If patients give an account of pain in the lower abdomen, heavy menstrual bleeding, constipation or problems with urination, for gynecologists the story becomes clear: At least 25 percent of all women of childbearing age suffer from fibroids. A more detailed investigation in the clinic reveals different localisations for these knotty troublemakers: in the muscle layer, in the mucous membrane, beyond or within the surrounding connective tissue of the uterus. Genetically at least, many fibroids are as alike as peas in a pod. This is what researchers at the University of Helsinki, Finland, have now found out. In total, they studied more than 200 specimens and identified in 70 percent of cases changes in the MED12 gene. This sometimes has the task of creating a working copy of the RNA from DNA, the first step in the production of proteins. For therapy purposes specifically, this finding is at present relatively worthless. Scientists have however also made great progress in other areas – surgical intervention such as the removal of the uterus (hysterectomy) or removal of the fibroids while preserving the organ (myomectomy, myoma enucleation) are not required quite so often.
The symptoms usually begin with severe pain. In acute cases, our old tried-and-tested friends NSAIDs, such as naproxen or ibuprofen, are helpful. As antagonists of prostaglandins, they reduce the contraction of uterine muscles. For heavy bleeding, tranexamic acid – an inhibitor of the body’s own blood-clot degradation system – can be used. At present, the substance has been approved for this indication by the U.S. Food and Drug Administration (FDA), but in rare cases deep vein thrombosis is possible. And mifepristone, made known as the agent in the “abortion pill” RU-486, also seems to have beneficial effects in low doses. The progesterone receptor antagonist showed in a study a significant improvement in symptoms in the women after six months. Also interesting is the effect of the drug given the laboratory abbreviations CDB-2914: In a randomised, placebo-controlled double-blind study, the drug reduced bleeding extremely effectively. The size of the fibroids also decreased significantly.
Menopause pill from the pack
Other approaches are brought into consideration due to the hormones involved: as long as there is oestrogen present, fibroids also keep enlargening. Only in menopause is there a cessation of growth, and a lot of ailments usually disappear almost by themselves. This fed the idea of intervening pharmacologically: GnRH analogues, ie artificial replicas of gonadotropin-releasing hormone (GnRH), reduce oestrogen levels in a permanent way and simulate a postmenopausal state – between 30 and 80 percent of all fibroids shrink after its use. However, this strategy also has its downside – typical consequences such as osteoporosis and hot flashes can’t be prevented. It’s true to say that once the drug is discontinued, adverse effects dissolve into thin air – however, fibroids tend to normally regrow quite quickly. Thus GnRH analogues are at best useful as a bridge over a short period up until menopause. Preoperatively, however, they make little sense, as a prospective, double-blind, placebo-controlled randomised study has recently shown. Surgeons have seen no significant difference between the control group and the placebo group in the outcomes of their interventions.
Using sound against the fibroid
As an alternative to medicine or scalpels, the use of bundled ultrasonics can be contemplated. Practitioners can, using MRI control, specifically target and “shave” the tumor. The trick: focused electromagnetic fields generate abiotically high temperatures in the knots – proteins are denatured, the tissue dies. The method yields good results and is well tolerated in itself, as research shows. Doctors treated 80 women, who had in total 147 fibroids, with MRI-guided, focused ultrasound. The average volume of the tumors directly after application was only 55 percent of the initial value and decreased after a half year to 31 percent. Nevertheless, the method is suitable only for tumors up to a maximum diameter of eight centimetres. Larger specimens can be reduced by doses of GnRH before the treatment. The conclusion from all data: patients recovered far faster than after surgery. Also, according to the USA’s FDA (Food and Drug Admninstration), significantly fewer side effects occurred. However, the method is not suitable for tumors that are located too close to the endometrium. Also an unfavourable anatomy, caused by intestines being too close, prevents the use of combined ultrasound. Nevertheless gynaecologists and radiologists together have worked out another method.
An infarct which heals
In many cases meanwhile, targeted Uterus Arterial Embolisation (UAE)) helps. For this procedure, surgeons introduce small plastic beads through the uteral crest into the uterine artery. These beads (Embozene®) have a diameter of 500-900 micrometers. They block the blood vessel involved – and all fibroids atrophy simultaneously. According to studies, heavy menstrual bleeding diminished quickly after the application, pain also disappeared relatively soon. The researchers tested the method on 121 patients, who had at times multiple fibroids. They achieved in total a devascularisation of 96 percent. After surgery, the volume of the tumors had reduced by four percent within four weeks, after three months by 52 percent and 78 percent after six months. A year later, the drop added up to as much as 91 percent. During this time, menstrual bleeding normalised in 92 percent of those affected, and general health likewise improved. Through this follow-up, the safety of embolisation in particular has been demonstrated, the authors stress. Researchers from the Frankfurt University Hospital have refined the process further: In addition to the gentler technique, patients were exposed to only one third of the usual radiation dose. A success story: will the UAE soon become the gold standard in fibroid therapy?
Not everything is rosy
Nevertheless, critics also register a critical word: As part of a radiological-gynaecological consensus meeting, colleagues from several professional societies do indeed evaluate the UAE as a generally “well-established, safe and effective procedure”, but at the same time point out its limits. Extensive studies comparing surgical techniques with embolistion do not exist as yet. This is especially problematic in female patients with a desire to have chidren, so they are just left out – unless their only alternative would be a hysterectomy. Also, the authors point out, a UAE should be performed only in clinics with the appropriate gynaecological and radiological expertise. Before the indicated intervention, thorough investigation by ultrasound is required, if any doubt exists then also by MRI, as well as a blood count including a negative pregnancy test. A cytological report, not older than six months, should also be at hand.
A good reason exists: In rare cases benign tumors can turn out to be nasty malignant tumors, so-called leiomyosarcomas. GnRH analogues are also a taboo months before the procedure, as spasmodic contractions of the uterine artery are a threat. The authors of the paper also see contraindication in the form of acute infections of the genital tract as well as known allergies to contrast agents. Fibroids in the uteral mucosal membrane and endometriosis are likewise considered an impediment. Otherwise, very little can go wrong – sometimes after surgery, patients have reported absence of menstruation and pain and fever, often leading to discharge. Nevertheless, patients recover more quickly than after hysterectomies or myomectomies. Now all that’s lacking is high quality studies.