COMPARISON OF CONTINUOUS AND SEQUENTIAL TRANSDERMAL PROGESTOGEN WITH SEQUENTIAL ORAL PROGESTOGEN IN POSTMENOPAUSAL WOMEN USING CONTINUOUS TRANSDERMAL ESTROGEN - VASOMOTOR SYMPTOMS, BLEEDING PATTERNS, AND SERUM-LIPIDS

Objective-The efficacy, bleeding patterns, and safety of continuous tr ansdermal and sequential transdermal progestogen therapy were compared with those of oral progestogen therapy in postmenopausal women receiv ing transdermal estrogen. Methods-In an open-label, 1-year (13 treatme nt periods, 28 days each), randomized study, 774 postmenopausal women were assigned to receive 50 mu g/day of continuous transdermal estradi ol with either continuous or sequential transdermal norethisterone ace tate (NETA) in daily doses of 170 or 350 mu g in a single transdermal patch or sequential oral progestogen (1 mg norethisterone [NET] or 20 mg dydrogesterone/day). Results-The average number of hot flushes/day decreased from prestudy by over 90% (P < .001), and this reduction was unaffected by different progestogen regimens. With sequential progest ogen, bleeding incidence and the number of bleeding days did not chang e over the course of the study but were lower in the low-dose transder mal progestogen group. With continuous progestogen, the incidence of b leeding decreased in both the low-and high-dose groups, from 35% and 4 5% in treatment period 1 to 25% and 15%, respectively at the end of tr eatment. Adverse event incidence was similar in all groups, with 23% t o 36% of subjects reporting events possibly or probably related to HRT (excluding vaginal bleeding). Two cases of simple hyperplasia were re ported (one in each lour-dose progestogen group). Beneficial effects o n coronary heart disease risk factors, such as reductions in total cho lesterol and low-density lipoprotein cholesterol and increases in high -density lipoprotein-2 cholesterol levels, were measured in all treatm ent groups. Lipoprotein (a) was reduced in all but the oral progestoge n group. Conclusions-Continuous and sequential transdermal estrogen/pr ogestogen treatments with estradiol/NETA appear to be effective and sa fe alternatives to continuous transdermal estrogen and oral sequential progestogen for the treatment of menopausal symptoms. Continuous tran sdermal therapy with estradiol/NETA may be more acceptable for a major ity of patients, i.e., those who wish to avoid monthly bleeds, whereas the sequential regimen may be preferable when the clinician and/or pa tient believes monthly bleeding to be appropriate.