Lupron Depot (leuprolide acetate) is an injectable therapy marketed by AbbVie to help manage the pain that is a symptom of endometriosis.

How Lupron Depot works

Endometriosis is a condition where the endometrium, or the lining of the uterus, begins to grow outside the uterus. This commonly occurs around the reproductive organs, bladder, or rectum. These abnormal growths are also known as lesions.

In response to hormones, such as estrogen, the endometrium normally thickens, breaks down, and is passed from the body as part of the monthly menstrual cycle. Endometriosal lesions are also affected by hormone cycles and thicken and break down, but they cannot be removed during menstruation. This may lead to severe pain, and scarring that can result in organs being stuck together.

Lupron Depot is a type of medication called a gonadotrophin releasing hormone (GnRH) agonist. It acts to disrupt the production of female reproductive hormones, preventing the menstrual cycle and thereby reducing pain and the number of new lesions.

GnRH is a naturally occurring hormone, a key part of the pathway that stimulates the production of hormones such as estrogen that control the menstrual cycle.

As a GnRH agonist, Lupron Depot acts by stimulating the same pathway as GnRH. This results in an initial spike in estrogen levels on first taking the medication, which may temporarily worsen symptoms. However, as Lupron Depot is at a higher prolonged concentration than is normal, the body quickly becomes desensitized to the hormone and stops reacting to it. As a result, while using the medication, levels of the reproductive hormones drop, monthly periods cease, and the symptoms of endometriosis should ease.

Generally, it is recommended that Lupron Depot is taken alongside an add-back therapy. This is a very low dose of either estrogen or progesterone, another reproductive hormone. These hormones have multiple roles in the body, besides their main role in reproduction, including keeping bones healthy. By providing just enough of the hormones to maintain healthy bones without triggering menstruation, Lupron Depot can be taken safely for an extended time. Add-back therapy may also reduce other treatment side effects.

Lupron Depot in clinical trials

Lupron Depot was investigated in several clinical trials as an endometriosis therapy, both before and after its approval by the U.S. Food and Drug Administration (FDA) in 1990.

The results of a randomized, double-blind, placebo-controlled trial in 52 endometriosis patients in the U.S were published in the journal Fertility and Sterility in 1990. They showed that Lupron Depot successfully inhibited menstruation and significantly reduced symptoms of pain compared to patients taking a placebo.

The Lupron Add-Back Study assessed the safety and efficacy of Lupron Depot alone or in combination with one of three hormonal add-back treatments. This trial treated 201 endometriosis patients over a one-year period. Results demonstrated that Lupron Depot could successfully reduce pain regardless of the combination. However, Lupron Depot alone had a higher risk of side effects, such as loss of bone density. The most effective combination was Lupron Depot and an add-back therapy with the hormone progestin (norethindrone acetate). Trial findings were published in the scientific journal Obstetrics and Gynecology in 1998.

More recently, a U.S-based Phase 2 clinical trial (NCT00474851) assessed the safety and efficacy of Lupron Depot in combination with norethindrone acetate, or with norethindrone acetate and conjugated equine estrogens. In total, 51 patients, ages 15 to 22, were enrolled to randomly receive one of the two regimens for one year. Results, published in Obstetrics and Gynecology, suggested that the two add-back therapy combination was more effective in maintaining bone health compared to  Lupron Depot plus norethindrone acetate.

Patients completing this trial were also contacted about the treatment’s long-term effects, 21 to 65 months following the end of the trial. The results of a questionnaire for the 25 patients who responded were published in the Journal of Pediatric and Adolescent Gynecology. Most reported experiencing some side effects, with nine out of 20 patients reporting side effects that they considered irreversible because they were continuing at this follow-up. These included bone density loss, memory loss, insomnia, anxiety, decreased libido, and hot flushes. Still, 12 of 25 patients rated the treatment as the most effective they had tried at treating endometriosis-associated pain. Overall, 16 patients said they would recommend the treatment: 11 were from the group that received  Lupron Depot plus the two add-back therapy combination, the five others were treated with Lupron Depot and norethindrone acetate alone.

Other information

Lupron Depot was originally developed by Takeda-Abbott Pharmaceuticals (TAP), a partnership between Takeda Pharmaceuticals and Abbott Laboratories, to which AbbVie also originally belonged. Following the end to the joint venture, AbbVie retained the rights to Lupron Depot.

Lupron Depot may cause hot flushes and sweating, headaches or migraines, decreased libido, depression, forgetfulness, dizziness, nausea, vomiting, pain, vaginal dryness, and weight gain or loss.

Lupron Depot may cause a reduction in bone density that can persist for some time even after therapy has ceased. The risk of this occurring can be reduced by taking an add-back therapy along with Lupron Depot.

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