HRT: Rethinking What We Know About Hormone Therapy
For more than two decades, hormone replacement therapy has carried a reputation that has made many women hesitant to consider it. Following publication of the Women’s Health Initiative in the early 2000s, concerns about breast cancer, cardiovascular disease, stroke, and blood clots became firmly associated with HRT. Subsequent research has provided a more nuanced understanding. HRT is neither universally dangerous nor appropriate for everyone. Age at initiation, time since menopause, hormone formulation, dose, route of administration, and individual health history all influence the balance between benefit and risk. (1,2)
The Study That Changed the HRT Conversation
The Women’s Health Initiative, or WHI, was the largest randomized trial of hormone therapy ever conducted. When findings were released in 2002, reports of increased breast cancer, coronary heart disease, and stroke associated with combined hormone therapy received widespread attention and shaped women’s perceptions of HRT for decades. (1,5)
Several important details, however, were largely lost in the public conversation:
The average participant was 63 years old, and many participants were more than a decade beyond menopause, a very different population from women beginning HRT during perimenopause or early menopause. (5)
The WHI included two hormone therapy trials. Women with a uterus received conjugated equine estrogen combined with medroxyprogesterone acetate, while women who had undergone hysterectomy received conjugated equine estrogen alone. The outcomes were not identical. (5)
The study evaluated specific oral formulations and doses and was not designed to evaluate lower doses, transdermal estrogen, or other hormone formulations commonly used today. (5)
The widely reported 26% relative increase in breast cancer risk with combined therapy represented approximately 8 additional cases per 10,000 women per year. This important distinction between relative and absolute risk received far less attention. (5)
Long term follow up of the estrogen alone trial found lower breast cancer incidence and breast cancer mortality among women who received estrogen alone compared with placebo. (5)
The WHI findings remain important, but more than 20 years of follow up have provided greater context. The findings from specific populations and hormone formulations should not automatically be generalized to every woman or every type of hormone therapy. (5)
Timing Matters
Evidence increasingly supports the importance of when hormone therapy is initiated. Beginning HRT during perimenopause or relatively close to menopause can have a different benefit and risk profile than initiating therapy many years later. Evidence summarized in the literature suggests a more favorable overall profile when therapy is initiated within approximately 10 years of menopause, generally before age 60, in appropriately selected women. (2,3,5)
The SWAN study (Study of Women’s Health Across the Nation) found hormone therapy initiation was associated with a 22% lower risk of cardiovascular events in perimenopausal and recently postmenopausal women with vasomotor symptoms. (6)
The association was strongest when hormone therapy was initiated within 10 years of menopause, further supporting the importance of timing. (6)
These findings do not support using HRT specifically to prevent cardiovascular disease. (6)
Route and formulation matter as well:
Transdermal estrogen bypasses first pass hepatic metabolism and is associated with a lower risk of blood clots and stroke than oral estrogen, particularly at low to moderate doses. (1,3)
Micronized progesterone differs from the synthetic progestins used in some older hormone regimens and may have a more favorable breast, cardiovascular, and metabolic profile. (1,3)
Dose and treatment should be individualized according to symptoms, health history, and treatment goals. (1,2)
From the Menstrual Cycle to Perimenopause
Before menopause, estrogen and progesterone participate in a coordinated hormonal rhythm. During the follicular phase, estrogen rises as ovarian follicles develop. Hormonal signaling then triggers ovulation, followed by the luteal phase when progesterone rises in preparation for a possible pregnancy. If pregnancy does not occur, estrogen and progesterone fall and menstruation begins. (1)
During perimenopause, this predictable rhythm begins to change. Ovarian hormone production becomes increasingly variable, ovulation becomes less predictable, menstrual cycles may change, follicle stimulating hormone (FSH) generally increases, and estradiol eventually declines. This transition commonly begins during a woman’s 40s and may last approximately 4 to 8 years. Symptoms can include hot flashes, night sweats, sleep disturbances, mood changes, and changes in menstrual patterns. (1)
These hormones influence much more than reproduction, which helps explain why the menopausal transition can affect multiple aspects of a woman’s health and quality of life. The experience can also vary considerably from one woman to another.
What Are the Benefits of HRT?
Hormone therapy remains the most effective treatment for moderate to severe vasomotor symptoms associated with menopause and is also effective for genitourinary symptoms. Potential benefits for appropriately selected women include: (1,2)
Reduction in hot flashes and night sweats
Improvement in sleep disturbances related to menopausal symptoms
Relief of vaginal dryness and other genitourinary symptoms
Support for vaginal and urinary tissues
Preservation of bone mineral density and prevention of menopause related bone loss and osteoporosis
Declining estrogen contributes to accelerated bone loss and increased fracture risk, making bone health an important consideration during and after the menopausal transition. (1,2)
What About the Brain?
The relationship between estrogen and brain health continues to be studied. A 2020 meta-analysis, including 21 epidemiological studies, found that women who had used estrogen therapy had approximately 33% lower odds of Alzheimer’s disease and approximately 53% lower odds of Parkinson’s disease compared with nonusers. (4)
These findings show an association, not proof that HRT prevents either disease. The Women’s Health Initiative Memory Study also found increased dementia risk with combined estrogen and progestin therapy among women who began treatment at age 65 or older. (4) Current clinical guidance therefore does not recommend initiating HRT specifically for the prevention or treatment of dementia. (2)
Who May Benefit From the HRT Conversation?
HRT is not necessary or appropriate for every woman, but it may be worth discussing with a qualified medical provider for appropriately selected women experiencing:
Moderate to severe hot flashes and night sweats
Genitourinary syndrome of menopause
Increased risk for osteoporosis or menopause related bone loss
Premature ovarian insufficiency or early menopause
Menopause induced by ovarian surgery or other medical treatment (1,2)
For many healthy, symptomatic women younger than 60 or within approximately 10 years of menopause, the overall benefit and risk profile is generally more favorable than when systemic therapy is first initiated later in life. (1,3,5)
Medical history remains essential. Certain hormone sensitive cancers, unexplained vaginal bleeding, thromboembolic disease, cardiovascular conditions, uncontrolled hypertension, and active liver disease may affect whether systemic HRT is appropriate or require additional evaluation. Women with an intact uterus receiving systemic estrogen also require appropriate endometrial protection with a progestogen. (1,2)
Introducing Women’s Wellness Empowered
Hormones are only one part of women’s health. Nutrition, movement, sleep, stress, metabolic health, cardiovascular health, and bone health all play important roles, and a woman’s needs change throughout the reproductive years, perimenopause, menopause, and beyond.
That whole woman approach is the foundation of Women’s Wellness Empowered, a new Crossroads Apothecary program combining medical care, education, and lifestyle support, including women focused nutrition consulting. Our goal is to help women understand their changing bodies, explore their options, and develop practical strategies to support health at every stage of life.
Join us for the Women’s Wellness Empowered Open House on October 24, 2026, from 1:00 to 3:00 PM at Crossroads Apothecary. Come meet the team, learn about the program, and explore a more comprehensive approach to hormonal health, nutrition, menopause, and healthy aging. You can sign up here: https://docs.google.com/forms/d/e/1FAIpQLSeNv_iaGy7JsP_DMFhB8HfBFfpBubGAEg6GHlZ0O0WTEtH5sg/viewform
Kisha Henry, DCN, MSN - PhD in Nutrition Sciences
References
Yanachkova V, Vasileva Slaveva M, Kostov S, Yordanov A. Reconsidering hormone replacement therapy: current insights on utilisation in premenopausal and menopausal women: an overview. J Clin Med. 2025;14:7156.
Review of clinical practice guidelines for hormone replacement therapy in peri and postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2024;303:294–301.
Cano L. The case for starting HRT early. [Educational handout]. Women’s Wellness Empowered; 2026.
Cano L. Estrogen and the aging brain. [Educational handout]. Women’s Wellness Empowered; 2026.
Cano L. The WHI, reinterpreted: how we misread the study that changed hormone therapy and what 20 years of data actually show. [Educational handout]. Women’s Wellness Empowered; 2026.
Wang Z, Swanson SA, Brooks MM, et al. Menopausal hormone therapy and cardiovascular risk in midlife women with vasomotor symptoms. JAMA Intern Med. Published online September 8, 2026. doi:10.1001/jamainternmed.2026.2922.
