Differences between the pre-menopausal and post-menopausal uterine fibroid vasculature
Introduction
Uterine fibroids are a significant health problem. They are the most common indication for a woman to undergo a hysterectomy [1], [2]. The risk of operative and post-operative complications with a hysterectomy has been estimated at 12.5%, with a 0.04% mortality rate [3], thus leading to the ongoing search for less invasive treatment options for uterine fibroids. In recent years these treatments have included uterine artery embolization and GnRH agonists.
There is good evidence that fibroids are dependent on estrogen and progesterone for their growth, as they only appear after menarche, and reduce in size after menopause or after a course of GnRH agonists [4]. The changes in fibroids after the menopause represent an opportunity to study natural mechanisms of fibroid regression for possible medical therapeutic targets.
Although non-invasive vascular treatments such as uterine artery embolization have been used for treatment of fibroids [5], angiogenesis has received little attention as a possible mechanism involved in fibroid growth and regression. It has been reported that the microvascular density of the fibroid is reduced compared with the adjacent myometrium [6], associated with the altered expression of angiogenesis promoters and inhibitors [7]. However, the literature lacks quantitative studies specifically examining changes in the microvasculature of fibroid uteri after the menopause.
Efforts to discover medical options for reducing fibroid growth via manipulation of angiogenesis will benefit from a greater understanding of the changes occurring with the natural regression occurring after the menopause. The aim of our study was thus to examine and quantify microvascular density changes after the menopause, and secondarily to see how the administration of hormone therapy (HT) affected those changes.
Section snippets
Sample collection
Ethical approval for the collection of fibroid and myometrial tissue was obtained from Southern Health Human Research and Ethics Committee B, and informed consent was obtained from all patients.
Samples of fibroid and adjacent myometrium were excised and fixed in formalin from a total of 34 uteri at hysterectomy. Fibroid and myometrium samples were divided into three groups: pre-menopausal, post-menopausal, and post-menopausal with hormone therapy. Pre-menopausal women were defined clinically as
Within-pair comparison of myometrial and fibroid microvascular density (MVD)
The MVD of the pre-menopausal paired specimens was significantly higher in the myometrium than in the fibroid, as expected, with a mean difference in MVD of 5.81 (95% CI: 2.06, 9.57, p = 0.0046) (see Fig. 1). There was considerable variation in the ratio between the 18 pre-menopausal pairs, with 2/18 having a higher MVD in the fibroid than in the myometrium (myometrial: fibroid MVD ratio <1.0), and 3/18 having roughly equivalent MVD (myometrial: fibroid MVD ratio = 1.0–1.3), but the majority showed
Discussion
This study is the first to quantitatively examine changes in the vasculature of different compartments of the post-menopausal fibroid uterus. Here, we show that, after the menopause, the myometrial microvascular density increases, and the fibroid MVD remains the same. It is the change in myometrial MVD that causes the relative decrease in fibroid vascularity after the menopause.
The increase in the myometrial MVD seen post-menopause may be due to the atrophy of the non-vascular component of the
Acknowledgements
Thanks are due to Sisters Nancy Taylor and Nicki Sam for the collection of tissue samples and to Dr Mark Lawrence and the various gynaecological surgeons affiliated with Monash Medical Centre who provided subjects for the study. PAW Rogers is a Principal Research Fellow of the National Health and Medical Research Council of Australia (Fellowship grant #143805).
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