The focus of this review is
hormone replacement therapy (HRT) with continuous administration of micronized, oral 17beta-estradiol 1 mg/day (herein referred to as continuous
estradiol) plus micronized, oral
norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent
norgestimate). According to data from randomized, comparative trials of 1 year's duration, continuous
estradiol 1 mg/day plus intermittent
norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal
atrophy) in postmenopausal women. Continuous
estradiol 1 mg/day plus intermittent
norgestimate 90 microg/day appeared as effective as
estradiol 1 mg/day alone or continuous
estradiol 2 mg/day plus continuous
norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous
estradiol 1 mg/day plus intermittent
norgestimate 90 microg/day was as effective as continuous
estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomized, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral
estradiol 1 mg/day plus intermittent
norgestimate 90 microg/day than in placebo-treated patients. Two randomized, double-blind studies indicated that the addition of
norgestimate 90 microg/day to continuous
estradiol 1 mg/day did not attenuate the beneficial effects of
estradiol on
lipid parameters. Continuous
estradiol 1 mg/day plus intermittent
norgestimate 90 microg/day was associated with increases in mean serum
high density lipoprotein (
HDL)-cholesterol levels and decreases in total
cholesterol,
low density lipoprotein (
LDL)-cholesterol and
lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in
triglyceride levels. In comparative trials, continuous oral
estradiol 1 mg/day plus intermittent oral
norgestimate 90 microg/day was well tolerated.
Headache,
breast pain or discomfort,
abdominal pain or discomfort,
uterine bleeding,
dysmenorrhea,
edema,
nausea and depression were the most commonly reported adverse events. Continuous
estradiol 1 mg/day plus intermittent oral
norgestimate 90 microg/day was associated with a favorable
uterine bleeding profile that improved over time. In a randomized trial, 80% of women were free from
bleeding (irrespective of
spotting) during month 12 of treatment.
Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of
endometrial hyperplasia by continuous
estradiol 1 mg/day. In conclusion, data from a limited number of randomized studies indicate that HRT with continuous
estradiol 1 mg/day plus intermittent
norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous
estradiol 1 mg/day. The
norgestimate component of the regimen provides good endometrial protection and is associated with a favorable
bleeding profile. Long-term studies investigating the associated risk of
breast cancer and thromboembolic events in recipients of continuous
estradiol plus intermittent
norgestimate are needed. In the meantime, continuous oral
estradiol plus intermittent oral
norgestimate can be regarded as an effective new option for HRT in postmenopausal women.