Hormone therapy (HT) for menopause, also called hormone replacement therapy, is getting a lot of press lately. For over 20 years, all types of hormone therapy maintained a black box warning from the U.S. Food and Drug Administration, the highest degree of safety-related warnings that medications can receive.
Now, the FDA has announced it will remove the warnings. Instead, labels will include age-specific guidance indicating that women who start treatment within 10 years of the onset of menopause may experience long-term health benefits.
But there are still individual risks to HT, based on many factors. It will now be up to women, in consultation with their doctor, to gauge those risks.
We spoke with Dr. Julie Gutierrez, a gynecologist and menopause specialist at Houston Methodist, about the different types of HT and the known risks for the medications.
What is hormone therapy — and why has it gotten such a bad rap?
Hormone therapy is a low dose of estrogen and progesterone — or just estrogen, if a woman has had a hysterectomy — given around the time of menopausal transition to help relieve classic menopause symptoms: hot flashes, night sweats, sleep issues and more.
HT received a black box warning based on findings from the Women's Health Initiative (WHI) study, the largest randomized, placebo-controlled study of hormone therapy ever conducted. The intent of the rigorously designed study, published in 2002, was to test the benefits and risk of hormone therapy for chronic diseases — at the time, it was common to prescribe HRT to prevent heart disease and other chronic issues.
"In this study, they gave thousands of post-menopausal-aged women by-mouth estrogen, a drug called Premarin, and also medroxyprogesterone acetate if they had a uterus," Dr. Gutierrez says. "If they didn't have a uterus, they just gave them the estrogen by mouth. The researchers followed up with these women over time and had to stop the trial early because of an increased risk of death due to thromboembolic disease like blood clot, stroke and heart attacks."
In addition to the heart-related issues, the study also showed a slightly elevated risk of breast cancer. The WHI trials were successful in that they indicated that HRT should not be used in post-menopausal women for chronic disease prevention.
"If you take an older person whose body hasn't seen hormones for decades and who may have already developed some amount of heart disease and throw hormones at them, that can be very harmful, increasing the risk of blood clot, stroke or dementia," Dr. Gutierrez says.
The study's focus was not on younger women in perimenopause — most women enter perimenopause between ages 45 and 55 — but the fallout among all age groups was swift: Just over 20% of women were receiving HT in 2000, and by 2010, only 4% received HRT, according to a study in Obstetrics & Gynecology.
"For decades there was a big fear about prescribing hormones and the black box warning originated during that time," Dr. Gutierrez says.
The study was revisited in the Journal of the American Medical Association in 2024 with a focus on a perimenopausal age group.
"When the data was reanalyzed and isolated for younger age groups, they saw a lower risk of mortality in women who were taking hormones," Dr. Gutierrez says. "That's thought to be due to the really positive, beneficial effects of estrogen on cholesterol, the progression of diabetes, and visceral fat. The increased risk of blood clot is still there, but it's much less significant in a younger age group for systemic hormones."
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Types of hormone therapy
There are two types of HT used for addressing perimenopausal symptoms: estrogen therapy and combination therapy, which includes both estrogen and progesterone. The delivery method can be either localized or systemic.
Localized hormone therapy
Localized hormone therapy, usually estrogen, is meant to be used directly on the vagina to combat the genitourinary symptoms that can occur during menopause.
"The pH of the vaginal epithelium (vaginal skin) increases, raising the risk for yeast infections and bacterial vaginosis," Dr. Gutierrez says. "The skin becomes drier and has poorer blood flow, which can cause more frequent vaginitis or infections. Atrophic vaginitis, which is really uncomfortable, constant itching and burning, can also occur and make having sex painful, and may sometimes cause bleeding after sex as well."
The best way to deliver hormones to the vagina to manage these issues is through a localized estrogen, via cream, tablets or a ring that secretes estrogen, according to Dr. Gutierrez. The amount of estrogen absorbed into the blood is not in high enough concentrations to stimulate growth in the lining of the uterus.
"Because it's a really local effect, you don't have to give progesterone with a vaginal preparation," Dr. Gutierrez says. "It's safe for women with an intact uterus to use these creams without issue — this is different than whole body or systemic HT."
The side effects and long-term effects of local estrogen therapy are minimal, Dr. Gutierrez emphasizes. Some people may experience short-term side effects such as vaginal discharge and, rarely, spotting.
"There's really no risk to localized, vaginal preparations," Dr. Gutierrez says. "Sometimes it can be costly and may be a little inconvenient for some to apply, but they're very safe. Vaginal atrophy tends to get worse as someone gets older and further from menopause, so we use it very safely in women in their 80s and 90s.
"There is also some evidence to support vaginal estrogen use for women who have recurrent urinary tract infections and also may be helpful for some people who struggle with urge incontinence as well. We commonly prescribe it in post-menopausal women, and it can be used by breast cancer survivors. It really does make medical sense for the black box warning to be removed at least for vaginal preparations."
Localized estrogen therapy should not be used in women who are pregnant, in breast cancer treatment or have unexplained vaginal bleeding.
Systemic hormone therapy
"Systemic hormone therapy — which is most commonly used as a patch, but also can include pills, sprays and gels — delivers systemic hormones into the bloodstream," Dr. Gutierrez says. "Systemic hormones are going to be beneficial for those early menopausal and perimenopausal women who are having classic perimenopausal symptoms, the hot flashes, the trouble sleeping, the decreased libido, those sorts of symptoms."
Systemic hormone therapy has been the main focus of concern around significant risks to health. From the Women's Health Initiative study, Dr. Gutierrez says we know the heart health risks with blood clot is about two to four times higher in women taking oral estrogen. However, newer studies have found that using transdermal estrogen (the patch) doesn't appear to be high risk.
And while the results of the WHI study concerned a post-menopausal group of women, those with existing heart health risk factors or a family history of heart issues will want to work with their gynecologist to understand their risks.
"You would not recommend estrogen therapy for someone who has a history of blood clots or a very high risk of blood clot, heart attack or stroke," Dr. Gutierrez says.
Combination therapy, using both estrogen and progesterone, are essential to preventing uterine cancer from developing.
"Anyone with a uterus being prescribed systemic estrogen also will need progesterone, because the estrogen alone will cause the lining of the uterus to grow and then eventually could cause uterine cancer," Dr. Gutierrez says.
Dr. Gutierrez says that OB-GYNs now typically prescribe a different type of progesterone than what was used in the Women's Health Initiative study. She says there are some studies suggesting that these other types of progesterone may carry a lower risk profile for breast cancer.
Interested in hormone therapy? Understand your risk profile
Dr. Gutierrez says that the risks with hormone therapy are typically lower when HT is started before age 60 or within 10 years of the final period. Risk for complications increase if HT is begun more than 10 years after the final period.
But your individual risk factors largely come down to your health history and your family's health history.
"We're very mindful about the patient's risk profile when we're prescribing hormone therapy," Dr. Gutierrez says. "Providers will take a detailed history, learning about someone's symptoms and what they're hoping to gain and improve with hormone therapy. I typically do like to have a recent lipid test to make sure that they're not at high risk for heart disease already. And I do think it's good practice to do general Well Woman labs and have an overall sense of someone's cardiovascular health."
If someone seeking relief from bothersome menopausal symptoms isn't a great candidate for hormone therapy, Dr. Gutierrez emphasizes that there are multiple non-hormonal options available to target various symptoms.
The Menopause Society does not recommend frequent blood draws for testing hormone levels, Dr. Gutierrez notes. Instead, providers focus on changing doses based on someone's symptoms.
But the first step is talking about your symptoms with a gynecologist you trust.
"I would find a gynecologist with expertise in menopause and have a conversation with them," Dr. Gutierrez says. "Menopause has been a really hot topic lately, which is good because for a long time we were neglecting a whole population of people who were really suffering. Hormone therapy without the supervision of a physician can be very harmful, and so I think that finding an experienced gynecologist and having an open conversation with them is your best first step."
