ABOUT FEMARELLE® (DT56a)
MENOPAUSE SYMPTOMS & FEMARELLE®
BONE HEALTH SUPPORT:
*Health Canada has not approved Femarelle for vaginal atrophy. Using Femarelle for vaginal atrophy would be considered off-label use.
*Femarelle is not recommended for use in breast cancer patients.
Clinical Study: Bone Health
Femarelle (DT56a)- a New Phyto-Selective Estrogen Receptor Modulator-like Substance for the Treatment of Postmenopausal Bone Loss. Yoles I. et al. Menopause 2003
The effect of Femarelle® was assessed on human bone through dual-energy x-ray absorptiometry (DEXA) scan of the hip and the spine.
In a clinical trial, healthy post-menopausal women (n=98) were randomly allocated, on a double-blind basis, to receive either the recommended dosage of Femarelle® (644 mg/day) or a low dosage of DT56a (344 mg/day), supplemented with calcium, for twelve months. A comprehensive health questionnaire, and physical, laboratory and pelvic sonography examinations were performed at the start of the trial and every 3 months thereafter. Bone mineral density (BMD) was assessed by DEXA of the lumbar spine and femoral neck at enrollment and after twelve months of treatment.
Results: Following twelve months of treatment, BMD in the Femarelle® group was increased by 3.6% in the lumbar spine and by 2.0% in the femoral neck. In the low-dose group, BMD was decreased by 0.6% both in the femoral neck and in the lumbar spine (Figure 11).
Conclusion: Femarelle® selectively affects estrogen receptors in the bone, increasing BMD without affecting the uterus. Since the hormonal blood profile was left unchanged this means that although the estrogen receptors were affected in target tissues, the body does not perceive Femarelle® as estrogen.7 Note: Health Canada has approved Femarelle® for the relief of menopausal symptoms and to support bone health.
Pre-Clinical Study: Mechanism of Action in Skeletal Tissues and Uterus
Femarelle (DT56a), selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the uterus. Somjen D., Yoles I. J. of Steroid Biochemistry & Molecular Biology 2003
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®, 17ß-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.
Result: As early as after several days of treatment with Femarelle®, an increase in CK activity was observed in both the diaphysis and the epiphysis of the bone (Figure 12a).
Conclusion: Relative to the control, both Femarelle® and E2 significantly stimulated bone structure. 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.8 Health Canada has approved Femarelle® for the relief of menopausal symptoms and to support bone health.
Pre-Clinical Study: Histology of Skeletal Tissues
Treatment with Femarelle® and with E2 prevented the bone loss following OVX, maintaining all parameters to non-OVX control levels (Table 1).
Histological techniques and histomorphological measurements, by enabling direct observation of the tissues, yield highly accurate data on the effects of a product on bone. We compared the effects of long-term daily treatment with Femarelle® (DT56a), E2, and placebo on the skeletal histology of ovariectomized (OVX) and non-OVX rats in order to study the dynamics of their effects on the rebuilding process in different parts of the bone.
Thirty rats were divided into four groups. Rats in the control group were left with intact ovaries and those in the other groups underwent ovariectomy. The OVX rats were treated for 2 months with Femarelle®, E2, or placebo (control). Histomorphometry of the trabecular bone volume (TBV) in each rat (expressed as a percentage of the total bone volume), as well as cortical thickness and growth plate width, were recorded by a computerized system. In addition, CK-specific activity, a marker of estrogen receptor activation, was analyzed in the skeletal tissues and in the uterus.
Results: The OVX rats showed substantial losses of TBV, cortical thickness and growth plate width, with the result that they were markedly osteoporotic relative to non-OVX rats (Figure 13).
Figure 13: Sample histology slides showing the effects of treatment with Femarelle®, E2, and a vehicle on bone
A significant increase in CK activity was found following E2 and Femarelle® treatment in the skeletal tissues (Epiphysis and Diaphysis). However, while E2 produced significant CK activation in the uterus, Femarelle® had no stimulatory effect in that site.
Conclusion: Since peak bone mass in women is reached around the age of 30, comparing the bone structure of a young rat to that of an OVX one following treatment with Femarelle® provides the best indication regarding the properties of Femarelle® on bone build-up and bone health preservation. This study serves as further proof of the beneficial effect of Femarelle® on the bone without affecting the uterus.9 Health Canada has approved Femarelle® for the relief of menopausal symptoms and to support bone health.