Treatment

Expectant Management

Avoiding specific therapy is considered when patients have minimal or no symptoms and have minimal or mild endometriosis. Patients in this category may benefit from cyclic oral contraceptives to retard

progression of the disease and protect against unwanted pregnancy. Minimal pain symptomatology is usually controlled by nonsteroidal antiinflammatory drugs or analgesics. Infertile women with minimal and mild disease have also commonly been observed without treatment.

A meta-analysis found that up to 60 percent of such women will conceive within one year despite their disease. In addition, the three-year estimated pregnancy rate was similar for patients managed expectantly or with surgery. If pregnancy occurs, regression or complete resolution of the disease is common. On the other hand, surgical treatment may increase pregnancy rates over expectant management. The optimal therapy of infertile women with minimal or mild endometriosis is laparoscopic surgery. Endometriotic implant growth is suppressed in the absence of ovarian hormone production after menopause. Thus, women approaching the menopause may be managed expectantly even when the disease is more advanced.

Medical Treatment

The dependence of endometriotic implants on ovarian steroids has led to numerous attempts to "hormonally" simulate pregnancy or menopause, the two physiologic states believed to inhibit or delay progression of endometriosis by interrupting cyclic ovarian hormone production. Progestins alone or in combination with estrogen hormonally mimic pregnancy. Danazol and gonadotropin-releasing hormone (GnRH) analogs induce a state of "pseudomenopause."

Advantages of medical therapy over surgery include:

1. Avoidance of the surgical risks of damaging pelvic organs and causing postoperative adhesion formation, and

2. Treatment of implants that are not visible at surgery.

Disadvantages of medical therapy are :

1. associated side effects,

2. high recurrence rates following discontinuation of treatment,

3. lack of effect on adhesions and endometrial cysts, and

4. the inability to conceive because of the absence of ovulation during treatment.

Medical therapy alone is not appropriate for women with advanced stages of endometriosis and adhesions because medical therapy has not been shown to enhance fertility (in contrast to surgery), for women desiring pregnancy. In contrast, medications may be considered for women with earlier stages of disease who are not having adequate pain relief with a nonsteroidal antiinflammatory drug (NSAID) and for those patients with recurrent endometriosis and pain.

The three medications most commonly used to treat endometriosis are progestins, danazol, and GnRH analogs. They should be considered only after a definitive diagnosis of endometriosis has been established by direct visualization of the implants.

Progestins

Progestins inhibit endometriotic tissue growth by directly causing initial decidualization, and eventual atrophy. Progestins also inhibit pituitary gonadotropin secretion and ovarian hormone production. Treatment consisting of medroxyprogesterone acetate (10 mg three times a day) or norethindrone acetate (5 mg daily) is generally continued for six months.

Medroxyprogesterone can also be given as an injection (100 to 150 mg monthly). Side effects include irregular menstrual bleeding, nausea, breast tenderness, fluid retention, and depression. The effectiveness of progestins in eliminating implants, and the risk of recurrent endometriosis following treatment are not precisely known. Pain relief is uniformly excellent with progestins; over 80 percent of women have partial or complete relief. Pregnancy rates in patients with less severe stages of disease are equivalent to expectant management and conservative surgery.

Danazol

Danazol is a 19-nortestosterone derivative with progestin-like effects. Its mechanisms of action include inhibition of pituitary gonadotropin secretion, direct inhibition of endometriotic implant growth, and direct inhibition of ovarian enzymes responsible for estrogen production. Danazol is given orally in divided doses ranging from 400 to 800 mg daily, generally for six months. Most women taking danazol have side effects which can be dose-dependent, but only a small percentage of patients discontinue the drug because of them. Side effects include weight gain, muscle cramps, decreased breast size, acne, hirsutism, oily skin, decreased high density lipoprotein levels, increased liver enzymes, hot flashes, mood changes, and depression.Danazol is effective in resolving implants when treating mild or moderate stages of disease. More than 80 percent of patients experience relief or improvement of pain symptoms within two months of treatment. In contrast, large endometriotic cysts and adhesions do not respond well.

Pregnancy rates following treatment with danazol approximate 40 percent and are independent of the disease severity. Danazol is not more effective than expectant management for treating infertility in patients with mild or moderate disease.

GnRH analogs

GnRH analogs inhibit pituitary gonadotropin secretion, thereby profoundly suppressing ovarian estrogen production. These medications are administered by nasal spray, and monthly subcutaneous or intramuscular injections. The usual dose is 400 to 800 mg daily for nasal nafarelin, 3.6 mg for monthly subcutaneous goserelin, and 3.75 mg for monthly intramuscular leuprolide.