Endometriomas. For patients with endometriomas that are causing pain, sometimes surgery is the best first-line treatment. Laparoscopic excision of the endometrioma and the cyst wall appears to be superior to drainage and ablation of the endometrioma. Women who had undergone laparoscopic endometrioma excision had lower rates of endometrioma recurrence and reduced rates of postoperative dysmenorrhea, dyspareunia, and pelvic pain. Surgical excision of endometriomas should provide postoperative pain relief; however the long-term effects on fertility and ovarian reserve are less clear. Aggressive removal of endometriomas appears to reduce ovarian reserve and potentially future fertility. For women with a clear diagnosis of endometrioma who wish to have children, drugs are preferable to surgery.

Gonadotropin-releasing hormone agonists. GnRH agonists can be used in patients who have failed oral contraceptives or who decline surgery, or both. They work by inducing a menopausal state through down regulation of gonadotropin secretion and a resulting drop in estrogen production. But there’s no good evidence that they provide greater pain relief than OCs plus NSAIDs.

Furthermore, the side effects of GnRH agonists include bone loss and vasomotor symptoms. To avoid these side effects when choosing GnRH agonists, be sure to prescribe them with add-back therapy consisting of 5 mg daily of norethindrone acetate, especially for patients who are treated for more than 6 months. The addition of add-back therapy does not diminish the efficacy of the GnRH agonists in reducing pain.

Alternative add-back approach. Also consider estrogen/progestin add-back therapy using low-dose conjugated equine estrogens (CEE) daily and a progestin in these patients. Keep in mind, however, that higher doses of estrogen add-back therapy, such as 1.25 mg daily of CEE daily, may not suppress pelvic pain symptoms as much.

Adding norethindrone. This medication—with or without estrogen add-back therapy—can reduce bone loss in women taking GnRH agonists, and this combination therapy can be continued for at least 12 months. Pain will usually return within 60 to 90 days of discontinuing GnRH agonists, though, with up to 75% of patients having recurrent symptoms. For women with clinically suspected endometriosis who fail OCs and NSAIDs, you can give a standard 6-month trial with GnRH agonists plus add-back with either 2.5 to 5 mg of norethindrone daily or 0.3 to 0.625 mg of CEE daily plus 2.5 to 5 mg of medroxyprogesterone acetate daily. There’s almost never a reason to use a GnRH agonist alone in this setting.

Progestins alone. These can also be used to treat endometriosis, as they cause decidualization and atrophy of the endometrial cells and reduce ovarian production of estrogen. Norethindrone can be started at 5 mg per day or medroxyprogesterone acetate at 10 mg two or three times a day. However, effective pain control may require higher doses and some patients cannot tolerate the adverse side effects of progestins, such as bloating, depression, or weight gain.

Danazol. Although this medication isn’t used as frequently as it used to be in the United States to treat endometriosis, it’s still widely used in Europe and throughout the world. It is just as effective as GnRH agonists or progestins, but use waned in this country due to side effects like acne and hair growth. However, the androgenic effect might be a plus for patients who complain of decreased libido while taking other drugs that all reduce androgens.

Newer medical treatments. These include the levonorgestrel-releasing intrauterine device (LNG-IUD). This approach has been investigated in patients who have had an LNG-IUD placed postoperatively after surgery for endometriosis to inhibit the growth of endometriosis implants. In one randomized trial, an LNG-IUD reduced the postoperative recurrence of dysmenorrhea. Alternatively, progesterone given vaginally can be particularly helpful for patients with rectovaginal endometriosis.

Aromatase inhibitors (AIs). These are another novel treatment option for patients with endometriosis who fail first-line medical therapy. Endometriosis expresses the aromatase enzyme and can therefore make its own estrogen. Aromatase inhibitors work by blocking estrogen production in the endometriosis lesions as well as in the ovary and at peripheral sites. Since AIs also increase FSH with resultant ovarian stimulation, you’ll only want to use them along with a progestin or GnRH agonist for treating endometriosis. When used in conjunction with a GnRH agonist, AIs significantly improved pain compared to GnRH agonists alone.

Progesterone antagonists. These hold promise in treating endometriosis. It’s thought progesterone antagonists work by inhibiting endometriosis progression or by suppressing the production of endometrial prostaglandin. Mifepristone, when used in doses of 50 mg per day, can decrease pain symptoms and also cause a regression of endometriosis lesions.