Low-dose oestrogen preparations should not be emphasised as being safer than traditional dosages, according to a recent review from the University of California, Los Angeles, United States.
Recent guidelines have recommended restricting long-term hormone therapy use due to safety concerns, and it has been suggested that lower-dose oestrogen therapy may serve as a safer alternative.
Carolyn Crandall, MD, FACP, reviewed the Medline database for randomised controlled trials to determine how low-dose preparations perform in relation to hot flashes, endometrial hyperplasia, vaginal bleeding, breast tenderness, and bone density.
Although there is a general lack of direct comparison studies, available data suggest that many of the outcomes have dose-response relationships. For example, some low dose therapies can suppress hot flashes, but the reduction is often less than that seen with traditional dosages. All low-dose preparations were associated with breast tenderness, but the incidence was lower compared with higher dosages for some preparations.
Limited 2-year safety data suggest that conjugated equine oestrogen (CEE) with medroxyprogesterone acetate (as dosed in the HOPE trial), estradiol combined with norethindrone acetate (NETA) 1mg/0.5mg, or estradiol with cyclical norgestimate 1mg/90Âµg do not cause unacceptable rates of hyperplasia. All low-dose preparations were associated with vaginal bleeding, but some had better bleeding profiles than higher doses.
Some low-dose preparations appear to preserve lumbar and femoral bone density, but this effect is dose dependent for CEE, transdermal estradiol, ethinyl estradiol with NETA, oral estradiol, and esterified oestrogens. Thus, early menopausal women using oestrogen for hot flashes may not derive adequate bone protection with low-dose oestrogens.
Dr. Crandall notes that there are no data demonstrating lower cardiovascular risk or incidence of breast cancer with low-dose estrogens. “It is, thus, not apparent that serious adverse effects linked with traditional doses of estrogens can be averted by the use of low-dose oestrogen preparations,” she concludes.
With respect to osteoporosis prevention, Dr. Crandall supports existing guidelines suggesting that alternatives to oestrogen should be considered, and recommends that, “adequate calcium supplementation should be assured.”