Different Progestogens And Their Risks

Pharmacist Dr Alfred Mueck is a leading expert on hormonal contraception and hormone therapy. He recently spoke at the World Menopause Congress on different progestogens (the most important being progesterone) and whether they convey different risks.


Here is a summary of his presentation:

The link between  HRT and breast cancer still is very unclear. In 5 recent publications (Shapiro et al.) evaluating the most important studies (including Collaborative Reanalysis 1997, WHI 2002/2004 and Million Women Study 2005), using the Bradford Hill criteria for statistical evaluation, we concluded that it seems not possible to get an answer in clinical studies. So we need the mechanisms.

Progestogens can influence the proliferation of breast cancer cells via genomic and non-genomic mechanisms. Two recent editorials in the journal ‘Menopause’ on our research regarding the importance of membrane-bound receptors pointed out, that the results in the WHI-study may be explained by mechanisms caused by those receptors. We found that patients with breast cancer express those receptors in malignant but not in benign breast tissue. We have shown that certain progestogens increase the estrogen-induced proliferation in presence of those receptors. MPA (medroxyprogesterone acetate – Provera®), NET (norethisterone- Primolut N®) and also other synthetic progestogens much faster proliferate the cells compared to progesterone.

In contrast the proliferation with estrogen-only is slow, and carcinoprotective mechanisms can work which can explain the results in the WHI-E-only-study. Thus the choice of progestogen is important and future screening for those receptors may identify women who are at increased risk regarding these mechanisms.


Dr Mueck comments highlight the difference between synthetic progestogens and natural progesterone.  Progesterone receptors within the body are fussy as to what ‘key’ switches them on and synthetic progestogens do not interact with these receptors in the same way as natural progesterone. This is why synthetic progestogens are not helpful if a women has estrogen dominance. We know that estrogen has a stimulatory effect on breast tissue and that progesterone tempers that effect. Therefore when choosing which progesterone to use for hormone replacement therapy these important differences should be considered with natural progesterone being a superior choice.


For more information on Natural Progesterone click on the booklet below,

Progesterone for women booklet

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