HRT dosing regimens: continuous versus cyclic-pros and cons.

The introduction of new products, lower dosages, and better continuous and cyclic regimens allows for individualized treatment aimed at minimizing risk and side effects, while maximizing confidence and compliance. Since the major side effect of HRT that discourages long-term use is vaginal bleeding, newer regimens are designed to minimize it. The lowest doses of estrogen currently approved by the FDA for prevention of osteoporosis include 0.3 mg esterified estrogens, 0.025 microg transdermal estradiol patch, and 0.5 mg micronized estradiol. In most naturally menopausal women or those over 65 years of age, conjugated estrogen 0.3 mg (with adequate calcium intake) is protective against bone loss and cardiovascular disease. These low doses are often used with cyclic progestins every 3 to 4 months. Advantages of cyclic therapy using low-dose estrogen include minimal progestin exposure, low rate of withdrawal bleeding, lowered side effects, and, often, higher comfort level. Cyclic estrogen regimens with higher doses have been in use longer, but they often necessitate more frequent progestin treatment and may result in cyclic bleeding or breast tenderness. While HDL- and LDL-cholesterol changes are greater and more beneficial during higher-dose oral cyclic therapy, the large increase in triglycerides is of concern. The most commonly used continuous combined regimens include conjugated estrogen plus daily progestin orally or the combination estradiol/norethindrone acetate transdermal patch. Continuous combined regimens are simple and easy-to-use, and are designed to minimize bleeding. Multiple studies suggest that the mechanism of benefit provided by estrogen goes beyond estrogen's favorable impact on lipoproteins, which is blunted by daily use of synthetic progestins.