Newsletter August 2002
vol 1 no 1

Welcome to the first edition of our newsletter.
Contents

1. The latest in Hormonal Replacement Therapy for Menopausal Women.
2. Why is substances with a progestin effect necessary in post menopausal women with a uterus ?
3. The management of the menopause

The Latest In Hormonal Replacement Therapy (HRT) For Menopausal Women. How safe is it?
There are two important female hormones namely estorgen and progesterone. The body stops to produce both when the menopause starts. During the reproductive years the female body produces estrogen nearly continuously but progesterone is only produced once a month for about 10 days.( the ten days before the onset of mentruation).
A women with a womb should receive both hormones if she is taking HRT. There are a few ways to give the progesterone. It can be given:
(i) Cyclic. A progesterone containing preparation is given for 10 -12 days every month and a menstruation induced.
(ii)Every three to four months. A progesterone preparation is given every 3 -4 months for 10 -12 days to induce a period (bleeding).
(iii)Continuously. A progesterone preparation is taken every day and menstruation does not occur.
Estrogen alone in a women with a womb has undesirable effects on the lining of womb. Progesterone is necessary to keep the lining (endometrium) healthy.
In women who had hysterectomies, preparations containing estrogen only, is usually used.
Several media reports appeared during the past few weeks casting doubt about the safety of HRT. The reasons for the reports was the preliminary release of a National Institute of Health (USA) study into the long term ( 5 years and longer) effects of HRT. The study is known as the Women's Health Initiative study (WHI study).
The study started in 1996 and consists of two arms.
The one arm is studying the long term effects of estrogen alone in women who had hysterectomies. This arm of the study is not effected and is continuing. No health risks were observed until now in this arm. Women who are taking estrogen only preparations should not be concerned. Clear it with your medical practitioner if you are unsure what you are taking.
The other arm of this research project studied the effects of the combination of continuous estrogen and progesterone on women who still have a womb.
This leg of the study was discontinued on 31 May 2002 due to undesirable health risks. The results were published on 17 July 2002 and caused great concern.
The results were publish in the Journal of the American Medical Association (JAMA). (Ref JAMA 2002; 288:321-333)
The researchers found an increased risk for breast cancer and coronary heart disease among users.
They also found a decrease risk for hip ( femur neck) fractures and colon cancer.
The risks for heart disease and breast cancer were small but exceeded predetermined levels.
Women who had hysterectomies and who are only taking estrogen containing preparations have no reason to be concerned.
At the moment we are concerned about progesterone containing preparations. The study implicated the daily continuous use of progesterone .
In the next article we will discuss the reasons for adding progesterone and why estrogen alone is not advised in women with a uterus.

Why Is Substances With A Progestin Effect Necessary In Post Menopausal Women With A Uterus ?
Menstruation takes place due to changes in the lining or the mucous membrane lining the cavity inside the womb. This lining is highly sensitive to the female hormones estrogen and progesterone. Estrogen causes the lining to swell and to become thick. Progesterone is only formed in your body after ovulation occurs ( ovulation = release of an egg cell from the ovary). Progesterone increases the blood supply and blood flow in the lining (causing it to become vascular with enlarged blood vessels). The lining is prepared for pregnancy. In case a pregnancy doesn't happen , your body temporally stops producing hormones. The inner two thirds of the lining mentioned above needs the female hormones to function . If there is no hormones to support it the inner two thirds of the lining is discarded and menstruation starts.
The medical term for this lining or mucous membrane is the endometrium. We will refer to it as the endometrium from here onwards.
If the endometrium is continuously exposed to estrogen without being opposed by progesterone it will continuously swells and thickens. If this continue for years changes that can lead to cancer can occur in the endomtrium.
If a post menopausal women with a womb is exposed to continuous estrogen treatment for years her endometrium will be over stimulated and endometrial cancer can occur. It is therefor necessary to oppose or balance the estrogen with progesterone. There are different ways of doing this. The one possibility is to add progesterone for ten days every month and than to temporarily stop both hormones for seven days to mimic a normal period. Another possibility is to add progesterone every few months ( usually every 3 -4 months) for 10 -15 days and than to temporary stop all hormonal treatment for 7 days. This will induce a endometrial bleeding ( also called a withdrawal bleeding). The inner two thirds of the endometrium will be shed and abnormal thickening of the endometrium prevented.
Most post menopausal women dislike the idea of continuing periods and this is the reason why a third method of administrating progesterone was developed. Progesterone and estrogen are both contentiously administrated together. This method keeps the endomtrium thin , prevents changes that might lead to cancer and also prevents endometrial bleeding ( menstruation). This third method was used in the abandoned arm of the WHI study.
Progesterone is given to post menopausal women to prevent abnormal thickening of the endometrium that might lead to cancer.
There are several natural occurring estrogen molecules in the female body. They are all chemical related molecules with small differences in their chemical structure. The chemical name of the most common occurring estrogen is 17 beta oestradiol.
There are only one type of progesterone occurring in the female body, in other words only one type of molecule with progesterone effects is present in the human body.
When we swallow tablets it passes through the stomach. The stomach contains rather high concentrations of hydrochloric acid ( a very strong acid) All substances absorbed from our intestines also pass through the liver before they are released to the rest of body.
The effect of stomach acid and liver enzymes on medication ( including hormones) made it necessary to alter or change medicines ( including hormones) to ensure that they are still active after they passed through the stomach and liver. It is obvious that for the same reason substances were developed that are able to be absorbed via the skin. Most of you are aware that HRT are also available in in so called patches that are applied to the skin and that some are also available in the form of ointments.
The natural progesterone is not active if taken orally. All the progesterones used in HRT preparations are modified to allow them to stay active after the digestive process.
We included the previous paragraph to illustrate that there are different chemical substances available with estrogenic or progestogenic effects. The substances used in the WHI study was conjugated oestradiol ( a estrogen obtained from mares) and medroxyprogesterone acetate ( a synthetic progesterone) It appears that the medroxyporgesterone acetate with dose of ug mg daily was the substance causing the risks that lead to the closure of combination therapy arm of the study. More studies will now be necessary to study the safety of other types of medicinal progesterones.
Studies are also necessary to study the safety of cyclic administration of progesterone (10 days every month or 10 days every third or fourth month).
The synthetic alteration of hormonal substances also raised another debate . The "natural " versus the "synthetic " substances debate will be discussed in our next issue.
In our next article we will discuss the management of the menopause in the light of the new evidence.

The Management Of The Menopause
There is much more to menopause than the use of hormonal replacement therapy (HRT).
Before we discuss the use of HRT let us look at other important issues that effect life during the menopause.
Your life style influences your health. You should try and live healthy. This include quitting smoking ,keeping as near as possible to your ideal weight and exercises regularly. ( at least 20 minutes a day)
Smoking increases the risk of osteoporosis , heart attacks and strokes substantially , much more than any other risk factor. Obesity on its own is associated with an increase risk of breast cancer. Conditions such as diabetes and high blood pressure are also negatively influenced by smoking, obesity and a lack of physical activity . It is difficult but try and change your poor life style to a healthy one.
Annual medical check ups are very important The value of regular medical checkups can never be over emphasized. The general check up includes a papsmear and endometrial sampling if you have an intact uterus. Over and above a normal full medical checkup you should also have a transvaginal ultrasound (sonar) examination if you still have a uterus and/or ovaries. The endometrium's form and particularly its thickness are check. This help to detect endometrial diseases ( like cancer) at an early stage.
The ovaries should also be examined via a vaginal ultrasound . It should be done anually. Enlargement of the ovaries are than detected early. This is done in an attempt to diag ovarian cancer early.
Mammograms should also be done annually. A mammogram diagnose breast cancer very early ( before there is lump). Unfortunately it is not 100% reliable and a manual breast examination is still very important. You should do regular self examination of your breasts and a doctor should examine them at least anually.
It is also advisable to have bone density test soon after entering the menopause to check the strength of your bones. Subsequent measurements depends on your bone structure, life style and medications you are on. Your medical service providers will advise you when it is necessary for further bone tests.
All chronic diseases should be properly manage. Common chronic diseases occurring during the menopausal years include hypertension (high blood pressure), diabetes mellitus ( sugar disease), hypercholesterolemia (high cholesterol levels) hypothyroidism ( under function of the thyroid gland) and different kinds of arthritis. It is not always possible but when it is, all these diseases should be monitored with the advise of a medical specialist in the particular field. An example is high blood pressure. It is nowadays more aggressively managed than in the past. The aim is to get the blood pressure as near as possible to the normal levels. (This is done to prevent strokes).
A further very important issue is the quality of life. This is very difficult to measure and differs from person to person. It includes physical, mental and spiritual well being. You must feel good about yourself and enjoy being alive. It is possible for people with physical handicaps to have a better quality of life than a person with excellent physical health. Fear about the side effects of medication and their consequences can also effect somebody's quality of life. For this very reason drugs are usually thoroughly tested to keep undesirable effects to a minimum.
We are now at the essential part of this discussion : To use or not to use HRT.
or What is the role of HRT in the management of the menopause.
Estrogen are used to relief the menopausal symptoms of which hot flushes are the most common. The severity of the symptoms will have a major influence on the decision to use or not to use HRT.
Estrogen replacement was originally use to control the menopausal symptoms. (hot flushes, dry vagina, painfull sexual intercourse, dry skin, tiredness and emotional instability (short tempered, crying etc)).
While managing these individuals with estrogen a few interesting observations were made:
* there was a reduction in osteoporosis , spinal and hip fractures.
* there was a reduction in myocardial infarctions ( heart attacks)
* they developed Alzheimers disease at a later age
* colon ( large bowel) cancer was less common among them
Unfortunately there were also a few negative observations.
* If a women who still has a womb received estrogen alone , she was at an exceptional high risk of developing cancer of the endometrium. (the endometrium is the skin lining the cavity inside the womb). This risk was prevented by adding the other female hormone, progesterone.
* An increase in cases of intravascular clotting (clotting of blood while circulating in the vessels) especially in women who smoked.
* Conflicting reports about its effects on the breast and breast cancer. Some researchers observed no effect while others observed a very slight increase in breast cancer.
Questions were asked. Is there a difference in the life styles of women taking HRT and those who do not take them or took them for only a short while. Is the beneficial effects observed due to life style diferences or due to a direct effect of estrogen.
These questions resulted in studies like the WHI study (discussed in the first part of this news letter)
All these possibilities and factors must be taken into account. The WHI study only doubt the safety of progesterone if continuously used in combination with an estrogen in women with a womb. It is not applicable to women who had a hysterectomy. At this stage is seems safe for women without a womb to continue taking estrogen only.
The decision to use HRT should be made by the woman in consultation with her health care providers. All the factors mentioned in this newsletter should be taken in consideration. Her response to treatment and the effect it has on her quality of life will play a major role in the decision to continue or not to continue.
A fear of cancer can adversely effect a person's enjoyment of life . If somebody is to scared to take HRT her decision should be respected, especially if it is an informed decision.
We must repeat the fact that WHI study that caused the recent media scare , does not apply to women without a womb, taking only estrogen replacemant.
Visit our site at Female Health Made Simple for more background information. It also contains more information about the function and diseases effecting the female reproductive organs.

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