BACKGROUND: HRT relieves vasomotor symptoms in postmenopausal women but is associated with adverse side effects. Low-dose HRT has been shown to reduce side effects, but its effectiveness for the relief of vasomotor symptoms is uncertain.
POPULATION STUDIED: A total of 241 predominantly white (88%) women who reported at least 7 daily moderate-to-severe baseline hot flushes or at least 50 total hot flushes per week were evaluated. The subjects were chosen from 2673 healthy postmenopausal women who were aged 40 to 65 years, had intact uteruses, and were within 20% of normal body weight. Exclusion criteria included use of hormones or medicines known to affect vasomotor symptoms. This population is similar to the healthy postmenopausal patients of many family physicians.
STUDY DESIGN AND VALIDITY: The participants were randomized in a double-blind manner (concealed allocation assignment) to 1 of 8 treatment groups including combinations of either placebo or conjugated equine estrogens (CEE) with or without medroxyprogesterone (MPA) for 1 year (13 cycles of 28 days each). Daily dosing regimens were: CEE 0.625 mg, CEE 0.625 mg and MPA 2.5 mg, CEE 0.45 mg, CEE 0.45 mg and MPA 2.5 mg, CEE 0.45 mg and MPA 1.5 mg, CEE 0.3 mg, CEE 0.3 mg and MPA 1.5 mg, or placebo. The patients recorded the number and severity of hot flushes on daily diary cards that were collected at office visits scheduled for cycle 3, 6, 9, and 13. The mean daily number and the mean daily severity of hot flushes were calculated and compared using paired t tests. Vaginal atrophy was assessed by a vaginal maturation index (VMI) that was performed twice. This analysis was done in an intention-to-treat population.Unfortunately, data presentation was ambiguous: No numerical data or confidence intervals were given, making it difficult to both quantify the decrease in number and severity of hot flushes in the treatment groups and to assess clinical significance of the results. The lack of correlation between VMI and symptoms of vaginal atrophy make this information clinically meaningless. Finally, the withdrawal rate of the evaluable population was not given.
OUTCOME MEASURED: The number and severity of hot flushes experienced and the change of the VMIs over the 13 cycles were measured. Cost, quality-of-life improvement, and symptoms of vaginal atrophy were not addressed.
RESULTS: The baseline characteristics of the women in the various groups were similar. All active treatment groups experienced a decrease in the mean number of daily hot flushes when compared with the placebo group (P <.05), and there was no difference observed between the standard dose of HRT therapy (CEE 0.625 mg/MPA 2.5 mg) and low-dose HRT. The CEE 0.625 mg group reported fewer hot flushes than the other lower estrogen-only groups (P <.05). Results were similar for the mean daily severity of hot flushes. All active treatment groups experienced a decrease in severity of hot flushes compared with placebo (P <.05), and there was no significant difference between the standard dose and the lower dose combinations. The CEE 0.625 mg group experienced less severe hot flushes than the other lower estrogen-only treated groups by cycle 3 (P <.05). All active treatment groups reported a significant increase in VMI at cycle 6 and 13 when compared with placebo (P <.001).
For healthy, nonobese, white, postmenopausal women with severe vasomotor symptoms, lower dosages of CEE and CEE/MPA (CEE 0.3 or 0.45 mg/MPA 1.5 mg) are as effective as standard HRT dosages (CEE 0.0625 mg/MPA 2.5 mg). Currently there are no 1.5-mg dose commercial formulations of medroxyprogesterone available. A complementary study1 reported that lower dosages also resulted in higher rates of amenorrhea and no bleeding. This data further encourages the use of low-dose HRT to treat hot flushes, while limiting side effects that are known to decrease continuation rates.