Depo Provera (Depot medroxyprogesterone acetate) is a type of hormone therapy that can help ease the symptoms of endometriosis.

Depo Provera is produced by Pfizer and generic versions are also available. Generally prescribed as a long-acting contraceptive, it has been used off-label for the treatment of endometriosis since the 1950s.

How Depo Provera works

In endometriosis, a tissue similar to the endometrium (the lining of the uterus) develops elsewhere in the body, forming lesions. In response to hormones such as estrogen, the endometrium — as well as the endometrial lesions — thicken and break down. But while the endometrium exits the body as part of the monthly menstrual cycle (if no pregnancy occurs), endometrial lesions cannot because no route exists. This process can lead to inflammation, severe pain, and potentially permanent damage.

As endometriosis is affected by hormonal cycles, these cycles have been the focus of many treatment approaches. Depo Provera is a type of progestin therapy. It is a synthetic, or man-made, version of the female reproductive hormone, progesterone, which together with estrogen is involved in the menstrual cycle. By providing a constant progesterone mimic, Depo Provera suppresses the further production of both progesterone and estrogen.

The exact mechanism behind how it acts to relieve the symptoms of endometriosis is still unknown. However, Depo Provera suppresses the growth of the existing lesions and may prevent new lesions from forming. Depo Provera can also help reduce inflammation caused by endometriosis, which can be a source of pain.

Depo Provera in clinical trials

Depo Provera is a well-established treatment for endometriosis despite not being investigated specifically as an endometriosis treatment in clinical trials. Several studies have used it to compare endometriosis treatments, however, and it has been shown to be effective at easing the symptoms of the disease.

For example, Depo Provera has been shown to be equally as effective at reducing endometriosis-associated pain as other hormone therapies such as Lupron Depot (leuprolide acetate) and Orilissa (elagolix). However, compared to Lupron Depot, Depo Provera has fewer damaging side effects, such as a reduced impact on bone mineral density, which can reduce the risk of osteoporosis when taken long-term. This was demonstrated in a study published in the journal Human Reproduction in 2006.

A randomized, double-blind, Phase 2 trial (NCT00437658) compared Orilissa and Depo Provera. In total, 252 endometriosis patients were enrolled at 58 U.S.-based sites. The results, published in Reproductive Sciences, demonstrated that both therapies were equally effective at reducing pain with minimal effect on bone mineral density over a 24-week period.

The PRE-EMPT study (EudraCT Number: 2013-001984-21) is currently recruiting women, ages 16 to 45 who are currently scheduled to have laparoscopy surgery to treat endometriosis, at several sites across the U.K. This is a randomized controlled trial that aims to assess whether long-acting progesterone therapy is more effective at reducing endometriosis symptoms compared to the combined oral contraceptive pill or no hormone therapy, following surgery to remove lesions. The treatment arms include Depo Provera, Mirena (levonorgestrel coil), the combined oral contraceptive pill, or no medical treatment.

Its main outcome is the recurrence of symptoms after 36 months, determined by the 30-point endometriosis health profile (EHP-30). The comparison will also take into account other measures, such as the cost of the medication and the type and severity of side effects.

At the last update, the PRE-EMPT trial had enrolled 121 patients of an estimated 400.

Other information

Depo Provera is administered as an injection, generally once every three months.

The long-term use of Depo Provera can reduce bone mineral density, which may lead to osteoporosis. However, bone density should slowly return to normal after stopping injections. Other side effects include headaches, acne, hair loss, decreased sex drive, mood swings, and weight gain.

As it is a contraceptive medication, Depo Provera should not be taken by women who are intending or trying to conceive.


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