Oestrogens

Oestrogens refer to a class of molecules that have oestrogen-like activity in the body. Many molecules are oestrogens, but the principal oestrogens in a woman are estradiol, estrone, and estriol, but each with a different degree of effectiveness in different tissues.

Estradiol is the most potent of the oestrogens produced by the ovary. A very small amount circulating in the blood can cause potent changes in oestrogen-responsive tissues. Estrone is a metabolite of estradiol and is considerably less potent. Estriol is a further metabolite of estradiol and is quite weak.

Estradiol, estrone, estriol, and all of their metabolites are bio-identical hormones found naturally in the body. Bio-identical hormones are defined as compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body.

In contrast, the most commonly prescribed oestrogens formulation for hormone replacement therapy is a mixture of estradiol, estrone, and 10 or more horse oestrogens that are exogenous to humans. Some of these hormones are very potent oestrogens, even more so than estradiol. Unfortunately, there are no readily available tests for monitoring the levels of these foreign hormones.

Menopause & Aging

The decline of oestrogens and progesterone is not gradual like other hormones.

As a woman enters her mid-thirties, her reproductive capacity starts to decline, with a decrease of oestrogens and progesterone production.

When she reaches 40 - 45, the oestrogens levels can swing from very high to very low. This can result in alternating sensations of enlarged and tender breasts with bloating and irritability when oestrogens are dominant; and hot flushes, confused thinking or lack of concentration, memory difficulties and vaginal dryness when the oestrogens level plummets. There may be time with no bleeding, followed by heavy bleeding accompanied by severe cramps. This is referred to as peri-menopause.

5 - 10 years later the menopause finally arrives, the production of oestrogens and progesterone by the ovaries stops completely and results in permanently low levels, which can be measured by blood tests. Replacement of oestrogens and progesterone is a common and effective treatment for symptoms associated with menopause.

Potential Benefits of Replacement

The low oestrogens levels can cause a lot of undesirable effects on the body:

• Hot flushes
• Vaginal dryness
• Decreased libido
• Dry skin & loss of skin elasticity
• Shrinking breasts
• Decreased mood and energy
• Difficulty concentrating and memory problems
• Cardiovascular diseases
• Accelerated bone losses
• Osteoporosis and fracture
• Diabetes
• High blood pressure
• Strokes
• Alzheimer's disease.

Hormone replacement therapy (HRT), particularly with the bio-identical hormones, may reverse many of these problems and risks.

Treatment Options

Oral

• The majority of women take their HRT in pill form by mouth. While very convenient, a large amount of oestrogens goes through the intestines and then hits the liver within a short period, which is different from the gradual release of oestrogens from the ovaries. This changes the metabolism of the liver and results in a number of deleterious effects:
  Increase in clotting factors, hence the possible side effect of causing an increase in blood clots in the leg veins.
• Increase in sex hormone binding globulin (SHBG), which binds more testosterone and results in symptoms of low testosterone - decreased libido, vaginal dryness, thinner bones, loss of lean muscle and increase in fat.
• Alcohol intake will dramatically increase the level of oestrogens to as much as 300%, which is even higher than in a normal menstrual cycle. This may be one of the causes of an increased risk of breast cancer with oral HRT.
• Increase in the incidence of gall stones.
• Increase in triglycerides, which is a risk factor for heart disease.
• Increase in C-reactive protein, which is a potent risk factor for coronary artery disease.

Transdermal

With transdermal application, the daily dose is released gradually into the circulation, just as when the ovaries are functioning naturally. As a result, the above problems occur much less likely, and there is only a 30% increase in oestrogens level with alcohol consumption.

This can be done by either a patch, or transdermal cream.

Side Effects & Safety

The most commonly reported adverse events of oestrogens include headache, breast pain, irregular vaginal bleeding or spotting, stomach or abdominal cramps, bloating, nausea and vomiting, and hair loss.

There is some controversy regarding the positive or negative effect of HRT in causing cardiovascular diseases and breast cancer. There seems to be an increased risk when taking oral HRT. Doctors supporting the opposite say that bio-identical HRT taken transdermally is safer, more effective and does not have the same problems.

A menopausal or post-menopausal woman should discuss her individual risks and benefits of HRT with her doctor. If she decides that HRT would be overall beneficial, then she should go ahead with a regime but with close monitoring as well.

In general, the following advices are still being made:

• It increases the chances of cancer of the uterus
• It may increase the chance of heart attacks, strokes, breast cancer and blood clots.
• It should not be used if you have unusual vaginal bleeding, currently or have had blood clots, certain cancers, had a stroke or heart attack in the past.

It may be popular to get the HRT from some compounding companies who make the custom-mixed formula, but they may pose risks in terms of purity, potency, efficacy, or safety. Bio-identical estridiol and progesterone are available in approved hormone replacement products, which come in many different doses and forms (patch, cream and gel).

Progesterone

Progesterone is secreted by the corpus luteum, which is the residual body after the ovulation. It serves to counteract the continuous stimulation on the uterine lining by oestrogens, and causes the regression of the lining, to result in a menstrual period, if the egg has not been fertilised.

It is prescribed together with oestrogens in HRT because it can protect the uterine lining from over stimulation, and therefore reduce the risk of cancer in the uterus.

One of the most commonly prescribed preparations is medroxyprogesterone acetate, which is formed by the addition of a molecule to progesterone, so that it is patentable and more orally absorbable. However, women who take this often feel irritable, depressed, have mood swings, fluid retention and bloating. On the contrary, bio-identical progesterone elevates mood and is calming, and there is complete resolution of the adverse symptoms when women are switched away from
medroxyprogesterone acetate.

In addition, bio-identical progesterone was found to have the best effect on HDL cholesterol, and does not have the potential negative effect in increasing the risk of coronary artery diseases. This may explain the results of some trials, which showed that oestrogens do not protect the heart as was thought, when it is combined with medroxyprogesterone acetate. The early slight increase in heart attacks in women with established cardiovascular disease could have resulted from its negative effect on the coronary arteries.

Replacement therapy can be delivered transdermally as patch or cream, which is better than taken orally in capsules.