Treatment options for adenomyosis supported by limited high-quality data

EXPERT ANALYSIS FROM THE AAGL GLOBAL CONGRESS

LAS VEGAS – Levonorgestrel and hysterectomy are probably the best treatments for adenomyosis – or at least the most well-supported medical and surgical options. 

There are other therapies, Dr. Jason Abbott said at a meeting sponsored by AAGL, but almost every treatment has limited high-quality data. 

Hysterectomy cures the problem of pain and uterine bleeding completely with no serious adverse effects. But it’s invasive and irreversible, said Dr. Abbott of the Royal Hospital for Women, Australia. And many women, no matter how bad their symptoms or where they are in their reproductive life, simply don’t want to give up their uterus. 

“Hysterectomy, as a therapy for adenomyosis, is beautiful,” Dr. Abbott said. “We love it because it cures the condition – but it’s an end game, for sure.”

Intrauterine levonorgestrel systems are probably the best-supported medical therapy, he said.

“The levonorgestrel intrauterine system does work and there are a number of randomized controlled trials comparing this to hysterectomy,” Dr. Abbott said. “It controls adenomyosis very well, and if you look at iron and anemia outcomes a year after treatment initiation, there is no difference – so that is a very good outcome.”

Levonorgestrel is also fully reversible – a must for women who want to conceive in the future. And it’s cheap, especially compared to surgery. 

“Even if you allow for the 18%-20% who won’t like it and have it removed, then there’s a pretty good chance you’ll still come up on the positive side compared to hysterectomy, even if you have to repeat the 5-year course two, three, or four times,” he said.

While there are no economic data comparing it directly to hysterectomy, conclusions can be extrapolated from studies that compared endometrial ablation and the surgery.

“You need a 40% failure of ablation for the levonorgestrel to be less economically effective, because then you are getting into having two procedures,” he said. “With levonorgestrel, we have a much lower 20% failure rate and you’re already starting with a much lower cost. So I would say this is entirely reasonable, and a very good place to start. We should continue to offer this to our patients.”

Dr. Abbott noted other treatment options as well:

• Danazol

“This has been around since the 1970s and it works. But women absolutely hate it. They don’t want to look or sound like a man,” Dr. Abbott said. “It’s fallen pretty much by the wayside and [is] only used when we are absolutely desperate.”

There are, however, data suggesting that contraceptive devices loaded with danazol have much less systemic absorption and can be effective without the androgenic effects. A 2010 case series of 35 infertile women found that both a cervical ring and intrauterine device effected endometrial atrophy but did not inhibit ovulation; 13% of those using the IUD and 66% of those using the ring were able to conceive. 

• Gonadotropin-releasing hormone agonists

“These are used for a lot of issues with endometriosis, but there’s only one randomized controlled trial on adenomyosis, which compared it with aromatase inhibitors,” Dr. Abbott said. “Both were effective in reducing the symptoms. Once you induce amenorrhea, you don’t have pain with periods.” 

There are also studies comparing GnRH agonists with oral contraceptives in adenomyosis. “They do work equally well, but the problem is these are only short-term studies [6-24 months]. Once you stop, your symptoms do come back, and women could have 10-15 years before menopause stops the problem. So this is a short-term solution to a long-term problem,” he said.

The GnRH agonist side effect profile can be problematic, he added.

• Oral contraceptives

“The pill is fantastic and we all use it to control abnormal bleeding. It’s cheap, and it’s been around forever. However, a lot of women now don’t want to use any hormones in any way, shape, or form. There are also no randomized data for its use in adenomyosis,” Dr. Abbott said. “I think pragmatically, yes, it can give very good symptom control and if there’s no direct evidence against it, what’s the worst that can happen? They don’t like it and then you take them off. I think it’s a perfectly reasonable option.” 

• Ablation

There are no randomized data supporting endometrial ablation in adenomyosis. “What we’ve got are the randomized data in studies of abnormal uterine bleeding, which suggest a 25% failure rate,” he said. “I think it’s a reasonable procedure for adenomyosis.” 

• Resection

Surgery for adenomyosis is very difficult to perform and carries some not inconsiderable risks. “You’re removing a big chunk of myometrium and you’re never sure if you’re getting it all anyway, so there’s a big chance of persistence and recurrence,” Dr. Abbott said. There’s also the chance that the surgery will introduce abnormal tissue into unaffected myometrium, he added.

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