Tag Archives: hormone replacement therapy

Compounded Bioidentical Hormone Therapy

Breast Cancer, Medical Treatments with Cancer Risks, , , ,

Keris KrennHrubec, Meg Seymour, & Diana Zuckerman, PhD

To avoid the risks of conventional hormone therapy, more and more women are seeking alternatives. But how safe are compounded bioidentical hormones?

When women enter menopause, their bodies produce less estrogen and progesterone. This can cause hot flashes, night sweats, insomnia and other symptoms. Hormone therapy can supplement those hormones, but it increases the risk of breast cancer and other serious diseases. What are your options if the symptoms of menopause are difficult to cope with?

In 2002, a major research study reported that FDA-approved hormone therapy can increase a woman’s risk of heart disease, breast cancer, and stroke. (For more information, please visit: Hormone Therapy and Menopause). As a result, women started to look for alternatives to conventional hormone therapy. Custom-compounded bioidentical hormone therapy (CBHT) has been marketed as more natural and safer, but does the scientific evidence support those claims?

Natural and Safe?

Many of the hormones used in conventional hormone therapy are derived from animal products. Bioidentical hormones, on the other hand, are from plants and are more similar (although not necessarily identical) to the hormones that naturally occur in the human body. However, the term “bioidentical” is misleading and has no scientific value. Bioidenticals are created in laboratories through at least 15 chemical reactions, and they are not identical to hormones produced by human bodies.[1,2] To date, no studies have shown that bioidenticals are safer than conventional hormone therapy and experts used to assume they have similar benefits and risks for patients.[3,4]

The FDA asked the National Academies of Sciences, Engineering and Medicine to form a committee that would assess whether cBHT is an adequate substitute for the traditional therapies that are FDA-approved. In 2020, the committee issued a report that there was not sufficient data to say that cBHT is a safe and effective treatment for menopause. Although some people have reported anecdotal claims that cBHT is safe and effective, these anecdotes are not scientific data.[5] 

The Pros and Cons of Compounding

Some bioidentical hormones (such as small particles of progesterone and estradiol) have been approved by the FDA,[1] but most are not. Instead, they are prescribed as a compound with ingredients that are mixed and blended by pharmacies to “create a customized medication for an individual patient”.[6,7] Since compounding is used to make individualized medication, it is not approved by the FDA. Compounding of some medications is necessary for some patients, such as patients who are allergic to one component of an approved drug or who need a particular dosage that differs from the FDA-approved medicine. However, since it is not monitored the way an FDA-approved drug is, compounded drugs are not proven to be safe or effective.[7]

Women who are considering compounded bioidentical hormones often start by getting their individual hormone levels checked through saliva or serum tests. This may create the impression that the bioidentical drugs will be customized for each patient, but research has not shown that these hormonal tests are meaningful or can ensure a safe or effective product.[1,3]

Risks Through Compounding

In addition to not being approved by the FDA as safe or effective, compounded drugs have an additional risk of being contaminated [3] or having an inaccurate dosage.[6] Either can be dangerous. Since compounded drugs are not FDA-approved, they also lack warnings on labels about possible side effects, including serious ones.[1,8] Several of the ingredients that are commonly used in bioidentical hormones – such as testosterone – have not been approved by the FDA for use for postmenopausal women.[3]

Despite these concerns, many women have been prescribed bioidentical hormones for menopause. That’s why the FDA announced in 2018 that they will expand research on compounded bioidentical hormone therapy.[9]

How Do I Know If My Hormone Therapy Has Been Compounded?

Compounded bioidentical drugs are legal if they are in response to a doctor’s prescription.[7] It is unlawful for a pharmacy to simply give you modified drugs without consent. However, even if it is legal, that doesn’t mean it will be safe or effective. If you have any questions or concerns about your hormone therapy, you should talk to your doctor or pharmacist.[10]

You can recognize FDA-approved hormone therapy by the use of brand names such as Premarin, Vagifem and Estrace. The bioidenticals micronized progesterone (brand name Prometrium) and estradiol (brand name Vivelle) have also been approved by the FDA. If your medication has been compounded, you will see terms such as estrone, estradiol, testosterone or progesterone instead of brand names. You are probably receiving CBHT if you have been asked for a saliva or serum test to establish an individualized treatment course.[1,2]

Traditional hormone therapy can be effective for menopausal symptoms, but can increase the risk of cancer and other serious diseases. Bioidentical hormones may have the same risks. You can find more information on the FDA-approved hormone therapies here.

 

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

  1. American College of Obstetricians. (2012). Compounded bioidentical menopausal hormone therapy. Fertility and Sterility, 98(2), 308-312. (reaffirmed in 2018)
  2. Gass, M. L., Stuenkel, C. A., Utian, W. H., LaCroix, A., Liu, J. H., & Shifren, J. L. (2015). Use of compounded hormone therapy in the United States: report of the North American Menopause Society Survey. Menopause, 22(12), 1276-1285.
  3. Pinkerton, J. V., & Pickar, J. H. (2016). Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy. Menopause (New York, NY), 23(2), 215.
  4. National Institute on Aging. (June 2017). Hot Flashes: What Can I Do? Retrieved from: https://www.nia.nih.gov/health/hot-flashes-what-can-i-do#risks
  5. The National Academies of Sciences, Engineering and Medicine (July 2020). Report: The Clinical Utility of Compounded Bioidentical Hormone Therapy (cBHT) A Review of Safety, Effectiveness, and Use. Retrieved from: https://www.nap.edu/resource/25791/cBHT%20Consensus%20Study%20Report%20Highlights.pdf
  6. FDA (June 2018). Report: Limited FDA Survey of Compounded Drug Products. Retrieved from: https://www.fda.gov/drugs/human-drug-compounding/report-limited-fda-survey-compounded-drug-products
  7. FDA (June 2018). Compounding and the FDA: Questions and Answers. Retrieved from: https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers.
  8. FDA (June 2018). Compounding Oversight. Retrieved from: https://www.fda.gov/drugs/human-drug-compounding/compounding-oversight
  9. FDA (September 2018). FDA announces new and expanded compounding research projects. Retrieved from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-new-and-expanded-compounding-research-projects
  10. FDA (February 2018). Menopause: Medicines to Help You. Retrieved from: https://www.fda.gov/consumers/free-publications-women/menopause-medicines-help-you

Hormone Therapy and Menopause: Facts and Fiction

Breast Cancer, Medical Treatments with Cancer Risks, ,

Diana Zuckerman, P.h.D., and Akashleena Mallick, MD MPH, National Center for Health Research

Do women need to “replace” hormones as they age? Millions of women struggle with the decision about hormones during and after menopause: should I go on, should I stay on, or should I go off?

There is considerable debate about the risks and benefits of hormone therapy, and that is partly because some studies are better than others, and very few health professionals have read all the research. However, the research evidence is now clear: on average, the risks of hormones outweigh the benefits for most women. It is important to read articles like this one to help you talk to your physician about whether the risks are greater than the benefits for you.

What the FDA Said in November 2025

At a press conference in November 2025, Health and Human Services Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary announced that women had been misled about the dangers of hormone therapy for menopause. Experts can disagree, but in this case, the evidence is complicated, the results are nuanced, but overall, the hormone pills that the  FDA has approved for the symptoms of menopause are likely to cause harm that outweighs the benefits. However, low-dose vaginal creams seem to be safer than expected. We will explain what the best evidence shows.

What the Research Says

In December 2017, the experts at the U.S. Preventive Services Task Force issued a clear recommendation:  post-menopausal women should NOT take hormones to prevent chronic health conditions, such as increasing bone strength to avoid fractures. The reason is that the risks of these hormones outweigh the benefits.1

This recommendation was based on clear evidence that taking hormones to “replace” those that are reduced in menopause is often bad for your health. The best evidence is based on randomized clinical trials called the Women’s Health Initiative (WHI), sponsored by the National Institutes of Health (NIH). These included more than 27,000 women in three different trials to study the effect of hormones on women’s bodies.2,3,4 The 3 trials were: 1) the Estrogen Plus Progestin Trial, 2) the Women’s Health Initiative Memory Study, and 3) the Estrogen-alone Trial.

The researchers found that women taking a combination of estrogen and progesterone hormones were more likely to develop breast cancer, stroke, and blood clots, and at least as likely to develop heart disease, compared to women taking a placebo. Those on estrogen alone were more likely to have a stroke or a dangerous type of blood clot called deep vein thrombosis (DVT).

The Memory Study (WHIMS) was a randomized double blind study that found that women taking a combination of estrogen plus progesterone were twice as likely to develop Alzheimer’s Disease and other forms of dementia compared to women on a placebo.3

All three trials were stopped early for ethical reasons when it became clear that women taking hormones were more likely to be harmed than helped. While there are some short-term benefits to taking hormones, the researchers concluded that for most women, the risks of hormone therapy outweigh the benefits.

Cancer

Following the release of these findings, use of hormone therapy in the U.S. dropped significantly.  Since then, several large studies have pointed out that breast cancer incidence also dropped a few years after the decline in hormone use for menopause.5,6 This unexpected and unprecedented drop in breast cancer incidence suggests that HRT has a more dramatic impact on breast cancer risk than previously thought.7

For example, in 2021, a meta-analysis of more than 4,000 women in 4 different studies of women previously being treated for breast cancer found that those who subsequently took hormone therapy (combined estrogen plus progesterone) were much more likely to have a recurrence of cancer than breast cancer survivors who took a placebo.8 The women who had estrogen receptor-positive breast cancer prior to hormone therapy were 80% more likely to have a recurrence than women taking a placebo, which was a statistically significant difference that did not occur by chance. The women who had estrogen receptor-negative breast cancer were 19% more likely to have a recurrence than the women taking a placebo, which was a small difference that might have occurred by chance.

Hormone therapy for menopause as a possible cause of breast cancer is particularly controversial. Studies indicate that hormones can increase or decrease the chances of developing breast cancer depending on the age and other traits of the women, and the types of hormones involved.  However, the two most recent studies indicate that hormones can increase the chances of younger women and women with dense breasts developing breast cancer. 9

In 2009, a study found that hormone therapy increased the risk of dying of lung cancer among women who smoked or previously smoked, compared to smokers or former smokers who did not take hormone therapy. For more information, click here.

Heart Disease

Experts who promote the use of hormones for menopause have criticized the WHI for enrolling women after menopause rather than just before or in the earliest stages.  So, it is important to note that in 2014, a study of 727 women in early menopause showed that hormone therapy did not prevent atherosclerosis (artery thickening), as had been claimed previously.  Following women on HRT for 4 years, the researchers from the Kronos Longevity Research Institute, a pro-HRT research institute, and other institutions, found no difference in artery thickening between the women who took HRT and those who didn’t.10 

Although the average age of the women in the WHI was 60, the study included over 27,000 women in their 50s.  When the younger women were evaluated separately, the researchers still found the harms were greater than the benefits. 12

Memory Loss and Mood

In 2015, the same group published an article admitting that hormone therapy also had no impact on “cognitive decline,” despite claims that it would prevent Alzheimer’s and memory loss.11 Although the authors focused on a small improvement in mood related to using hormone pills for 4 years (but not found with hormone creams), they downplayed the more important finding: no impact on depression as measured by the valid and reliable Beck Depression Inventory.

Is Hormone Therapy a Good Idea for You?

For younger women with debilitating symptoms of menopause who are not otherwise likely to develop breast cancer or heart disease in the next few years due to family history, the increased health risks of hormone therapy may be worth it to them.  That is very different from urging all women to take hormone therapy for menopause.

To emphasize that lost hormones don’t necessarily need to be replaced, the term “hormone replacement therapy” was changed to “hormone therapy” or menopausal hormone therapy (MHT). Many experts have advised women to use hormone therapy only for severe symptoms of menopause that reduce the quality of life, such as severe hot flashes, night sweats, insomnia, and vaginal dryness. Women have been urged to take hormones at the lowest dose that is effective and for the shortest possible period of time. We think this is still the best advice.

However, research has shown that topical hormone creams for vaginal dryness are safe for short-term use. Better research is needed to know how safe these creams are for long-term use, but there is reason to believe that they are safer than hormone pills.

One of the misleading statements made by government officials in 2025 about hormone therapy was that it would prevent dementia, so that issue deserves particular attention.  In addition to the previously mentioned WHI Memory Study that showed an increase in dementia among women taking hormone pills for menopause 3, a 2015 Cochrane review confirmed that hormone therapy for menopause does not prevent dementia. 13

In contrast, there are no well-designed studies that support the FDA claim that hormone therapy prevents Alzheimer’s or any other type of dementia.  For example, a study by Simpkins and colleagues reviewed rodent studies and other research that could not accurately establish the impact of hormone therapy on women. 14 A 30-year-old study by Paganini-Hill and Henderson (1996) was not a randomized trial and used death certificates to ascertain Alzheimer’s disease. 15

 Death certificates are not accurate enough to determine dementia, and since this was not a randomized clinical trial, it did not statistically control for other differences between the women who were reported as having dementia and those who did not.  A study focused on APOE4 carriers, which is a group at extremely high genetic risk for dementia, and only 29 of whom had used hormone therapy. 16 That study is not generalizable to most women because it focused on a small number of women, all of whom were more likely to develop dementia than the general population of women.

The Bottom Line

The risks and benefits of hormone therapy depend on the woman involved. It is important to take into account the research, but since the risks vary so much, a major issue is that the only proven benefits are reducing unpleasant symptoms of menopause and the temporary benefit of reducing the chance of developing osteoporosis. There are many safe ways to cope with hot flashes, and numerous studies show that women on a placebo often report their hot flashes have been cut almost in half, indicating the importance of mind over matter.  Low-dose estrogen cream is safer than hormone pills for vaginal symptoms. Osteoporosis can often be prevented with diet and exercise.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.

References:

  1. Jin J. Hormone therapy for primary prevention of chronic conditions in postmenopausal women. JAMA. 2017;318(22):2265-.
  2. Writing Group for the Women’s Health Initiative Investigators, Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-33.
  3. Craig MC, Maki PM, Murphy DG. The Women’s Health Initiative Memory Study: findings and implications for treatment. The Lancet Neurology. 2005;4(3):190-4.
  4. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701-12.
  5. Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA. The decrease in breast-cancer incidence in 2003 in the United States. New England Journal of Medicine. 2007;356(16):1670-4.
  6. Katalinic A, Rawal R. Decline in breast cancer incidence after decrease in utilisation of hormone replacement therapy. Breast Cancer Research and Treatment. 2008;107(3):427-30.
  7. Colditz GA. Decline in breast cancer incidence due to removal of promoter: combination estrogen plus progestin. Breast Cancer Research. 2007;9(4):1-3.
  8. Poggio F, Del Mastro L, Bruzzone M, Ceppi M, Razeti MG, Fregatti P, Ruelle T, Pronzato P, Massarotti C, Franzoi MA, Lambertini M. Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Research and Treatment. 2021:1-7.
  9. O’Brien, K. M., House, M. G., Goldberg, M., Jones, M. E., Weinberg, C. R., de Gonzalez, A. B., Bertrand, K. A., Blot, W. J., DeHart, J. C., Couch, F. J., Garcia-Closas, M., Giles, G. G., Kirsh, V. A., Kitahara, C. M., Koh, W. P., Park, H. L., Milne, R. L., Palmer, J. R., Patel, A. V., Rohan, T. E., … Sandler, D. P. (2025). Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group. The Lancet. Oncology, 26(7), 911–923. https://doi.org/10.1016/S1470-2045(25)00211-6
  10. Harman SM, Black DM, Naftolin F, Brinton EA, Budoff MJ, Cedars MI, Hopkins PN, Lobo RA, Manson JE, Merriam GR, Miller VM. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Annals of Internal Medicine. 2014;161(4):249-60.
  11. Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, Brinton EA, Cedars MI, Lobo RA, Merriam GR, Neal-Perry G. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS–cognitive and affective study. PLoS Medicine. 2015;12(6):e1001833.
  12. Manson, J. E., Crandall, C. J., Rossouw, J. E., Chlebowski, R. T., Anderson, G. L., Stefanick, M. L., Aragaki, A. K., Cauley, J. A., Wells, G. L., LaCroix, A. Z., Thomson, C. A., Neuhouser, M. L., Van Horn, L., Kooperberg, C., Howard, B. V., Tinker, L. F., Wactawski-Wende, J., Shumaker, S. A., & Prentice, R. L. (2024). The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review. JAMA, 331(20), 1748–1760. https://doi.org/10.1001/jama.2024.6542
  13. Boardman, H. M., Hartley, L., Eisinga, A., Main, C., Roqué i Figuls, M., Bonfill Cosp, X., Gabriel Sanchez, R., & Knight, B. (2015). Hormone therapy for preventing cardiovascular disease in post-menopausal women. The Cochrane database of systematic reviews, 2015(3), CD002229. https://doi.org/10.1002/14651858.CD002229.pub4
  14. Simpkins, J. W., Singh, M., Brock, C., & Etgen, A. M. (2012). Neuroprotection and estrogen receptors. Neuroendocrinology, 96(2), 119–130. https://doi.org/10.1159/000338409
  15. Paganini-Hill, A., & Henderson, V. W. (1996). Estrogen replacement therapy and risk of Alzheimer disease. Archives of internal medicine, 156(19), 2213–2217.
  16. Saleh, R. N. M., Hornberger, M., Ritchie, C. W., & Minihane, A. M. (2023). Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimer’s research & therapy, 15(1), 10. https://doi.org/10.1186/s13195-022-01121-5