Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy

Abstract

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.

Development of low-dose reproductive hormone therapies in China

“…bone loss, CVD and central nervous system dystrophy) in postmenopausal women. While low-dosage HRT has been increasingly investigated recently [22][23][24], the effective dose range and regimen remain elusive. Furthermore, even today the risk-benefit ratio of long-term use of low-dosage HRT, which is necessary for delaying postmenopausal degenerative processes, has not been completely assessed.…”

“…However, the lack of confidence and the continuing confusion caused by this episode have left an important gap in knowledge of the effects of HRT to be resolved, especially regarding the length of time that HRT may be administered, the doses to be used, and the balance between the beneficial and adverse effects of sex hormone treatment in aging women. We believe that this is a good time to determine the effects of low-dose HRT [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Regimens must be tested that will retain estrogen's beneficial cardiovascular effects while reducing estrogen-associated risk [24].…”

“…The WHI caused massive concern and defection from HRT [19][20][21][22][23][24][25], even though the apparent conflict between the randomized and observational studies was eventually resolved. Subgroup analyses of the WHI that indicated that WHI women who were in the same age group when they began HT as those in the observational NHS were protected from cardiovascular events to the same extent as were the women in the NHS, i.e.…”

“…We believe that this is a good time to determine the effects of low-dose HRT [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Regimens must be tested that will retain estrogen's beneficial cardiovascular effects while reducing estrogen-associated risk [24]. Most of the previously reported observational investigations were done in women receiving HRT at dosages for relieving menopausal symptoms that may be higher than necessary for delaying degenerative process (e.g.…”

Flaxseed Does not Antagonize the Effect of Ultra-Low-Dose Estrogen Therapy on Bone Mineral Density and Biomechanical Bone Strength in Ovariectomized Rats

“…However, evidence showing that lower dose estrogen therapies (Ettinger et al, 2004;Richman et al, 2006) are effective at inhibiting bone loss and have fewer side effects has stimulated a renewed interest in hormone therapy for treating postmenopausal bone loss. Specifically, estrogen therapy at low and ultra-low doses reduces bone turnover and loss of bone mineral density (BMD) at the hip and lumbar vertebrae (LV), while reducing the likelihood of unacceptable side effects such as vaginal bleeding and breast tenderness (Ettinger et al, 2004;Gambacciani et al, 2008;Lindsay et al, 2002;Prestwood et al, 2003).…”