Hormone Replacement therapy in menopause


Hormones, dosis, and administration ?

Normal steroid concentrations

Normal concentrations range from low to high with most having a median concentration.
Bioavailability after 1 pill varies at least 4 times.
First choice is a dose with concentrations around the median

Principle 1: No Contra-indication. The only contra-indications are those for which the ovaries are removed; otherwise they are at best relative and need to be discussed

Principle 2. Hormone replacement  is replacing hormones as they were before. Compare to reading glasses: the aim is to read normally, not to read a little bit better. Most women receive a dose that is too low since commercial products being designed for the ‘medial’ woman. To avoid a dose that is too high in some,  the dose is too low in 3/4.

regimen of hormone replacement in menopause
Principle 3 . Sequential – continuous combined or estrogen only  Sequential mimics the normal menstrual cycle  with menstruations. Continuous combines means estrogens and progestins together. In women without a uterus sstrogens only are given.

Principle 4 . Individualisation of dose   A first dose needs to be adapted to what a moman needs and to her resorbtion Therefore the dose will vary at least 4 times between women.

Principle 5 . Individualisation of products   The 4 available estrogens and more than 10 progestagens all have slightly different brain and tissue effects. Not every dress is perfect for everybody .

Principle 6 . Individualisation of administration  transdermal products and implants have a constant release ; oral products have peak blood concentration some after 30 min some after 5 hours .

This a itrial and error process based on knowledge of endocrinology but mainly guided by experience of the clinician. This is the most imortant aspect of hormone replacement therapy, since  inexperience results in a one size fits all solution, which is not appriopriate for most women.

Unfortunately this is incompatible with the available standard solutions because of the >100 combinations

The administration

hormonale substitutietherapie voor menopauze
Oral intake  need to be resorbed with a first pass and higher concentrations in the liver, which can be a contra-indication for women with liver problems.

The liver is metabolically very active and transforms some streroids  e.g. oestradiol into estrone for 98%  but not ethinylestradiol.

hormonale substitutietherapie voor menopauze

Transdermal Steroid hormones are stored in the skin and slowly resorbed in blood. Transvaginal administration is similar but with slightly higher uterine concentrations known as the first pass effect in the uterus.

Transnasally unfortunatally did not make it to the market.


The first menopause clinic on the continent

hormonale substitutietherapie voor menopauze
I started in 1981 in Leuven the first menopause clinic on the continent   We then had 15 years of experience with oral contraception. 


What is menopause ?

Menopause starts when the ovaries stop producing estrogens . Estrogen secretion and ovulation are linked, and ovulation stops around 50 years when few oocyates are left.

In women hormone secretion stopts abruptly in contrast with all other ageing problems that occur progressively such as vision, hearing etc. Also in men the secretion of male hormone decreases PROGRESSIVELY g-from 30-35 year , often causing (hidden) problems from f 60-70 year onwards.

Could menopause be a disease?   Diabetes is when the pancreas no longer produces insulin. The problem of menopause is that a shortage of estrogens has not immediate associated mortality, only flushes, sleeping problems, irritation, loss of memory, wrinkles, musche pain and only later osteoporosis, more bowel cancers and heart problems.

Why is hormone replacement needed in menopause

Menopauze: hormonale substitutie therapie

Homone replacement is like glasses permitting to read normally, not improving a little

Menopause is a natural mistake. For reproduction 40-45 year are enough since oocytes become damaged afterwards. Mammals in the wild do not live long enough to experience menopause. They only experience menopause in the zoo and at home i.e. with regular food, shelter and a veterinarian. Also the human rarely achieved menopause in ancient times.  If we could reduce the rate of oocyte loss we could program menopause at 40, 50, 60, 70 year or later. What age would you choose ?

hormone relacement therapyhormone relacement therapy is comparable to reading glasses. You need to add oil when a motor has little oil left.

A little homones is something different: , when only complaints are treated as vaginal dryness a minimal dose is given .

Products in Belgium and Italy

Oestrogens Natural estrogens are 17b-estradiol, estrone en estriol (less active). Oestradiol is poorly soluble and needs micronisation to be (variably) resorbed (e.g. Zumenon, Estrofem).  Resorbtion can be chemically modified as in Ethinyl-estradiol (very active and used in oral contraception) and oestradiol-valerianaat (Progynova) or geconjugated estrogenens (Premarin).  Estriol is soluble but poorly active ( Aacifemine).

Progestagens. Progesterone is niet not soluble in water but can be used transdermally and transvaginally. Oral progestagens are chemically altered such as stereoisomeer ( Duphaston),  modified progesterone (Farlutal, Provera, Lutenyl) or modified nor-testosterone (Primolut, Orgametril) and the many progestagens used in oral contraceptives.

Androgenens .  DHEA is a precursor and metabolised to estrogens and androgens and needed by most women without a uterus .

SERMS (specific estrogen receptor modulators).differentiate the estrogen effect on  the brain, breast and uterus  from the effects on the bone and the cardiovascular system. (2 different receptors) .

LIVIAL has a small  estrogen, progesterone and andtrogen effect


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