To Replace Or Not To Replace? Bio-Identical Hormone Replacement Therapy
Bio-identical hormone replacement therapy, or BHRT, is used to replace estrogen and progesterone to treat menopause symptoms.
In this blog, you will learn:
- What is BHRT
- What are the benefits & risks of HRT
- When & for how long should HRT be used
We will use the abbreviation HRT to refer to hormone replacement therapy in this blog. Much of the existing research has been done on HRT. We recommend bio-identical hormone replacement therapy and work with bio-identical hormones in our clinic. However, research has been done on HRT so we will use the term HRT in this blog when citing research.
Hormone replacement is used to replace hormone levels that have dropped too low due to the menopausal transition. It typically refers to replacing the hormones estrogen and progesterone which decline as a result of menopause. HRT can also be used to replace testosterone.
HRT is the gold standard treatment for managing menopausal symptoms. Tailored HRT therapies raise hormone levels to more natural levels.
The benefits of HRT are significant. It can reduce menopause symptoms and even all-cause mortality (Colacurci N, 2024). Quality of life can be greatly improved.
HRT + natural strategies is even more effective to manage or even eliminate severe menopause symptoms. Lifestyle approaches, such as diet, herbs & supplements, adequate sleep, and regular exercise are important natural strategies to manage menopausal symptoms (Colacurci N, 2024).
Bio-Identical Hormones
BHRT using bio-identical hormones is different from traditional hormone replacement therapy. Bio-identical hormones are chemically identical to those that the body produces. They are considered safer because they are chemically identical to natural hormones. They are derived from plants, animals or chemical synthesis.
Estrogen, progesterone and testosterone are the most commonly replicated hormones used for hormone replacement. Bio-identical hormones come in pills, patches, creams, gels and injections.
Mechanism of Action
The fall in estrogen levels during menopause can cause many symptoms like vasomotor issues (hot flashes & night sweats), neurodegenerative symptoms (cognitive decline or brain fog), increased osteoporosis risk & bone fractures, weight gain, poor sleep, worse metabolic health and increased cardiovascular risk.
To correct low estrogen, we can use HRT. HRT with estrogen is thought to affect the hypothalamus via a signaling pathway related to reproductive and thermoregulatory responses (Harper-Harrison, 2025). This pathway contributes to regulating body temperature. By modulating this pathway, estrogen therapy can improve vasomotor and other symptoms of menopause (Harper-Harrison, 2025).
Types of BHRT
A woman with an intact uterus should take estrogen + progesterone. Estrogen therapy alone will cause the endometrial lining to grow (Harper-Harrison, 2025). This could potentially lead to endometrial hyperplasia (pre-cancer) or malignancy (cancerous cells). Progestogen with estrogen protects the endometrium and prevents the lining from proliferating abnormally (Harper-Harrison, 2025). If a woman has had a hysterectomy, then progesterone is unnecessary (Harper-Harrison, 2025).
It is important to work with your Functional Medicine doctor to determine what hormone replacement formulation will work best for you.
Out-of-Date Thinking on HRT
Research from 2002 distorted perceived risks of HRT and the HRT benefit/ risk profile (Langer R, 2021). This research was incorrectly interpreted, which led to unreasonable concerns about the safety of HRT. Doctors avoided using HRT clinically. Now we have newer research and we know that the benefits greatly outweigh the slight risks.
Issues with the Women’s Health Initiative research in 2002: (Gersh F, 2024)
- Older inferior types of hormone formulations were used in the WHI. Today there are newer and better types of hormone formulations.
- The WHI included many women who started HRT too late. We now know that the timing of starting HRT is extremely important and should not be started too late.
- Women with pre-existing medical conditions were in the WHI. This skews results and made HRT look higher risk than it actually is.
- Estrogen dosing was very low in the WHI. Too low dose E can result in HRT not working very well. The right dose and formulation are important to get the benefits of HRT (Gersh F, 2024).
- This study used HRT and not bio-identical HRT. Bio-identical hormones are superior and safer than synthetic hormones.
Current Research on HRT & BHRT
Current research is often not using the same variables. Different studies use different forms of the hormones E and P. Some replace just E; some replace a combined E+P. Most studies are done on synthetic hormones, not bio-identical hormones. Some studies look at HRT only in the short term. Some studies start HRT too late in the menopause transition. There are not enough long-term, placebo-controlled, double-blind studies on bio-identical HRT in peri and menopausal women. These inconsistencies make it challenging to get consistent data on HRT.
Unfortunately, we are unlikely to see long-term, placebo-controlled, double-blind studies on bio-identical HRT conducted. This is because estrogen and progesterone are available as generic drugs. These studies are expensive to do and pharmaceutical companies are not incentivized if they cannot get a patent at the end (Gersh F, 2024).
Despite these issues, HRT can still provide benefits to many women.
What are the Benefits of BHRT?
HRT can improve quality of life, reduce menopause symptoms, protect against heart disease or dementia and improve bone health without causing harm (Gersh F, 2024). HRT improves menopause symptoms like sleep quality, muscle mass maintenance, weight management, mood issues, skin elasticity, vaginal dryness, hair loss, joint pain, metabolic health and quality of life (Harper-Harrison, 2025).
When to use BHRT is important. HRT is safe when started at the right time; early in menopause (Gersh F, 2024).
Vasomotor Symptoms (Hot Flashes & Night Sweats)
Vasomotor symptoms are hot flashes and night sweats. They can be debilitating (The Menopause Society, 2024):
- 70% to 80% of women experience vasomotor symptoms that worsen quality of life and productivity (Nappi R, 2021).
- Women with moderate-to-severe hot flashes/ night sweats may have sleep problems, fatigue, anxiety, depression. These issues can affect the ability to work and fulfill daily responsibilities.
- Hot flashes last for 7-11 years (Nappi R, 2021).
- 40% of women in their 60s and 10- 15% in their 70s continue to have hot flashes (The Menopause Society, 2024).
Hormone therapy is the most proven and effective treatment for managing hot flashes and vaginal dryness (The Menopause Society, 2024).
- Estrogen-only and estrogen + progesterone HRT significantly reduce vasomotor symptoms by 85% (Harper-Harrison, 2025).
- Resolving hot flashes improves quality of life and sleep quality (Harper-Harrison, 2025).
- HRT should be started early for hot flashes and painful intercourse. There is no maximum length of treatment time (Zouboulis CC, 2022).
Cardiovascular Disease (CVD) Risk
Cardiovascular disease (heart disease & stroke) is the most common cause of death in women worldwide. The risk of CVD increases after menopause.
HRT, started at the right time early in the menopause transition, reduces potential cardiovascular risks. HRT has CVD benefits, with a lowered incidence of atherosclerosis and CVD events (Gersh F, 2024).
In menopause, the drop in estrogen causes several risk factors for CVD to increase. Visceral fat increases, glucose tolerance decreases, hypertension develops and cholesterol increases. These can lead to insulin resistance, overweight, pre-diabetes/diabetes, high cholesterol, high blood pressure and other factors that increase CVD risk (Gersh F, 2024).
- Estrogen and progesterone support the heart and vascular structures (Gersh F, 2024). Estrogen helps protect the cardiovascular system, maintain blood vessel flexibility and regulates cholesterol.
- Falling estrogen can cause an increase in LDL cholesterol.
HRT started too late in post menopause may increase CVD risk.
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Bone Health & Bone Mineral Density (BMD)
HRT can help improve bone mineral density and prevent osteoporosis after menopause (Harper-Harrison, 2025).
In research (Sheedy AN, 2023):
- Baseline total hip bone density was highest in women taking HRT. Women who stayed on HRT showed no bone loss after 5 years of HRT.
- Women who discontinued HRT showed the greatest loss in hip bone density.
- Women who never used hormone therapy had some loss of hip bone density.
- Typical physical activity did not markedly affect bone mineral density in any group.
- Women taking HRT for 3 years had a 3.7% increase in total hip BMD, compared with no increase in women not taking HRT (Rozenberg S, 2020).
- In the WHI study there was a 34% decrease in hip and vertebral fractures (Rozenberg S, 2020). There was also a decrease in other osteoporotic-type fractures.
- Over 5.6 years of follow-up, fracture risk for women taking HRT was significantly reduced (Rozenberg S, 2020).
Discontinuing HRT treatment contributes to BMD loss and, over time, becomes similar to never having taken HRT (Rozenberg S, 2020). But the time on HRT is valuable because it delays the start of BMD loss. Delaying BMD loss with HRT helps maintain healthy bone mass over a longer period of time and slows the start of osteoporosis developing (Rozenberg S, 2020).
Muscle Strength
Estrogen is important for skeletal muscle. The drop in estrogen can lead to decreased muscle mass and strength, otherwise known as sarcopenia. Sarcopenia can reduce mobility and quality of life in older people.
Estrogen impacts muscle mass, strength, mitochondrial function and muscle regeneration after injury (Zhang C, 2024). Estrogen is needed for skeletal muscle homeostasis and motor ability.
The exact mechanism is thought to be related to mitochondrial metabolism (Zhang C, 2024):
- Estrogen affects mitochondrial function and homeostasis to offset sarcopenia.
- Lower estrogen is associated with increased expression of atrophy markers.
- Estrogen replacement reduces muscle atrophy.
When HRT is combined with resistance training, women see better muscle and grip strength increases compared to women not taking HRT (Wright VJ, 2024).
Cognition & Dementia
Estrogen supports cognitive function. There is a likely link between menopause and Alzheimer’s disease (AD).
- Over time, 60% of women experience some degree of cognitive impairment (Beltz CR, 2024).
- Postmenopausal women account for 70% of the population affected by AD (Silva GB, 2024).
Estrogen is important for brain metabolism, synaptic plasticity and cognitive function. Estrogen is neuroprotective. Estrogen reduces neuronal loss and amyloid beta plaque formation (Silva GB, 2024).
Starting HRT early in menopause can positively affect cognition, especially attention and cortical volume in the central nervous system (Beltz CR, 2024). Research reports better memory and attention in women taking HRT (Beltz CR, 2024).
Estrogen therapy lessens neuronal injury and cell death. This is important because these can lead to neurodegeneration (Mosconi L, 2024). HRT started at the right time, early in menopause in midlife, has positive effects on cognition. It has less benefit once neurological disease has already started to develop (Mosconi L, 2024).
As menopause approaches, there is a critical window of opportunity to detect signs of neurological risk. The brain of postmenopausal women may undergo changes due to lower estrogen up to the age of 65 years old. This is the time window for therapeutical intervention with estrogen replacement therapy to decrease risk by raising estrogen (Mosconi L, 2024).
- Women who used HRT in midlife had a 26% reduced risk of dementia compared to never-users (Andy C, 2024).
- Women starting HRT within 5 years of menopause had better cognitive performance than those who took HRT later in life (Andy C, 2024).
Starting HRT too late in life can conversely increase the risk of dementia (Andy C, 2024). The effects of HRT on cognition and overall health are strongly based on the formulation and timing of HRT.
What are the Risks of HRT?
There can be an increased risk of blood clots, stroke and gallbladder disease. In women who have had or are at high risk for certain conditions, HRT may not be safe. These prior conditions include blood clotting disorders, cardiovascular disease, breast cancer and stroke.
It may be that heart disease and breast cancer risk increase in older women who start HRT too late or use HRT for too long. Risks can increase significantly when HRT is started a decade or more after menopause onset (Andy C, 2024). HRT should not be taken more than 10 years after menopausal onset.
There are risks of endometrial hyperplasia and endometrial cancer with estrogen only therapy in women with a uterus. When women have an intact uterus, E+P replacement should be the recommended treatment.
Risk can likely be greatly reduced by choosing the right type, timing and delivery method of HRT. For example, the rare increased risk of gallbladder disease, stroke and blood clots may be managed by using transdermal bioidentical estradiol therapy (instead of oral estrogens) and bioidentical progesterone (instead of synthetic). The rare but increased breast cancer risk may be reduced by using bioidentical progesterone instead of synthetic P.
Breast Cancer
Estrogen helps healthy cells function normally and grow. If cells become cancerous, estrogen can encourage growth, causing cancer cells to multiply and spread.
It has been commonly thought that the risk of breast cancer is high with HRT. However, this is not necessarily true. For most women, the benefits of up to 5 years’ HRT use for symptom relief exceeds any potential harm (Marsden J, 2024).
In fact, breast cancer risk due to HRT is comparable to, or even less than, other lifestyle risk factors for breast cancer. Risk factors such as obesity, excessive alcohol, poor diet, sedentary lifestyle and a family history of breast cancer are more relevant in breast cancer risk (Marsden J, 2024).
There is no increased risk in breast cancer for estrogen only therapy. E + P HRT can be associated with an increased risk, which appears to depend on how long HRT is taken for.
The WHI study in 2002 did find a slightly higher risk of breast cancer in women taking estrogen and progestogen. But this risk was not statistically significant and amounted to less than one additional case of breast cancer per 1,000 users annually.
- This is equal to the higher breast cancer risk from obesity + a sedentary lifestyle.
- This is less than the risk of two glasses of wine per day.
The rare but increased breast cancer risk may be reduced by using bioidentical progesterone instead of synthetic progesterone. Bioidentical progesterone has not been linked to the same breast cancer risk as synthetic progesterone.
Women who have already been diagnosed with hormone related cancer should not take HRT.
When should HRT be started? Timing is Everything
It is critical to start HRT at the right age (Langer R, 2021). HRT should be started within 10 years of the start of menopause and under the age of 60 (Zouboulis CC, 2022). The risks of HRT are low for healthy women when introduced at the right time (<60 years of age or within 10 years of menopause onset) (Zouboulis CC, 2022).
Starting hormone therapy more than a decade after menopausal onset means a woman will have had a prolonged period of estrogen deprivation, which diminishes potential benefits of HRT and may increase potential risks (Zouboulis CC, 2022).
For How Long should HRT be Taken?
Ongoing individualized HRT does not have an age limit. HRT can be continued indefinitely. It is important to monitor the situation, on a case-by-case basis, with your FM doctor to find the right decision for you.
One analysis looked at women older than 65 years still using HRT to understand the benefits of staying on HRT (The Menopause Society, 2024). The most common reason to continue HRT beyond age 65 years was to control hot flashes (55%), to have a better quality of life (29%) or to reduce chronic pain and arthritis symptoms (7%) (The Menopause Society, 2024).
- No strokes, myocardial infarctions or uterine cancers occurred in these women (The Menopause Society, 2024).
Many women aged 65 years or older continue to have menopause symptoms that severely affect their quality of life. HRT can help them.
Discontinuing HRT simply because you’ve reached a certain predetermined age does not make sense. Assess your specific risk factors, symptoms, quality of life and health status with your doctor to decide for your individual case.
Conclusion
HRT is not just for symptom reduction. It can be used to help achieve healthy longevity, decrease CVD and osteoporosis risk, improve cognitive and metabolic health and to optimize overall health (Gersh F, 2024).
If you are suffering from menopause symptoms, then get in touch with us at the Medicine with Heart clinic. We can help you decide if HRT is right for you and optimize your menopause experience!
