Progestin for endometriosis

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Progestin for endometriosis


Oral (pill)

Generic NameBrand Name
megestrol acetate [50 mg a day]Megace
norethindrone Micronor
norethindrone acetate 
norethindrone acetate plus estrogen Loestrin
norethindrone plus estrogenBrevicon

Norethindrone is started at 5 mg and increased at 2.5 mg increments until your periods stop (amenorrhea occurs).

Injection (into a muscle or under the skin)

Generic NameBrand Name
medroxyprogesterone acetateDepo-Provera [150 mg]

One injection is given every 90 days.

Intrauterine device (IUD) with progestin

Generic NameBrand Name
levonorgestrel IUD [LNg IUD]Mirena

Megestrol and Depo-Provera are high-dose progestins.

How It Works

Progestin shrinks endometriosis growths—which are also called implants—and reduces pain for most women.

Progestin is similar to the body's hormone progesterone. Taking progestin creates levels in the body similar to pregnancy. This stops monthly growth of the uterine lining (endometrium) and endometriosis implants elsewhere in the body. Progestin also reduces estrogen production, which stops ovulation and menstrual periods in most women.

The levonorgestrel (LNg) intrauterine device (IUD) has recently been studied as an endometriosis therapy.2 It releases a lower daily dose of levonorgestrel, a form of progestin, directly into the uterus. This causes fewer side effects than high-dose progestin pills or injections. In addition to reducing cramping and heavy menstrual bleeding, the LNg IUD is a highly effective method of birth control.

Why It Is Used

Progestin is a second-choice treatment for endometriosis. It is as effective as other hormone therapies. But it is typically used after birth control pills and/or gonadotropin-releasing hormone agonist (GnRH-a) therapies have not relieved endometriosis pain. This is because high-dose progestin, when given by mouth or injection, may cause bone-thinning and unpleasant side effects.1 (Megestrol and Depo-Provera are high-dose progestins. The progestin IUD is not known to have effects on the bone and causes fewer side effects because the progestin dose is lower.)

Progestin injection and the LNg IUD also effectively prevent pregnancy.

How Well It Works

Like all hormone therapies and surgery, progestin does not cure endometriosis.

Progestin may improve symptoms of endometriosis, such as pain during periods and pelvic pain. When compared with other hormone therapies, it has proved to be equally effective. Generally about 80% to 90% of women gain relief with any particular hormone therapy.2

Pain recurrence

After treatment with progestin or 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.

Side Effects

When taken in high doses (such as Depo-Provera or megestrol), progestin can cause:

  • Absence of menstrual bleeding (amenorrhea).
  • Abnormal vaginal bleeding, such as irregular spotting to light vaginal bleeding.
  • Mood changes or depression.
  • Breast tenderness.
  • Water retention.
  • Weight gain.

The progestin IUD is least likely to cause mood changes, breast tenderness, water retention, and weight gain.

Risks of long-term use

Depo-Provera use for 2 or more years may cause bone loss.3 This is thought to rapidly improve after stopping treatment. But bone loss may not be fully reversible after stopping the medicine.2 Bone loss can lead to osteoporosis in later life, which makes bones weak enough that they are more likely to break.

For teens using progestin, bone thinning is a concern, because the teen years are an important bone-building period. But one study suggests that this bone loss reverses. After 12 months of not using Depo-Provera, teens' bone density seemed to be at expected levels for their age.4

Talk to your health professional about taking calcium and vitamin D if you are using progestin.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

If you plan to become pregnant soon after treatment, there is no hormone therapy that will suit your needs. It can take awhile for your menstrual cycle to get back to normal after hormone treatment. After Depo-Provera use in particular, it can take months to be fertile again.

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.



  1. Winkel CA (2003). Evaluation and management of women with endometriosis. Obstetrics and Gynecology, 102(2): 397–408.
  2. Speroff L, Fritz MA (2005). Endometriosis. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 1103–1133. Philadelphia: Lippincott Williams and Wilkins.
  3. 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:
  4. Scholes D, et al. (2005). Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Archives of Pediatrics and Adolescent Medicine, 159(2): 139–144.


By Healthwise Staff
Primary Medical Reviewer Sarah Marshall, MD - Family Medicine
Primary Medical Reviewer Anne C. Poinier, MD - Internal Medicine
Specialist Medical Reviewer Deborah A. Penava, BA, MD, FRCSC, MPH - Obstetrics and Gynecology
Last Revised March 29, 2010

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