Black box warning on menopause hormone therapies should be removed, experts say

By Katia Hetter, CNN

(CNN) — All menopause treatments containing the hormone estrogen are mandated by the US Food and Drug Administration to carry a black box warning on the label, stating that the treatments could increase the risk of strokes, blood clots, dementia and breast cancer.

Now, that advisory may be going away. Last week, a panel of experts convened by the FDA urged the federal agency to remove the cautionary language on at least some forms of hormone therapy.

I wanted to understand more about why these warnings were first added and the arguments for and against removing them now. What are hormone therapies used for, and what are the different forms of treatment? What is the history behind adding black box warnings, and why are some experts pushing to remove them? What should women know about managing menopause symptoms?

I turned to CNN wellness expert Dr. Leana Wen to answer these questions. Wen is an emergency physician and adjunct associate professor at George Washington University. She previously was Baltimore’s health commissioner.

CNN: When does menopause occur, and what kinds of symptoms do women experience during menopause?

Dr. Leana Wen: Menopause is the stage in a woman’s life when her menstrual periods permanently stop. It marks the end of fertility and is accompanied by a decline in reproductive hormones such as estrogen and progesterone.

In the US, most women begin the menopause transition between ages 45 and 55, and the average age is 52. The definition of menopause is a full year without having a period. Except in situations where menopause is induced by surgery (for example, removal of ovaries) or specific medical conditions, this period is generally preceded by a stage called perimenopause, when women may have irregular periods and start experiencing menopause symptoms.

Symptoms associated with menopause can include hot flashes and night sweats. Hot flashes are sudden sensations of heat, skin flushing and sweating that can significantly disrupt daily activities. About one-third of women have more than 10 hot flashes per day.

When they occur at night, they can disrupt sleep and increase fatigue and irritability during the day. Menopausal declines in estrogen also may cause vaginal dryness, decreased libido and discomfort during intercourse. Some women experience other symptoms such as mood changes, anxiety, difficulty concentrating, dry skin and weight gain.

Moreover, while this is not a symptom of menopause per se, the risk of developing chronic conditions such as cardiovascular disease and osteoporosis increases significantly after menopause. This rise in risk is thought to be linked to the decline in estrogen levels, as estrogen has a protective effect on maintaining healthy blood vessels and supporting bone density.

CNN: What are hormone therapies used for? What are the different forms of treatment?

Wen: Hormone therapies are prescription drugs that are used to treat menopause symptoms. They replace the hormones that decline during menopause.

It’s important to differentiate between two types of hormone therapy. The first is systemic therapy in which hormones are given in a way that is absorbed into the bloodstream. That could be through taking pills or using patches, sprays or gels. Systemic therapy is used to treat symptoms that affect the entire body, such as flashes and night sweats.

The second type is low-dose vaginal estrogen therapy. This is a cream or suppository administered into the vagina to treat vaginal dryness and reduce tissue thinning. Unlike systemic therapy, this type of therapy works locally; its purpose is not to raise hormone levels throughout the body.

CNN: What is the history behind adding black box warnings, and why are some experts pushing to remove them?

Wen: For decades, hormone therapy was considered the standard of care for menopause-related symptoms. Then, in the early 2000s, a landmark study called the Women’s Health Initiative was published that suggested hormone therapy increased the risk of breast cancer, heart disease and stroke. It concluded that the benefits of this therapy did not outweigh these risks, leading to the FDA adding the black box warning in 2003.

Many researchers have since examined the methodological problems of the study. One significant issue was that the average age of participants was 63. The women studied were mostly postmenopausal, so the question answered was regarding the risks and benefits to postmenopausal women, not menopausal women.

Last year, scientists — including some of the original researchers of the Women’s Health Initiative — published an updated analysis in the journal JAMA. They concluded that, in fact, hormone treatment with a combination of estrogen and progesterone is safe and effective for treating hot flashes and other systemic symptoms if started before age 60 or within 10 years of starting menopause and if the woman does not have specific contraindications — for instance, an estrogen-sensitive breast cancer.

This updated analysis is one reason cited by many advocates to remove the warning. Another major reason is that the black box warning is currently on all types of hormone treatments, including vaginal therapies that deliver far lower doses and do not have the systemic effect of, say, an estrogen-containing pill. Advocates argue that putting all forms of hormone therapy under the same warning misrepresents risk and makes it harder for women to receive relief from troublesome symptoms. Women are still able to access the therapies despite the warning, but some may be more hesitant to use them after seeing the warnings.

CNN: What are other arguments for and against this change?

Wen: In his opening argument, FDA Commissioner Dr. Marty Makary remarked that systemic hormone therapy, when started within 10 years of the onset of menopause, can actually reduce cardiovascular disease. This finding is suggested by some recent studies, which also show a benefit for bone health.

Not everyone agrees that hormone therapy should be taken for preventive purposes. There is also some controversy about process; specifically, the panelists who spoke at last week’s FDA meeting were all selected by Makary and all favored hormone therapy. Some have said they would appreciate more balance by hearing from experts who have more nuanced views. In addition, there was no presentation by internal FDA scientists, who, in the past, have given their own analysis during these types of meetings.

CNN: While the FDA is considering changing the warning label, what is your advice for women about managing menopause symptoms?

Wen: The most important thing is that women who are experiencing significant symptoms during menopause don’t need to suffer in silence. Effective treatments exist. Women should speak with their physicians about lifestyle measures that can help as well as hormonal and nonhormonal prescription therapies. They should also speak with their providers about preventive care to improve heart health and prevent bone loss. Those who want additional resources should look to the Menopause Society, which also has a searchable database of clinicians who are certified menopause practitioners and trained to guide women through this transition.

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