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.
B. Analgesic Therapy
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.
C. Hormonal Therapy
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.
1. Oral contraceptive pills (OCPs) - Generally monophasic products are used and the patient is prescribed 1 pill a day continuously for 6-12 months. The continuous exposure to combination oral contraceptive pills results in decidual changes in the endometrial glands. In cases of breakthrough bleeding additional estrogen may be added. Use of oral contraceptive pills is considered suppressive and not curative in nature. Side effects are breast tenderness, bloating, headache, irritability, and the other side effects associated with oral contraceptive use. Rate of pregnancy following discontinuation of therapy can be as high as 50%.
2. Progestational agents - 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 megestrol acetate prescribed as a 40-mg daily dose. Depot medroxyprogesterone acetate 150 mg IM can also be given as a single injection every 3 months. Side effects associated with these regimens include irritability, depression, breakthrough bleeding, and bloating. Treatment with progestational agents does not seem to affect pregnancy rates.
3. Danazol - Danazol is a weak androgen that is the isoxazole derivative of 17α-ethinyl testosterone (ethisterone). Danazol acts via several mechanisms to treat endometriosis. It acts at the hypothalamic level to inhibit gonadotropin release, inhibiting the midcycle surge of LH and FSH. Danazol inhibits steroidogenic enzymes in the ovary. 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 800 mg/d in divided doses for 6 months. Because of its high cost, attempts have been made to reduce this daily dosage.
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. However, upon discontinuation of therapy symptoms recur in 1 year.
4. Gestrinone - Gestrinone is a 19-nortestosterone derivative that suppresses the secretion of FSH and LH. It is not currently available in the U.S. Although use of gestrinone was effective, androgenic side effects were prominent, and ovulation was not inhibited.
5. GnRH agonists - 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 200 mg twice daily, or subcutaneously as goserelin 3.75 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.
Recent studies have examined the role of 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 equine estrogen 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.
6. Surgical treatment - In women with complaints of infertility who have severe disease or adhesions or are older, 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. A recent randomized controlled trial evaluated the effects of laparoscopic surgery in infertile women with mild or minimal endometriosis. Results suggest that laparoscopic resection or ablation of minimal or mild endometriosis enhances fecundity in infertile women. Presacral neurectomy or uterosacral ligament ablation to relieve pain and a uterine suspension procedure may be performed as required, although the efficacy of these treatments is controversial. Conservative surgery has traditionally been performed at laparotomy, but a laparoscopic approach is associated with a shorter hospital stay and less morbidity, and it may be 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 following 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.
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.
7. Assisted reproduction - Infertile women with endometriosis who are older, or who have failed other therapies for infertility, can undergo assisted reproduction (in vitro fertilization, gamete intrafallopian transfer, etc) with success rates similar to those seen in women with other diagnoses. The relatively short time required with this option may make it the most efficacious of all infertility therapies for endometriosis. Women with more severe disease have decreased success.
Revision date: June 14, 2011
Last revised: by Dave R. Roger, M.D.