Could prolactin, the hormone responsible for lactation and uterine contraction after the birth of a child, have a sinister side?Today researchers from Germany reported (subscription required) in the Journal of the American College of Cardiology that stopping lactation with bromocriptine, a direct inhibitor of prolactin, facilitated the resolution of peri-partum cardiomyopathy in two patients.
Peri-partum cardiomyopathy has been a heretofore poorly understood disease that causes a diffuse weakening of the heart in woman that develops within the last month of pregnancy or within five months immediately following pregnancy. It carries with it a high degree of mortality in women afflicted with the disease from heart failure or sudden death.
Today's report offers a unique insight as to a possible mechanism for the cardiomyopathy:
Prolactin exists in at least 2 biologically active forms with opposing effects. The physiological full-length 23 kDa prolactin promotes angiogenesis and protects endothelial cells whereas the cleaved 16 kDa derivate induces endothelial cell apoptosis and disrupts capillary structures. Recent data showed that oxidative stress promotes the postpartum generation of 16 kDa prolactin, which is causally related to PPCM. In turn, prolactin blockade with bromocriptine was successful in preventing onset of PPCM in mice and in patients at high risk for the disease.Translating this: a shorter-than-normal piece of the prolcatin molecule is thought to lead to cell death and disrupts tiny blood vessels, possibly leading to the reduced heart function seen in peripartum cardiomyopathy (PPCM). Production of the specific form of dangerous prolactin (16 kDa) can be blocked with administration of bromocriptine in mice, so it was used in two cases in women and appeared to have beneficial effects, restoring heart muscle function in each of them.
The authors admit that the women were also receiving treatment with more conventional beta blocker and angiotensin converting enzyme inhibitors and these may have been responsible for the two patient's recovery, and that some patients recover despite any therapy. But the elucidation of the potential role of prolactin in the pathophysiology of this disease sheds light on a potentially exciting area to be evaluated in a prospective, multicenter trial.
-Wes
Reference: Denise Hilfiker-Kleiner, PhD, Gerd Peter Meyer, MD, Elisabeth Schieffer, MD, Britta Goldmann, MD, Edith Podewski, MD, Ingrid Struman, PhD, Philipp Fischer, MD and Helmut Drexler, MD. "Recovery From Postpartum Cardiomyopathy in 2 Patients by Blocking Prolactin Release With Bromocriptine," J Am Coll Cardiol, 2007; 50:2354-2355, doi:10.1016/j.jacc.2007.10.006
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1 comment:
DA antagonists such as domperidone and metaclopromide are used for increasing prolactin levels to enhance breastfeeding. What do you think of a study that investigates a correlation of PPCM and women who have had their prolactin levels pharmacologically increased? (This would really only consider at the post-partum women though). Anyway, the idea popped in my head as I read this post.
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