TL;DR:
Is hormone replacement therapy safe? For many women, the answer is more nuanced than outdated research once suggested. When started at the right time and tailored to the individual, HRT can safely relieve symptoms like hot flashes, brain fog, sleep disruption, and mood changes.
Because risks and benefits vary, the best approach is a personalized, whole-body evaluation that considers your brain, hormones, and overall health.
Medically reviewed by Kandace Licciardi, MD, Medical Director, Amen Clinics
Hot flashes that wake you in the middle of the night. Brain fog that makes it hard to find the right word. Mood swings, anxiety, or irritability that feel unfamiliar or hard to control.
For many women, these symptoms of perimenopause and menopause can be disruptive, frustrating, and even alarming. But this once-overlooked stage of life is finally getting the attention it deserves, and more women are feeling empowered to seek answers and find solutions that help them feel like themselves again.
One option that often comes up is hormone replacement therapy (HRT), also known as hormone therapy (HT).
But with decades of conflicting information, many still wonder: Is HRT safe?
Much of the concern around HRT can be traced back to the 2002 Women’s Health Initiative (WHI) study, which reported a potential link between HRT and increased risks of breast cancer, heart disease, and stroke. Following these findings, HRT use declined sharply.
Today, however, medical experts acknowledge the WHI study was flawed and believe the warnings were overstated. Indeed, both research on HRT and treatment options have evolved.
It is now accepted that HRT can be safe and effective for many women when used appropriately. Its safety depends on factors such as age, health history, timing, and the specific type of therapy used. That means many women struggling with symptoms like hot flashes and disrupted sleep, brain fog, anxiety, discomfort during sex, and low mood could find relief with HRT.
Understanding what’s true and what’s outdated is key.
In this blog, you’ll learn about the risks and benefits of HRT, how it may affect brain health and mood, and why a personalized, whole-body approach is essential during this stage of life.
Experts increasingly believe that HRT can be safe for many women when prescribed appropriately. However, its safety depends on factors such as age and health history, as well as the HRT’s timing and formulation.
For most women, experts agree that HRT can help manage moderate to severe menopause symptoms such as hot flashes when initiated within 10 years of onset of menopause or under age 60.
One of the critiques lodged against the WHI study was that the subjects studied were older (an average age of 63, or post-menopausal).
Experts now advise women to work closely with a qualified healthcare professional to weigh your individual benefits and risks based on your medical history, age, and symptoms.
HRT safety varies based on several factors. these include:
In the early 2000s, the WHI findings created widespread concern. According to a report from the Yale School of Medicine, nearly 15 million U.S. women were taking an estrogen-based menopausal treatment in the 1990s. Within six months of the WHI study being published, HRT usage declined by nearly 50 percent.
However, research has since revealed that the safety and risks of HRT vary by factors like age, formulation, and timing. In light of these findings, the U.S. Food and Drug Administration (FDA) recently clarified labeling changes regarding the benefit-risk considerations of HRT in an official statement.
In 2025, the FDA removed warnings that linked HRT products with cardiovascular diseases, breast cancer, and probable dementia, as well as endometrial cancer (except in systemic estrogen-alone drugs). It also removed a previous dementia-related warning while adding that HRT is suitable for moderate to severe symptoms in women under 60 years old, or fewer than 10 years since menopause.
HRT can offer relief for women who are experiencing perimenopause and menopause symptoms, including sleep disruption from hot flashes and night sweats, cognitive problems, pain during sex, and mood issues.
The potential documented benefits of HRT include:
While HRT does not prevent or cure any disease, it can also offer positive long-term effects. A recent article in JAMA pointed to evidence linking hormone therapy, initiated within a decade of the onset of perimenopause, with various health benefits, including:
There are many indirect benefits that come from HRT as well. When hot flashes and night sweats are reduced, sleep is not disrupted. Restful sleep is essential to emotional regulation and good decision making. There’s a ripple positive effect that happens when sleep is improved.
Additionally, sexual intimacy and satisfaction are important aspects of well-being for women. In perimenopause and menopause, women may experience any of the following symptoms that can have a dramatic negative impact on their sex lives:
In one study, more than 91 percent of the participating menopausal women experienced sexual dysfunction, and this was found to negatively impact their marriages.
Research shows that there are types of HRT that can help to increase libido in menopausal women. In other studies, HRT has been shown to help with vaginal dryness, thinning, and related pain during intercourse. These are significant benefits for a woman’s overall mental well-being.
While HRT is associated with easing symptoms around perimenopause and menopause, many still ask: Is HRT safe for women?
Like with any medication, there are risks to consider. Some of the possible dangers of HRT include:
On the whole, these risks are very small. Factors such as the timing of treatment (considering a woman’s age as well as years since menopause) are associated with lower risks.
This is true for increased breast cancer risk. It varies based on the type of HRT, duration of use, and age. For example, the risk is generally higher when HRT involves both estrogen and progestogen, or with a longer duration of use, according to the Breast Cancer Research Foundation.
Of course, individual risk factors (such as smoking, family history, and clotting disorders) should also be taken into consideration before starting HRT.
Experts agree that, when deciding to take HRT, it’s important to weigh both risks and benefits.
That said, HRT is generally not recommended for women with a history of breast cancer, endometrial cancer, or other estrogen-dependent cancers. It is also contraindicated for those with active liver disease, stroke, cardiovascular disease, blood clots, or unexplained vaginal bleeding.
As a woman transitions through perimenopause and menopause, reproductive hormone levels, estrogen and progesterone, naturally fluctuate and then drop. Eventually, her ovaries stop releasing eggs and she has her last menstrual period.
Perimenopause takes place over months or years, starting from the first signs and symptoms of menopause. Menopause officially occurs when 12 consecutive months pass without menstruation, after which a woman is considered postmenopausal.
During this menopausal transition, hormonal shifts impact the brain, influencing the prefrontal cortex, hippocampus, hypothalamus, and amygdala. These areas are associated with key functions, including sleep regulation, learning, memory, and temperature regulation.
Estrogen also interacts with serotonin, dopamine, GABA, and brain blood flow. Therefore, in addition to symptoms like hot flashes, women may be more vulnerable to mental health disturbances, as well as sleep disorders. Progesterone, meanwhile, affects calming pathways of the brain and offers neuroprotective benefits, research shows.
During menopausal hormonal shifts, women may experience irritability or effects that mimic:
As menopause takes place, many of these symptoms are simply a byproduct of changing hormones and can be stabilized.
Related: Reproductive Mental Health: PMS, Perimenopause, and More
Considering hormones’ effects on the brain, it’s no surprise that the hormonal changes around menopause and perimenopause can take a toll on mental health. For example, they may trigger mood shifts, as well as sleep disruption (which, itself, can negatively affect mood and increase anxious symptoms).
What shows up as depression and anxiety can indeed be symptoms of underlying hormonal changes.
A 2023 study pointed to the risk of thyroid dysfunction in perimenopausal and postmenopausal women, which can also trigger mood-related symptoms. The researchers noted that thyroid dysfunction is common in women but can be overlooked due to overlapping symptoms during menopause, making diagnosis more difficult.
But it is not just anxiety and depression.
Changes in cortisol levels are also associated with menopause-related hormonal fluctuations. According to a 2025 study, elevated cortisol in midlife is “correlated with increased amyloid deposition, specifically in post-menopausal women.” Therefore, researchers concluded that post-menopausal women with high midlife cortisol have an increased risk of Alzheimer’s.
With hormonal changes impacting brain and mental health in so many ways, it’s important to rule out medical causes for symptoms before making any psychiatric diagnosis.
If you are in perimenopause or menopause and are struggling with mental health symptoms, mood, memory issues, brain fog, or cognitive issues, a comprehensive evaluation at Amen Clinics may help identify what’s underlying your symptoms.
This can be very helpful when there are multiple factors influencing symptoms such as hormonal changes, an existing mental health condition, poor sleep, or stress.
We take a whole-body approach to mental health, using precision medicine. Our clinicians look at the brain and the entire person, not just symptoms. We use brain SPECT imaging as part of our comprehensive evaluation to determine the underlying brain blood flow and activity patterns behind symptom clusters.
Additionally, our clinicians take time to get to know you by getting a detailed personal history, as well as administering neuropsychological testing.
This combined data is analyzed and with the insights gained, our clinicians develop a tailored treatment plan geared to optimize your brain and body. Practicing holistic psychiatry, they combine cutting-edge neuroscience with natural ways to treat mental health conditions.
A treatment plan may include lifestyle recommendations, like diet, nutrition, exercise, sleep, and relaxation. It may also include therapy or medication, when appropriate. It is designed to address and heal what’s going on in your brain and body that is fueling your symptoms.
In addition to our comprehensive evaluation, for those interested in HRT, Amen Clinics also offers hormone evaluation and replacement therapy.
Our specialists in hormone therapy have a depth of experience in understanding how hormones affect the regulation of the body and brain. Based on your history, age, genetics, potential lab work, and current health status, risks and benefits can be assessed and discussed with you.
If you should decide to go ahead with HRT, our specialists are highly trained in balancing and optimizing hormone levels to restore health and get you back to feeling like yourself again. This can be a monumental relief if you have been struggling with hormone fluctuations during perimenopause and menopause.
At Amen Clinics, we recommend bioidentical hormones, rather than synthetic ones, at individually customized dosages for maximum safety and effectiveness. In some cases, this can be referred to as bioidentical hormone replacement therapy (BHRT).
Our personalized approach to treatment offers more than a “one size fits all” approach. Our clinicians understand that no two people are exactly the same and effective treatment needs to be personalized. And, since our bodies are so sensitive to hormone levels, our doctors order specific lab tests to help gauge the most precise dose for your unique needs.
Related: 7 Tips to Manage Emotional and Physical Menopause Symptoms
Weighing the risks and benefits of HRT, certain populations may be good candidates. You may consider HRT if you:
If you’re considering hormone replacement therapy, consider getting a professional evaluation to evaluate whether it’s right for you.
While HRT can be safe in many cases, some women should use caution and be aware of risks. Factors to consider include:
Again, medical supervision will help you determine if HRT benefits outweigh the risks, or vice vers, so you can make the most informed decision.
Even today, many people are misinformed or confused about HRT. Here are some common myths, as well as the facts that help clarify them:
Clearly, HRT is a nuanced topic, which is why professional evaluation is crucial for women considering this option as they transition through perimenopause and menopause.
Instead, seek a professional evaluation that includes:
Like with any medication, it’s important to weigh an individual’s unique risks and benefits when considering hormone replacement therapy. However, for many women, studies indicate that the benefits can outweigh the risks. This underscores the importance of receiving a thorough and professional evaluation before taking HRT.
In the past, studies raised concerns about HRT among older women. However, research published in 2024 suggests that the risks of HRT beyond age 65 vary, with HRT type, delivery, and dosage all being factors to consider.
As hormone fluctuations affect brain and mental health, some menopausal women may experience depression symptoms. HRT may help reduce or prevent these symptoms and improve mood.
A large U.K. study published in 2024 indicated that hormone therapy might have moderate effects on brain health. These benefits depend on certain factors, including the duration of treatment and a woman’s age.
Before stopping HRT, consult your doctor. Some women continue taking HRT over the long term, while others lower dosage or stop altogether after a certain amount of time. A brain health-focused, whole-body approach, as offered at Amen Clinics, will help you evaluate risks and benefits and make the most informed recommendations about starting, reducing, or stopping HRT.
With research ongoing over decades, experts now believe that HRT can be safe for many women when prescribed thoughtfully.
However, brain health matters when it comes to making decisions about taking hormones, and personalized care leads to better outcomes. Women in perimenopause or menopause who are experiencing persistent mood or cognitive symptoms should seek evaluation.
If you have noticed mood changes, brain fog, or other disruptive menopausal symptoms, consider a comprehensive evaluation that looks at both hormones and brain health. Amen Clinics’ holistic, whole-body approach considers the individual, risks, and benefits to make the most informed treatment recommendations possible regarding hormone replacement therapy.
Menopause-related brain fog, mood changes, anxiety, and other mental health conditions can’t wait. At Amen Clinics, we practice precision medicine—using brain SPECT imaging and comprehensive evaluations to understand what’s really happening in your brain, not just your symptoms.
Our whole-body approach to holistic psychiatry combines cutting-edge neuroscience with natural ways to treat mental health conditions, including targeted nutrition, supplements, lifestyle strategies, therapy, and medications (when necessary). Every treatment plan is personalized to address the root causes of your struggles and support the health of your brain, body, and mind.
Don’t settle for guesswork. You deserve answers—and a plan built specifically for you. Speak with a Brain Health Advisor today at 888-288-9834 or visit our contact page to get started.
About the Reviewer
Kandace Licciardi, MD, Medical Director, Amen Clinics
Dr. Kandace Licciardi is a double board-certified psychiatrist in adult and forensic psychiatry and serves as Medical Director of Amen Clinics. She takes a comprehensive, whole-person approach to care, integrating evidence-based psychiatric treatment with lifestyle, social, and wellness factors. Dr. Licciardi has extensive experience treating depression, anxiety, bipolar disorder, psychotic disorders, and borderline personality disorder, with special expertise in early psychosis intervention. She completed her psychiatry residency at Maimonides Medical Center and her forensic psychiatry fellowship at New York University.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; 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 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321. PMID: 12117397.
https://jamanetwork.com/journals/jama/fullarticle/195120
WHI clinical trial revisit: Imprecise scientific methodology disqualifies the study’s outcomes. Ostrzenski, Adam et al. American Journal of Obstetrics & Gynecology, Volume 193, Issue 5, 1599 – 1604. https://www.ajog.org/article/S0002-9378%2805%2901186-5/fulltext
Yale School of Medicine. After Decades of Misunderstanding, Menopause is Finally Having Its Moment. By Kira Berman. April 14, 2025. https://medicine.yale.edu/news-article/after-decades-of-misunderstanding-menopause-is-finally-having-its-moment/
FDA Requests Labeling Changes Related to Safety Information to Clarify the Benefit/Risk Considerations for Menopausal Hormone Therapies. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations
Makary MA, Nguyen CP, Høeg TB, Tidmarsh GF. Updated Labeling for Menopausal Hormone Therapy. JAMA. 2026;335(2):117–118. doi:10.1001/jama.2025.22259
Yildirim F, Duman NB, Kulakaç Ö. The Effect of Menopause on the Sexual Functions and Marital Adjustment of the Spouses. J Midlife Health. 2023 Jul-Sep;14(3):170-175. doi: 10.4103/jmh.jmh_90_23. Epub 2023 Dec 30. PMID: 38312762; PMCID: PMC10836430.
Scott A, Newson L. Should we be prescribing testosterone to perimenopausal and menopausal women? A guide to prescribing testosterone for women in primary care. Br J Gen Pract. 2020 Mar 26;70(693):203-204. doi: 10.3399/bjgp20X709265. PMID: 32217602; PMCID: PMC7098532.
Tomczyk K, Chmaj-Wierzchowska K, Wszołek K, Wilczak M. New Possibilities for Hormonal Vaginal Treatment in Menopausal Women. J Clin Med. 2023 Jul 18;12(14):4740. doi: 10.3390/jcm12144740. PMID: 37510854; PMCID: PMC10380877.
Breast Cancer Research Foundation website, “Does HRT Increase Your Risk of Breast Cancer?”, Accessed April 3, 2026. https://www.bcrf.org/about-breast-cancer/hrt-breast-cancer-risk/
Guennoun R. Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant. Int J Mol Sci. 2020 Jul 24;21(15):5271. doi: 10.3390/ijms21155271. PMID: 32722286; PMCID: PMC7432434.
Frank-Raue K, Raue F. Thyroid Dysfunction in Periand Postmenopausal Women-Cumulative Risks. Dtsch Arztebl Int. 2023 May 5;120(18):311-316. doi: 10.3238/arztebl.m2023.0069. PMID: 37013812; PMCID: PMC10398375.
Salardini A, Himali JJ, Abdullah MS, et al. Elevated serum cortisol associated with early-detected increase of brain amyloid deposition in Alzheimer’s disease imaging biomarkers among menopausal women: The Framingham Heart Study. Alzheimer’s Dement. 2025;21:e70179. https://doi.org/10.1002/alz.70179
The Menopause Society. Women aged older than 65 years may be able to safely continue taking hormone therapy. April 10, 2024. https://menopause.org/press-releases/women-aged-older-than-65-years-may-be-able-to-safely-continue-taking-hormone-therapy
eLife Sciences Publications: Study highlights complexity of menopausal hormone therapy’s impact on brain health. https://elifesciences.org/for-the-press/2925efa3/study-highlights-complexity-of-menopausal-hormone-therapy-s-impact-on-brain-health
