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Hormone Replacement therapy in menopause

 

Basics

Normal steroid concentrations

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

 

 

Hormones, dosis, and administration?

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 are 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 menstruation. Continuous combined means estrogens and progestins together. In women without a uterus, estrogens only are given.

Principle 4 . Individualisation of dose   A first dose needs to be adapted to what a woman needs and to her resorption 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 and some after 5 hours.

This is a trial and error process based on knowledge of endocrinology but mainly guided by the experience of the clinician. This is the most important aspect of hormone replacement therapy since inexperience results in a one size fits all solution, which is not appropriate 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 needs 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 steroids, 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 unfortunately 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 oocytes are left.

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

Could menopause be a disease?   Diabetes is when the pancreas no longer produces insulin. The problem with menopause is that a shortage of estrogens has no immediate associated mortality, only flushes, sleeping problems, irritation, loss of memory, wrinkles, muscle pain and only later osteoporosis, more bowel cancers and heart problems.

Why is hormone replacement needed in menopause?

Menopauze: hormonale substitutie therapie

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

Menopause is a natural mistake. For reproduction, 40-45 years 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, humans rarely achieved menopause in ancient times.  If we could reduce the rate of oocyte loss, we could program menopause at 40, 50, 60, 70 years or later. What age would you choose?

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

A little hormones 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).  Resorption can be chemically modified as in Ethinyl-estradiol (very active and used in oral contraception) and oestradiol-valerianate (Progynova) or conjugated estrogens (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 stereoisomers ( 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 is 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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