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Pre-clinical study: Effect of Femarelle® on the Skeletal Tissues and on the Uterus
An in-vivo study in rats investigated the mechanism of action of Femarelle®, on bone buildup and its safety in the uterus.
The study measured Creatine Kinase (CK) activity, an assay of estrogenic response, in the skeletal tissues and in the uterus. The activity of CK in bone tissue serves as an indirect marker of estrogen participation in the processes of cell growth and bone formation, and a direct indicator of mediation of these processes through estrogen receptors. In this study measurement of the specific activity of CK was used to compare the effects of Femarelle®, 17β-estradiol (E2), and a vehicle (control) on bone and cartilage in non-ovariectomized (non-OVX) and ovariectomized (OVX) female rats.
OVX rats were fed by placebo (control), E2 or Femarelle®, and CK activity was measured in the epiphyseal cartilage and the diaphyseal bone (the tissue-building sites in the bone) as well as in the uterus.
Raloxifene, which acts as an estrogen receptor blocker, was added in order to determine whether the mechanism of action of Femarelle® is through estrogen receptors.
Results
As early as after several days of treatment with Femarelle®, an increase in estrogen receptor activation was observed in both the diaphysis and the epiphysis of the bone.
Effects of treatment with Femarelle®, E2 and a vehicle (control) on creatine kinase activity
Effect on bone
Contrary to estrogen Femarelle® did not induce any effect on the uterus.
Effect on the uterus
The effect on bone growth was lost when the estrogen receptors were blocked with Raloxifene.
Effect after blockage of estrogen receptors with raloxifene
Conclusion
Femarelle® significantly stimulated bone structure and produced bone cell growth and bone formation. However, whereas E2 stimulates estrogen receptors in the uterus, Femarelle® does not. The raloxifene-induced inhibition of both E2 and Femarelle® activity points to their common mechanism of action through estrogen receptors. These findings identify Femarelle® as a SERM, capable of selectively activating bone formation via estrogen receptors without inducing any estrogenic activity in the uterus.
Publication
J. of Steroid Biochemistry & Molecular Biology 2003; 86(1):93-98: “DT56a (Tofupill/Femarelle), selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the uterus” Somjen D, Yoles I.
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