Hormone therapy: myths and facts

At a Glance

• Hormone therapy remains the most effective treatment for symptoms of perimenopause and menopause.
• Many concerns about its safety stem from interpretations of the Women's Health Initiative (WHI) study published in 2002.
• The hormones used in that study are not necessarily the same as those commonly prescribed today.
• The risks and benefits of hormone therapy vary depending on age, health status, the type of hormones used, the route of administration, and when treatment is started.
• Current recommendations are based on a much larger body of scientific evidence than was available in 2002.

Why Does Hormone Therapy Still Cause Concern?

If you've heard that hormone therapy increases the risk of cancer, stroke, or cardiovascular disease, you're not alone.

Much of this concern can be traced back to the publication of the Women's Health Initiative (WHI) study in 2002, one of the largest studies ever conducted on hormone therapy.

Following its publication, hormone therapy prescriptions declined dramatically around the world. Many women stopped treatment, and many healthcare professionals adopted a much more cautious approach.

More than twenty years later, researchers acknowledge that the study's findings were sometimes oversimplified or interpreted without adequate context.

What Was the WHI Study?

The 2002 Women's Health Initiative study was designed to evaluate the effects of hormone therapy—specifically conjugated equine estrogens and medroxyprogesterone acetate—on the health of postmenopausal women.

The study consisted of two major trials and included more than 27,000 women.

However, several characteristics of the participants are important to understand.

The average age of participants was approximately 63 years old, well beyond the age at which menopause typically begins.

Many participants had already been menopausal for years before starting hormone therapy. Approximately 40% had been menopausal for more than 15 years.

In other words, the study population did not primarily consist of women in the early stages of the menopausal transition experiencing new symptoms, as is often the case when hormone therapy is considered today.

This distinction is important because the effects of treatment may vary depending on when it is initiated.

Were the Hormones Used in the Study the Same as Those Used Today?

Not necessarily.

The WHI study primarily evaluated two hormones:

• Conjugated equine estrogens (CEE)
• Medroxyprogesterone acetate (MPA)

These hormones differ from the bioidentical hormones that are commonly prescribed today.

What Is a Bioidentical Hormone?

A bioidentical hormone has the same molecular structure as a hormone naturally produced by the human body.

The most common examples are:

• Estradiol
• Micronized progesterone

Because they replicate the structure of human hormones, they interact with hormone receptors in a way that closely resembles the body's own hormones.

What Is a Synthetic Hormone?

Synthetic hormones have a chemical structure that differs from hormones naturally produced by the body.

While they may produce similar effects, their metabolism and some of their biological effects can differ.

Medroxyprogesterone acetate, the progestin used in the WHI study, is one example.

This distinction is important because the scientific evidence accumulated over the past two decades suggests that not all hormone therapies have the same risk-benefit profile.

What Did the Study Actually Show?

The study identified certain increases in risk among women receiving the hormones being evaluated.

The findings that generated the greatest concern included:

• Stroke
• Thromboembolic events, such as deep vein thrombosis and pulmonary embolism

These results were widely reported in the media.

However, they were often presented without considering important factors such as:

• The age of participants
• The number of years since menopause
• The type of hormones used
• Pre-existing cardiovascular risk factors

In the years that followed, additional analyses demonstrated that the risks observed were not necessarily the same in younger women or in women who began hormone therapy earlier in the menopausal transition.

What Do We Know Today?

Since the publication of the WHI study, hundreds of additional studies have been conducted.

Leading menopause societies now recognize that for most healthy women younger than 60 years of age or within ten years of menopause, the benefits of hormone therapy generally outweigh the risks when treatment is appropriately prescribed.

Hormone therapy remains the most effective treatment for:

• Hot flashes
• Night sweats
• Menopause-related sleep disturbances
• Many genitourinary symptoms of menopause

Treatment decisions should always be individualized based on symptoms, medical history, and personal preferences.

Myth or Fact?

Myth: "All hormone therapies are the same."

False.

Different types of estrogens, progestogens, and routes of administration may have different risk and benefit profiles.

Myth: "Hormone therapy is dangerous for all women."

False.

Risk depends on factors such as age, medical history, the type of hormones used, the route of administration, and when treatment is initiated.

Myth: "The results of the WHI study apply to all women using hormone therapy today."

False.

The study participants, their age, the time since menopause, and the hormones used often differed significantly from today's clinical practice.

Myth: "Bioidentical hormones are always risk-free."

False.

Even when bioidentical, hormones remain medications that require appropriate prescribing, monitoring, and follow-up.

Key Takeaways

More than twenty years after the publication of the WHI study, our understanding of hormone therapy has evolved considerably.

Many of the concerns that persist today stem from an oversimplified interpretation of findings obtained in a very specific context.

Hormone therapy is not appropriate for every woman, but it remains a safe and effective treatment option for many when prescribed following an individualized assessment.

The most important thing is to make informed decisions based on the most current scientific evidence rather than on myths or outdated information.

This article is the first in a series dedicated to hormone therapy. In upcoming articles, we will explore in greater detail the different types of hormones, routes of administration, potential benefits, and the real risks associated with treatments currently used in menopause care.

Looking Ahead

In an upcoming article, we'll take a closer look at bioidentical and synthetic hormones and explore the key differences between these treatment options.

References and Further Reading

1. Manson, J. E., Chlebowski, R. T., Stefanick, M. L., Aragaki, A. K., Rossouw, J. E., Prentice, R. L., Anderson, G., Howard, B. V., Johnson, K. C., Kooperberg, C., LaCroix, A. Z., Lewis, C. E., Liu, J., Martin, L. W., Ockene, J. K., O'Sullivan, M. J., Powell, L. H., Simon, M. S., Van Horn, L., ... Wallace, R. B. (2013). The Women's Health Initiative hormone therapy trials: Update and overview of health outcomes during the intervention and post-stopping phases. JAMA, 310(13), 1353–1368. https://doi.org/10.1001/jama.2013.278040

2. North American Menopause Society. (2022). The 2022 hormone therapy position statement of The North American Menopause Society. Menopause, 29(7), 767–794. https://doi.org/10.1097/GME.0000000000002028

3. Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., ... Writing Group for the Women's Health Initiative Investigators. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA, 288(3), 321–333. https://doi.org/10.1001/jama.288.3.321

4. Women's Health Initiative Steering Committee. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA, 291(14), 1701–1712. https://doi.org/10.1001/jama.291.14.1701