Bioidentical Hormone Replacement Therapy

Bioidentical Hormone Replacement Therapy: A Functional Medicine Approach

Bioidentical Hormone Replacement Therapy (HRT) designed around you — not a one-size-fits-all prescription

Hormones naturally drop in perimenopause and menopause, but every woman experiences these changes differently.

At 8th Sense Functional Medicine, we do not look at one hormone or one laboratory result in isolation. We look at the whole woman — her symptoms, medical history, metabolic and cardiovascular health, nutrition, lifestyle, detoxification, gut health, overall hormone metabolism and, where appropriate, genetics.

Our goal is simple:

Understand your biology first. Then personalise your hormone therapy.

How Is Our Approach Different?

Older forms of hormone therapy commonly used conjugated equine (horse) estrogens (CEE) and synthetic progesterone-mimicking medications called progestins are not identical to the hormones naturally produced by our bodies. [1]

Our approach focuses primarily on body-identical hormones — hormones with the same molecular structure as those naturally produced by the human body.

When systemic estrogen is appropriate, we generally prefer transdermal 17β-estradiol, delivered through the skin, rather than oral estrogen.

Because transdermal estradiol avoids first-pass metabolism through the liver, it has less effect on clotting factors and triglycerides and may be preferable for women with certain cardiovascular, metabolic or thrombotic risk factors. [7,8]

In selected women, estriol may also be used, particularly for vaginal and urinary symptoms, or combined with estradiol as part of an individualised treatment plan.

Hormone Therapy Is About More Than Hot Flushes

At 8th Sense Functional Medicine, we do not prescribe hormones simply to treat hot flushes and night sweats, nor do we automatically follow the old concept of the “lowest dose for the shortest possible time.”

Estrogen is not only a reproductive hormone. Estrogen receptors are present throughout the body, including the brain, cardiovascular system, bones, muscles, skin, immune system and gastrointestinal tract. The loss of estrogen at menopause therefore affects many aspects of a woman’s physiology.

Modern research supports important effects of appropriately selected menopausal hormone therapy on bone health and fracture prevention, cardiovascular and metabolic physiology, lipid profile and several aspects of brain function and cognition. [2,6,7,16–18] The effects depend strongly on the woman’s age, timing of treatment, hormone formulation and route of administration.

One recent meta-analysis found that estrogen therapy started in midlife or close to menopause was associated with improvement in verbal memory, while late initiation did not show the same effect. [16] Recent cardiovascular meta-analyses demonstrate effects of HRT on cardiovascular risk factors, while studies of transdermal estrogen report improvements in LDL cholesterol, ApoB and total cholesterol with certain regimens. [17,18]

Therefore, we recognise that restoring hormones can influence multiple interconnected systems — brain, bone, cardiovascular, metabolic, immune and gut health — far beyond simply controlling menopausal symptoms.

Our goal is therefore not the smallest dose for the shortest time, but the appropriate hormone, dose, route and duration for the individual woman, with regular assessment of benefits and risks.

Personalised Hormone Therapy Means Looking Beyond Estrogen

Menopause is not simply an estrogen-deficiency state.

Estradiol, progesterone, testosterone, DHEA, thyroid hormones, insulin and cortisol all interact within the body’s endocrine and metabolic systems.

For this reason, personalised hormone therapy does not simply mean deciding how much estrogen to prescribe.

In a personalised approach, other hormones — including progesterone, testosterone or DHEA — may also be considered according to a woman’s symptoms, hormone levels, stage of life, health and individual needs.

Just as importantly, we consider how hormones are metabolised. Hormones influence one another, and changes in one hormonal pathway may affect the activity, availability or metabolism of another.

Understanding hormone production, metabolism and elimination can therefore provide additional information when developing an individualised treatment strategy.

Estradiol and Estriol — Preferred Replacement

There are three different types of estrogens our bodies produce: estradiol, estriol and estrone.

Estradiol

17β-estradiol is the major naturally occurring estrogen during a woman’s reproductive years. Its effects extend far beyond reproduction. Estrogen receptors are found throughout the body, including the:

Brain • bones • cardiovascular system • muscles • skin • metabolism • breasts • vaginal and urinary tissues

This is one reason menopause can affect far more than hot flushes.

Estriol

Estriol is a weaker naturally occurring estrogen with a different receptor profile and relatively greater activity through estrogen receptor beta (ERβ) in some tissues.

It is particularly useful for vaginal and urinary symptoms such as dryness, burning and discomfort.

Estrone

We don’t prescribe estrone as part of hormone replacement therapy. After menopause, estrone becomes the predominant circulating estrogen, and higher endogenous estrone levels have been associated with increased postmenopausal breast-cancer risk in observational studies. [15]

Progesterone Is More Than “Protection for the Uterus”

Progesterone is often discussed only as the hormone that is added to estrogen to protect the uterus. Its physiology is broader than that.

Progesterone receptors and progesterone-related signalling are present in multiple tissues, including the brain, breasts, bones and reproductive system.

For a woman with a uterus who receives systemic estrogen, adequate progesterone is essential to protect the endometrium from excessive estrogen stimulation and reduce the risk of endometrial hyperplasia and cancer. At 8th Sense, we generally prefer body-identical micronized progesterone.

Bioidentical micronized progesterone is not the same as a synthetic progestin

Micronized progesterone has the same molecular structure as progesterone naturally produced by the body. Synthetic progestins are different molecules designed to produce some progesterone-like effects. Their effects throughout the body are not necessarily identical.

This distinction matters.

In the WHI, estrogen combined with the synthetic progestin medroxyprogesterone acetate (MPA) was associated with increased breast-cancer risk. [1] The large E3N study subsequently found that breast-cancer risk differed according to the type of progestogen used, with estrogen combined with micronized progesterone showing a more favourable risk profile than with several synthetic progestins. [9] That is why we always use bioidentical micronized progesterone.

Research has also found differences in blood-clot risk between micronized progesterone and some synthetic progestogens. [8,10,11]

It is essential that progesterone and synthetic progestins should not automatically be considered the same treatment. Using them interchangeably confuses women and their understanding of what is better for their bodies.

What if I have had a hysterectomy?

A woman without a uterus does not usually require progesterone solely for endometrial protection. However, Functional Medicine considers progesterone as a hormone with biological effects beyond the uterus.

In selected women, Dr Nedic (MD, IFMCP) may therefore consider individualised progesterone therapy even after hysterectomy, depending on symptoms, clinical circumstances, other hormones and the potential benefits and risks. The decision is personalised, and each woman is involved in this decision.

We Look at Your Overall Health — Not Just Your Hormones

Hormones do not work independently of the rest of the body.

Before starting or adjusting hormone therapy, we may assess:

Insulin resistance • body composition • cardiovascular risk • blood pressure • lipids • thyroid function • liver and kidney function • nutritional status • sleep • stress • all other hormone levels • estrogen detoxification and elimination capacity • personal and family history

Where appropriate, we may also use genetic and hormone-metabolite testing to provide additional information about individual hormone metabolism. These are interpreted together with symptoms, medical history, examination and conventional laboratory testing.

Two women can have the same estradiol level but respond very differently. That is why we do not simply ask: “Which hormone is low?” We ask: “Which hormones does this woman need? How will her body process them? How will they interact? And is her overall health optimised to benefit from treatment?”

What Has Modern Research Taught Us?

Our understanding of hormone therapy has changed considerably since the original Women’s Health Initiative (WHI) was published, and hormones were abruptly stopped, leaving one whole generation deprived of hormone replacement therapy. This study was re-evaluated, as it used older, non-bioidentical hormones in an older population [1] and should not be interpreted to mean that every estrogen, every progesterone or progestin, every route and every woman carries the same risk.

Modern studies such as ELITE, KEEPS, DOPS and REPLENISH have helped demonstrate the importance of timing, formulation, route and individual health. [2–5]

The question is therefore no longer simply:

“Is HRT safe?”

The better questions are:

For which woman? At what age? How long since menopause? Which hormones? Which route? Which dose? And what is her individual health and risk profile?

What About Breast-Cancer Risk?

Breast-cancer risk is not identical for every hormone regimen. Hormone therapy needs to be discussed according to the actual hormones being prescribed, not simply under the single label “HRT”.

Randomised trials of estrogen-alone therapy have not demonstrated an overall increase in breast-cancer incidence.

A 2024 meta-analysis of 10 randomised trials involving more than 14,000 women reported an approximately 23% lower relative breast-cancer incidence with estrogen alone compared with placebo. [13]

When a progestogen was added, the risk changed.

Evidence associates estrogen combined with certain synthetic progestins with higher breast-cancer risk, particularly with longer use, while observational evidence suggests a more favourable profile for micronized progesterone than for several synthetic progestins. [1,9,12]

The important message is:

Estrogen alone ≠ estrogen + synthetic progestin ≠ estrogen + micronized progesterone.

The 8th Sense Approach

1. Understand the woman
   Her symptoms, medical history, lifestyle, nutritional status and goals.
2. Assess her overall health
   Including metabolic, cardiovascular and other relevant risk factors.
3. Understand the complete hormone picture
   Not only estrogen, but progesterone, androgens and other interacting hormonal systems where clinically relevant.
4. Consider hormone metabolism
   We always investigate how hormones are being processed and eliminated and how this may influence their interaction.
5. Personalise treatment
   We select the personalised hormone or combination of hormones, route and dose.
6. Monitor and adjust
   Hormone therapy is not a “set and forget” prescription. Treatment is reassessed as the woman’s health, symptoms and needs change.

Frequently Asked Questions

Are bioidentical hormones the same as compounded hormones?

No. Bioidentical describes the molecular structure of a hormone. Compounded describes how a medication is prepared.

Pharmaceutical products can also contain body-identical estradiol and micronized progesterone.

Why do you prefer transdermal estradiol?

It avoids first-pass liver metabolism and has less effect on clotting factors and triglycerides than oral estrogen. This may be particularly important in women with cardiovascular, metabolic or thrombotic risk factors. [7,8]

Why do you prefer micronized progesterone?

When progesterone is appropriate, we generally prefer body-identical micronized progesterone. Evidence suggests that it may have a more favourable breast and thrombotic risk profile than several synthetic progestins. [8–12]

Do I need progesterone if I have had a hysterectomy?

Not for protection of the uterine lining because the uterus is no longer present. However, progesterone has biological effects beyond the uterus. In selected women, its use may still be considered based on symptoms, clinical circumstances and the overall hormone picture.

Do you prescribe testosterone or DHEA?

When clinically appropriate.

Personalised hormone therapy is not limited to estrogen and progesterone. Androgens such as testosterone and DHEA may be assessed and, where there is a correct clinical indication, considered as part of an individualised treatment strategy.

Do I need genetic or hormone-metabolite testing to start HRT?

These tests are used by Functional Medicine doctors to provide additional information about how an individual woman produces, metabolises and eliminates hormones and how hormones interact with each other.

I am over 60 and have never taken HRT. Is it too late?

Not necessarily, but treatment requires a more careful individual assessment.

The benefit-risk profile is generally most favourable when systemic hormone therapy is started before age 60 or within approximately 10 years of menopause. Starting substantially later requires greater consideration of cardiovascular, stroke and blood-clot risk. [6,14]

Age alone, however, does not automatically exclude treatment.

Should I stop HRT when I turn 60 or 65?

Not automatically.

There is no universal age at which every woman must stop hormone therapy. Women already benefiting from treatment should be periodically reassessed according to their symptoms, health and individual risks. [14]

Does hormone therapy only treat hot flushes?

No.

Hormone therapy is not only about controlling hot flushes and night sweats. Depending on the woman, her age, health, timing of treatment and individual indication, hormone therapy may also: improve sleep, mood, sexual wellbeing and overall menopausal quality of life; improve vaginal and urinary symptoms associated with genitourinary syndrome of menopause; prevent bone loss and reduce the risk of osteoporotic fractures; favourably influence several metabolic and cardiovascular risk factors, including body-fat distribution, insulin sensitivity and lipid metabolism; current research is also examining the effects of estrogen on the brain, cognition and healthy brain ageing.

Our Philosophy

Bioidentical Hormone Replacement therapy is not simply about replacing what is missing.

It is about understanding the woman, her overall health, her different hormones, how those hormones are metabolised and how they interact with one another.

At 8th Sense Functional Medicine, we combine evidence-based hormone therapy with a Functional Medicine assessment to develop treatment that is individualised, carefully monitored and responsive to each woman’s biology.

Because personalised hormone therapy begins with understanding the person — not simply treating a laboratory number.

Selected Scientific References

1. Rossouw JE, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002.
2. Hodis HN, et al. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016. ELITE.
3. Harman SM, et al. Arterial Imaging Outcomes and Cardiovascular Risk Factors in Recently Menopausal Women. Ann Intern Med. 2014. KEEPS.
4. Schierbeck LL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women. BMJ. 2012. DOPS.
5. Mirkin S, et al. 17β-estradiol and progesterone for vasomotor symptoms and endometrial protection. REPLENISH.
6. Boardman HMP, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev.
7. The North American Menopause Society. 2022 Hormone Therapy Position Statement. Menopause. 2022.
8. Canonico M, et al. Hormone therapy and venous thromboembolism: impact of route of estrogen administration and progestogens. Circulation. 2007. ESTHER.
9. Fournier A, et al. Unequal risks for breast cancer associated with different hormone replacement therapies: E3N cohort. Breast Cancer Res Treat. 2008.
10. Canonico M, et al. ESTHER Study. Circulation. 2007.
11. Canonico M, Scarabin PY. Progestogens and venous thromboembolism: updated meta-analysis. Climacteric. 2018.
12. British Menopause Society. Progestogens and endometrial protection.
13. Chlebowski RT, et al. Randomized trials of estrogen-alone and breast cancer incidence: a meta-analysis. Breast Cancer Res Treat. 2024.
14. British Menopause Society & Women’s Health Concern. Recommendations on hormone replacement therapy in menopausal women.
15. Albers FEM, et al. Sex-steroid hormones and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis. Cancer Causes Control. 2024;35(6):921-933.
16. Andy C, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition. Front Endocrinol. 2024;15:1350318.
17. Gu Y, et al. The benefits and risks of menopause hormone therapy for the cardiovascular system in postmenopausal women: a systematic review and meta-analysis. BMC Women’s Health. 2024;24:60.
18. Zhou F, Prabahar K, Shu J. The effects of transdermal estrogens combined with medroxyprogesterone acetate on cardiovascular disease risk factors in postmenopausal women: a meta-analysis of randomized controlled trials. Diabetol Metab Syndr. 2025;17:111.