Medications:

The basic approach in hormonal treatments for endometriosis is to block production of female hormones (estrogen and progesterone) or to prevent ovulation. Hormonal drugs are used for pain relief only. They do not improve fertility rates and in some cases may delay conception. Specific hormonal drugs may have different effects for women with endometriosis.

• Inducing Pseudopregnancy. Oral contraceptives that contain estrogen and progestins mimic a pregnant state and block ovulation. (Progestins are natural or synthetic forms of progesterone). Progestins may also be used alone, since they have specific effects that can cause the endometrial tissue to atrophy.
• Inducing Pseudomenopause. Gonadotropin-releasing hormone (GnRH) agonists reduce estrogen and progesterone to their lowest levels.
• Inducing On-going Blockage of Ovulation. Danazol, a derivative of male hormones, is a powerful ovulation blocker but has very unpleasant side effects.

Most women achieve pain relief after taking these drugs. To date, comparison studies have found few differences in effectiveness among the major hormonal treatments. Differences occur mostly in their side effects. Women should discuss the effects of particular medications with their doctors to determine the best choice.

Oral Contraceptives

Oral contraceptives (OCs), commonly called "the Pill," contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestin). For some patients, OCs may provide better endometriosis pain relief than gonadotropin releasing hormone agonist drugs.

When used throughout a menstrual cycle, OCs suppress the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevent ovulation. There are many brands available. The estrogen compound used in most oral contraceptives is estradiol. Many different progestins are used, and there are many brands. None to date have proven to be superior over others. Women should discuss the best options for their individual situations with their doctor.

Standard OCs come in a 28-pill pack that contains 21 active pills and 7 inactive pills. Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These OCs contain a combination of estradiol and the progesterone levonorgestrel but use extending dosing of active pills.

OCs with continuous dosing include:

• Seasonale, contains 81 days of active pills followed by 7 days of inactive pills. Women have on average a period every 3 months.
• Seasonique produces about 4 periods a year. A woman takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.
• Lybrel, supplies a daily low dose of levonorgestrel and estradiol with no inactive pills. Because it contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. Over 50% of women in clinical trials completely stopped menstrual periods by the end of the first year. Some women, however, had occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Estrogen and progestin each cause different side effects. The most serious side effects are due to the estrogen in the combined pill. Uncommon but more dangerous complications of OCs include high blood pressure and deep-vein blood clots (thrombosis), which may contribute to heart attack or stroke.

[For more information, see In-Depth Report #91: Birth control options for women.]

Progestins

Progestins alone may be helpful and are the oldest drugs used for endometriosis. Progestins can prevent ovulation and reduce the risk for endometriosis in the following ways:

• They block luteinizing hormone (LH), one of the reproductive hormones important in ovulation.
• They change the lining of the uterus and eventually cause it to atrophy.
• They may provide pain relief equivalent to the more powerful hormone drugs. Some doctors recommend them as the first choice for women with endometriosis who do not want to become pregnant.

Specific Progestins. Progestins are available in various forms. They include:

• Intrauterine Device. The levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena) has proved effective for treating heavy menstrual bleeding (menorrhagia), and studies indicate that it helps control the symptoms of minimal-to-moderate endometriosis. Progestin released by the IUD mainly affects the uterus and cervix and causes fewer widespread side effects than other forms of progestins. Studies indicate that the LNG-IUS works as well as gonadotropin releasing hormone agonists in managing endometriosis pain, and causes less loss of estrogen.
• Injection. Medroxyprogesterone (Depo-Provera) is administered by injection every 3 months. A low-dose formulation is called Depo-subQ Provera 104. Depo-Provera can cause loss of bone mineral density, a condition associated with osteoporosis, but GnRH agonists may cause even more bone thinning. Depo-Provera can cause persistent infertility for up to 22 months after the last injection.
• Pill. Oral progestins include norethindrone (Micronor, Aygestin, Norlutate). Norethindrone is also known as norethisterone.

Side Effects of Progestins. Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that uses only progestin, although they may be less or more severe depending on the form and dosage of the contraceptive. The most common side effects include:

• Changes in uterine bleeding, such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods
• Weight gain
• Water retention and swelling in the face, ankles, or feet
• Breast tenderness
• Headaches
• Nausea
• Mood changes

[For more information, see In-Depth Report #91: Birth control options for women.]

GnRH Agonists

Gonadotropin releasing hormone (GnRH) agonists are effective hormone treatments for endometriosis. They block the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. Ovulation and menstruation resume around 4 - 10 weeks after stopping the drug. The specific length of time depends on the type of GnRH agonist used.

Specific GnRH Agonists. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, nafarelin (Synarel).

Side Effects and Complications. Commonly reported side effects (which can be severe in some women) include menopause-like symptoms, including hot flashes, night sweats, vaginal dryness, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. [For more information, see In-Depth Report #18: Osteoporosis.] In general, doctors recommend that women not take GnRH agonists for more than 6 months.

GnRH treatments can increase the risk for birth defects. Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Danazol

Danazol (Danocrine) is a synthetic drug that resembles a male hormone (androgen). It suppresses the pathway leading to ovulation. Many women stop taking this drug because of its adverse side effects, which include bloating, acne, irregular vaginal bleeding, and muscle cramps. Danazol can also cause male characteristics, such as growth of facial hair, reduced breasts, and deepening of the voice. Side effects virtually always disappear after stopping the medication. It may increase the risk for unhealthy cholesterol levels. Because GnRh agonists cause far fewer side effects, danazol is rarely used these days for endometriosis treatment.