- Sarah Millard, Medically reviewed by Luke Wright, PharmD
- Jul 9
- 5 min read
HRT and the FDA: what changed and why
Have you heard? The United States Food and Drug Administration has begun approving significant changes to the labeling of menopausal hormone therapy (HRT).
On February 12, 2026, the FDA approved updated labeling for the first six products. The revised labels remove risk statements related to cardiovascular disease, breast cancer, and probable dementia from the boxed warning.
These updates prompt patients and providers to investigate the decisions' credibility. Breaking down the science of yesterday and the reality of HRT today will help us better understand this long-awaited initiative.
The science of yesterday
Before the 21st century, hormone therapy was an ongoing subject of study in research laboratories and a first-line treatment option prescribed by clinicians.
In 2002, a Women's Health Initiative (WHI) report claimed harmful effects from HRT, specifically the combination of the synthetic hormones conjugated equine estrogen and medroxyprogesterone acetate.
As a result, the FDA issued a boxed warning, its strongest safety warning, on all estrogen-containing menopausal hormone therapies. The aftermath? HRT prescription rates plummeted and patient use rapidly declined.
The report's details have been refuted since publication, with misreporting of nonsignificant results, misinterpretation of data, and fundamental selection bias among the contributing issues. The study is now understood to be flawed and failed.
The FDA panel
After over 20 years of analysis, research, and advocacy by scientists, medical doctors, and medical institutions, the FDA assembled the "FDA Expert Panel on Menopause and Hormone Replacement Therapy for Women." In July 2025, the expert panelists met to address the 2002 WHI report and discuss the benefits and risks of HRT. On November 10, 2025, the FDA announced its decision to reverse HRT boxed warning labeling, helping to end the stigma associated with menopausal hormone therapy.
FDA Expert Panel on Menopause and Hormone Replacement Therapy for Women
Roberta Diaz Brinton, PhD
Director, Center for Innovation in Brain Science
Regents Professor, Departments of Pharmacology and Neurology
College of Medicine - Tucson, University of Arizona
Kelly Casperson, MD
Board Certified Urologist
Expert and Advocate for Sexuality and Hormones
Heather Hirsch, MD, MS, NCMP
Board Certified Internist
Founder and CEO, Health by Heather Hirsch MD Collaborative
Howard N. Hodis, MD
Harry J. Bauer and Dorothy Bauer Rawlins Professor of Cardiology
Professor of Medicine and Population and Public Health Sciences
Professor of Molecular Pharmacology and Toxicology
Director, Atherosclerosis Research Unit
Division of Cardiovascular Medicine
Keck School of Medicine
University of Southern California
Barbara Levy, MD, FACOG, FACS, MSCP
Clinical Professor, Obstetrics and Gynecology
The George Washington University School of Medicine and Health Sciences
Voluntary Clinical Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences
University of California, San Diego Health Sciences
Chief Medical Officer, Visana Health
JoAnn E. Mason, MD, DrPH, MACP
Chief, Division of Preventive Medicine
Brigham and Women's Hospital
Professor of Medicine and the Michael and Lee Bell Professor of Women's Health
Harvard Medical School
Mary Jane Minkin, MD
Clinical Professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences
Yale University School of Medicine
JoAnn V. Pinkerton, MD, MSCP, FACOG
Professor of Obstetrics and Gynecology
Division Director Midlife Health
The University of Virginia Health System
Past President and Emeritus Executive Director, The Menopause Society
Chair 2017 NAMS PS on Hormone Therapy
Rachel S. Rubin, MD
Urologist and Sexual Medicine Specialist
Assistant Clinical Professor in Urology and Georgetown University Hospital
Phillip Sarrel, MD
Professor Emeritus of Obstetrics, Gynecology, and Reproductive Sciences and Psychiatry
Yale School of Medicine
James A. Simon, MD, CCD, NCMP, IF
Clinical Professor
George Washington University
Founder and Medical Director, IntimMedicine Specialists
Vonda Wright, MD, MS
Orthopedic Surgeon
Associate Professor of Orthopedic Surgery
University of Central Florida
Founder & CEO - Precision Longevity
What we know about hormone health today
Is menopausal hormone therapy safe?
Today, proteomics studies, advanced technologies such as liquid chromatography tandem mass spectrometry, and other analytical techniques and instruments, allow researchers to explore and understand health conditions, assess and develop drugs and treatments, and identify biomarkers that help diagnose diseases. So, is menopausal hormone therapy safe today? Here's what we know:
1. Menopause accelerates the risk of diseases
In 2020, the American Heart Association published a scientific statement regarding the relationship between menopause and cardiovascular disease (CVD), the leading cause of death for women. As it turns out, the risk for CVD increases during menopause due to changes in the body, particularly the decrease in estrogen. The symptoms of menopause, such as hot flashes, poor sleep, and depression, are linked to increased CVD risk as well. Additionally, the decline in estrogen levels experienced during menopause is a significant contributor to the increased risk of osteoporosis and poor bone health, diabetes, and cognitive decline.
2. Timing is everything
The average age of the participants of the WHI study was 12+ years after menopause. The Critical Window Hypothesis, popularly known as the Timing Hypothesis, states that HRT should be prescribed under the age of ~60 and within ~10 years of menopause.
Here's why: when estrogen declines, the body compensates by increasing the number of receptors the estrogen binds to. However, the number of estrogen receptors decreases in response to the permanently low estrogen levels seen during menopause and vascular aging. When you start HRT during the recommended time frame, when estrogen receptor levels are relatively high, then HRT has something to bind to. If you start HRT later in life, when estrogen receptor levels are permanently low, then estrogen has nothing to bind to, which can lead to health complications and adverse outcomes.
3. Formulation and route matter
The molecular roles, binding actions, and downstream effects of hormones differ from one to another, but the WHI study did not study every hormone currently available. The researchers primarily evaluated oral conjugated equine estrogens (CEE), either alone or combined with medroxyprogesterone acetate. Meaning the study analyzed an entirely different compound from a different organism than the ones used in our current standard of care.
Today, HRT may involve different estrogens, progestogens, doses, combinations, and delivery systems, including oral tablets, transdermal patches, gels, spray, vaginal products, and other dosage forms.
4. Menopausal hormone therapy has benefits
HRT can help manage menopausal symptoms like night sweats, joint pain, and vaginal dryness, along with hot flashes and sleep disturbances, which contribute to an increased risk of CVD.
There is a compelling argument for estrogens' neuroprotective effects on cognitive function and decline when initiated before the age of 65. Interestingly, a study published in the American Journal of Primatology found that visuospatial attention significantly improved after 1 month of estrogen therapy in monkeys with surgically removed ovaries and remained improved throughout the 14-month study.
Additionally, in patients with a uterus who use systemic estrogen, an appropriate progestogen is generally included to protect the endometrium and may help to improve sleep, stabilize mood, and protect bone health and strength.
The future of menopausal hormone therapy
The February 2026 approvals are an initial step. Unfortunately, the 2003 FDA boxed warning decision continues to have real-world consequences. As we educate ourselves and dismantle the misconceptions associated with HRT, stigma will decrease and access to the treatment option will improve. By understanding HRT's past, we can better equip ourselves with the knowledge and tools to improve longevity and overall well-being today.
Esatto is committed to better health outcomes through evidence-based science and safe, effective treatment options.