Management of Endometriosis

Endometriosis

Endometriosis is one of the most common gynecological diseases in women of reproductive age. It is an estrogen-dependant disease that affects 10 to 15% of women of reproductive age.¹

It is diagnosed in about 20% of women who undergo laparoscopy for pelvic pain or infertility.²   The prevalence rate of laparoscopically biopsy-proven endometriosis in patients with chronic pelvic pain can be as high as 28%.³

Definition

It is defined as the presence of endometria-like tissues outside of the uterine cavity commonly located in the gravitationally dependent area of the pelvis, including ovaries, peritoneum, bowel, cul-de-sac, uterosacral ligments and fallopian tubes.⁴

Etiology

Endometriosis is a polygenic disease with a complex, multifactorial etiology. The etiology and the molecular mechanisms responsible for the initiation and development of this disease remain largely unknown.⁵

Prostaglandin E(2) (PGE(2)), a versatile eicosanoid that exe  rts numerous physiological and pathological functions, has been implicated to play critical roles in the development of endometriosis. A growing body of evidence demonstrates that PGE(2) regulates many pathophysiological processes including cell proliferation, antiapoptosis, immune suppression and angiogenesis, during the development of endometriosis.⁵

Symptoms

Endometriosis is the primary cause of infertility in women. Women with endometriosis suffer from symptoms which significantly reduce the quality of life. Various symptoms are:⁵

• Chronic pelvic pain
• Dysmenorrhea
• Dyspareunia
• Infertility.

Furthermore, studies on assisted reproduction treatment have shown that women with endometriosis have higher rates of pregnancy loss, complication of preterm delivery, pre-eclampsia and infants small for gestational age.

Diagnosis

It is often difficult to evaluate the extent of endometriosisby physical examination and clinical history review.⁵  Due to the limitations of clinical examination, additional explorations, such as transvaginal sonography and magnetic resonance imaging, are required to precise mapping of endometriotic lesions.¹   Doppler ultrasonography mayshow, low blood flow to an endometrioma; normal flow to normal ovarian tissue; and increased flow to an ovarian tumor.⁶

The preferred and definitive method for the diagnosis of endometriosis is direct visualization of ectopic endometrial lesions (usually via laparoscopy) accompanied by histologic confirmation of the presence of at least two of the following features: hemosiderin-laden macrophages or endometrial epithelium, glands, or stroma. Diagnosis based solely on visual inspection requires a surgeon’s experience in identifying the many possible appearances of endometrial lesions (Figure 11).⁷   When infertility complicates endometriosis, both the female patient and her male partner should be evaluated.

Staging

Visualization at surgery is the definitive method to stage endometriosis and evaluate disease recurrence after treatment. Based on lesion type, location, appearance, depth of invasion, and the extent of disease and adhesions, endometriosis staging ranges from I (minimal disease) to IV (severe disease). However, stage of endometriosis does not correlate with pain severity or predict treatment response.⁶

Management

The options for treating endometriosis being offered by conventional modern medicine depends on the severity of the disease, with the main aim being to help alleviate the key symptoms of pain and infertility. There are general points which should be taken into consideration when deciding from different treatment option available and these include:⁸

• The severity of the symptoms
• The type of symptoms
• The age of the patient
• The desire to get pregnant or not
• Length of treatment
• Coping with side-effects of drug treatment
• Cost (more important in developing countries and where women have to pay for the treatment).

Options for the Management of endometriosis

The principal objective in treating endometriosis is symptomatic relief to patients. Because of the chronic nature of this disease, long-term or repeated courses of medical and/or surgical therapy are required to control these symptoms mainly chronic pelvic pain.⁶

In addition to relieving pain, the other goals of treatment for patients with endometriosis are to prevent or delay disease progression by reducing endometriotic implants through surgical treatment or medically induced atrophy of the implants.⁷

Algorithm for management of endometriosis is shown in Figure 12.

Medical treatment

Medical treatment aims to decrease pain by various mechanisms, such as decrease in inflammation (nonsteroidal anti-inflammatory drugs [NSAIDs]), interruption or blockade of cyclic ovarian hormone production or estradiol (oral contraceptives [OCs]), and suppression of menstruation (Gonadotropin-releasing hormone [GnRH] agonists).⁶

Pharmacologic therapies currently in use include combination oral contraceptives (COCs), danazol, GnRH analogues and progestins. Although some agents show efficacy in relieving pain; all differ in their side effects, making it difficult to achieve a balance between efficacy and safety. Efficacy has been demonstrated with danazolor GnRH analogues; however, treatment is limited to6 months because of significant metabolic side effects. Alternatives for longer-term management of symptoms include add-back therapy with GnRH analogues, COCs or progestins. Newer options for treatment of endometriosis include depot medroxyprogesterone acetate subcutaneous injection, as well as several agents under investigationthat may prove to have therapeutic potential.⁷

New treatment possibilities for the management of endometriosis

Because of the systemic hypoestrogenic symptoms associated with currently available hormonal therapies that block ovarian function, new approaches to the medical therapy of endometriosis that have the potential to target the estrogen-dependent growth of endometrial lesions more selectively are under investigation and these include aromatase inhibitors, selective estrogen receptor modulators (SERMs) and selective progesterone receptor modulators (SPRMs).⁷

Role of progestins

The biological rationale for using progestins (used as therapy for endometriosis worldwide for more than 40 years) includes their suppression of the hypothalamic-pituitary-ovary (HPO) axis, a process that induces anovulation and reduces serum estrogen levels. Progestins also have direct effects on the endometrium, causing marked decidualization and atrophy of both the eutopic endometrium and endometriotic lesions. In addition, progestins have been demonstrated to inhibit angiogenesis, required for maintenance of endometriotic implants and decrease markers of intraperitoneal inflammation. All these factors, along with the reduction or elimination of menstrual flow associated with progestin use (which can limit the pelvic contamination of retrograde menstruation), are likely to benefit patients undergoing treatment.⁷

Progestogens e.g. norethisterone are the most commonly used medical treatment and are effective in about 80% of cases. They work by thinning out and shrinking down the endometriosis and also by suppressing the normal cycle of the ovary.⁹

Surgical treatment

Surgery for endometriosis-related pain can be used as initial therapy or in women in whom medical treatment is ineffective. Surgical options include excision, fulguration, or laser ablation of endometriotic implants on the peritoneum; excision or drainage or ablation of endometriomas; resection of rectovaginal nodules; lysis of adhesions; and interruption of nerve pathways through presacral neurectomy. Of women with debilitating pain, not relieved by medical or initial surgical treatment, hysterectomy with bilateral salpingo-oophorectomy relieves pain in 80% to 90%, but pain may recur in 10% within 1 to 2 years.⁶

Treatment option when infertility complicates endometriosis

Currently available medical therapies for endometriosis act by attempting to mimic periods during which a woman does not menstruate: menopause (GnRH analogues), amenorrhea (chronic anovulation with danazol) or pregnancy (oral contraceptives [OCs] or progestins). As many of these agents are also used as effective contraceptives, they are a disadvantage for women desiring pregnancy in the near term, as conception is generally not possible during therapy. Therefore, before choosing therapy, an individual woman’s family plans and fertility status should be considered.⁷

References

1. Darai E, Bazot M, Ballester M. [Endometriosis] [Article in French].Rev Prat. 2010 May 20;60(5):603-5, 607-9. PMID: 20564839.
2. Eskenazi B, Warner ML. Epidemiology of endometriosis.Obstet Gynecol Clin North Am 1997;24:235-58[Medline].
3. Stanford EJ, Koziol J, Feng A. The prevalence of interstitial cystitis, endometriosis, adhesions, and vulvar pain in women with chronic pelvic pain.J Minim Invasive Gynecol 2005;12:43-9.
4. Giudice LC, Kao LC. Endometriosis.Lancet 2004;364:1789-99.
5. Wu MH, Lu CW, Chuang PC, Tsai SJ. Prostaglandin E2: the master of endometriosis?Exp Biol Med (Maywood). 2010 Jun 1;235(6):668-77. PMID: 20511671.
6. Barclay L. Endometriosis management reviewed [From Medscape medical news]. Availablt at: http://www.medscape.com/viewarticle/724033. Accessed on August 13, 2010.
7. Crosignani P, Olive D, Bergqvist A, Luciano A. Advances in the management of endometriosis: an update for clinicians.Human Reproduction Update, Vol.12, No.2 pp. 179-189, 2006 doi:10.1093/humupd/dmi049.
8. Treatment options for endometriosis [Endo resolved]. Available at: http://www.endo-resolved.com/treatment.html. Accessed on August 13, 2010.
9. Medical Treatment of Endometriosis. Available at: http://www.womens-health.co.uk/endo4.asp. Accessed on August 26, 2010.