Endocrine Abstracts

Introduction: The human endometrium has a remarkable capacity for repeated repair following the inflammation of menstruation. This occurs without scarring or loss of function but mechanisms involved remain undefined. Aberrations in endometrial repair may lead to pathology such as heavy menstrual bleeding (HMB). The transforming growth factor-β superfamily has been implicated in efficient wound repair and has a potential role in menstrual repair. Downstream of TGF-β, phosphorylation of Smad2/3 initiates binding with Smad4 to regulate target genes.

Hypotheses: Women with HMB have i) delayed endometrial repair and ii) aberrant endometrial TGF-β signalling compared to women with normal loss (NMB).

Methods/results: Endometrial biopsies (n=44) were collected with ethical approval and consent from women with no structural abnormalities. Stage classification was based on day of cycle, histology and serum hormone levels at time of biopsy. Objective measurement of menstrual blood loss was performed using the alkaline–haematin method to classify women as having HMB >80 ml or NMB <80 ml. Menstrual pictograms were completed simultaneously. Of note, women with HMB bled for 6 days on average, compared to 4 days for women with NMB (P<0.01). Gene expression between these two groups was compared using RT-PCR. Menstrual phase endometrium from women with HMB had significantly less SMAD3 mRNA expression than those from women with NMB (P<0.05). There were no significant differences in SMAD3 expression at any other phase of the menstrual cycle. Phosphorylated SMAD2/3 protein was identified by immunohistochemistry in menstrual phase endometrium, present in a nuclear location in glandular epithelial cells. Minimal staining was seen in proliferative and early secretory tissue.

Conclusions: The prolonged bleeding identified in women with HMB is consistent with defective endometrial repair. The presence of active SMAD2/3 protein at menstruation and decreased SMAD3 expression at this time in women with HMB implicates TGF-β signalling in the pathogenesis of this common disorder.