The Black Box Everyone is Talking About

The good, the bad, and the ugly about this week’s big announcement.

You know what I would love? An uncomplicated, drama-free conversation or announcement regarding menopause hormone therapy (MHT). But alas, it’s 2025. I should have known not to get my hopes up. Shame on me.

A little background on this week’s big announcement from Health and Human Services:

When a prescription drug may cause side effects, the FDA requires drug companies to include warnings about those side effects on the product packaging. There are different levels of warnings, and the most serious is the “black box warning”, which is designed to catch your attention to make sure you are aware of the risks of the medication you are planning to take.

After the 2002 Women’s Health Initiative debacle, the FDA changed the labeling on estradiol (the estrogen used in menopause hormone therapy) to include a black box warning due to increased risk of blood clots, heart disease, stroke and breast cancer.

However, two things are important to know here:

1. Vaginal estrogen used to treat genitourinary syndrome of menopause (which nearly all menopausal women will experience) does not carry the same risks as systemic estrogen, since so little of the vaginal estrogen is absorbed into the bloodstream.

2. The risks of systemic MHT vary depending on when you start taking it, the type of hormone you are taking and the delivery method of that hormone (pill, patch, cream, etc.). And that if you account for those factors, the risks of taking MHT go way down.

Clinicians have been asking the FDA for years to remove the black box warning label from vaginal estrogen, which is known to be very safe for most women.

And this past Monday, the FDA announced it is removing the black box warnings from vaginal estrogen and systemic MHT. The updated product labeling will hopefully better reflect current understanding about the risks associated with various forms of MHT.

While this is good news - the blanket warnings absolutely should be reconsidered - the process behind the decision was not what it was supposed to be, which compromises the scientific integrity of the decision. Given the strong bias in favor of MHT during the review process, some menopause experts worry the pendulum will swing in the opposite direction and we still won’t have accurate, evidence-based labeling for these drugs. Instead, we may end up with labels that inappropriately minimize the risks of systemic MHT for some women.

And to add insult to injury, the announcement was rife with misinformation surrounding menopause and menopause hormone therapy.

So let me briefly set the record straight about some of the misinformation given at the press conference on Monday:

• Menopause is not a disease but a normal biological process and it does not lead to early death.

• There is no legitimate scientific data supporting the claim that MHT lowers the risk of heart disease and dementia or that it extends a woman’s life by ten years.

• We have no data supporting the claim that a lack of MHT leads to divorce.

• And finally, you don’t need to get your hormone levels tested before starting MHT (here’s why).

(Excuse me while I go bang my head against a wall.)

The Menopause Society - an internationally respected organization made up of a wide array of menopause experts - responded to the announcement with the following statement:

We agree with the FDA’s decision to remove the boxed warning on low-dose vaginal estrogen therapies used to treat genitourinary symptoms associated with menopause. The boxed warning may have been a deterrent to the use of the low-dose vaginal estrogen, which is a safe and effective therapy for a condition that affects most menopausal women. Systemic estrogen still comes with potential risks in certain individuals that should be reviewed in detail with women initiating therapy.

As stated in The Menopause Society’s hormone therapy position statement, the risks are low for younger, healthy women initiating hormone therapy closer to the menopause transition. Risks are greater when initiated in older women and in those who are further from menopause onset. Medical comorbidities, personal and family histories, symptoms, and personal preferences all need to be reviewed with patients considering the use of hormone therapy for management of menopause symptoms or prevention of bone loss.

Despite problems with both the review process and the announcement from Health and Human Services, by all accounts this seems to be a net gain for women. We still have a long way to go to improve menopause care (like, a really really really long way to go), but a step in the right direction is still a step in the right direction.

So this is me taking some deep breaths and cracking open a cold, crispy Diet Coke - cheers to a future of better menopause care!

xo, Rebecca

P.S. Me vs. Winter

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