Should I use hormone therapy to treat endometriosis?

Introduction

This information will help you understand your choices, whether you share in the decision-making process or rely on your health professional's recommendation.

Key points in making your decision

If you have endometriosis, you probably already know that estrogen "feeds" endometriosis growth. This is why endometriosis only affects women during their high-estrogen adult years. When your menstrual periods stop around age 50 (menopause) and your estrogen levels drop, endometriosis growth and symptoms will probably also stop. (In some cases, endometriosis scar tissue remains after menopause and can cause problems.)

There is no known cure for endometriosis. But controlling estrogen with hormone therapy can help relieve endometriosis pain. Hormone therapy may reduce the number and size of growths (implants) and limit the spread of endometriosis. But it does not improve fertility.

Consider the following when making your decision:

• Unless infertility is your main concern, hormone therapy is the first-choice treatment for endometriosis. If pain continues after using one or more types of hormone therapy, surgery may be an option.
• Only birth control hormones (patch, pills, or ring) are safe for long-term use until menopause. They are often paired with anti-inflammatory therapy. The other hormone therapy options are limited to shorter-term use, because they have serious side effects after a few months of use. Be sure to consider the side effects of each option before deciding to use a hormone therapy.
• Hormone therapies are effective for 80% to 90% of women. Different women have different results with each kind of therapy.
• For some women, hormone therapy offers only a temporary solution because pain relief lasts only a few months after treatment. For others, relief is long-lasting.
• For women who have had endometriosis surgically removed, using hormone therapy after surgery may relieve pain for a longer time by preventing the growth of new or returning endometriosis.¹

Medical Information

What is endometriosis?

The endometrium is the tissue that lines the uterus. During each menstrual cycle, a new endometrium grows, getting ready for a possible pregnancy. If you don't become pregnant during that cycle, the endometrium sheds, which you know as your menstrual period.

Endometriosis is endometrium tissue that grows outside of the uterus, usually on the ovaries or fallopian tubes, the outer surface of the uterus, the bowels, or other abdominal organs. In rare cases, it can affect other organs and structures in the body.

Endometriosis growths are called 'implants.' These implants grow, bleed, and break down with each menstrual cycle, just like the endometrium does. This can cause pain and can make it difficult to become pregnant (infertility). In some cases, scar tissue forms around implants. Scar tissue can also cause pain and infertility and can interfere with an organ's normal function.

How will endometriosis affect me?

Endometriosis is usually a long-lasting (chronic) disease. While some women with endometriosis never have symptoms or problems, others develop mild to severe symptoms or infertility. Between 20% and 40% of women who are infertile have endometriosis.² In any given case, it is impossible to know whether endometriosis will get worse, improve, or stay the same until menopause.

Endometriosis growths (implants) go through the same growing, breaking down, and bleeding that the uterine lining (endometrium) goes through with each menstrual cycle. This is why endometriosis pain often starts as mild discomfort a few days before the menstrual period and why it usually improves during the period. But if an endometriosis implant grows in a sensitive area such as the rectum, it can eventually cause constant pain or pain during certain activities such as sex, exercise, or bowel movements.

Endometriosis symptoms often improve during pregnancy, and they usually disappear after menopause. These are times when estrogen levels are low, which slows or stops endometriosis growth.³ For most women, endometriosis symptoms also improve with hormonal treatments that lower estrogen levels.

How does hormone therapy work?

Hormone therapy reduces estrogen levels in your body. Because of this, you cannot use hormone therapy if infertility is your main concern.

• Birth control hormones (patch, pills, or ring) control the menstrual cycle. This stops ovulation and endometrium growth and shrinks endometriosis implants. For most women, this therapy is doesn't usually have serious side effects, lowers ovarian cancer risk (which is higher with endometriosis), and can be used long-term until menopause. For more general information on birth control hormones, see Birth control pill, patch, or ring.
• Gonadotropin-releasing hormone agonist (GnRH-a) therapy (such as Lupron, Synarel, or Zoladex) lowers estrogen to the levels women have after menopause. GnRH-a therapy is limited to a short period of time (3 to 6 months) because it thins the bones, which can lead to osteoporosis. It is usually used with a little added estrogen and progestin (add-back therapy) to prevent bone loss and menopause side effects. Using GnRH-a therapy after surgery may relieve pain for a longer time by preventing the growth of new or returning endometriosis.⁴
• Progestin creates progestin levels in the body that are similar to pregnancy. This stops monthly ovulation and lowers estrogen, which shrinks endometriosis implants and reduces pain for most women. High-dose progestin (such as the Depo-Provera shot) is not a long-term treatment-two or more years of treatment may weaken your bones.⁵ Talk to your doctor about whether the progestin intrauterine device (Mirena) might offer you progestin benefits with lower side effect risks.
• Danazol therapy lowers estrogen levels and raises male hormone (androgen) levels, which puts the body in a state similar to menopause. This shrinks endometriosis implants and reduces pain for most women. But danazol side effects are usually worse than GnRH-a side effects, making danazol a last-choice therapy.
• Aromatase inhibitors stop estrogen production. In small studies, aromatase inhibitors have been shown to reduce pain and the chance of endometriosis growths coming back. Aromatase inhibitors may help women with endometriosis who have not had relief with hormonal treatments. Aromatase inhibitors are used in combination with a hormonal treatment (such as birth control hormones or progestin). Long-term use of aromatase inhibitors may cause bone loss. More research needs to be done before it is known how well this treatment works and what the side effects are.⁶

How well does hormone therapy work?

All hormone therapies are effective for 80% to 90% of women. While one may work for you, it won't necessarily work for someone else. You may have to try one, then another, before finding one that works for you. The major differences between hormone therapy options are their side effects. Some, especially danazol, can cause very unpleasant side effects. Others-such as GnRH-a or high-dose progestin-thin the bones, so they cannot be used long-term.

If taking birth control hormones works for you, you can use them for years (unless you plan a pregnancy). Long-term use may prevent endometriosis from getting worse, lower your ovarian cancer risk, and effectively prevent pregnancy. For some women in their 40s, they also improve or prevent perimenopausal symptoms that can make life difficult as menopause approaches.

For some women, hormone therapy offers only a temporary solution because pain relief lasts only a few months after treatment. For others, relief is long-lasting.

Pain recurrence. After treatment with any hormone therapy, endometriosis pain can, but does not always, return:²

• Each year, up to 20% of all women treated will have pain that returns after hormone treatment.
• About 37% of women who use hormone therapy for mild endometriosis have pain 5 years later.
• About 74% of women who use hormone therapy for severe endometriosis have pain 5 years later.

What are the risks of taking these medicines?

Birth control hormones, GnRH-a, progestin, and danazol each have different possible side effects and risks. The reduction of estrogen produces a condition similar to menopause, with many of the same effects. Side effects can include the following:

Birth control hormones. Side effects do not affect every woman and are generally mild. They often go away after the first few months of use. They can include spotting between periods, nausea, headaches, breast tenderness, mood changes, depression, less interest in sex, and lighter or absent periods. Risks include an increased risk of dangerous blood clots. Your health professional will not prescribe birth control hormones if you have risk factors for blood clots, have a history of breast cancer, or are older than 35 and smoke.

GnRH-a (such as Lupron, Synarel, or Zoladex). Side effects can be reduced by taking a little estrogen with or without progestin (add-back therapy) with GnRH-a therapy. Side effects are like menopause and can include hot flashes, mood swings, vaginal dryness, less interest in sex, insomnia, and headaches. Risks include rapid loss in bone density of up to 1% per month, a decrease in "good" cholesterol, and an increase in "bad" cholesterol. Add-back therapy prevents some but not all bone loss (but it may make cholesterol changes worse). Bone density improves after treatment, but it may not fully recover. This is why GnRH-a therapy is limited to 3 to 6 months. No more than 2 rounds of therapy are recommended, with time in between to recover bone loss. (After careful discussion with your gynecologist.)

Progestin. Side effects may include mood changes and depression, bloating and weight gain, weight loss, breast tenderness, and absent or light irregular periods. With high-dose progestin (such as the Depo-Provera shot), risks include loss in bone density after 2 years of use. Bone density is thought to rapidly improve after treatment, but teens may not fully recover lost bone. Fertility can take a year or more to return after high-dose progestin therapy.

Danazol. Side effects are common with this therapy and are caused by higher male hormone (androgen) levels. Side effects include decreased breast size, muscle cramps, more facial and body hair, depression, weight gain, acne, skin rash, and oily skin and hair along with deepening of the voice, which can be permanent. Risks include an increase in "bad" cholesterol (more likely than with GnRH-a); worsening of liver, heart, or kidney disease; and increased risk of ovarian cancer.⁷ No more than 6 to 9 months of therapy is recommended.

Aromatase inhibitors. Side effects include headache, nausea, diarrhea, and hot flashes. Risks include bone loss with long-term use. This treatment is still being studied for use in endometriosis. More research needs to be done before it is known how well this treatment works and what the side effects are.

If you need more information, see the topic Endometriosis.

Your Information

Not all women with endometriosis have pain or get worse over time. During pregnancy, endometriosis usually improves, as it does after menopause. If you have mild pain, are planning a pregnancy, or are getting close to menopause (around age 50), you may not feel a need for any treatment. That decision is up to you.

Your choices are:

• Use no medicine and no hormone therapy. This is especially important if you are trying to become pregnant.
• Use home treatment with nonsteroidal anti-inflammatory drug (NSAID) therapy for mild pain. (Talk to your health professional first.)
• Try birth control hormones (patch, pills, or ring) for several months. (If your pain is severe, your health professional may recommend that you skip this and try GnRH-a with add-back therapy first).
• Try GnRH-a with add-back therapy for up to 6 months (if you cannot take birth control pills, if several months of pill use were not effective, or if you have severe pain).
• Try progestin or danazol (if birth control pills and GnRH-a were not effective and you think you can tolerate the side effects) OR consider surgery. Surgically removing endometriosis is usually done laparoscopically, through small incisions. For more information, see the Surgery section of Endometriosis.

The decision about whether to treat endometriosis with prescription medicines takes into account your personal feelings and the medical facts.

These personal stories may help you make your decision.

Wise Health Decision

Use this worksheet to help you make your decision. After completing it, you should have a better idea of how you feel about treating endometriosis. Discuss the worksheet with your doctor.

Circle the answer that best applies to you.

*NA = Not applicable

Use the following space to list any other important concerns you have about this decision.

What is your overall impression?

Your answers in the above worksheet are meant to give you a general idea of where you stand on this decision. You may have one overriding reason to use or not use hormone therapy to treat endometriosis.

Check the box below that represents your overall impression about your decision.

Return to the topic Endometriosis.

References

Citations

1. Johnson N, Farquhar C (2006). Endometriosis, search date April 2006. Online version of Clinical Evidence (15).

2. Speroff L, Fritz MA (2005). Endometriosis. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 1103-1133. Philadelphia: Lippincott Williams and Wilkins.

3. Mishell DR Jr, et al. (2001). Endometriosis and adenomyosis. In MA Stenchever et al., eds., Comprehensive Gynecology, 4th ed., pp. 531-564. St. Louis: Mosby.

4. Winkel CA (2003). Evaluation and management of women with endometriosis. Obstetrics and Gynecology, 102(2): 397-408.

5. U.S. Food and Drug Administration (2004). Black box warning added concerning long-term use of Depo-Provera contraceptive injection. FDA Talk Paper No. T04-50. Available online: http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01325.html.

6. Attar E, Bulun S (2006). Aromatase inhibitors: The next generation of therapeutics for endometriosis? Fertility and Sterility, 85(5): 1307-1318.

7. Cottreau CM, et al. (2003). Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer. Clinical Cancer Research, 9(14): 5142-5144.