Flaxseed does not enhance the estrogenic effect of low-dose estrogen therapy on markers of uterine health in ovariectomized rats.

Flaxseed (FS) is an oilseed rich in phytoestrogens and n-3 polyunsaturated fatty acids, compounds that may attenuate bone loss during aging. We previously demonstrated using the ovariectomized (OVX) rat model of postmenopausal osteoporosis that 10% dietary FS combined with low-dose estrogen therapy (LD) preserves vertebral bone mass and strength more so than either treatment alone. However, it was prudent to also consider the effect of this intervention on uterine tissue as LD, and possibly FS, may have estrogenic, and thus negative, effects on uterine tissue. The present study investigated if FS enhances the estrogenic effect of LD on markers of uterine health in OVX rats. Three-month-old rats were randomized to groups: (1) SHAM, (2) OVX, (3) OVX+FS, (4) OVX+LD, or (5) OVX+FS+LD. Ground FS was added to the AIN-93M diet (100 g/kg of diet), and LD was delivered by subcutaneous implant (0.42 µg of 17ß-estradiol/kg of body weight/day) to mimic LD in postmenopausal women. After 12 weeks, histological analyses of uterine tissue demonstrated flattened or cuboidal luminal epithelia organized in a single layer in the OVX group, while FS, LD, and FS+LD induced a single layer of elongated luminal epithelia, columnar in shape. The SHAM group had the greatest epithelial mass. Cell proliferation was similar among all OVX groups. Therefore FS and FS+LD similarly induce estrogen-like effects on the morphology of luminal epithelia that are weaker than in the SHAM group without inducing cell proliferation in OVX rats. Thus, FS does not enhance the estrogenic effect of LD on markers of uterine health in OVX rats.

Flaxseed combined with low-dose estrogen therapy preserves bone tissue in ovariectomized rats.

OBJECTIVE: Flaxseed is rich in lignans and alpha-linolenic acid, compounds that may promote healthy skeletons. Many postmenopausal women consume complementary health products such as flaxseed or its components in addition to pharmacological agents such as low-dose estrogen therapy for additional support for menopausal symptoms and related conditions. However, their combined effect on bone health is unknown. The aim of this study was to determine the effects of 10% dietary flaxseed, low-dose estrogen therapy, or their combination on bone mineral density, biomechanical strength, and skeletal fatty acid composition in an ovariectomized rat model of postmenopausal osteoporosis. METHODS: Ovariectomized rats received (1) basal diet (negative control), (2) 10% flaxseed, (3) low-dose estrogen implant (13 microg, 90 day release), or (4) flaxseed + low-dose estrogen implant for 12 weeks. A sham-operated group was included as a positive control. Bone mineral density, biomechanical strength, and fatty acid composition were measured at multiple skeletal sites. RESULTS: Flaxseed + low-dose estrogen therapy resulted in the highest bone mineral density and peak load at the lumbar vertebrae, with no effect on bone mineral density or strength in the tibia and femur. Flaxseed and flaxseed + low-dose estrogen therapy resulted in significantly higher relative levels of alpha-linolenic acid and eicosapentaenoic acid and lower levels of linoleic acid, arachidonic acid, and n-6/n-3 ratio in the lumbar vertebrae and tibia compared with all other groups. CONCLUSION: Flaxseed + low-dose estrogen therapy provides the greatest protection against ovariectomy-induced bone loss at the lumbar vertebrae. Moreover, this study is the first to demonstrate that flaxseed, rich in alpha-linolenic acid, alters fatty acid composition in the ovariectomized rat skeleton.