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Investigators reported results from a
small (20 subjects) open-label trial of transdermal 17-beta-estradiol
for alleviation of depression in perimenopausal and postmenopausal
women. A significant difference in response was seen, with 6
of 9 perimenopausal women reporting full remission of depressive
symptoms, whereas only 1 of 11 postmenopausal women reported
comparable response. Interestingly, improvement of vasomotor
symptoms was independent of effect on mood.
Dr. Cohen has worked with reproductive hormone-related mood
disturbance for roughly 15 years. As background information,
he noted that there is a significant prevalence of depressive
symptoms among perimenopausal women. However, the risk appears
to be much higher for recurrent depression than for new-onset
major depression.
His group decided to conduct an open-label trial of transdermal
17-beta-estradiol for depressed perimenopausal and postmenopausal
women based on results from two randomized, double-blind,
placebo-controlled parallel study trials that were published
in the past few years.
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Recent clinical trials on short-term
estradiol as
an antidepressant strategy
| Schmidt/Rupert (NIMH). Tested 50 mcg/day of estradiol
in perimenopausal women over 6 weeks; found dramatic response by week 4 through
end of study | ・ | Suarez
et al (Mass. General Hospital). Tested estradiol in transdermal form in perimenopausal
women over 12 weeks. Found early response that was maintained through washout
period at study's end |
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Depressive Symptoms (MADRS Scores)
and
Perimenopausal Symptoms (BKMI Scores)
in women receiving Estradiol: Intent-to-Treat Analysis
- | Estradiol
(n = 25) | Placebo
(n = 25) | P
value |
| MADRS Scores | Baseline | Week
12 | Week
16 (after
washout) |
|
24.60 ± 6.69
8.60 ± 5.02
12.24 ± 5.31
|
21.84 ± 4.43
16.34 ± 6.29
19.36 ± 5.12
|
0.02
<0.01
<0.01
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| BKMI Scores | Baseline | Week
12 | Week
16 (after
washout) |
|
29.56 ± 7.94
10.60 ± 6.76
24.25 ± 8.50
|
25.84 ± 9.94
19.08 ± 9.88
22.21 ± 10.51
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0.14
<0.01
0.44
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MADRS-Montgomery-Asberg
Depression Rating Scale
BKMI- Blatt-Kupperman Menopausal Index
Source: Soares CN, et al. Arch Gen Psychiatry 2001;
58:529-534.
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The current study was set up as an open-label trial of 100
mcg transdermal estradiol. It used an expanded population
of perimenopausal and postmenopausal women and sought to answer
the question of whether any definable subgroups of women would
benefit most from hormone therapy.
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Study design and subject characteristics
・ | Open-label,
4-week trial | | 20 women, 9 perimenopausal and 11 postmenopausal,
40-60 years of age, all with FSH >20 | | 11 women with major depression, 6 with
minor depression, 3 with dysthymia | | Mean
baseline CGI score 4.0 ("moderately ill" population)
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No subjects dropped out of the study, and no side effects of
estradiol therapy were noted other than slight weight gain (averaging
1.5 pounds across the population).
Overall, 50% of subjects reported significantly improved
depression, and 50% of subjects reported significantly improved
vasomotor symptoms. As with the earlier studies, the onset
of improvement, where noted, was rapid, occurring before the
end of the 4-week study.
On analysis, improvement in vasomotor symptoms was found
to be independent of change in depressive symptoms.
On analysis, a strong difference was found between perimenopausal
and postmenopausal women in response of depression to hormone
therapy: six of nine perimenopausal women reported full relief
of symptoms, whereas only one of 11 postmenopausal women reported
full relief.
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Remission of depression following
4 weeks of
treatment with Estradiol
- | Perimenopausal
(n = 9) | Postmenopausal
(n = 11) | P
value | | Full
remission of depression(mean MADRS scores <9)
| 6
(66%) | 1
(9.1%) | 0.017 |
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The authors concluded that short-term transdermal treatment
with estradiol is safe and effective for perimenopausal women
with depression, but appears less effective for postmenopausal
women. Dr. Cohen believes that it is premature to recommend
estradiol therapy for depressed perimenopausal women until
further research clarifies the characteristics of women most
likely to benefit from hormonal treatment.
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