A lot is known about the hormonal influences and genetics of fibroids, but the short answer is that gynaecologists and medical researchers do not know exactly why some women develop fibroids and why fibroids form.
Genetic causes of fibroids
Certainly genetics plays a role in the development of fibroids. There are families in which there is a very strong tendency for fibroids to grow. In some families, every generation of women develop fibroids. There are other families where the women on the mother's side of the family (the maternal relatives) do not get fibroids, but the women on the father's side of the family have major problems with fibroids. In other words the cousins and aunts on the paternal side are badly affected by fibroid problems. It seems that it is possible to inherit a genetic tendency for fibroids via either your mother or father.
Why are the genes that causes medical problems passed on?
It is known that genes that cause diseases often have a beneficial effect as well. A well known medical example is the gene for sickle cell anaemia. Being a carrier for sickle cell anaemia prtotects against malaria.
In the past when lifespans were shorter, many women died in childbirth and women rarely lived to their forties, even if women had an inherited tendency to fibroids, few women actually had fibroids. In addition, those few women who did have fibroids had less symptoms because women spent more years being repeatedly pregnant or breast feeding. The genes that caused fibroids may have had some as yet unknown benefit.
Gynaecologists also think that there are many different types of fibroids which result from many different genes. Medical specialists say that "fibroids are a phenotype or expression of disease that results from many different genotypes or different root causes".
Environmental causes of fibroids
It is likely that factors in the environment acting alone, or in interaction with genetic factors influence the formation and growth of uterine fibroids. Medical studies have shown that diet, smoking and various types of contraception affect the risk of developing fibroids. There has also been research into chemicals which women are exposed to and whether these chemicals can cause fibroids to form and grow.
Another possibility is that current environmental factors may cause genes which have been dormant in previous generations to exert their influence. Scientists and doctors are concerned about chemicals such as pesticides or toxins which have an estrogen-like affect. These are known as xenoestrogens.
Steroid Hormones - Estrogen and Progesterone
It is known that fibroids respond to and are affected by the steroid hormones estrogen and progesterone. Gynaecologists debate which of these two hormones have a greater effect. A lot of early research has shown that estrogens are the most important hormone, but recent research suggets that progesterone may be equally or even more important.
Fibroids do not develop until after puberty and generally shrink (but not always) after the menopause. This makes it very likely that fibroids are dependent on and influenced by estrogen and progesterone. This theory is supported by the fact that one of the most potent medical treatments for fibroids is gonadotrophin releasing hormone (GnRH) agonists , which work by decreasing levels of both estrogen and progesterone. Gynaecologists report that there are times when progesterone appears to be the more important hormone. But why do some women develop fibroids and some do not, as all women have significant levels of estrogen and progesterone circulating in their bodies and affecting their uteri.
Problems with fibrosis – are fibroids a disease of fibrosis?
There is some medical evidence that fibroids are a disease of abnormal fibrosis. Keloid scars are the result of the body producing too much extracellular matrix (ECM or scar tissue) in a disordered way. There are biological similarities between uterine fibroids and keloid scars. It may be important that black women who are at increased risk of developing fibroids are also at increased risk of developing keloid scars.
Are Fibroids a disease of abnormal uterine blood vessels?
A paper published in 1912 by J.A. Sampson suggested that a problem with blood vessels in the uterus was responsible for the abnormal bleeding seen with fibroids. Sampson described local dysregulation of the vascular structures in the uterus. The original medical studies were carried out by injecting the blood vessels of the uterus with a substance similar to latex, after a hystercetomy had been performed. This research showed that when fibroids were present there was an increase in the number of arteries and veins in the uterus. The medical term for this is angiogenesis.
Angiogenesis is an abnormal formation of new blood vessels that can occur in many organs of the body. For example, in diabetes, new blood vessels grow in the retina and may bleed and cause visual problems. When cancers develop and grow, new blood vessels are also formed and angiogenesis is an important factor in the growth of many cancers. It is important to note that the uterus and ovaries are different from other organs in the body because new blood vessel formation takes place every month in the uterus and ovaries at the onset of a new menstrual cycle. It is known that there are a number of angiogenic growth factors present in increased amounts in uterine fibroids. Angiogenic growth factors are factors that stimulate new blood vessels to form and grow. The most commonly reported angiogenic growth factor is called basic fibroblast growth factor (bFGF). It is likely that there are many other angiogenic factors which are important in the growth of fibroids in the uterus.
The studies that involved injections of latex into the blood vessels of the uterus showed a condition which has been called venule ectasia. What was found was that the veins had an increased capacity and had become more floppy.
What causes this venule ectasia to take place in the uterus?
Originally it was thought that the fibroids physically compressed and blocked the flow of blood through the veins. However it is now thought that this is unlikely to be the complete explanation. It is probable that the development of venule ectasia also has a molecular explanation. It is possible that the veins in the fibroids uterus have an abnormal structure. Another explanation is that the vessels may be normal structurally, but the surrounding extracellular matrix (ECM) leads to ectasia by permitting the blood vessels to stretch abnormally or possibly by preventing the blood vessels from contracting and clotting following menstruation.
Are fibroids a disease of altered menstruation patterns?
For most of human history, women spent most of their lives either pregnant or breastfeeding and therefore the pattern of monthly periods and menstruation is relatively new. Effective contraception has resulted in women having constant regular menstrual cycles, and this may have played a role in the formation of uterine fibroids as well as other gynaecological diseases. Sometimes we think of fibroids as being unchanging static lumps of tissue, but it is known that fibroids are constantly being remodelled as certain genes are turned on and others are turned off each month as a result of the changing hormonal levels of oestrogen and progesterone during the normal menstrual cycle.
One theory is that these constant changing levels of oestrogen and progesterone may result in problems within the uterine tissue that lead to the formation of uterine fibroids. Having, on average, 13 menstrual cycles every year for up to 40 years gives room for many mistakes to take place within the tissues of the uterus.
Another explanation, is that because women with fibroids often report having periods which are heavy and or painful from a young age, some gynaecologist speculate that loss of blood supply (ischaemia) during menstruation may cause damage in the uterus that then leads to fibroids formation. Therefore, genetic or environmental factors plus having regular menstrual periods may be the initial problem and uterine fibroids are the resulting endpoint of the tissue damage which occurs because of these factors. Some gynaecologist speculate that if this is the case then preventing the cause of painful periods (dysmenorrhoea) in adolescence and in young women may lead to a reduction in fibroid development in older women.
One theory of the development of fibroids is the theory that fibroids are myometrium that considers itself to be pregnant all the time. It has been found that the genes expressed in the myometrium of pregnancy are similar to the genes that are turned on inside fibroids when compared with the normal myometrium. Medical research has also found that the process of the uterus returning to normal size (this is known as involution) following pregnancy can get rid of small fibroids. This may be why being pregnant protects against the development of fibroids. Therefore, the fact that modern women have less pregnancies may lead to an increase in fibroids that grow and are diagnosed.
These various theories are not necessarily mutually exclusive. Because fibroids can develop for different reasons, some of these theories may apply only to certain individual women. Alternatively, many theories may apply in other cases of uterine fibroids. To give an example, an environmental trigger may interact with a genetic reason for sensitivity to oestrogen or progesterone hormones.
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