VANCOUVER, B.C. – A medical cocktail of tranexamic acid, gonadotropin-releasing hormone agonist, and an aromatase inhibitor stops bleeding from uterine arteriovenous malformations and eliminates the malformations on Doppler ultrasound within a few months, according to a small case series from Western University in London, Ont.
The finding could be a “game changer,” if it holds up under further testing, since it appears to resolve uterine arteriovenous malformations (AVMs) without compromising fertility, unlike uterine artery embolization or hysterectomy, said Dr. Angelos Vilos of Western University, the study’s lead investigator.
“We believe that we have come up with a novel and advantageous cocktail [that is] accessible to all physicians,” he said. “It eliminates uterine bleeding and AVMs. We know it’s safe, and all these medications are readily available.”
Dr. Vilos said he plans to use the drug cocktail as a first-line therapy in patients with uterine bleeding from AVMs.
The investigators used uterine tamponade, as needed, to control bleeding in nine women, then gave them oral tranexamic acid (Cyklokapron) 1 g three times daily for 5 days to clot AVM bleeders. The women also received gonadotropin-releasing hormone (GnRH) agonist injections to shrink the uterus and its vasculature – usually one shot of leuprolide, but goserelin was used for one woman – plus oral letrozole 2.5 mg/day for 5 days after the first injection to prevent GnRH flare.
The uterine AVMs “disappeared” on Doppler ultrasound within 3 months, Dr. Vilos said.
Four of the women went on to conceive spontaneously and have live births. Four others are on oral contraceptives. The ninth woman opted for a subsequent tubal ligation.
“We were able to preserve fertility and the uterus in all of these women,” he said.
The patients had been bleeding from uterine AVMs for up to 6 months, most following spontaneous or therapeutic abortions. They all had negative beta–human chorionic gonadotropin and Doppler-confirmed AVMs in the myometrium. Retained products were ruled out in all of the patients. Two women had failed embolization with coils and gel foam, and two women required transfusions before treatment. One woman required uterine tamponade before the protocol.
“These women weren’t resolving on their own,” Dr. Vilos said at the meeting sponsored by AAGL.
Based on previous work, Dr. Vilos said he and his team were comfortable using GnRH agonists and letrozole for endometriosis, and they frequently use tranexamic acid for acute bleeding. “So we kind of put these ideas together,” he said.
Several of the women were hemorrhaging in the middle of the night, and the community hospitals where they were being treated couldn’t do embolization. The hospitals called Western University, a tertiary care center, for assistance. “We initiated the protocol, and they resolved,” Dr. Vilos said. “[It’s] an effective management strategy.”
Dr. Vilos is an advisor for Bayer Healthcare and Actavis. The investigators did not receive outside funding for the work.