The aim of this study was to assess the systemic absorption of a daily dose of natural progesterone cream administered in conjunction with transdermal estrogen as part of continuous combined hormone replacement therapy. Each patient was supplied with clearly labelled separate containers of Progestelle® (6% progesterone cream) and estradiol gel, Sandrena® sachets, which amounted to a total daily 40mg dose of progesterone and 1mg of estradiol over 48 weeks. Assessments were conducted at 12-week intervals throughout the study to determine any improvements to menopausal symptoms. After 24 and 48 weeks, there were highly significant reductions in anxiety, depression, vasomotor symptoms and lipid problems compared with baseline. There was also a statistically significant reduction in anxiety symptoms after the first 24 weeks. Plasma levels of progesterone and estradiol were measured in women who completed the study and these showed significant increases in both hormone levels from baseline levels at each time interval.