Menopausal patients with rheumatic diseases may benefit from the increased use of hormone therapy in light of the FDA’s recent decision to lift black box warning labels.

The FDA initiated the removal of boxed warning labels from hormone therapy products used to treat women in menopause in November 2025. Hormone therapy is FDA-approved to manage menopausal symptoms, including night sweats, mood changes, vaginal dryness, and hot flashes.

Managing menopausal women with rheumatic diseases is often complex and involves the input of a multidisciplinary care team, including rheumatologists, obstetricians and gynecologists, and primary care physicians. Consideration for potential drug interactions and side effects are important in the unique setting of hormone therapy use by women with rheumatic disease.

Clinicians should collaborate to develop a game plan for this niche group of patients who are in menopause and also living with rheumatic diseases, and there needs to be a discussion regarding the antibody profile and type of disease being managed, noted Catherine A. Sims, MD, MHS, an assistant professor of medicine at Duke University School of Medicine and a rheumatologist at Duke Health, both in Durham, North Carolina.

“The first obstacle for a lot of patients is who is going to prescribe the hormone therapy. And thinking from the perspective of the gynecologist or the primary care doctor, who don’t have specialized training in autoimmune conditions and they may know that there is some theoretical risk of blood clots or disease flare, it is understandable that the primary care physician or gynecologist would be very uncomfortable in that space, so there has to be collaboration between and a discussion between the rheumatologist and these other providers who may be more comfortable prescribing hormone therapy,” Sims told Medscape Medical News.

Women’s Health Initiative Study and the Black Boxed Warning

Boxed warnings were initially added to labels for hormone therapy products following results from the 2002 Women’s Health Initiative (WHI) study. The WHI study highlighted potential risks for breast cancer, heart disease, and dementia with the use of hormone therapy.

The credibility of the study data has recently been called into question due to the age of the cohort and the hormone therapy evaluated. Notably, the study cohort had a mean age of 63 years, which is more than 10 years over the average age of women in menopause. Moreover, the study involved the use of a hormone therapy formulation that is no longer being used to treat patients today.

“The Women’s Health Initiative study was a flawed study because they failed to study the right population or the population of interest. And that’s really hurt the number of our patients who could have benefited from hormone therapy,” said Robert P. Kauffman, MD, MSCP, a professor in the Department of Obstetrics and Gynecology at Texas Tech University Health Sciences Center, Amarillo, Texas.

“We are still dealing with 20 years of bad publicity from the Women’s Health Initiative when we know that hormone therapy can be safe and quite effective and prevent perhaps many diseases, such as bone loss and osteoporosis, in those who have menopause,” Kauffman told Medscape Medical News.

Following the release of these study results, there was a significant decline in the use of hormone therapy. A 2012 study highlighted a decline in use among women older than 40 years, with overall use being at 22.4% in 2000, down to 4.7% overall in 2010.

“That 4.7% includes vaginal estrogen — it’s not just systemic because they couldn’t separate the two in that paper, but we are about to publish data showing that 1.7% of women are using systemic hormone therapy in this country,” said Stephanie Faubion, MD, MBA, director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida

In light of the misinterpretation of the WHI findings, other studies also brought into question the potential risks for breast cancer, dementia, and cardiovascular events by demonstrating hormone therapy may not actually be harmful in these instances.

A 2004 meta-analysis demonstrated that hormone therapy did not significantly affect cancer or cardiovascular related mortality risks.

A February 2023 report found that patients who began using hormone therapy within 10 years of menopause had a reduced risk for cardiovascular events and a lower risk for death than women who began treatment later.

A March 2017 study showed that there was a lower risk for Alzheimer’s disease among postmenopausal women who used hormone therapy.

A January 2024 study found that newly menopausal women who used transdermal or oral hormone therapy showed no signs of metabolic or cardiovascular adverse events or risk despite 4 years of hormone therapy use.

A July 2025 paper found that premenopausal or perimenopausal use of hormone therapy by younger women was linked to a reduced risk for breast cancer.

These studies helped to shape the FDA’s decision to remove boxed warnings from hormone therapy products’ labels for risks related to cardiovascular events, breast cancer, and dementia.

What the Removal Means for Clinical Practice

The American College of Obstetricians & Gynecologists backs the decision to remove these warnings. “By discouraging clinicians from prescribing low-dose vaginal estrogen, the current warning label harms patients by making inaccessible an effective treatment for symptoms that can significantly decrease health-related quality of life. We hope that this regulatory step forward will improve access to this important treatment option,” Steven J. Fleischman, MD, MBA, president of the American College of Obstetricians & Gynecologists, said in a press release.

The North American Menopause Society position statement also backs the use of hormone therapy in women within 10 years of menopause or who are younger than 60 years. They suggest that the risk-benefit profile in this patient group is favorable as long as the patient does not have contraindications.

In the group’s updated 2022 statement, they note a potential risk for dementia, stroke, heart disease, and venous thromboembolism in women who are older than 60 years or who start hormone therapy over 10 years out from the start of menopause.

Sims, the Duke University rheumatologist, pointed out that hormone therapy is underutilized in women with rheumatic conditions. “There’s been a lot of fear around the risk of flaring autoimmune conditions with being exposed to hormone therapy,” she told Medscape Medical News.

“There’s not a lot of research in perimenopause or menopause for women with rheumatic autoimmune conditions, so it is pretty neglected from both a research and a clinical standpoint,” Sims said.

Findings from some of the few research studies involving menopausal women with rheumatic diseases on hormone therapy have highlighted potential risks and benefits from its use.

A February 2020 study found that women who used hormone therapy around menopause had a lower risk for hand osteoarthritis.

An October 2025 study showed that a lower duration of postmenopausal hormone therapy was associated with increased disease activity among women with rheumatoid arthritis.

The removal of boxed warnings could result in expanded use of hormone therapy, but clinicians need to consider that every patient is different when prescribing these medicines. Treatment plans should be developed in collaboration between rheumatologists and primary care providers, who are more likely to prescribe hormone therapy for menopause, especially in those with rheumatic diseases, noted Alexa Meara, MD, a rheumatologist and a clinical associate professor at The Ohio State University Wexner Medical Center in Columbus, Ohio.

“It’s a discussion of what is their disease, what drugs are they on, and what is their goal, and how do we think that hormone replacement is going to affect their disease,” Meara continued.

The American College of Rheumatology 2020 guidance supports the use of hormone therapy in select postmenopausal women to alleviate severe vasomotor symptoms, like night sweats and hot flashes. The guidance indicates patients with systemic lupus erythematosus (SLE) and antiphospholipid antibody positivity may be an exception to these recommendations.

For patients with SLE, the guidance advises against the use of transdermal estrogen-progestin patch as this combination presents concerns about the potential risk for thrombosis or flare-up. When treating women with antiphospholipid antibodies, the guidelines also warn against combined estrogen-progestin contraceptives use as there is a potential risk for thromboembolism.

Adding hormones to the equation of managing autoimmune diseases, like lupus and myositis, and related symptoms could lead to flare-ups, Meara noted. “For those that have autoimmune disease, the biggest thing with hormones is that clotting can be a big issue, particularly with lupus or vasculitis, and so you have to be very careful and weigh the drug, the hormone, and the disease, and the risk-benefit ratio. Discuss that with the patient to ensure that they are not at more risk for those harms,” Meara told Medscape Medical News.

“The Women’s Health Initiative was such an expensive study that it will never be repeated,” Kauffman said. However, he noted that looking ahead, more research could be done looking into the other potential benefits of hormone therapy use in menopausal women, specifically as it relates to diabetes, skin health, and hair health.