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Individual hormone replacement therapy

Every woman is different 

One size does not fit all

Pro and Cons: EBM

The advantages and disadvantages of hormone replacement therapy (HRT) are well known.

Besides the treatment of symptoms, the prevention of wrinkles and bone loss and brain function, and the prevention of  cardiovascular accident, of bowel cancer and of the mortality of ovarian cancer and of breast cancer  are well documented. 

(read recent review)

HRT does not cause a clear increase in breast cancers if all cofounding factors are taken into account.

The disadvantages of hrt are a minimal increase in the risk of deep vein thrombosis and of premenstrual tension in women who experienced this before menopause. In women with a uterus menstrual or irregular blood loss can be a problem.

Notwithstanding these important advantages, are not that many women using hormones.  For us, the most important reason is the lack of individualization of hormone replacement therapy, which requires the right products in the right dose  with focus on the mental tonic effect and well-being.

Brain effects, well-being

Estrogens,  progestagens and androgens have brain effects .  That brain effects and well-being are the key drivers for the patient, is not recognized sufficiently since Individual variability does not fit with EBM and since brain effects are more difficult to measure.

Individualisation does not fit with EBM

Evidence based medicine is the evidence that a treatment is effective and safe. Although the randomised controlled trial (RCT) is mathematically correct it is often forgotten that this is only true if the investigated population is homogeneous. We therefore have to be careful whne extrapolating conclusions of a study to another country, race, population etc.

However we are individuals with differences. This is not only true for height and color of hair,  but also for differences in hormone concentrations which for estrogens  vary between 200 and 400 pgr/ml. Only recently we begin to understand the underlying genetic and epigenetic differences, and their translation into individualized medicine is emerging. The aim is to individualise the patient in order to give her the appropriate therapy.

It should be clear that traditional statistics and research are inappropriate for a non- homogeneous population.As we recently demonstrated for endometriosis, results of medical treatment can have different effects  and can even  have opposite effects in different women or lesions. As an example,   a therapy that will improve 80% of women but deteriorate 20%  of women will still be considered statistically  effective while the negative effects in 20% of women will remain invisible.

Brain effects are difficult to quantify

While true for all biological effects,  individual variability is even more pronounced for brain effects.

The commercial bias

All commercially available hormone replacement products  are designed for the median woman. Since 1 size does not fits all, these products are not suited for all.  In addition in order to avoid negative side effects even in the most susceptible women, most products tend to be low in estrogens to avoid thrombosis also in women with very severe varicose veins. They also contain too much progestagens in order to offer endometrial protection in the most susceptible women.

Another bias is the commercial bias. Clinical trials are expensive and will therefore rarely be performed for inexpensive products if not patent protected. For this reason  studies on androgen supplements  in women are rare, notwithstanding we know that DHEA decreases in women (like men) with age and that all androgens drastically decrease after ovariectomy.

In conclusion,

individual variability, and especially brain effects, are ignored by EBM and by the pharmaceutical industry since there is actually no valid statistical solution to interpret and apply the data. For brain effects, the  difficult measurement is another problem

Individual HRT

individual hrt

Therapy has to be individualized since one size does not fit all, and HRT must be integrated with all aspects of life.

Many possible combinations
individual hromone replacement therapy

More than 100 individually suited combinations of dose, type of estrogen, progestagen and androgens  exist. In addition, the bio-availability or resorption of steroid hormones  varies more than 4-fold between women.

Variable bioavailability

Each type and dose of estrogen, androgen and progestagen have slightly different brain effects. These brain effects are unfortunately poorly studied,  since variable between women and since brain effects are  difficult to measure exactly. Besides the direct effects, sex steroid hormones increase the cell contact in the brain  (synaptic density) , through a growth process which takes at least 9 months.  They also increase speed of signal transmission.  Brain effects and well-being moreover vary with environmental factors.

 

 

 

 

 

 

Other factors : microbiota

In order to make menopause therapy even more complex, we know that the microbiota of the intestine metabolize and change these hormones and that these hormones change the bowel microbiota.

Although not yet fully understood, it is clear that microbiota affect  a lot of diseases,  especially immunologic disorders (see  our article on microbiota and endometriosis),  Microbiota  probably explain the decreased incidence of bowel cancer in women taking hormone replacement therapy.

Bowel microbiota together with the peritoneal microbiota, explain that food intake, food supplements and exercise can be beneficial for endometriosis.  Food intake, supplements and exercise by extension should also be taken into account in menopausal individualized hormone replacement therapy.

In addition, the emphasis on well-being and brain effects strongly suggest a cooperation between hormone replacement clinics and beauty centers.

Conclusions 

individual hrt

Treatment of menopause today is like most aspects of medicine a scientifically  educated art, which combines individualization of risk and benefits with emphasis on brain effects and well-being.  To ‘prescribe hormones’ is like a child who has learned to recognize  letters which is far from reading and writing,

 

This requires experience and interest to listen to the patient. Moreover individualization does not  fit with EBM,  traditional trials and evidence and statistics . Therefore individualisation data get difficultly published and evidence is scanty. However, if individualization is not taken into account, the majority of women will not feel perfect with hormone replacement therapy and stop treatment; This is what I learned by experience since starting a menopause clinic at KULeuven in 1981.

Above, a picture from a presentation in 1985 for Belgian gynecologist.  My dream since then has been to integrate menopause therapy, with all other aspects of menopause as food intake, supplements, exercise and even beauty centers.

Prof Philippe R. Koninckx

21-10-20

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