Treatment options are dictated by the patient's desire for future fertility, her symptoms, the stage of her disease, and to some extent her age. It must be emphasized that therapy for endometriosis requires operative inspection of the lesions for correct diagnosis and staging and to be sure that the patient's symptoms are attributable to endometriosis only.
In asymptomatic patients, those with mild discomfort, or infertile women with minimal or mild endometriosis, expectant management may be appropriate. Although endometriosis is generally felt to be a progressive disease, there is no evidence that treating an asymptomatic patient will prevent or ameliorate the onset of symptoms later. Many reports have found expectant management of infertile women with minimal or mild endometriosis to be as successful as medical or surgical therapies.
Analgesic treatments include nonsteroidal anti-inflammatory agents and prostaglandin synthetase-inhibiting drugs. These drugs are appropriate sole therapy for endometriosis when the patient has mild premenstrual pain from minimal endometriosis, no abnormalities on pelvic examination, and no desire for immediate fertility.
The goal of treatment with hormonal therapy is to interrupt the cycles of stimulation and bleeding of endometriotic tissue. This can be achieved with various agents.
Oral Contraceptive Pills (Ocps)
OCPs are a good choice for patients with minimal or mild symptoms. Generally monophasic products are used, which are prescribed either cyclically or continuously for 6–12 months. The continuous exposure to combination oral contraceptive pills results in decidual changes in the endometrial glands. Continuous use of OCPs has been shown to be effective in decreasing dysmenorrhea and may also retard progression of endometriosis.
These agents work via a mechanism similar to that of the OCPs, causing decidualization in the endometriotic tissue. Oral medroxyprogesterone acetate can be prescribed as a 10–30-mg dosage daily. An alternative regimen is norethindrone acetate 5 mg daily or megestrol acetate prescribed as a 40-mg daily dose. Depot medroxyprogesterone acetate 150 mg administered intramuscularly can also be given as a single injection every 3 months.
The levonorgestrel-releasing intrauterine device has also been shown to relief dysmenorrheal and pelvic pain. Eighty percent of women treated with progestins have a partial or complete relief of pain.
Danazol is a 19-nortestosterone derivative with progestin-like effects. Danazol acts via several mechanisms to treat endometriosis. It acts at the hypothalamic level to inhibit gonadotropin release, inhibiting the midcycle surge of luteinizing hormone and follicle-stimulating hormone. Danazol also inhibits steroidogenic enzymes in the ovary that are responsible for estrogen production. As a result, a hypoestrogenic environment is created. This, in addition to the androgenic effects of danazol, prevents the growth of endometriotic tissue.
The dosage of danazol is 400 to 800 mg/d in divided doses for 6 months. Side effects of danazol include acne, oily skin, deepening of the voice, weight gain, edema, and adverse plasma lipoprotein changes. Most changes are reversible upon cessation of therapy, but some (such as deepening of the voice) may not be.
Pain relief is achieved in up to 90% of patients taking danazol.
Gonadotropin-releasing hormone (GnRH) agonists are analogues of the 10-amino-acid peptide hormone GnRH. With the continuous administration of GnRH analogues, suppression of gonadotropin secretion occurs, resulting in elimination of ovarian steroidogenesis and suppression of endometrial implants. Pain related to endometriosis is relieved in most cases by the second or third month of therapy. GnRH agonists can be administered intramuscularly as leuprolide acetate 3.75 mg once a month, intranasally as nafarelin 400 to 800 μg daily, or subcutaneously as goserelin 3.6 mg once a month.
The use of these agents is generally limited to 6 months because of the adverse effects associated with a hypoestrogenic state, particularly loss of bone mineral density. Other side effects include vasomotor symptoms, vaginal dryness, and mood changes.
Many side effects can be minimized by providing add-back therapy in addition to the GnRH agonists in the treatment of endometriosis. The addition of 2.5 mg of norethindrone or 0.625 mg of conjugated estrogens with 5 mg/d of medroxyprogesterone acetate seems to provide relief of vasomotor symptoms and decrease bone mineral density loss in a 6-month treatment period. The addition of 5 mg of norethindrone acetate alone or in conjunction with low-dose conjugated equine estrogen seems to eliminate the loss of bone mineral density effectively as well. Adding bisphosphonates, parathyroid hormone, or calcitonin can also minimize the bone loss.
Anastrozole (1 mg daily) and letrozole (2.5 mg daily) are the most commonly used aromatase inhibitors. They act by inhibiting the enzyme aromatase, which functions in the conversion of androgens to estrogens. They can be used as an adjuvant treatment combined with other agents such as GnRH analogs.
In women who want to preserve fertility, who have severe disease, or who have adhesions, conservative surgical therapy is the treatment of choice. This surgery attempts to excise or destroy all endometriotic tissue, remove all adhesions, and restore pelvic anatomy to the best possible condition. Conservative surgery has traditionally been performed at laparotomy, but a laparoscopic approach is associated with a shorter hospital stay and less morbidity, and it is more cost effective. This is particularly true in contemporary practice, where this therapy is usually performed at the time of the initial diagnostic laparoscopy. Reported pregnancy rates after conservative surgery are inversely proportional to the severity of disease and vary greatly. In counseling patients, approximate pregnancy rates of 75% for mild disease, 50–60% for moderate disease, and 30–40% for severe disease should be quoted; however, individualization of therapy is stressed.
Presacral neurectomy to relieve pain should be performed only in selected cases, such as women with recurrent endometriosis, severe incapacitating dysmenorrhea, or disease that did not respond to initial treatment, as efficacy of this treatment is controversial.
If the patient does not desire future childbearing and has severe disease or symptoms, definitive surgery is appropriate and often curative. This entails total abdominal hysterectomy, bilateral salpingo-oophorectomy, and excision of remaining adhesions or implants. If endometriosis remains after excision, postoperative medical therapy may be indicated. After this or after complete excision, hormone replacement therapy is indicated. Estrogen-progestin therapy may be used without reactivating the endometriosis, but individualization of therapy is required.
Infertile women with endometriosis who are older, or who have failed other therapies for infertility, can undergo assisted reproduction, such as ovulation induction with intrauterine insemination or in vitro fertilization (IVF). However, it was found that women with endometriosis undergoing IVF have significantly lower pregnancy rates, fertilization rates, implantation rates, mean number of oocytes retrieved, and peak estradiol concentrations as compared with women with tubal factor infertility. The need to treat women surgically or medically before starting an IVF cycle remains unclear.
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