Despite extensive research, there remains a paucity of definitive, evidence-based literature regarding the most effective treatment methods for endometriosis. Primary goals of initial treatment are usually directed toward the relief of pain symptoms and promotion of fertility. Long-term therapy is focused at preventing progression and recurrence of the disease. Treatment options for endometriosis include medical, surgical, or a combination of both.
A variety of medications have been shown to reduce pain-associated endometriosis including nonsteroidal antiinflammatory drugs (NSAIDs), oral contraceptives, gonadotropin-releasing hormone (GnRH) agonists, danazol, and progestins.
Historically, danazol was one of the first medications approved for the treatment of endometriosis in the 1970s. This drug is a synthetic androgen, and through suppression of the luteinizing hormone surge produces a hypoestrogenic, hyperandrogenic state resultingin atrophic changes in endometrial tissue.61
The prominent androgenic side effects of danazol including acne, weight gain, hirsutism, adverse lipid profiles, and voice deepening significantly limit its routine use.
NSAIDs are the most commonly used first-line treatment for women with pelvic pain and endometriosis. Their mechanism of action relates to the inhibition of prostaglandins, which in part, are responsible for the pain and inflammation associated with endometriosis. Another option for patients with pain is combination oral contraceptive pills (COCs).62
Ovarian suppression with COCs induces decidualization and atrophy of endometrial tissue. A double-blind, randomized, placebo-controlled trial demonstrated a significant improvement in dysmenorrhea associated with endometriosis with COC use compared with placebo.63
The study also found a significant decrease in the size of endometriomas with COCs. Adverse effects associated with COCs primarily relate to the increased risk of hypertension and deep-vein thrombosis with use of exogenous estrogen.
If symptoms are unresponsive or contradictions exist to COCs alternative therapies may be appropriate. Progestins antagonize estrogenic effects on the endometrium resulting in decidualization and endometrial atrophy. Various compounds include oral progestins, depot medroxyprogesterone acetate (DMPA), and the levonorgestrel-releasing device (LNG-IUD). A randomized controlled trial by Telimaa and colleagues showed oral MPA significantly reduced endometriosis-associated pelvic pain and resolution of peritoneal implants occurred in 60% of patients at second-look laparoscopy, compared with 18% in the placebo group.64
Side effects of DMPA include weight gain, irregular bleeding and prolonged period to resumption of ovulation.
Recent observational trials have shown the device to effectively improve symptoms of endometriosis.65
Petta et al found the LNG-IUD to be equally as effective as GnRH agonist therapy without provoking hypoestrogenic side effects.66
LNG-IUD requires only one medical intervention every 5 years, and accordingly may be an attractive management option for women with endometriosis.
Gonadotropin releasing hormone (GnRH) agonist therapy results in pituitary desensitization and loss of ovarian steroidogenesis, thus producing a medical menopausal state.67
The side effects of GnRH agonist therapy are hot flushes, vaginal dryness, insomnia and decrease in bone mineral density. Therapy is usually limited to a 6-month course, particularly because of the potential effects on bone density. To minimize bone loss and vasomotor symptoms, GnRH agonists and add-back regimens using progestins alone or low does progestin/estrogen combination pills will minimize both bone loss and vasomotor symptoms allowing for a longer duration of therapy without sacrificing efficacy.
Endometriosis is a complex disease with immense variation and the choice between medical management and surgical therapy must be individualized. There is little evidence to support one treatment strategy over another. In general, surgical therapy is reserved for women who have failed medical management or those with known moderate to severe disease and worsening symptoms such as acute cases of ureteral obstruction, bowel obstruction, or rupture of large endometriomas. The primary goals of surgical management are to remove all visible lesions of endometriosis and restore normal anatomy. Some of the challenges to successful surgical treatment lie in the surgeon's ability to recognize and remove endometrial implants. Histologic analysis often shows incomplete resection of implants in even experienced surgeons.68
A variety of operative techniques are utilized including resection, laser vaporization, coagulation, and electrocautery. Severe cases of endometriosis can be technically challenging due to obliteration of dissection planes from dense disease and associated adhesions. Lesions can often be found infiltrating or adjacent to the bowel, bladder, or ureter where coordination between the gynecologist and colorectal surgeon will ensure optimal surgical debulking of disease.
Definitive surgical management, including hysterectomy, bilateral oophorectomy, and removal of all visible disease, offers the most prompt, effective, and long-term relief of pain from endometriosis. According to a study at Johns Hopkins Hospital, women who had ovarian conservation at the time of hysterectomy were six times more likely to have a recurrence of chronic pelvic pain and eight times more likely to require additional surgery, compared with those who underwent bilateral oophorectomy at the time of hysterectomy.69
More recently, Modugno and colleagues have found women with endometriosis to be at increased risk of developing ovarian cancer.70
Thus, hysterectomy alone has little role in the modern management of chronic pelvic pain associated with endometriosis in women who have completed childbearing.
Laparoscopy versus Laparotomy
Operative laparoscopy is the surgical treatment of choice for pelvic pain related to endometriosis. It confers many advantages over laparotomy, such as treatment at the time of diagnosis, decreased postoperative morbidity and mortality, shorter recovery time, and reduction in adhesion formation.71
Laparoscopy also provides optimal visualization of the posterior cul-de-sac and allows for magnification of peritoneal surfaces to aid in identification of subtle disease. One randomized controlled trial found laparoscopy with fulguration of endometrial implants and uterosacral nerve ablation provided symptom relief in 62.5% of women, compared with 22.6% of diagnostic laparoscopy alone.72
Laparotomy is most useful is cases of dense pelvic adhesions and large endometriomas. Deep invasion of the rectovaginal septum, extensive bowel, or urinary tract involvement and infiltration near the uterine vessels may also be optimally approached via laparotomy.
Occasionally denervation procedures, such as presacral neurectomy or uterine nerve ablation, may be performed in cases of severe midline pain, deep dyspareunia, and dysmenorrheal. The presacral neurectomy (PSN) is one option for the treatment of midline pelvic pain associated with endometriosis. PSN is a technically challenging procedure and vascular complications can be severe, thus it is used sparingly in carefully selected patients who only complain of midline pain. Early reports of the laparoscopic uterosacral nerve ablation (LUNA) were promising for the treatment of endometriosis-associated pelvic pain; however, findings have not been reproduced in randomized controlled trials. Thus, based on the current available evidence, the routine use of LUNA in women with endometriosis is not supported.
Combination Medical and Surgical Therapy
Comprehensive management of endometriosis involves a combination of medical and surgical interventions. Intuitively, some clinicians postulate preoperative disease suppression with hormonal agents will decrease vascularity and allow for easier tissue dissection, thereby decreasing operative time and postoperative adhesion formation. However, a clinical trial of patients undergoing laparoscopy for endometrioma excision found no reduction in operating time or recurrence rate of disease at 1 year for those treated preoperatively with a 3-month course of GnRH agonist compared with those with no preoperative treatment.73
On the other hand, if a patient does not desire to attempt immediate conception, postoperative medical therapy may prolong the duration of pain relief and reduce the risk of adhesion recurrence.74,75
A randomized controlled trial by Vercellini et al reported in patients undergoing operative laparoscopy secondary to endometriosis, moderate or severe dysmenorrhea recurred in 10% of patients treated postoperatively with LNG-IUD versus 45% of those expectantly managed.76