Oral Contraceptives (Numerous brands)
Birth control pills (oral contraceptives or OCPs) have been used to treat endometriosis for more than 40 years. The treatment was based on the early observation that pregnancy, with high levels of both hormones, produces improvement of pain. Today, oral contraceptives are the most commonly prescribed treatment for endometriosis symptoms.
Side-effects of OCPs are multiple, but not terribly frequent. Estrogens may cause nausea, high blood pressure, blood clots, and enlargement of the uterus. The progestogen portion of the pill may cause effects such as acne, hair loss, increased muscle mass, decreased breast size, and deepening of the voice.
Oral contraceptives have been documented to improve endometriosis-related pain symptoms in about 80% of women, making this the first-line drug for treatment of the disease due to the low cost and few side effects. Unfortunately, many women will have symptoms that progress to the point that OCPs no longer provide relief.
Danazol (Danacrine)
Danazol is a derivative of the male hormone testosterone. It was originally thought to work by medically producing a hormonal state similar to menopause, but subsequent studies have revealed the drug to act primarily by causing a shutdown of ovulation. It may also work to interfere with the production of the body's hormones and increase the amount of male hormone in the blood, resulting in an antagonism of the effects of female hormones. The recommended dosage of danazol for the treatment of endometriosis is 600 to 800 mg/day; however, these doses have substantial side effects such as increased hair growth, mood changes, deepening of the voice (possibly irreversible), and rarely, liver damage (possibly irreversible and life-threatening) and blood clots in the arteries. Studies of lower doses as primary treatment for endometriosis-associated pain have been small and there is limited information. However, there is a suggestion that very low doses such as 50-100 mg/day can substantially reduce the pain of endometriosis without the hormone’s side effects. The usual course of therapy lasts 6-9 months, but there is considerable variation from patient to patient.
Pain relief has been well demonstrated with danazol, with 84 to 92 percent of women showing improvement. Recent evidence suggests the average time to pain recurrence following discontinuation of the medication is 6.1 months. Thus, the drug does seem to produce pain relief, but for a limited duration in many. There is no evidence that danazol will enhance rates of conception in women with endometriosis-associated infertility.
Progestogens (Provera, Aygestin, Mirena IUD)
Progestogens are a class of compounds that act like the natural hormone progesterone. These drugs have been shown to decrease pain associated with endometriosis.
The most extensively studied progestogen is medroxyprogesterone. The drug was originally used orally for the treatment of endometriosis, with doses ranging from 20mg to 100mg daily. However, the injectable form has also been used, in a dose of 150mg every three months. This injectable form, called Depo-Provera or depot medroxyprogesterone acetate, has recently been approved for use to treat endometriosis-associated pain by the Food and Drug Administration. Side effects of medroxyprogesterone are multiple and varied. A common side-effect is vaginal bleeding, which occurs in 38% to 47%. This is generally well tolerated and, when necessary, can be adequately treated with a small change in hormone dose. Other side effects include nausea (0% to 80%), breast tenderness (5%), fluid retention (50%), and depression (6%). All of the adverse effects mentioned here resolve upon discontinuation of the drug.
Norethindrone acetate (Aygestin) has also been utilized as a treatment for endometriosis in doses of 5mg to 20 mg daily. Side effects are similar to those seen with medroxyprogesterone.
Levonorgestrel has also been utilized recently, via an intrauterine device delivery system called the Mirena IUD. It has been touted as an excellent treatment for deep pelvic endometriosis and particularly pain with intercourse, although there are few studies to support this. Nevertheless, many patients get considerable relief from the IUD, and enjoy its ease of use (it lasts for up to 5 years). However, in some the discomfort occasionally associated with the device may lead to early removal.
Studies of the effectiveness of these agents in combating pain suggest that progestogens are as effective as other medical treatments in easing the pain of endometriosis, but with a different side-effect profile. Thus, over 80% can expect to get some relief. There is no evidence that progestogens can improve fertility rates in women with endometriosis.
GnRH-agonists (Lupron, Synarel)
Gonadotropin releasing-hormone agonists (GnRH agonists) result in a low estrogen state similar to that of menopause. It does this by preventing the production of hormones that stimulate the eggs in the ovary. This causes the ovary to produce very little estrogen, just like in women after menopause.
This drug can be given intranasally, subcutaneously, or intramuscularly depending upon the specific product, with frequency of administration ranging from twice daily to every three-months. The side effects are vaginal bleeding, hot flashes, vaginal dryness, decreased interest in sex, breast tenderness, insomnia, depression, irritability and fatigue, headache, brittle bones and decreased skin elasticity.
A recent modification of GnRH-agonist treatment is to “add back” small amounts of hormone in a manner similar to that used in the treatment of post-menopausal women. Add back therapy results in an equivalent rate of pain relief with far fewer side effects than GnRH agonist alone. The add-back regimens found to be of value are combinations of small doses of estrogen and progestogen (Prempro, FemHrt) or progestogen alone (Aygestin). Estrogen alone is not effective as add-back, as pain quickly returns in patients so treated. The same is true for using birth control pills as add-back, as the dose of estrogen is too high in these pills (even the low dose pills).
The effectiveness of GnRH agonists in the treatment of endometriosis-associated pain has been shown time and again in many studies. While it may be no better than other therapies initially, it is the “go to” drug when patients have failed the easier, less expensive therapies. Its use with add-back therapy is now the standard of care; there is no reason today to take these medications without add-back therapy and suffer the side effects of menopause.
Treatment of endometriosis-associated infertility with GnRH-agonist has not proven to be of value.
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