Hormone replacement therapy (HRT) is often prescribed to ease symptoms of menopause — such as hot flashes, bone loss, fatigue, insomnia, vaginal dryness and night sweats. But many women are confused about the risks and benefits of HRT (sometimes called menopausal hormone therapy, or MHT). That’s because of conflicting study reporting, lumping results from different types of natural versus synthetic hormone studies, clarifications from subsequent reports of initial research findings and lack of detailed hormone treatment training. As a result, many doctors and patients may think that HRT raises a women’s risk for developing breast cancer and other cancers.
Years of misunderstandings have come from combining study results that used different hormone doses and formulations of natural or synthetic hormones in different populations of women and describing the findings as if they were one therapy. As a result, many patients and their doctors are confused about the benefits and potential risks of HRT, says Linda Bosserman, M.D., Ph.D., F.A.S.C.O., F.A.P.C., a medical oncologist, sexual health cancer specialist at City of Hope® Cancer Center. Dr. Bosserman, who has closely studied the medical literature on HRT after completing her doctorate on the topic, has drawn some reassuring conclusions for women considering HRT. The big picture: Many studies have confirmed that natural hormone replacement therapies are safe, while manmade (synthetic) hormone drugs carry some risks, she says.
Dr. Bosserman attributes much of the confusion about HRT to media reports that misinterpreted the findings of one of the most comprehensive HRT studies — the Women's Health Initiative (WHI), in the 1990s — and notes that later research clarified the risks and benefits of the synthetic progestin and horse urine estrogens used in that study. Subsequent studies have confirmed the benefits of natural HRT.
“Risks and benefits are not one-liners and media reports distorted the original WHI findings,” she says. “Doctors who rely on guidelines and summary services didn’t get the key updates of the long-term results: Estrogen alone reduces breast cancer risk 23% in 20 years and [there are] no increased breast cancer risks with estrogens in 10 randomized controlled trials with either horse urine estrogens (known as conjugated equine estrogen or Premarin®) or with natural bioidentical estradiol.”
She adds that only synthetic progestins — but never natural progesterone — may increase breast cancer risk when paired with an estrogen, but only slightly (about 1 in 1,000 cases). That’s about the same risk posed by drinking alcohol daily, being obese and smoking, she says.
Dr. Bosserman says patients considering HRT should work closely with doctors who are able to evaluate the risk and benefits of various hormones and combinations, taking into account how long they might be taken and the specific health profiles of individual patients.
“None of this provides one-liners or dramatic headlines,” she explains.
In this article, we’ll explore the pros and cons of HRT to help women weigh the risks and benefits, including:
- What is HRT and what does it treat?
- HRT and cancer risk
- Pros and cons of HRT: To use or not to use?
- Bioidentical hormones and other medicines for medicine
If you or a loved one is concerned about possible signs or symptoms of cancer and would like an initial consultation or a second opinion, call us 24/7 at 877-460-4673.
What is HRT and What Does it Treat?
HRT — sometimes called menopausal hormone therapy (MHT) or postmenopausal hormone therapy (PHT) — involves the use of female hormones that are lost starting in perimenopause and during menopause. Traditional HRT involves estrogen and progesterone (and/or combinations of the two), which are produced by the ovaries and other organs.
The three primary types of estrogen are:
- Estradiol, produced by a woman’s ovaries and in many other tissues of the body
- Estrone, which is made mainly in fat tissue
- Estriol, produced by the placenta during pregnancy
Lab-made (synthetic) forms of these hormones were the most commonly prescribed to replace the estrogen lost after menopause until the WHI report. The most common of these was conjugated equine estrogens (CEEs, estrogens from horse urine) taken orally or used as a vaginal cream. Natural, bioidentical estradiol is available in several forms: oral pills, skin and vaginal low-dose creams, patches, gels and vaginal rings. Both estradiol and CEEs may be given alone or in combination with progesterone.
Medicines that act like progesterone are called progestins and include:
- Medroxyprogesterone acetate (MPA)
- Norethindrone acetate
- Levonorgestrel
These medicines are available in pill form, as a patch or as an intrauterine device (IUD) put into the vagina. They are all synthetic variants which last longer in the body and activate many other receptors other than progesterone, likely causing the increased risk of breast cancer.
Some HRT preparations contain both estrogen and a synthetic progestin or the natural progesterone, a combination called estrogen-progestin therapy (EPT).
HRT and Cancer Risk
HRT first gained popularity in the 1960s as a way to manage unpleasant menopausal symptoms. The U.S. Food and Drug Administration (FDA) first approved the treatment only for symptom relief, but by the 1990s researchers were also studying HRT’s impacts on heart disease, cancer and other health conditions.
The landmark Women's Health Initiative (WHI), which began in 1991, examined breast cancer risk in women, median age of 63 and over 10 years after menopause with higher risks of heart disease, obesity and smoking to measure the impact of oral HRT with estrogen (CEE) and progestin (synthetic medroxyprogesterone acetate-MPA) in women with a uterus or estrogen (CEE) alone if women had no uterus, for five years. Researchers found a non-clinically significant but slightly increased breast cancer risk in women taking only the combination of CEE and synthetic progestin (MPA) as well as increased incidence of heart disease, blood clots and stroke during study year one only. As a result, researchers halted the study and its authors advised the risks of HRT outweighed the benefits but did not specify that that women at risk were in early menopause. Out [KS1.1]of fear, women and their doctors stopped prescribing hormone therapy for all women although the study results later showed less breast cancer in women who got estrogen therapy alone and 23% less breast cancer over 20 years while feeling better.
But the study had significant limitations that its authors and the media frenzy ignored. For one thing, researchers only tested the synthetic hormones, CEE alone (horse urine estrogens, sold under the brand name Premarin®) in women without a uterus or with MPA (brand name Depo-Provera®) for women with a uterus — which were the primary forms of HRT promoted to doctors for patients in the 1990s and early 2000s, Dr. Bosserman notes. The study also involved only older women with a median age of 63 who had already spent over 10 years in menopause without hormone replacement.
Since then, follow-up studies have found that natural HRT — as opposed to synthetic hormones — is highly beneficial in reducing death rates overall as well as those from heart disease and osteoporosis without significantly increasing the risk for developing breast cancer, ovarian cancer or other cancers. In fact, many studies show lower risks of breast and colon cancer with HRT without synthetic progestins. Research has also found that any cancer risks are not increased and maybe decreased when HRT approved by the FDA is given to women soon after starting menopause or to women who are younger than 60 years old.
“Natural, bioidentical, FDA-approved oral estradiol has no increased clot risk, is a cheap, generic, highly effective natural estradiol with no increased clot risk in 14 randomized clinical trials alone or with natural progesterone, which is also bioidentical and FDA approved and a cheap generic,” Dr. Bosserman says. This is another example of misguided medical information from attributing results from synthetic products with the natural hormones. What’s more, oral estradiol effectively prevents blood vessels from developing the plaque that causes clots, strokes and heart disease. Dr. Bosserman adds that clinical trials have found natural HRT reduces overall causes of death by 40% and heart disease by 30% to 50%. In addition, it lowers the risk for developing dementia and bone loss, while improving quality of life, wellbeing and reducing menopause symptoms. In addition, HRT with natural hormone replacement, and even in the CCE arm of the WHI, significantly reduces breast cancer risk.
Pros and Cons of HRT: To Use or Not to Use?
Many factors should be weighed when deciding whether to use hormone replacement therapy, Dr. Bosserman says. That’s why choosing to use HRT is a decision each woman should make with her doctor and care team.
“It is key that each woman have time with trained, knowledgeable clinicians to fully understand individual risk and benefits, specific hormone options, time from menopause, goals and priorities for health,” she says. “Given the lack of clinician education over the last 23 years, it is critical that more doctors become educated on the science of natural hormone therapies and that patients seek care from doctors with updated training.”
In addition, doctors should consider each patient’s age, her priorities for her health and sexual function, her lipid profile and cardiovascular risks, bone health and brain function and menopause issues.
Dr. Bosserman adds that the benefits of HRT are greatest when started at menopause and during perimenopause, before a woman’s body stops producing natural hormones. It’s also important for patients to have regular follow-up care while taking HRT, so their provider may track how well the therapy is working, monitor for side effects and revisit the risks and benefits over time.
Bioidentical Hormones and Other Medicines for Menopause
Bioidentical hormones have the same chemical structure as those the body makes naturally. But this term is also sometimes used to describe combinations of hormones that are custom made by compounding pharmacies, often with doses adjusted based on blood or saliva hormone tests.
Although compounded bioidentical hormones are often marketed as being more natural, which may make them seem safer than other forms of hormone therapy used for menopause, these products use FDA-sourced hormones but the final formulations are not tested by the FDA. The FDA has approved bioidentical forms of estradiol and progesterone. The FDA also removed the non-evidence-based warnings against breast cancer, stroke, dementia and heart disease in November 2025 after years of petitions from citizens and experts.
No long-term studies show compounded hormone therapies are safer or cause fewer side effects than the FDA-approved bioidentical estradiol available in pills, gel and patches, or the oral micronized progesterone available and covered by most insurance. Doses may be tailored and mixed for ease of use when preferred. When a compounding pharmacy is chosen, it’s best to use one that does third-party testing. All are regulated by the FDA. For this reason, they should be assumed to have at least the same health risks as any other type of MHT, the American Cancer Society (ACS) advises.
And the discussions have not included the most common hormone in women, testosterone, which begins to diminish in the late 20s and 30s and has the most impact on improving libido as well as sexual satisfaction and other elements of sexuality. It also has impacts on brain, muscle, wellbeing, mood and menopause symptoms. Dr. Bosserman notes that 36 randomized controlled trials have shown testosterone therapy is safe, yet there is no FDA-approved formulation for women in the United States while five other countries — Australia, New Zealand, United Kingdom, Italy and South Africa — have formulations designed for women.
“Full MHT should include a discussion of all side effects, health priorities and issues a women may be experiencing or concerned about and should include all three major female hormones: progesterone, testosterone and estradiol,” she says.
Many over-the-counter “natural” or herbal products are also promoted as helpful with menopausal symptoms. These include vitamins, soy-based products, and herbs like black cohosh and red clover. These products are sold as dietary supplements, not medicines.
But most haven’t been evaluated by the FDA to make sure they work or are safe. Some have been tested in small, short-term clinical trials, but their long-term safety is unclear. It’s also hard to apply results from one version or dose of a supplement to others that weren’t tested and may be different.
The ACS warns women to be cautious of products with “secret formulas” or hormone-like ingredients. Some imported natural supplements have been found to contain actual drugs, including ones banned in the United States. Most single herbs used for menopausal symptoms are likely to have a low risk of harm for most women, but some can interact with other drugs or cause unexpected side effects. That’s why women should discuss any herbs or supplements they’re considering with a doctor before taking them.
Well-controlled research is needed to know if these products work, how well they work compared to the current hormone therapies now in use and if they are safe. Learn more about dietary supplements and safety.
If you or a loved one is concerned about possible signs or symptoms of cancer and would like an initial consultation or a second opinion, call us 24/7 at 877-460-4673.