen and progesterone) followed by ectopic implants proliferating and cytokines releasing that lead to inflammatory reaction that is associated with adhesions, fibrosis, scarring and anatomical distortion.3
For a long time, the treatment of endometriosis has been based primarily on the radical surgical removal of lesions. This is still a mainstay of therapy in cases of bowel and ureteral stenosis or adnexal masses with ultrasonographically doubtful characteristics. Moreover, in the past two decades, it has become progressively evident that the overall ‘amount’ of
84
Current Medical Treatments for Endometriosis Gonadotropin-releasing Hormone Agonists and Antagonists
Gonadotropin-releasing hormone agonists (GnRHas) induce a reversible hypo-estrogenic state by down regulation of gonadotropin-releasing hormone (GnRH) receptors and desensitation of pituitary. Agonist/analogs, such as triptorelin, leuprolide, goserelin, and buserelin, which are 50–100 times more potent than GnRH and available as depot preparation, have become well established therapeutic tools for the treatment of sex steroid dependant disease. Acute administration of
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Current medical management of endometriosis is based on three major mechanisms of action: iatrogenic menopause, pseudopregnancy, and antinflammatory drugs. In the future, other possible sites of action may be the inhibition of angiogenesis or tissue invasion, or the activation of apoptosis (see Figure 1).
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