New treatment approved for endometriosis pain

OB/GYN News, May 1, 2005 by Michele G. Sullivan

Subcutaneous medroxyprogesterone acetate has been approved for the treatment of endometriosis-related pelvic pain. It is the first new treatment to be approved for this indication in 15 years.

Depo subQ provera 104 (DMPA-SC), which contains 104 mg medroxyprogesterone acetate, treats endometriosis pain as effectively as leuprolide acetate, but is associated with significantly less bone loss and fewer vasomotor symptoms, according to data provided by Pfizer Inc., which manufactures the agent.

The Food and Drug Administration granted approval for the endometriosis pain indication in March. Depo-subQ provera 104 received FDA approval for use as a contraceptive in December 2004. Pfizer said depo subQ provera 104 would be widely available this month.

Depo subQ provera 104 is a new formulation of medroxyprogesterone acetate, which is the active ingredient in Depo-Provera Contraceptive Injection (medroxyprogesterone acetate injectable suspension), but with 30% less hormone.

Depo subQ provera 104 is available in prefilled syringes each containing 0.65 mL (104 mg) of medroxyprogesterone acetate sterile aqueous suspension.

Administered by subcutaneous injection four times a year (every 12-14 weeks), DMPA-SC halts menstruation, which results in thinner, more compact endometrial tissue, the company said. This in turn halts the growth of endometrial implants, relieving endometriosis-associated pain.

The package insert contains a black box warning concerning possible bone loss: Women who use DMPA-SC may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of depo-subQ provera 104 during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk of osteoporotic fracture in later life. Depo-subQ provera 104 should be used as a long-term birth control method (that is, longer than 2 years) only if other birth control methods are inadequate.

Pfizer's phase III randomized controlled trial showed that DMPA-SC is associated with significantly less bone loss than leuprolide acetate for depot suspension, the only other drug approved for treatment of endometriosis-related pain.

The 18-month study included 274 women aged 18-49 years who had diagnoses of endometriosis-associated pelvic pain. They were randomized to 6 months of treatment with either DMPA-SC (104 mg every 3 months) or leuprolide (11.25 mg IM every 3 months), and 12 months of follow-up.

There were no significant differences in pain symptom reduction. Women in both groups showed some bone mineral density declines at the end of treatment, but the mean losses were significantly less for women taking DMPA-SC in both the femur (0.3% vs. 1.65%) and the spine (1.1% vs. 3.95%).

In women who had been taking DMPA-SC, bone mineral density return to pre-treatment levels 12 months after discontinuing treatment. Those who had been taking leuprolide showed continued bone mineral density losses of 1.3% in the femur and 1.7% in the spine.

DMPA-SC was also associated with significantly fewer vasomotor symptoms, especially hot flashes.

It's important to remember that the only cure for endometriosis is aggressive surgical excision, David Red-wine, M.D., Endometriosis Association advisor, said in an interview. Surgery has been repeatedly shown to have a cure rate of about 60% in even resistant cases.

"Excision is the only treatment which has documentation of cure, although this information is typically withheld from patients as they consider their treatment options. The result is that patients undergo repeated rounds of medical therapies without eradication of their disease," Dr. Redwine said. "Depo subQ 104 adds another form of medical therapy for endometriosis to be used by physicians who cannot treat the disease effectively by surgery."

The bone loss associated with any hormonal therapy for symptoms is worrisome, he said, especially in women who are still actively laying down bone. "I am concerned about young women being exposed to medicines that do not treat a disease and that can produce systemic side effects, the permanency of which are not fully known," said Dr. Redwine, medical director of the endometriosis treatment program at St. Charles Medical Center in Bend, Ore.

Daniel Watts, a Pfizer spokesman, said depo subQ provera 104 will offer a much-needed alternative to women who don't elect surgery.

"Not all patients are appropriate candidates for surgery," Watts said in an interview. "There are also associated risks with surgery, thus making it a less attractive option for some women. Depo provera subQ is a valuable option, because it has significantly less decline in bone mineral density and lower incidence and severity of menopausal symptoms, such as hot flashes, compared with leuprolide acetate, the commonly used treatment."

BY MICHELE G. SULLIVAN

Mid-Atlantic Bureau