Female sex hormones and Rheumatoid

Arthritis

There are many mysteries attached to rheumatoid arthritis (RA). One of them is that we do not know what triggers it. There are some mysteries which seem to point to the role of female sex hormones in its development and expression. One of the major female sex hormones is called oestrogen. The features of rheumatoid arthritis that suggest that female sex hormones, oestrogens, may be playing an important role:

1. Women who take oral contraceptives containing oestrogens are less likely to develop rheumatoid arthritis.
2. Women who are receiving oestrogen replacement therapy are also less likely to develop rheumatoid arthritis.
3. For most women, rheumatoid arthritis (RA) improves during pregnancy and worsens after delivery. These changes in disease activity coincide with changes in the levels of oestrogens circulating in the blood.

How could oestrogens modify the expression of RA? This question cannot be answered simply by observing patients with rheumatoid arthritis. This complex situation can only be answered by experiments. These experiments are usually carried out in mice. I do hope that those of you reading this article have no moral objections to experiments carried out in mice under ethical and humane guidelines. With that proviso in mind, I will now describe to you the experiments of Liselotte Jansson and Rikard Holmdahl from Lund University, Sweden, who have tried to unravel this conundrum.

They used arthritis in female mice and asked the question 'What would happen to the arthritis if these mice were given extra oestrogens?' As expected the arthritis in these mice was considerably improved. The improvement in disease could have been due to one of many of the effects of oestrogen hormones. Specific effects of oestrogen hormones are due to effects on cells within the body. They, therefore, gave the mice a chemical which blocked the effect of oestrogens on cells. The arthritis on these mice was, as you would expect, worsened. Very interesting, however, the doses of oestrogen and of inhibitor used were such that they did not interfere with the normal female cycle in these mice.

Thus, the conclusion from these experiments is that oestrogens have a beneficial effect in rheumatoid arthritis by a mechanism that is independent of their ability to act as sex hormones. You may very well ask, 'What is the relevance of these experiments to human rheumatoid arthritis?' That is a very valid question especially as these experiments have been carried out on animals. The answer to that question is that it is possible that drugs could be designed and manufactured that could have this effect of oestrogens without having the female hormonal effect. After all, it would not be advisable to give oestrogen hormones to men with rheumatoid arthritis. It also would not be very wise to give extra oestrogens to women because of the possibility of long term side effects such as increased heart disease and increased cancers.

This is a very interesting advance in our scientific understanding of rheumatoid arthritis. As usual, this increased understanding also gives an insight into how future new therapies could be developed.

Jansson L and Holmdahl R. Enhancement of collagen-induced arthritis in female mice by estrogen receptor blockage. Arthritis Rheum 2001; 44 (9): p2168-2175.

Reference can be found at:  http://www3.interscience.wiley.com/journal/76509746/home