The focus of this review is
hormone replacement therapy (HRT) with continuous oral
17 beta-estradiol (herein referred to as
estradiol) 2 mg/day plus sequential oral
dydrogesterone 10 or 20 mg/day for 14 days of each 28-day cycle. According to data from nonblind trials, this regimen relieves climacteric symptoms, preserves bone mineral density (BMD) and improves the cardiovascular risk profile in postmenopausal women. Increases in mean BMD in the lumbar spine of 2.4 to 6.4% have been reported after 2 years' treatment. The effect on BMD of oral
estradiol plus sequential
dydrogesterone was similar to that achieved with transdermal
estradiol plus sequential oral
dydrogesterone or with oral
tibolone. Good protection against
endometrial hyperplasia and
cancer is provided by the
dydrogesterone component. Cyclical
vaginal bleeding occurs in most treatment cycles, but is generally light to moderate and the time of onset is highly predictable. Noncyclical
bleeding occurs in < 10% of cycles. Mean serum
high density lipoprotein-cholesterol levels are increased and
low density lipoprotein-cholesterol levels are decreased during treatment with oral
estradiol plus sequential
dydrogesterone.
Insulin resistance appears to be improved. Blood pressure and bodyweight are not generally affected to any clinically important extent. Serum
homocysteine levels were reported to decrease in postmenopausal women with high pretreatment levels. No data are available on the general tolerability profile of this regimen. However, the adverse events that most commonly led to discontinuation of treatment in clinical trials were typical of those associated with HRT, including
vaginal bleeding headache, bloating and breast tenderness. Although the risk of
breast cancer has not been specifically assessed for this regimen, it is unlikely to carry a greater risk than that of other HRT regimens. In summary available data indicate that treatment with continuous oral
estradiol plus sequential
dydrogesterone is effective in relieving climacteric symptoms and preserving BMD in postmenopausal women. The
dydrogesterone component provides good endometrial protection and cycle control without negating the cardiovascular benefits of
estradiol. Comparisons with other standard HRT regimens and long term data (including clinical end-points) are needed. In the meantime, this regimen can be regarded as an acceptable HRT option.