A Huge Step To Righting One Of The Greatest Wrongs in Medical History For Women

In a historic move this month, an FDA expert advisory panel recommended removing the longtime “black box” warning label on menopausal hormone therapy (HRT), a warning that discouraged millions of women from pursuing effective, science-backed relief.

Why is that such a big deal?

Because the warning was rooted in a study that caused widespread fear of HRT, based on misleading results, many of which have now been debunked or revised based on decades of new research.

The original warning, issued in 2002 after the Women’s Health Initiative (WHI) study, linked estrogen therapy to breast cancer, stroke, and cardiovascular disease.

The impact was immediate and dramatic, perhaps the single most impactful press release in women's health.

HRT became synonymous with breast cancer, and the fear this created had widespread effects:

HRT prescriptions plummeted
Millions of women went untreated
Symptoms worsened, and long-term health risks rose

Now, after extensive reanalysis of the original data and additional studies, the FDA concluded that the original warning overstated the risk and failed to reflect newer evidence.

“The boxed warning made it appear that estrogen is dangerous for all women at all times. That’s not true. Timing, formulation, and delivery method all matter.” – Dr. Stephanie Faubion, NAMS

How HRT Got a Bad Name: The Women’s Health Initiative (WHI)

In 2002, the Women’s Health Initiative (WHI), a massive randomized trial conducted in women aged 50–79, was halted early. Its data suggested that combined estrogen-progestin therapy increased risks of breast cancer, strokes, and blood clots. It concluded there was no cardiovascular benefit and coined HRT as dangerous for most women. These findings triggered a mass reversal in prescribing HRT and public confidence plummeted.

While the WHI study had good intentions, one of the largest sample sizes, and put an enormous effort into understanding the effects of HRT, there were several issues. A combination of study design flaws and incomplete data interpretation led to a grave misunderstanding.

Here’s what skewed the results:

The Subject Population: The average participant was 63, well past menopause onset. Most had existing risk factors for cardiovascular disease.

The Hormones: The study used synthetic hormones such as conjugated equine estrogen and a synthetic progestin (medroxyprogesterone acetate), not bioidentical estradiol or micronized progesterone. It was the use of these synthetic hormones that has since been linked to many of the negative health outcomes in the study. Our cells have very specific receptor sites for our hormones. Synthetic hormones have a slightly different molecular structure than our natural hormones and connect to cell receptor sites by mimicking the shape and chemical properties of the natural hormones they're designed to replace. However, their structural variations can lead to different binding affinities and potentially different cellular responses compared to natural hormones.

The synthetic progesterone used in the study is known to bind to and activate the glucocorticoid receptor (GR) in addition to the progesterone receptor. Glucocorticoids, like cortisol, have wide-ranging effects on various physiological systems.

The activation of Glucocorticoids by the synthetic progesterone leads to various effects, similar to those seen with excess cortisol, including:

Metabolic changes: Glucocorticoids can affect glucose and lipid metabolism, potentially contributing to the increased risk of cardiovascular events observed in the WHI, according to the National Institutes of Health (NIH).

Vascular effects: Some research suggests MPA's glucocorticoid activity might play a role in promoting procoagulatory activity in the vessel walls, potentially increasing the risk of blood clots and stroke.

Mood and cognitive effects: Glucocorticoids can impact mood and cognitive function, and some studies suggest MPA may have negative effects on the brain, including memory impairment, and antagonize the benefits of estrogen, according to The Atlantic.

In essence, the synthetic progesterone, activating the glucocorticoids, mimics a stress response in the body. With this in mind, it makes sense that some women in the study experience the various chronic conditions that have been associated with stress.

How The Data Was Interpreted: The media reported a 26% increase in breast cancer. In addition to the other issues listed above, which affected the results, this percentage was grossly misrepresented. The 26% was the relative risk between study groups, meaning the test group had a 26% increase in breast cancer compared to the control group. The actual increase in risk translated to less than 9 additional cases per 10,000 women per year, or 0.8% [1].

Rushed Reporting: The results of the study were released and reported to the media before it was officially published, and before the results of the study were thoroughly reviewed by both the principal investigators and the wider scientific community. The sensational headlines caused widespread panic and created fear of HRT in both the medical community and wider population.

As a result, hormone therapy was demonized, without context or nuance.

What the Latest Science Reveals

Newer, more sophisticated studies, and long-term follow-ups from WHI itself, tell a very different story:

✅ When started within 10 years of menopause or before age 60:

Reduces all-cause mortality
Protects cardiovascular health
Improves cognitive function
No increased risk of stroke or breast cancer when using transdermal estrogen + progesterone [2][3]

✅ Safer options are now widely available:

Bioidentical hormones
Transdermal estrogen (patch, gel, spray) avoids liver metabolism and clot risk
Micronized progesterone is better tolerated and may reduce breast cancer risk compared to synthetic progestins

**What’s the Risk of Not Using HRT?**

Estrogen isn’t optional; it’s an essential regulatory hormone with hundreds of functions. Untreated estrogen deficiency may increase the risk of:

Osteoporosis and fractures
Heart disease
Insulin resistance, belly fat, and metabolic syndrome
Depression, anxiety, and brain fog
Urogenital atrophy, pain with sex, urinary incontinence
Loss of vitality, motivation, and quality of life
Loss of muscle and strength
Accelerated aging

One study found that women who went through early menopause and did not take HRT had increased mortality from all causes, including heart disease [4].

The Real Takeaway: It’s About Timing, Type, and You

If you're a woman in your 40s or 50s and struggling with hot flashes, fatigue, brain fog, or hormonal weight gain, know this:

✅ You are the ideal candidate for hormone therapy.
✅ The risks are far lower, and the benefits far greater, when HRT is started within the first 10 years after menopause.
✅ Bioidentical hormones and safer delivery methods are now widely used.

You no longer need to fear your hormones or the therapy that can restore them.

Research Spotlight

Timing matters: Starting HRT before age 60 or within 10 years of menopause reduces heart disease by 30–50% and lowers all-cause mortality [2][3].
Delivery matters: Transdermal estrogen carries no increased risk of stroke or blood clots [5].
Formulation matters: Micronized progesterone may reduce breast cancer risk compared to synthetic progestins [6].

The Bottom Line

The WHI caused a wave of fear and confusion, but science has evolved. The FDA’s panel vote to remove the boxed warning marks a new chapter. And that means you get to write your own story!

At Svasta Wellness, we guide women to make empowered, informed choices rooted in science, Ayurveda, and personalized care.

Need Help Navigating Your Hormone Options?

Let’s make this personal.

💬 Schedule your FREE Discovery Callto learn if HRT is right for you, and how to feel like yourself again.

References

[1] Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the WHI. JAMA. 2002.
[2] Hodis HN & Mack WJ. Hormone therapy and coronary heart disease: The timing hypothesis. J Am Coll Cardiol. 2005.
[3] Boardman HM et al. Cochrane review on hormone therapy for preventing cardiovascular disease. Cochrane Database Syst Rev. 2015.
[4] Rivera CM et al. Association of early menopause with increased mortality. Menopause. 2009.
[5] Canonico M et al. Estrogen and risk of venous thromboembolism: role of route of administration and progestogens. Circulation. 2007.
[6] Fournier A et al. Use of different postmenopausal hormone therapies and breast cancer risk. Breast Cancer Res Treat. 2008.