Today’s Subject: Hormone Replacement Therapy (HRT) – Part 1.

I thought I better do this in two parts as it can be quite a heavy subject. Menopause is a condition which all reproducing females will go through, and majority of these will use some form of hormone replacement in order to manage this period of life.

Hormone replacement therapy (HRT) is the administration and management of synthetic oestrogens and progestogen which is used to replace the depleting hormone levels which occur during menopause.
The two most common forms of hormone replacement therapy for menopausal females is oral oestrogens, and combined oestrogen and progestogen.

Oral oestrogens are often referred to as hormone therapy with oestrogen only (HT-E) are also known as conjugated combined equine oestrogens (CEE). It is recommended for females who have undergone a hysterectomy. A progestin is added to the oestrogen (HT-EP) in menopausal females if they still have a uterus in order to prevent endometrial cancer or hyperplasia. HT-EP is more commonly prescribed due to the fact that most females reaching menopause have not under gone a hysterectomy.
It used to be common practise that when a female started to experience menopausal symptoms HT-EP was recommended as it was though that long term use of the hormone therapy would protect against osteoporosis (Padero et al 2002) and females were encouraged to stay on this treatment indefinitely.
In 2002 when the Woman’s Health Initiative (WHI) study came out and, although it showed that there was a reduction in coronary heart disease (CHD) short term, the long term effects of HT-E and HT-EP showed an excessive risk in CHD associated with long term use of these therapies.
Stroke, pulmonary embolism, breast cancer, ovarian cancer, lung cancer, dementia, hyperlipidaemia, gall bladder disease are also effects which synthetic HRT has on the body.
The WHI study concluded that there was consistencies in trials that showed HT-E and HT-EP increased the risk of stroke (Anderson et al 2004) as a result of the oestrogen component of the therapies.
The same study showed that increased risk of pulmonary embolism were observed in the HT-E but the risk was not thought to be “statistically significant” (Anderson et al 2004).
One of the major findings of the WHI study was the remarkable increase in cases of breast cancer in HT-EP therapies. HT-E surprisingly showed slight trend towards a lower breast cancer risk, however it was noted that that trend was not significant. The increase in breast cancer in the HT-EP trials is thought to be attributed to the addition of medroxyprogesterone acetate, a synthetic variant of progesterone (Prentice, Anderson 2008).
Ovarian cancer risk was observed in HT-E therapies particularly when taken for 10 years or more (Lacey et al 2002) but showed that HT-EP used short term did not increase ovarian cancer risk but that long term studies of HT-EP use still needed to be explored.
Chlebowski et al 2009 concluded a study on HT-EP and lung cancer in post- menopausal females and found that the use of HT-EP significantly increases the risk of the number of deaths in non-small-cell lung cancer in post- menopausal females. The trend which was observed however, was not statistically significant (Chelbowski et al 2009).

The level of risk in developing these conditions associated with HRT can be reduced if the most effective method of delivery is performed. HRT can be prescribed as local or systemic therapy. Local being the use of creams or rings. Systemic being oral drugs, transdermal patches and gels, or implants.
Oestrogen, in the form of oestradiol, is taken orally and converted in the liver to oestrone, a weaker oestrogen. But when oestrogen as oestradiol is used trans dermally as a patch or a gel, it enters the bloodstream as oestradiol. When oestrogen is ingested it is subjected to phase I drug metabolism and is processed through the liver. The phase I drug metabolism stimulates proteins associated with heart disease and stroke. Using a patch or gels to take oestrogen avoids phase I drug metabolism and the risks associated with it. The same level of blood concentration can be achieved using patches or gels and can avoid the serious side effects associated with oral oestradiol HRT. Current research shows that the transdermal route of oestradiol administration can also be advantageous for women with diabetes, hypertension and other cardiovascular risk factors.

Aly Curd


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