Why Is Hormone Therapy Still So Misunderstood?

Jen McDornan-Fish, a 51-year-old writer from Sacramento, first noticed mild hot flashes and occasional irritability eight years ago. She recognized these as early signs of perimenopause — the transitional phase before menopause when estrogen levels begin to fluctuate and decline. Back then, her symptoms were so mild that she didn’t see a need for treatment, even thinking of them as little more than “warm flashes.”

But more recently, McDornan-Fish, who has always been pretty even-keeled emotionally, has felt random moments of rage. She often wakes up in the middle of the night drenched in sweat, her heart racing and body shaking.

Now, as she begins to explore treatment for her worsening symptoms, McDornan-Fish, who has long COVID (a condition which 6.4% of U.S adults have reportedly experienced) and a history of migraines, finds herself with more questions than answers. While Hormone therapy (HT) — also called hormone replacement therapy (HRT) — is considered the “gold standard” in treating hot flashes and night sweats, it doesn’t come without risks. One such risk, though uncommon, is blood clots — affecting an estimated 2 to 4 women per 1,000 who take combined oral HRT, according to a 2019 study.

Emerging research suggests “micro” blood clots may be involved in long COVID, leaving McDornan-Fish to wonder if hormones might be too risky for her.

And so far, no one she’s asked seems to know the answer.

In talking with her doctors, McDornan-Fish realized there is no one-size-fits-all approach to HT. “There’s no easy chart of ‘if this, then this,’” McDornan-Fish explains. “I think that’s when I figured out how complex it was going to be.”

But it’s not just her or her complicated history with long COVID. As McDornan-Fish talked with friends, she discovered they were having just as much trouble figuring out the risks and advantages of hormone therapy as she was. “Everybody’s having very different journeys with symptoms and getting very different messaging from their doctors,” she says. “There’s so many potential problems and very different sources of information.”

McDornan-Fish’s experience is frustratingly common. One reason for all the confusion is the lack of doctors with standardized menopause training, something that’s fortunately begun changing. The Menopause Society, a nonprofit organization of healthcare professionals focused on menopause and midlife women’s health, and the publisher of the peer-reviewed journal Menopause, has seen its membership triple over the past four years.

The crux of confusion, however, goes far beyond gaps in providers’ knowledge. From social media influencers peddling their products and ideas, to insufficient research into women’s health, to all the misconceptions about hormone therapy that have grown over the years, making sense of the promise and perils of hormone therapy is no small task.

Complications and Poor Communication: Why We’re All So Confused About Hormone Therapy

While still commonly referred to as ‘hormone replacement therapy’ (HRT), the term ‘hormone therapy’ (HT) is being used more often in clinical and research settings, and is preferred by the Menopause Society. Historically, the thinking was that hormones “replaced” the estrogen a woman’s body stops producing during menopause. Now, medical professionals try to provide just enough estrogen to ease the most troublesome symptoms, making ‘replacement’ a less accurate term.

As hormone therapy has evolved, confusion about its risks still lingers — driven in large part by a lack of nuance in mainstream media coverage.

And while more recent evidence has emerged to update and, in some cases, overturn earlier understandings, The Menopause Society’s position statement on hormone therapy acknowledges how complicated things remain, stating, “risks of hormone therapy differ for women, depending on type, dose, duration of use, route of administration, timing of initiation and whether a progestogen is used.”

An increasing number of healthcare professionals are taking a proactive role in helping patients navigate menopause-related decisions. Stephanie Faubion, M.D., medical director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, explains that much of the confusion stems from the fact that women don’t all start with the same level of risk when they walk through a provider’s door.

“It matters what your age is, what your medical comorbidities are, and what your family history is… That’s why it’s so complicated,” notes Dr. Faubion.

But, she continues, doctors can do a better job trying to clairify this for women to help them understand the risks and benefits of hormone therapy for their individual needs.

The History of Hormone Therapy

The first estrogen product to treat menopausal symptoms, Premarin, was approved in 1942, but it wasn’t until the 1960s that HRT — as it was then exclusively called — started catching on as a way to manage the hot flashes, night sweats, and related symptoms that came with the approach of menopause.

As women approach the end of their reproductive years, declining estrogen levels trigger common symptoms associated with perimenopause, and later, menopause, which is defined as 12 consecutive months without a menstrual period. For physicians, it seemed logical that replacing lost estrogen could ease menopausal symptoms. The rise of the feminist movement in the 1960s, which reshaped women’s roles and extended life expectancy, further fueled interest in hormone therapy.

In 1975, researchers learned that taking estrogen increased the risk of endometrial cancer, which led to a decrease in HRT’s popularity. However, its use rebounded after the next landmark discovery: that adding progesterone — another hormone that plays a key role in menstruation and women’s reproductive functions — and lowering the estrogen dose canceled out that cancer risk in women who had an intact uterus.

By then, in the early 1990s, the FDA had approved HRT as a treatment to help prevent osteoporosis, and the American College of Physicians had issued its first guidelines on the therapy.

HRT’s popularity soared in the 1990s, and as data accumulated about its benefits, the Food and Drug Administration (FDA) called for bigger trials to assess its effects on other aspects of women’s bodies, including heart health.

What came next was perhaps the most famous — and infamous — study in all of women’s health, the Women’s Health Initiative (WHI).

The Implications of the Women’s Health Initiative

The WHI began recruiting women in 1993 with the goal of determining whether hormone therapy offered cardiovascular benefits. One trial included more than 16,000 women — whether or not they had menopausal symptoms — who were given a combination of estrogen and progesterone or placebo. Another trial, involving more than 10,000 women with prior hysterectomy, focused on estrogen alone.

When the first trial was stopped early because of safety concerns in 2002, news outlets reported the startling results: After five years of follow-up, women taking HRT had higher risks of heart disease, breast cancer, stroke, and pulmonary embolism (a blood clot in the lungs). Two years later, the second trial was stopped for similar reasons.

“Everybody was scared,” says Monica Christmas, M.D., an associate professor of Obstetrics and Gynecology,  the director of both the Center for Women’s Integrated Health and of the Menopause Program at the University of Chicago Medicine, and the Associate Medical Director of the Menopause Society.

“Doctors were scared to prescribe it, patients were scared to be on it, and because nobody was prescribing or using it, it wasn’t really being taught in medical school or residency programs.”

However, at the time, little media attention was paid to several critical factors now known to significantly influence how hormone therapy affects different groups of patients. Early dissent within the medical community likely further complicated the public messaging, as some researchers questioned how the study’s findings were being interpreted and applied.

Only one-third of the women enrolled in the study were in their 50s, the typical age range for the onset of menopause. The average participant was 63. Moreover, nearly 75 percent had never used hormone therapy before — meaning most began treatment a decade or more after menopause.

The study also did not assess vasomotor symptoms like hot flashes and night sweats, which have long been the primary reason women turned to hormone therapy. And it examined just one form of treatment: oral conjugated equine estrogens, given at a fixed dose, along with a single type of progestin.

Even JoAnn E. Manson, M.D., a principal investigator for the Women’s Health Initiative and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School, has acknowledged that follow-up research has exposed important limitations in how the WHI findings were originally interpreted. In a 2024 paper she co-authored, Dr. Manson emphasized that the timing of hormone therapy — particularly how close it is to the onset of menopause — plays a critical role in determining both risks and benefits. Starting treatment earlier, she noted, may be associated with a more favorable outcome.

Indeed, further analysis of the WHI data has helped clarify the actual risks of hormone therapy, particularly when broken down by age. For example, among women ages 50 to 59, there was no increased risk of death from cancer or heart disease over the 18 years after the study began.

Fear and Hype: How Social Media Is Pushing HT as a ‘Cure-All’

While the initial risks reported by the WHI received widespread media coverage, the findings that emerged in the years that followed — particularly those highlighting the role of timing in hormone therapy — have received comparatively less attention.

“There was this lull of almost 15 years where no one was talking about [HT],” says Dr. Christmas. But now the pendulum has begun to swing the other way, she adds.

Due to the rise of influencers promoting hormone therapy as a cure-all for various issues, often without solid scientific evidence to support their claims, too many women may be seeking hormone therapy as a panacea for concerns that it’s not proven to address.

Social media has played a large role in increasing public awareness of previously less-discussed medical topics and encouraging some patients to feel more comfortable discussing them with their healthcare providers. But Dr. Christmas cautions that this new level of awareness is not without its problems. “There’s no checks and balances on whether the information you’re getting is accurate,” she notes. “What’s happening a lot now is that you have people who are self-proclaimed experts who make it seem like hormone therapy is the antidote to aging, the magic jelly bean, the cure for all the things.”

For example, despite one popular menopause influencer linking HT to weight loss during menopause, clinical evidence does not currently support HT as an effective solution for weight loss, joint pain, or cognitive decline.

These overtly enthusiastic proclamations around the benefits of HT can become confusing to people, notes Dr. Christmas. “Because on the one hand, you have people saying, whether you’re having symptoms or not, everybody should be on hormone therapy for overall well being,” she explains. “But we really should not be telling everybody they should be on it because we don’t have good evidence to substantiate the efficacy of some of these things.”

McDornan-Fish has seen a lot of this hype, but as she moved through her menopause journey, she took care to critically evaluate what she heard and read before taking it at face value. “My advice is to look at the actual data and research that’s out there and to look at their conflicts of interest,” she notes.

The Many Factors Behind Hormone Therapy Risks: Why There’s No One-Size-Fits-All Answer

When talking about the risks of taking HT, it’s important to distinguish between common side effects and serious adverse events. “Side effects are you get a little vaginal bleeding and your breasts are sore. Serious adverse events are, you have a heart attack,” explains Dr. Faubion. “The [risks] we’re most concerned about are blood clots, heart attack, stroke, overall mortality, dementia risk, and breast cancer.”

But picking apart those risks requires understanding how they shift based on women’s personal health histories and age, the various HT options for formulations, and how the hormones are administered.

The Age You Start HT Matters — A Lot

The biggest factor affecting major risks of HT is a woman’s age when she starts it. Starting HT before age 60, or within 10 years of menopause, does not increase the risk of heart disease, heart attack, or stroke — in fact, coronary heart disease risks are lower. So it’s “potentially beneficial when started in the fifties,” notes Dr. Faubion, “and it’s more neutral in the 60s and potentially harmful as you get into the 70s.”

Starting HT after age 60 or more than 10 years after menopause does increase the risks of heart disease, stroke, and blood clots, and starting after age 65 may additionally increases the risk of dementia.

According to Dr. Faubion, one huge gap in the research, however, is that we don’t have good data on the long-term use of HT — beyond seven years — in women who start it before age 60 or within 10 years of menopause.

There are other factors that affect risk, too, especially when it comes to breast cancer. That’s the number one concern that Chrisandra Shufelt, M.D., a professor of medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, hears from women. But this risk depends on the type of HT and the route of administration.

Systemic Hormone Therapy VS Low-Dose Localized Estrogen: Different Categories, Different Risks

The FDA has approved HT for four things:

• Vasomotor symptoms, which are hot flashes and night sweats
• Prevention (but not treatment) of osteoporosis, or bone loss
• Premature loss of the body’s estrogen production because of surgically-induced menopause (such as removal of the ovaries) or primary ovarian insufficiency, where the ovaries stop working before age 40.
• Genital, vaginal, and vulvar symptoms that can occur when loss of estrogen thins out the vaginal lining, such as painful intercourse or dryness, itchiness, or irritation of the vaginal area.

When someone is prescribed HT, they will typically receive it in one of two forms, explains Dr. Christmas. There’s systemic HT, where the hormones circulate through the whole body, and low-dose localized estrogen, used only in the vaginal area. Local estrogen is either not absorbed into the bloodstream or is absorbed in such small amounts that it has no significant effects beyond the vaginal area.

These two categories have different purposes, formulations, and risks.

Systemic HT treats vasomotor symptoms, prevention of osteoporosis and premature loss of estrogen, but if a woman doesn’t need or cannot take systemic HT, localized estrogen can be used to treat vaginal symptoms.

Systemic hormone therapy typically includes both estrogen and a progestogen — either natural progesterone or a similar drug — for women with a uterus. This combination is necessary because estrogen alone can raise the risk of endometrial cancer, but adding a progestogen reduces that risk. Women who have had a hysterectomy don’t require a progestogen since they no longer have an endometrium, the uterine lining affected by estrogen.

Systemic estrogen can be given as an oral pill, as a flexible ring inserted into the vagina, or as a skin (transdermal) patch, spray or gel. Transdermal and oral estrogen are equally effective in treating hot flashes and night sweats, but we don’t have much research comparing the risks of one versus the other.

Progestogens can be given as oral pills or in combination skin patches with estrogen.

Localized estrogen can be delivered to the vagina in creams, gels, tablets, vaginal rings, or pessaries, which are devices inserted into the vagina to support the uterus, bladder or rectum from penetrating into the pelvic floor.

Research has not linked localized vaginal estrogen to many of the risks associated with systemic estrogen. For example, no evidence suggests that vaginal estrogen increases the risk of breast cancer.

Because systemic HT delivers a larger dose of hormones throughout the body, the risks are greater for certain groups of women. Those advised against oral and transdermal HT include women with any of the following:

• unexplained vaginal bleeding
• gallbladder or liver disease
• a personal history of an estrogen-sensitive cancer (including breast cancer)
• a personal history of coronary heart disease, stroke, heart attack, or a venous thromboembolism (massive blood clot). Women who have a family or personal history of a disease that greatly increases the risk of blood clots are also not advised to use systemic oral or transdermal HT.

However, some of these women may still safely use localized vaginal estrogen. For instance, women with a history of blood clots can often use vaginal estrogen, which has not been shown to raise the risk of heart disease or cancer.

While these are the current guidelines, they may evolve as new research provides greater clarity, and treatment decisions often depend on an individual woman’s preferences and specific medical needs.

Systemic HT and Breast Cancer Risk

As Dr. Shufelt points out, breast cancer is often a major concern for many women considering systemic hormone therapy. However, contrary to oversimplified claims from older studies and current influencers, the truth remains somewhat cloudy.

The increased risk of breast cancer in women using systemic HT with estrogen and progesterone is uncommon, around nine cases per 10,000 people a year, or just under one additional case per 1,000 women each year. And that risk increases slightly — to about three additional cases per 1,000 women — when estrogen plus progesterone is used for five years.

But here’s where things get just a bit more complicated: This breast cancer data is based on the WHI, which provided data only on oral HT with one type of estrogen and progesterone — not any other progestogens. And the risk may vary for transdermal HT or other systemic formulations and doses than the ones used in the WHI. Even if this risk doesn’t vary — again, there’s too little evidence to know — the nearly 1-in-1,000 risk seen with oral estrogen and progesterone is approximately equivalent to the increased risk of breast cancer from obesity, low physical activity levels or a daily glass and a half of wine, the Menopause Society position statement notes.

Meanwhile, the increased risks of breast cancer don’t appear to be any higher in women with a family history of breast cancer or a genetically increased risk for breast cancer, such as those with a BRCA 1 or 2 variant, but women with an increased family or genetic risk of breast cancer will still want to discuss their personal risks and potential benefits with their provider.

Bioidentical Hormones: FDA-Approved VS Compounded

When consulting their doctor or scrolling through a video by a menopause influencer on social media, many women are likely to encounter the term “bioidentical hormones.” Like every other aspect of HT, there is often confusion, and a lot of misinformation, around this term.

At its core, “bioidentical” simply means the hormones are plant-derived and chemically identical to those produced by the body. Synthetic hormones, by contrast, are artificially manufactured and mimic the hormones produced by the human body. Ambiguity can arise because bioidentical hormones come in two forms: FDA-approved options that have been rigorously tested for safety and effectiveness, and compounded versions, which are not subjected to the same level of scrutiny.

In general, compounded medications are custom-made by combining pharmaceutical ingredients to meet an individual person’s needs. While these drugs are not FDA-approved, federal regulations oversee who is authorized to produce them. A commonly touted selling point of compounded hormones is that they are “specially formulated” just for “you.” But the wide range of FDA-approved synthetic and bioidentical hormones and doses that are already available allow for a great deal of customization already.

FDA-approved bioidenticals have gone through the testing required before any drug approval. Bioidenticals made in compounding pharmacies can be riskier because they are not tested for quality, the doses may not be consistent, their safety has not been assessed by the FDA, and they don’t have a label outlining their risks.

In fact, some of the uncertainty surrounding hormone therapy risks stems from the unpredictability of compounded bioidenticals.

“There’s absolutely no need to go to a compounding pharmacy and possibly pay out of pocket when they have FDA-approved bioidentical hormones [that are probably] on your prescription plan,” explains Dr. Shufelt.

And what about the safety of bioidentical hormones versus synthetic hormones?

“We know that bioidentical hormones are as effective as synthetic hormones, but we don’t have a clinical trial with a head-to-head comparison to say one is safer over the other,” says Dr. Shufelt. “There is a misconception that one is safer because bioidentical sounds natural, but at the end of the day, it’s binding to that estrogen receptor [in the same way that synthetic hormones do] and we still need to take an individual woman’s risks and benefits into account.”

Big Questions Still Remain: Why We Need to Keep Studying Hormone Therapy

Despite significant progress in understanding the risks and benefits associated with hormone therapy, some questions remain unresolved. For instance, we still don’t know the long-term risks of using hormone therapy for more than a decade, even when a woman starts in her 40s or 50s.

Blood clot risk remains one of the major risks that continues to puzzle researchers, just as it was one of the concerns McDornan-Fish particularly wanted to better understand for herself.

There does appear to be a very small increased risk of blood clots in women who start oral systemic HT before age 60 or within 10 years of menopause, but lower doses of oral HT may carry a lower risk — we just don’t know yet.

Similarly, micronized progesterone (a bioidentical type of progesterone) may carry a lower risk of blood clots, and evidence so far suggests that blood clot risk is not higher with transdermal HT, though neither of those has been confirmed in randomized controlled trials, the most reliable type of study.

In essence, we still lack a clear understanding of how factors like dose, formulation, delivery method, and duration of hormone therapy impact the risk of blood clots.

What To Know Before Starting Hormone Therapy

The overarching goal of HT is to “be on a dose that’s effective against managing your symptoms,” no more and no less, says Dr. Christmas. She points to patient education sections of professional medical society websites, such as The Menopause Society and the American College of Obstetricians and Gynecologists.

But if you want an in-depth conversation about your individual risks for HT, the first step is finding a provider who’s certified in menopause care. You can find those providers, including those offering telemedicine across multiple states, on The Menopause Society website’s practitioner directory.

Women should know that some common side effects of HT include nausea, bloating, weight gain, retaining fluids, mood swings from progesterone, breakthrough bleeding, headaches, and breast tenderness. These vary by person. Some women may not experience any of these, and others may find these side effects intolerable.

“Before I start any woman on HT, I make sure all the preventive labs and screening tests have been done,” such as mammograms and cervical cancer screening, notes Dr. Shufelt. “Number two, I think [patients] need to know and describe [their] symptoms and why [they want to use] it,” she said. “And number three, I think it’s important to take into consideration family history.”

“But,” Dr. Shufelt concludes, “for the majority of women, hormone therapy is an appropriate option and is very effective and should be used at the time of menopause for symptom relief.”

Once a woman starts HT, Dr. Faubion says it’s important to reassess the decision each year. “Why are you taking it? Is it managing your symptoms? Do you still have symptoms? Has anything new happened with your health?” Any of that can change year to year, she notes, “so all of that needs to be reassessed on an annual basis.”

Since McDornan-Fish’s PCP was not confident regarding the potential risks in her situation, she was referred to an OB with menopause expertise.

“I am hoping to talk to somebody who can help me better evaluate the risks versus rewards potential, and then I hope she’ll be knowledgeable about alternatives to hormones if that’s the right thing for me,” says McDornan-Fish. Given how little is understood about long Covid and micro-clots, McDornan-Fish has a backup plan if the menopause specialist cannot offer adequate guidance.

“My next approach will be to change tactics and talk to somebody more knowledgeable about long Covid and vascular medicine,” including knowledge about whether micro-clots might interact with hormonal treatments, she says.

Her advice to others feeling lost is to follow a similar approach. Despite a healthy skepticism about medical interventions in general, McDornan-Fish still thinks the best strategy is talking with doctors and being willing to get a second, third, or even fourth opinion.

“If a doctor’s not listening to you or seems to be dismissing your complaints, then talk to somebody else,” McDornan-Fish says. “Don’t be afraid to be the squeaky wheel.”