Why should HRT now be considered safe with one small recent review study as opposed to two of the largest studies ever conducted in the history of HRT, around 2002, which showed categorically that it was unsafe?

Women who are suffering desperately are often asked to weigh up the pros and cons, given only little information, and speak to their doctors which in most cases amounts to the blind leading the blind when it comes to the mind boggling subject of HRT.

I hope to clarify some points here and hopefully give a clearer understanding of what women should really know about the latest study and how it may or may not be of benefit.   If women and doctors take the recent ‘HRT is Now Safe’ reports at face value, many women could unwittingly  be prescribed the most harmful combinations of HRT with disastrous results as was shown in the past major trials.

Last October, ironically breast cancer month, HRT was being hailed as being ‘safe’ again after the latest study from Denmark was published on the 9th October.  I and many others worried that some women would once more be led to believe that all is now well with HRT and could happily take it without any further ado or consequences.

However, if you scrutinise the study closely, much more can be understood as to why there were such positive effects when compared to the two lager trials in The Women’s Health Initiative (WHI) and The Million Women Study.  Both had some of the trials stopped early due to the rising negative effects of heart disease and breast cancer.

Firstly the Danish study did not say that HRT was now absolutely safe and reported that more research needed to be done as the time duration of the study could not be fully completed. This was due to women who may have been frightened to continue when negative results were coming through from the other two major studies and a time lag that made the breast cancer results uncertain.  However, it was suggested and reported in the national press that HRT may now be considered safe due to some very positive results at the end of part of the study.

Let’s clarify further.

  1. Overall the Danish study showed more benefits for post-menopausal women who took HRT at a younger age compared to older women.  The HRT preparations used were showing that they protected against heart disease, stroke, breast cancer and osteoporosis.  This is implying that the longer women leave their bodies without the protective benefits of HRT after the menopause, the more likely the ‘older’ woman’s body would not tolerate it as well.  If it is taken when the body is younger and healthier before it has had a chance to deteriorate more rapidly with the drop in progesterone and oestrogen, it is more likely to maintain that status.  This is thought to give not only short term benefits, but also the lasting ability to tolerate any possible negative effects in the long term.
  2. It is thought by many of the proponents of HRT that the two major studies, The One Million Women Study and the WHI were flawed due to recruiting mainly older women who were well passed the menopause and stated this right from the beginning.
  3. The Danish study was able to substantiate the above paragraphs, 1 and 2, to a degree with the main strength quoted as being in its longer duration of time (16 years) although the last 6 were not followed officially or had post-hoc analyses as the trial had to be stopped at 10 years due to the other major trials showing mostly negative results and also having to be halted before completion.

We have to be wary of the facts as they are presented, but I would also like to clarify some points for those who may not have had the time or inclination to study the report further.

My biggest question was why did two massive studies show different results compared to the much smaller Danish study as surely the age difference could not account for the huge discrepancies alone?

Well there was a difference and a significant one at that.  You see the same HRT preparations were not used.  The safer preparations were used some of which were also reported to be safer in the other major studies.

The difference between the main types of HRT studied and used in the trials.

  1. Prempro – conjugated human and horses oestrogens and medroxyprogesterone acetate (different types of joined oestrogens and a very potent synthetic progesterone).  This is given to women with an intact uterus.  The Progestogen is given to stop the oestrogen component from causing uterine cancer.
  2.  Premarin – conjugated human and horses oestrogens (joined oestrogens).
  3. 17-β-estradiol – a naturally occurring human oestrogen.
  4. Norethisterone acetate – a synthetic non-human Progestogen.
  5. Progesterone – a naturally occurring human Progestogen synthesised within the body.
  6. Natural progesterone –   a human Progestogen which is synthesised from plants to be bio-identical to the naturally occurring human Progestogen.

The female body produces 17-β-estradiol (oestradiol) and progesterone every month during a normal menstrual cycle. Oestradiol rises in the first half or the cycle and is involved with building up the uterine lining in preparation for a pregnancy.  At mid cycle, progesterone is released after ovulation and becomes the dominant hormone during the second half of the cycle.  It calms down the proliferative effects of oestradiol and further refines the bloody lining of the uterus.  If there is no conception at the end of the cycle, both hormones drop which instigates a period and then the whole process starts again.

The oestradiol oestrogen is our most potent reproductive hormone which plays and important role in multiplying cells and is produced in micrograms.  Progesterone balances any negative effects of oestradiol and is produced in milligrams. It has an extremely important role in keeping oestradiol under control not least stopping it from causing uterine cancer as well as other cancers.

In nature, the balance between these two hormones is extremely important for maintaining health.  If we are deficient in either and have adverse symptoms, supplementing with progesterone and oestrogen can be beneficial giving a much better quality of life.

However, whereas progesterone can be given alone as it is the precursor of oestrogen and keeps its harmful effects in check, oestrogen should never be given alone.

Most women will find that natural progesterone alone is enough to alleviate their symptoms, but sometimes women may need to supplement with a form of natural oestrogen.

So natural progesterone first with some natural oestrogen, if needed, would be a safe and effective treatment for those who have a deficiency in these same hormones.

The information above describes the ideal solution

When we run down on our natural female hormones through either menopause or hysterectomy and have undesirable symptoms as a consequence, we simply replace them with the same bio-identical hormones (progesterone and oestrogen) which the body can assimilate along the steroid hormone pathways as nature intended; right?

Well you would have thought so, but it is made to be much more complicated than that.
Going back to the three trials and why the Danish study showed more favourable results than the other two.

The One Million Women Study was not clear about which HRT preparations all the women were taking, but most would have been taking mainly Prempro, Premarin and 17-β-estradiol in different combinations.  Regardless the trial had to be stopped early due to the negative effects which showed that HRT had more risks than benefits.

The Women’s Health Initiative Study used mainly Prempro and Premarin which also had to be stopped early due to negative effects. The worse preparation being Prempro which contained a mix of one natural human oestrogen, two horses’ oestrogens and a synthetic Progestogen known to have many adverse side-effects.

However, the Danish study used the natural oestrogen 17-β-estradiol on its own for women who had a hysterectomy or with the synthetic Progestogen Norethisterone acetate for those with an intact uterus. They also used ‘alternatives’ or other ‘mechanisms’ for those who could not tolerate the combined preparations that contained synthetic Progestogen.  The only ‘alternatives’ I could establish in the data was natural progesterone and guess what?  It had the most favourable outcome of all preparations.  See here an extract taken from the study:

Several other mechanisms may explain the beneficial effects of hormone replacement therapy on cardiovascular endpoints. Different hormone replacement therapy regimens have been found to have positive effects on lipid metabolism26 27 28 and the combination 17-β-estradiol with norethisterone acetate has been shown to lower total cholesterol levels and improve endothelial function in healthy postmenopausal women.29 In other studies, however, gestogens have been found to blunt the positive effects of oestrogen.26 30 The type of progestogen used may be important, as natural progesterone seems to have more beneficial effects on the cardiovascular system than does medroxyprogesterone acetate.30 31

This is how I can clarify the results of the ‘recent’ Danish study.

The Danish study was originally started to trial the effects of HRT on prevention of osteoporosis which finished some years ago.  Its data was then used in a different study much later to evaluate the effects of HRT on the cardio vascular system.  The evaluators were also able to observe the effects of HRT on breast cancer incidences.

The conclusions showed positive results when HRT was used in younger menopausal and post-menopausal women and here is why this may have been the case:

  1. The women were younger and healthier and the body did not have a chance to deteriorate much over time due to the negative effects of a decrease in progesterone and oestrogen.
  2. Safer and natural forms of HRT were used compared to those used in the two major studies in which case, older women would have also shown positive effects who may now be neglected due to the negative report that seem to apply only to them.
  3. Natural progesterone and natural oestrogen indicated in the Danish trials, but not in the two major trials, could have contributed to the more favourable outcomes.  Numbers of women taking this combination were not stated.

All this, whichever way you look at it, supports the fact that hormones which are bio-identical to those that the body produces are better for us than hormones that are foreign to the body. Regardless of all the intricate studies, the bottom line is: if the body is low on a particular hormone and is causing unpleasant symptoms, give back the hormones that nature intended us to have.

One last very important point to consider is the fact that there was a sharp drop in oestrogen driven breast cancer incidences shortly after the two major HRT trials were halted.  This was reported as being directly linked to many women discontinuing their HRT due to the negative reports. See here