Temporal and Spatial Association of Matrix Metalloproteinases with Focal Endometrial Breakdown and Bleeding upon Progestin-Only Contraception1

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 12; pp. 4827 - 4834
• Main Authors: Galant, Christine, Vekemans, Marcel, Lemoine, Pascale, Kokorine, Isabelle, Twagirayezu, Pierre, Henriet, Patrick, Picquet, Christine, Rigot, Véronique, Eeckhout, Yves, Courtoy, Pierre J., Marbaix, Etienne
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-12-2000
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.85.12.7020

The pathogenesis of irregular endometrial bleeding, the main reason for
stopping contraception with progestins only, is unknown. Based on the
recent reappraisal of the mechanisms of menstrual bleeding, we
hypothesized that matrix metalloproteinases initiate this disorder.
Volunteers upon Norplant treatment provided endometrial biopsies at the
start of a bleeding episode and during nonbleeding intervals. Focal
stromal breakdown, collagen fiber lysis, and collagenase-1
messenger ribonucleic acid were evidenced in most bleeding
endometria, but never in the nonbleeding ones. In the breaking down
areas, immunolabeling for gelatinase A was strongly increased, and that
of progesterone and estrogen receptors was decreased. Explants from
bleeding endometria produced high collagenase and gelatinase
activities, whereas release from nonbleeding endometria was negligible.
Bleeding endometria released more latent and active forms of
collagenase-1 and active gelatinases A and B, but less tissue inhibitor
of metalloproteinases-1, than nonbleeding endometria. Collagenase-1
release closely correlated with that of interleukin-1α. In contrast,
N-acetyl-β-hexosaminidase and tissue inhibitor of
metalloproteinases-2 were similarly released in both groups. Thus,
endometrial bleeding occurs together with focal stromal breakdown,
collagen lysis, expression and activation of several matrix
metalloproteinases, and decreased production of tissue inhibitor of
metalloproteinases-1. These results may lead to new pharmacological
treatment of this common medical problem.