Goals of treatment should involve addressing patient’s primary complaints as well as reproductive wishes. The most comprehensive treatment plan will include relief of symptoms, removal of all endometriotic lesions, and restoration of pelvic anatomy and delaying progression of the disease. Despite important advances in treating endometriosis, the optimal therapy has not been yet identified. Medical and surgical therapies, individually or in combination, may be needed to achieve the appropriate treatment plan.
The mainstay of medical therapy focuses on the principle that endometriosis is an estrogen-dependent condition. Many clinical observations show that estrogen is essential for the growth of endometriosis. Endometriosis has been shown to regress and become inactive in states of amenorrhea and menopause. Therefore, treatment of endometriosis often relies on drugs that suppress ovarian steroids and induce a hypoestrogenic state that causes atrophy of ectopic endometrium. The most widely used agents to achieve this goal are oral contraceptives and gonadotropin releasing hormone agonists. The evidence-based support for medical therapy is mostly observational.
Oral contraceptives containing 20-35 µg of ethinyl estradiol can be used in a conventional regimen with monthly withdrawal bleeds or as a long-cycle regimen with continuous administration of oral contraceptives for 3 or 6 months followed by a hormone-free interval of 7 days. This regimen may be used for women who suffer from dysmenorrhea or pelvic pain. Symptomatic relief can be achieved in 75-100% of women in observational studies. Continuous use of oral contraceptives prevents the cyclic fluctuations of serum levels of ethinyl estradiol and progestogen and, hence, the cyclic variations of metabolic serum parameters. Although the long-cycle regimen is initially associated with an elevated rate of irregular bleeding, the total number of bleeding days that require sanitary product protection is lower than during conventional oral contraceptive treatment. Many physicians tend to prescribe extended oral contraceptive cycles for postponement of menstruation or reduction of frequency of regular bleeding.
Progestins can cause suppressed gonadotropin levels to induce a hypoestrogenic state. Because of its direct action on the endometrium resulting in atrophy and decidualization, it is believed the mechanism of action is similar on endometriosis. Medroxyprogesterone acetate (150 mg of the Depot product every 3 months) can be used as a treatment for endometriosis. The side effect of slow return to ovulation is often seen as an undesirable side effect in women desiring fertility.
Medroxyprogesterone acetate orally at 30 mg continuously for 90 days was shown to have benefit in women with laparoscopically confirmed mild to moderate endometriosis. After therapy a repeat laparoscopy revealed marked regression of endometriotic lesions and ovulation returned within two to three weeks of discontinuing treatment. Megestrol acetate at 40 mg per day has been found to provide symptomatic relief in as much as 85% of treated patients. The side effects of oral progestins can be breakthrough bleeding and spotting, depression, weight gain and breast tenderness. Norethindrone acetate has been used successfully in both symptomatic relief as well as resulting in regression of lesions in post-treatment surgical observation. The dosage should start at 5 mg daily to be gradually titrated to effect until a maximum of 50 mg maximum daily.
Gonadotropin Releasing Hormone Analogs
Gonadotropin releasing hormone analogs (GnRH) cause a temporaty medical menopause resulting in hypogonadism and hypoestrogenism by acting on the pituitary to reduce gonadotropin synthesis and secretion. Most of the side effects experienced occur because of the hypoestrogenic state including hot flashes, vaginal dryness, mood lability and decreased libido. The gonadotropin releasing hormone agonists have been shown to work well in reducing pain symptoms associated with endometriosis such as dysmenorrhea, dyspareunia, and noncyclic pelvic pain. gonadotropin releasing hormone agonists are often initiated with the onset of menses, but a more rapid response is observed with mid-luteal administration. A limit of 6 months per treatment course is required due to loss of bone mineral density during therapy, but this can be extended via the addition of ‘add-back therapy with estrogens. Retreatment with these drugs is supported by limited data. Several investigators have studied the use of gonadotropin releasing hormone agonists as surgical adjuncts. Their use preoperatively has not been shown to be of value. Similarly, 3 months of postoperative administration has failed to enhance treatment. However, 6 months of postoperative gonadotropin releasing hormone agonists appear to improve the duration of relief of pain symptoms. Symptoms often recur after discontinuation of therapy, and hypoestrogen-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.
Mifepristone, an antiprogestogen, is currently being studied. This appealing therapy to treat endometriosis may work without suppressing ovarian function. Aromatase inhibitors may have similar characteristics as they can inhibit estrogen production selectively in endometriotic lesions without affecting ovarian function; an observational trial in a small group of women who had exhausted all other medical therapies including gonadotropin releasing hormone agonists showed reduction in pain symptoms. Levonorgestrel intrauterine device has proven effective in relieving dysmenorrhea associated with endometriosis, as well as pain associated with rectovaginal endometriosis. This approach is promising in the long-term management of endometriosis as it limits systemic absorption of hormones, minimizing side effects. The most current research has targeted anti-inflammatory mechanisms and modulators of the immune system. TNF-binding protein-1 and IL-12 have been shown to be effective in reducing endometriotic lesions in animal models, while pentoxifylline and INF-alpha 2b have shown encouraging results in clinical studies.
Often surgical treatment is considered when medical therapy has failed. With advances in laparoscopy, this technique has become the method of choice in the surgical evaluation and treatment of endometriosis. Laparotomy may still be used in cases of severe endometriosis which may involve other major organs and if adhesive disease is suspected. However, in all other cases, laparoscopy offers both diagnostic and therapeutic capabilities by confirming the presence of endometriosis and then the option to resect if reasonable. Laparoscopy also has many advantages: (1) being an outpatient procedure (2) minimizing hospital stay (3) lowering morbidity (4) smaller incisions and (5) superior visualization of lesions.
Although there is controversy concerning the optimal approach to the treatment of endometriosis, the general opinion is if surgery is being performed then resecting as much of the visualized endometriosis as possible should be the goal. Laparoscopic resection of endometriosis utilizes various energy sources: electrocautery (monopolar and bipolar) and lasers. Excision of the lesions allows for safer and improved diagnostic results especially when evaluating superficial versus deeply infiltrating lesions in comparison to simple superficial fulguration and coagulation of endometriotic implants.
Since endometriosis is a progressive disease and the extent of disease varies at diagnosis, recurrence rates can be also variable. Less than a third of patients experience recurrence of symptoms within three years after laparoscopy and approximately 50% experience symptom recurrence five years after laparoscopy. In patients who have mild to moderate endometriosis, 90% will respond with improved symptoms in the first year. In the remaining 10%, one-third will show disease regression, another third show disease progression and the remainder show no change in disease. Most patients will obtain relief of symptoms after laparoscopy for at least a year.
Other surgical options exist for patients with ongoing pelvic pain especially mid-line pain with associated dysmenorrhea. LUNA (laparoscopic uterosacral nerve ablation) and presacral neurectomy (via laparoscopy or laparotomy) have been used with varying results. Patients who have ongoing symptoms and have completed childbearing should have the option of proceeding to a total abdominal hysterectomy with or without a bilateral salpingoopherectomy Even with this last approach, there is a small risk of recurrence (3%) so there should be long term followup of these patients.