Perimenopause often begins years before a woman reaches menopause, with fluctuating hormone levels and declining estrogen eventually giving rise to hot flashes, sleep difficulties, and mood changes. Unfortunately, many women do not recognize this transition until symptoms appear, which can be years into the process. This leaves them struggling to navigate significant physiological changes that impact every aspect of daily life with limited context or preparation. Additionally, decades of gaps in women’s health research and changing interpretations of evidence have left numerous questions about hormone replacement therapy (HRT) for perimenopause and menopause unanswered.
In this article, we examine HRT for perimenopause as a treatment option to help women manage unwelcome symptoms. We draw on current research to explain how hormone replacement therapy works, why the need for more clinical research remains, evidence-backed potential benefits of HRT, and common persisting myths requiring closer scrutiny.
Are you a clinical researcher or health professional in Virginia? Join Virginia Coordinated Clinical Research Network (VCCRN) for our September 9th Discovery Session to help strengthen statewide clinical research partnerships. Reach out to info@vccrn.org for more information on this topic and future discussions.
Key Takeaways:
- Hormone replacement therapy for perimenopause and menopause can help relieve symptoms such as hot flashes, vaginal issues, and mood changes.
- The benefits and risks of HRT depend on factors such as age, timing, formulation, route, and medical history.
- Longstanding concerns about HRT have been influenced by findings from earlier research and broad warnings that have since been reevaluated.
- Continued menopause research is needed to address unanswered questions and support more informed treatment decisions.
What Is HRT?
HRT, or hormone replacement therapy, is a medical treatment that uses estrogen or estrogen with progestogen to supplement hormones as ovarian hormone production changes during the transition to menopause. Sometimes called menopausal hormone therapy (MHT) or simply hormone therapy (HT), HRT aims to relieve the uncomfortable symptoms caused by declining hormones during perimenopause and menopause.
Medical professionals often recommend HRT to help treat common symptoms of reduced estrogen levels, including:
- Hot flashes
- Night sweats
- Sleep disturbances
- Vaginal dryness, itching, or burning
- Painful sex
- Urinary urgency or frequent urinary infections
- Bladder leakage
- Mood swings including irritability
- Mild depression or anxiety
- Brain fog or trouble focusing
Understanding these symptoms is the first step, but how HRT is administered depends largely on which specific issues you’re looking to address.
Systemic and Local Hormone Therapy
Hormone therapy can be delivered systemically throughout the body or locally to vaginal tissues, depending on a woman’s symptoms and treatment needs.
- Whole-Body Hormone Therapy: Also called systemic therapy, this treatment delivers hormones directly into the bloodstream so they can travel throughout the body. Depending on formulation, whole-body hormone therapy may be available as a pill, ring, patch, gel, cream, or spray to help relieve symptoms like hot flashes and night sweats.
- Low-Dose Vaginal Estrogen Therapy: This approach administers a low dose of estrogen directly to vaginal tissues via a cream, tablet, or ring. Because it offers minimal systemic absorption, it’s generally used to treat local vaginal and urinary symptoms such as vaginal dryness and discomfort.
The optimal therapy depends on factors such as whether a woman has a uterus, her symptoms, and her individual health history. Because there can be risks involved, women interested in HRT should discuss symptoms with their healthcare provider to determine whether HRT is the right treatment option.
Growing Need for Menopause Clinical Research
Perimenopause and menopause research and education have been underfunded for decades. This has made it difficult for healthcare providers to recommend effective treatment options, given the limited data on menopausal research, and even harder for women to educate themselves on up–to-date menopause literature.
A 2025 survey of U.S. women led by researchers from the University of Virginia (UVA) and the Flo App found that, of the 4,624 respondents, only about 21% of women consulted a medical professional about perimenopause or menopause. The highest age group for consultations were women aged 56 and older, comprising just over 50% of consultations.
Additionally, of those who sought a consultation, about 70% of women were told they were already experiencing perimenopause, despite the fact that current HRT literature suggests HRT is most effective and safe when taken within the first 10 years of menopause before age 60. Women previously considered too young to show perimenopausal symptoms reported “moderate” to “severe” on the Menopause Rating Scale (MRS) on the survey, including about 55% of women aged 30–35 and about 64% for women aged 36–40.
While the survey helps researchers plot the trajectory of perimenopausal symptoms in younger women, it also highlights a gap in understanding how to treat women approaching menopause. Further clinical research would turn unresolved healthcare questions into evidence to inform safer, more effective treatments.
Virginia clinical researchers are pushing for more research with active trials on the efficacy of HRT for perimenopausal women. The VCCRN September 9 Discovery Session will provide an opportunity for clinical researchers and healthcare providers to discuss these issues and exchange insights. The upcoming session will be led by Jennifer Parker, APRN-CNM, a board-certified nurse-midwife with Bon Secours Richmond OB/GYN in Virginia.
When Should Women Consider HRT for Perimenopause?
Current guidance describes a favorable benefit-risk ratio for women who are younger than 60 or within 10 years of menopause onset. This means women don’t need to wait until periods stop completely to discuss HRT. The appropriate timing depends on symptoms, health history, treatment goals, and individual risk factors.
One challenge with determining the right time to begin HRT is that perimenopause itself is hard to identify.
While the average age women start menopause is 52, perimenopause may begin as early as the mid-30s and as late as the mid-50s. UVA’s survey found that psychological symptoms typically manifested long before physical symptoms, both of which could often mirror other conditions. As a result, women may experience perimenopause without realizing the root cause.
More clinical research is necessary to address this gap in understanding and identifying HRT timelines.
5 Potential Benefits of HRT for Menopause and Perimenopause
HRT offers several potential health benefits for women experiencing painful or uncomfortable menopause or perimenopause symptoms.
1. Relief for Hot Flashes and Night Sweats
Up to three in four women experience hot flashes during menopause, making it the most common symptom. Women typically experience hot flashes as sudden and intense feelings of heat in the face, neck, and upper chest that are often accompanied by rapid heartbeat and sweating. Hot flashes and night sweats may continue for up to 14 years after menopause, but occur most frequently in the years before and after a woman’s period stops.
Research suggests that hot flashes and night sweats occur when decreasing estrogen levels cause the hypothalamus to respond to small shifts in body temperature. HRT helps balance estrogen levels, reducing discomfort caused by hot flashes.
2. Vaginal Health and Comfort
Declining estrogen levels can cause vaginal tissues to become drier and less elastic, leading to issues like itching, burning, and pain with intercourse. Both systemic and local estrogen therapy can relieve vaginal symptoms. Because vaginal estrogen delivers a low dose of hormones directly to the vaginal tissue, local therapy may be the more appropriate treatment for symptoms limited to the vaginal area.
3. Improved Genitourinary Symptoms
Genitourinary symptoms affect the vagina, bladder, and urethra. Unwelcome leakage, the strong urge to urinate often, and recurrent urinary tract infections often become increasingly frequent as estrogen levels decline during menopause.
A 2025 Menopause Society study involving over 3,000 women found that bladder health naturally declines with age, but low-dose hormone therapy is associated with improvements in genitourinary symptoms and reduced UTIs. In postmenopausal women, however, systemic HRT showed mixed effects and was linked to higher rates of incontinence. Researchers concluded that more research is needed to understand the complex effects of hormone therapy on bladder health.
4. Bone Density Protection
Declining estrogen levels also accelerate bone loss during the transition to menopause. Several studies have shown that women lose an average of 2.1–2.5% of lumbar spine density annually during phases of rapid bone loss. 80% of the 10 million Americans living with osteoporosis (8 million) are female, and nearly 1 in 2 women over 50 will suffer an osteoporosis-related fracture.
Starting HRT during the menopausal transition could reduce the risk of bone fractures by as much as 50–60%, with systemic estrogen therapy helping to prevent osteoporosis, or bone-thinning disease, as well as reduce fracture risk in some patients. However, further research could help clarify how age, treatment duration, and other personal risk factors impact the relationship between long-term bone health and HRT.
5. Mental Health Support
Many women experience changes in sleep and emotional well-being as they enter perimenopause. Common symptoms like low mood, irritability, and trouble concentrating are largely influenced by hormonal fluctuations and the vasomotor symptoms and sleep disruptions they cause.
Clinical trials have demonstrated that estradiol can provide short-term antidepressant effects in perimenopausal women, but how estrogen influences mood disorders during perimenopause remains unclear. Hormone therapy has also shown promise for reducing sleep difficulties that can impact mental health and often accompany menopause.
Mood changes require careful evaluation, so women experiencing significant or persistent emotional shifts should discuss their symptoms with a healthcare professional. They can help determine whether HRT, mental health treatment, a combined approach, or another option is the most appropriate treatment path.
Reevaluating the Science Behind HRT
Myths about HRT have persisted for decades, largely due to how findings from the 2002 Women’s Health Initiative (WHI) were interpreted and communicated. This study reported that women who took a specific type of estrogen and a synthetic progestin medication for over five years experienced increased risk of breast cancer, heart disease, and stroke. These findings generated widespread anxiety among patients and clinicians, but the study has undergone significant reevaluation in recent years.
HRT requires careful clinical evaluation and is not entirely without risk. However, current clinical evidence supports hormone therapy as an effective treatment for menopause-related symptoms when initiated in the appropriate clinical window.
5 Common Myths About HRT Risks
Myth #1: HRT Significantly Increases Breast Cancer Risk
Fact: Combined estrogen-progestin therapy is associated with a small increase in breast cancer risk. However, risk varies depending on the type of hormone therapy, duration of use, and individual factors. Additionally, estrogen-alone therapy (for women without a uterus) is associated with lower breast cancer risk and lower breast cancer mortality compared with placebo, based on a 20-year follow-up of a randomized trial.
Myth #2: HRT Increases Cardiovascular Risk
Fact: Modern data links HRT for early perimenopause with lower cardiovascular risk when started at the optimal time. The belief that hormone therapy damages cardiovascular health stems largely from the WHI study, in which 70% of study participants were over age 60. These women started HRT over a decade past menopause, which is not currently recommended, and took only one type of combined estrogen and synthetic progestin, leading to results not representative of HRT as a whole.
Later analyses have shown that age and timing are important factors when evaluating cardiovascular risks and benefits associated with HRT. Additionally, starting systemic HRT within 10 years of menopause onset, or before age 60, has been linked to reduced risk of cardiovascular diseases.
Myth #3: HRT Causes Cognitive Decline
Fact: The claim that HRT causes cognitive decline oversimplifies a body of evidence that actually depends heavily on a woman’s age and how early treatment begins. A 2002 Women’s Health Initiative Memory Study (WHIMS) found that women aged 65 and older who took certain hormone therapy regimens had an increased risk of dementia, but these findings came from women who began treatment later in life. Therefore, they should not be automatically applied to women starting hormone therapy around menopause.
More recent research offers a more encouraging picture: a 2023 study using data from the European Prevention of Alzheimer’s Dementia cohort found that hormone therapy use during the menopausal transition was associated with improved cognition and larger brain volumes in women at elevated genetic risk for Alzheimer’s. This suggests that when hormone therapy is started may matter more than whether it’s used at all. However, more research could help clinicians better understand how age and treatment timing affect cognitive health during perimenopause and menopause.
Myth #4: HRT Causes Weight Gain
Fact: Midlife and menopause are associated with changes in body composition, metabolism, and weight, but research does not support the idea that HRT inevitably causes weight gain. Instead, studies have found that hormone therapy may influence body composition and even limit the amount of weight gained during the early postmenopausal years.
Myth #5: HRT Isn’t as Safe as Natural Hormones
Fact: FDA-approved hormone therapy is held to a higher safety standard than “natural” alternatives, not a lower one. Many women turn to custom-compounded plant-derived hormones assuming they’re safer, but these products may lack the safety monitoring and standardized quality control required of approved options. FDA-approved therapies undergo rigorous evaluation for safety, effectiveness, and quality, with standardized dosing and manufacturing requirements.
Research on HRT for Perimenopause: Closing Gaps in Women’s Health
Collective knowledge around HRT continues to evolve, but continued research remains essential for understanding how perimenopause and menopause treatment can be used safely and effectively. Evidence supporting HRT shows that hormone therapy may help relieve painful or uncomfortable symptoms, prevent bone loss, and improve quality of life for women who are good candidates for treatment. Still, treatment decisions require careful evaluation and consideration of individual risk.
Research into HRT for perimenopause can help clinical researchers and healthcare professionals address unanswered questions and build stronger evidence to guide patient conversations and treatment decisions. VCCRN’s Discovery Sessions offer a forum for industry leaders to share perspectives and uncover opportunities to further women’s health research throughout Virginia.
Join VCCRN’s next Discovery Session to identify actionable solutions that drive patient care in Virginia. Submit a topic or speaker for a future Discovery Session by reaching out to info@vccrn.org.