Are Menopausal Women Taking a Big Risk with HRT? FDA Says NO!

Hormone replacement therapy (HRT) has been controversial for decades. Many gynecologists told women that estrogen-containing pills would eliminate hot flashes, night sweats and other symptoms of menopause. Sometimes physicians put icing on the cake. Take HRT and you will have less risk of chronic diseases. That means less likelihood of a heart attack, stroke, osteoporosis or Alzheimer’s disease.

The Women’s Health Initiative Study of HRT:

The classic study of HRT was the Women’s Health Initiative (WHI). In this double-blind, placebo-controlled trial, more than 27,000 women were randomized to receive estrogen plus progestin (Prempro), estrogen alone (Premarin) or placebo. The women took these treatments for several years (between 5 and 7). In the first analysis, researchers reported an increased incidence of breast cancer among women taking estrogen plus progestin. There were also more cardiovascular complications.

Since that time, however, there have been many critiques of the Women’s Health Initiative. You can read the whole story at this link:

Is Hormone Therapy Safe for Menopausal Women? Yes and NO!
There’s no simple answer to the question: is hormone therapy safe? Studies give different answers. The most recent research says age matters!

The FDA Removes HRT Black Box Warnings:

An article in JAMA (November 10, 2025) updates the “Labeling for Menopausal Hormone Therapy”:

“The FDA’s hormone therapy label updates include

• Removal of boxed warnings (cardiovascular disease, stroke, breast cancer, probable dementia), except for the boxed warning in systemic estrogen labels for endometrial cancer with unopposed estrogen in women with a uterus, as it is important to remind health care practitioners and patients that this serious risk can be mitigated by adding a progestogen.

• Removal of the recommendation to prescribe hormone therapy at the lowest effective dose for the shortest duration—treatment decisions are individualized and fall within the clinical judgment of a clinician in discussion with a patient.

• Tailored safety information: Instead of applying identical class-based language across all hormone therapy labels, safety data will be revised to reflect risks most relevant to each specific type of hormone therapy product (eg, combined estrogen plus progestogen vs estrogen alone).

• For the topical vaginal estrogen-only drug label, the emphasis is on the safety findings most relevant to topical vaginal use and not the broader warnings associated with systemic exposure.

• Timing information for systemic hormone therapy: Labels will include updated guidance on initiating treatment in women younger than 60 years or within 10 years of menopause onset to optimize the benefit-risk balance.”

The Bottom Line:

That is all pretty technical and designed for healthcare professionals. The bottom line is that the FDA now believes that manufacturers should remove the black box warning that accompanies hormone replacement therapies (estrogen plus progesterone).

In announcing the change, the FDA Commissioner, Dr. Marty Makary stated:

“After 23 years of dogma, the FDA today is announcing that we are going to stop the fear machine steering women away from this life-changing, even life-saving, treatment.”

A Quick Overview from The People’s Pharmacy:

Estrogen by itself increases the risk of uterine cancer (endometrial carcinoma). That has been known since the 1970s. And that is why doctors added progestin (or medroxyprogesterone) for women who had not undergone hysterectomy. Progestin counteracts the risk of overstimulating the uterine lining.

But adding progestin complicates things. There appears to be an increased risk of breast cancer among women getting HRT with both estrogen and progestin.

Here is what the National Library of Medicine’s MedlinePlus has to say on this topic:

“Combination hormone replacement therapy (estrogen and progestin) may increase the risk of heart attack, stroke, blood clots in the lungs and legs, and breast cancer.”

This warning may also disappear now that HHS and FDA are discounting the risk.

A review of the data published in JAMA Oncology, Oct. 30, 2025 introduces the topic this way:

“Breast cancer incidence is rising globally, particularly among premenopausal women, with worldwide projections estimating more than 3 million new cases and 1 million deaths annually by 2040. Hormonal contraceptives are a known risk factor, which, though conferring a modest risk at the individual level, translates into a substantial population-level impact given their widespread use. While estrogen’s role in promoting breast cancer through epithelial cell proliferation and oncogene amplification is well established, the role of progesterone and synthetic progestins is more debated, though some studies suggest they may also stimulate breast cell proliferation.”

The authors add:

“Progestins stimulate breast cancer cell proliferation mainly through binding to progesterone receptors.”

Meaning:

“These findings suggest that individuals at risk of breast cancer may benefit from avoiding desogestrel-containing hormonal contraceptives, particularly in progestin-only formulations.”

This recent study, of course, is about oral contraceptives and a progestin (desogestrel). The implication, though, is that progestin adds to the risk of breast cancer.

A study in Acta Endocrinologica (Jan-March, 2021) titled “Progestins and the Risk of Breast Cancer” concluded:

“To sum up, combined hormone therapy was associated with an increased risk for breast cancer. The risk was directly proportional to the duration of use, and in some studies the risk increased from the first 3 years of its use. Depending on progesterone or progestogen, several studies have agreed that natural micronized progesterone and dydrogesterone was associated with a lower to zero risk for breast cancer, compared to other progestogens, while, the risk increased significantly for testosterone-related progestogens, rather than progesterone – related progestogens.”

Final Words:

Confused? I would not blame you. The FDA now says that the risks from HRT are minimal. Dr. Makary is an enthusiastic booster of hormone replacement therapy. But estrogen by itself can increase the risk of endometrial cancer if a woman has an intact uterus. If the clinician prescribes progesterone to counteract that risk, the risk of breast cancer remains unclear. The article published in JAMA Oncology, Oct. 30, 2025 does not say the coast is clear.

We encourage women contemplating hormone replacement therapy containing both estrogen and progesterone to have a thoughtful conversation with their healthcare provider.