While Australian experts agree that the removal of the black box warning was the right move, the FDA is parroting statistics that have been roundly rejected by leaders in the field.
The US Food and Drug Administration has now removed its long-standing “black box” warning label on hormone replacement therapies for menopause – but it may be a case of reaching the right answer with the wrong methodology.
While the action will only apply to the United States, an Australian GP-led menopause advocacy group has already set up a petition asking Australia’s drug regulator to follow suit.
The Therapeutic Goods Administration has historically paid close attention to the FDA’s moves in this regard, and The Australian reports that the agency has already committed to reviewing the evidence.
The removal of the black box warning in the US is seen by many experts, including Sydney sexual health physician Dr Terri Foran, as a positive step.
The way that the FDA reached its decision, though, is far more controversial.
“Normally, when something like this happens in America it is a prolonged process, which goes through teams of experts and by the end it’s quite thoroughly investigated and rigorously endorsed,” Dr Foran told The Medical Republic.
“This does not appear to have happened on this occasion with a fairly hasty decision made to remove the warning. Â
“That always makes my antenna stand up as to whether or not the implications behind this are political.” Â
In the US, a black box warning is the highest safety label the FDA can place on a medicine. Theoretically, it is reserved for medications with potential severe side effects or major risks.
The TGA uses a similar system, known as a boxed warning.
While not all hormone replacement therapies are covered by a boxed warning – Estradot, for instance, does not seem to have one – there are some, like Femoston 1/10, which do have a boxed warning attached.
Warnings were only applied to menopausal hormone therapies in the early 2000s, following the findings of the Women’s Health Initiative (WHI) in relation to cardiovascular disease, thromboembolism, breast cancer and dementia.
The results of the WHI and the subsequent introduction of the warnings are largely understood to be the reasons behind a significant decline in menopausal hormone therapy usage.
This decline persisted despite widespread agreement that modern menopausal therapy is significantly safer compared to the preparations used by participants in the WHI, leading to calls for the warnings to be reevaluated.
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Groups like the Australasian Menopause Society, for example, have long recognised hormone therapy as the most effective treatment for vasomotor and genitourinary symptoms of menopause, as well as for the prevention of bone loss and fracture.
But the FDA’s official press release went somewhat off script, stating that women who initiate hormone replacement therapy may “reduce their risk of cardiovascular diseases by as much as 50% [and] Alzheimer’s disease by 35%”.
This was despite the four most recent large-scale studies showing a significant increased risk of Alzheimer’s in women who have used hormone therapy.
“There are statements for instance that hormone therapy reduces your risk of heart disease by 50%, and that’s not supported by the current evidence, as far as I’m concerned,” Dr Foran said.
“Neither does the evidence support the idea that it protects you against dementia.
“While I think that the outcome was a good thing, I’m concerned that some of the statements now going out to women are in many ways full of misinformation.”
In a somewhat ironic twist, US Department of Health and Human Services secretary Robert F Kennedy, Jr framed the decision as the government “standing up for every woman who has symptoms of menopause” and liberating them from “bad science and bureaucratic inertia”.
Catastrophising the symptoms of menopause, Dr Foran said, was also unhelpful.
“Menopause treatment has to be completely individualised to the woman sitting in front of you,” she said.
“Not only her medical history, although that’s really important, but also her preferences and her choices.
“I do see some women who would prefer to go through menopause without hormones, and that’s their choice. We should be supporting women in that choice.
“Similarly, I don’t think we should be over-egging the dangers and the risks of MHT … we need to take an objective look at all the evidence to hopefully put it back in the hands of the experts, rather than the influencers and the ill-informed.”
