Can Depo-Provera Treat Endometriosis?

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Endometriosis is a condition in which the tissue that normally lines the inside of your uterus (the endometrium) grows in other areas of the body—most commonly on the ovaries, fallopian tubes, and other organs in the pelvic region. It can cause pain and irregular bleeding.

Endometriosis is a common problem, affecting more than 6.5 million American girls and women of reproductive age. Symptoms also seem to get worse around the time of your period.

There is no cure for endometriosis. If it is not treated, though, it may lower your chances of being able to become pregnant in the future. Endometriosis is one of the top three causes of infertility.

The goal of treatment is to control pain and prevent the endometriosis from getting worse. Treatment can consist of medication and/or surgery. The type of treatment you may seek usually depends on the severity of your symptoms and whether or not you may want to become pregnant.

Depo-subQ Provera 104 is a contraceptive injection that contains a progestin(a hormone that blocks ovulation) called medroxyprogesterone acetate. It received approval from the U.S. Food and Drug Administration (FDA) in March 2005 for the treatment of endometriosis-related pain.

This FDA-approval served as the first new medical remedy for endometriosis pain relief in 15 years. Although the approval doesn't apply to the original Depo-Provera shot, the shot is used off-label for pain from endometriosis.

How Depo-Provera Helps Treat Endometriosis Pain

The progestin in Depo-Provera is thought to help suppress the growth of endometrial tissue and may also reduce endometriosis-induced inflammation.

During your normal menstrual cycle, your hormones cause the lining of your uterus to thicken in preparation for pregnancy. If you don’t become pregnant, the lining of your uterus sheds, and you bleed (this is what causes your period).

The hormones that control your menstrual cycle naturally rise and fall throughout your cycle. This rising and falling can cause endometriosis symptoms to become worse. Also, if you have endometriosis, when you have your period, the bleeding not only comes from the lining of the uterus, but the endometrial tissue that has grown outside your uterus also bleeds. When this blood touches other organs, it can cause scarring and inflammation, which is what causes pain.

The use of Depo-Provera allows your hormone levels to stay stable throughout your cycle. It helps to thin the lining of the uterus—this can lead to lighter periods or none at all. Depo-Provera may also prevent ovulation and lowers the amount of estrogen circulating in your body.

The idea here is that the less estrogen stimulation the endometriosis tissue receives, the less cell activity occurs. This slows down the growth rate of the tissue. Just like the lining of the uterus responds to these hormone levels, the endometriosis tissue does as well.

What Other Medications Treat Endometriosis?

Before the use of hormone therapy (like Depo-Provera) for the treatment of endometriosis, GnRH agonists (like leuprolide) have been the main medication prescribed for endometriosis pain relief.

This drug is a version of a naturally occurring hormone, known as a gonadotropin-releasing hormone, which helps to control the menstrual cycle. When you use leuprolide, it basically stops all hormone and ovarian activity.

Leuprolide Side Effects

Leuprolide is also associated with significant side effects, some of which include:

  • Vasomotor symptoms (hot flashes, palpitations, sweating)
  • Bone loss
  • Hypoestrogenic symptoms (vaginal dryness, mood swings, sleep disturbances)
  • Headaches
  • Depression
  • Decreased libido

What Does the Research Say About Depo-Provera vs. Leuprolide?

One of the most well-known studies in this area compared Depo-subQ Provera 104 and leuprolide use in 257 women who were laparoscopically diagnosed with endometriosis. For six months, 153 women used Depo-subQ Provera 104 and 146 women used leuprolide.

The results showed that:

  • Depo-subQ Provera 104 is equally as effective for treating pain caused by endometriosis as leuprolide.
  • Both Depo-subQ Provera 104 and leuprolide effectively reduced pain in the five main endometriosis symptoms: pelvic pain, dysmenorrhea, pelvic tenderness, dyspareunia (painful sex), and induration (hardening and thickening of tissue).
  • After 6 months of use, Depo-subQ Provera 104 resulted in less bone mineral density loss than leuprolide. At 12 months post-treatment, bone loss levels returned to pre-treatment levels for Depo-subQ Provera 104 users, but not for those who used leuprolide.
  • Both medications equally contributed to significant improvements in quality of life and total productivity.

The researchers concluded that Depo-subQ Provera 104 treats pain caused by endometriosis as successfully as leuprolide. However, women who used Depo-subQ Provera 104 reported fewer vasomotor symptoms (like hot flashes or sweats) and fewer hypoestrogenic symptoms (like sleep disturbances, mood changes, and vaginal irritation) and experienced significantly less decline in bone mineral density than women who used leuprolide.

Not only is it a highly effective contraceptive, Depo-subQ Provera 104 is an equally suitable and effective treatment option as leuprolide for the treatment of endometriosis-related pain.

Additional research confirms these results. In a later review, researchers analyzed all the studies that investigated the use of progestin for the treatment of endometriosis published between 1993–2003.

The combined results of all these studies showed that medroxyprogesterone acetate, the progestin in Depo-Provera, is just as effective as GnRH agonists (including leuprolide) in reducing endometriosis-related pain and in improving health-related quality of life issues.

The authors further explain that Depo-Provera use in women with symptomatic endometriosis resulted in a significant decrease in pain symptoms and lead to a reduction in new endometriosis tissue growth.

Depo-Provera

  • Equally effective at treating endometriosis pain as leuprolide

  • Reduces pain in the five main endometriosis symptoms

  • May result in less bone mineral density loss than leuprolide

  • May cause fewer vasomotor and/or hypoestrogenic symptoms

Leuprolide

  • Equally effective at treating endometriosis pain as Depo-Provera

  • Reduces pain in the five main endometriosis symptoms

Other Considerations

Depo-Provera has been used to successfully treat endometriosis. The main reason for its effectiveness is that Depo-Provera can help prevent ovulation. Depo-Provera directly affects the endometrial tissue by causing it to thin out—this leads to lower amounts of menstrual bleeding—which leads to pain relief.

However, Depo-Provera may be a more temporary treatment for endometriosis. Even though it is effective in the short-term, after stopping Depo-Provera, there is a high chance that endometrial tissue growth will return.

Depo-Provera also does not treat infertility associated with endometriosis. If you want to become pregnant, surgery may be the best treatment option for endometriosis.

Depo-Provera is as effective as leuprolide and other GnRH agonists in treating endometriosis-related pain. However, leuprolide is more expensive and is associated with more uncomfortable side effects. On the other hand, Depo-Provera comes with a black box safety warning—when used for more than two years, Depo-Provera can increase the thinning of your bones (which leads to an increased risk of osteoporosis).

Depo-Provera use may also delay the return of your fertility. About 50% of women will be able to get pregnant within 10 months after their last Depo-Provera injection, but it can take up to 18 months for fertility to return. Some women report irregular or continuous bleeding when using Depo-Provera along with other unwanted side effects.

Unfortunately, once you are given a Depo-Provera injection, if you are unhappy with the side effects, you must wait out the three-month time frame until all of the hormones from this contraceptive gradually leave your body.

So, if you're considering Depo-Provera to treat your endometriosis, make sure you talk to your doctor so the two of you can determine whether the pain-relief that Depo-Provera can offer outweighs these potential risks. Our Doctor Discussion Guide below can help you start that conversation.

Endometriosis Doctor Discussion Guide

Get our printable guide for your next doctor's appointment to help you ask the right questions.

Doctor Discussion Guide Woman
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Article Sources

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  2. FDA News. FDA Approves New Indication for Pfizer's Depo-SubQ Provera 104.

  3. Barra F, Scala C, Ferrero S. Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis. Expert Opin Drug Metab Toxicol. 2018;14(4):399–415. doi:10.1080/17425255.2018.1461840

  4. AbbVie, Inc. Lupron Depot for Endometriosis.

  5. Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod. 2006;21(1):248-56. doi:10.1093/humrep/dei290.

  6. Zhao J, Li Y, Zhang Q, Wang Y. Retraction notice to 'Does ovarian stimulation for IVF increase gynaecological cancer risk? A systematic review and meta-analysis' [Reproductive BioMedicine Online 31 (2015) 20-29]. Reprod Biomed Online. 2016;33(4):534. doi:10.1093/humupd/dmg030.

  7. Pfizer Canada, Inc. Product Monograph: Depo-Provera. Updated February 13, 2018.

Additional Reading

  • U.S. Department of Health & Human Services, Office on Women's Health. Endometriosis. Updated April 1, 2019.