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Menopause
Transdermal Estradiol May Be an Effective Antidepressant in Perimenopausal Women
By Bruce Jancin
Mar 2, 2003, 7:11pm

ALBUQUERQUE — Transdermal estradiol appears to be an effective antidepressant in perimenopausal women with various forms of depression, Dr. Paula Hensley said at a psychiatric symposium sponsored by the University of New Mexico.

But that doesn't mean it's time to start routinely using the estradiol patch for this purpose. While transdermal estradiol's antidepressant efficacy in a recent well-conducted randomized controlled trial is certainly thought provoking, Dr. Hensley stressed that she is “not at all” advocating using estrogen in any form as a treatment for depression in women.

The halt earlier this year of the HRT arm of the National Institutes of Health–sponsored Women's Health Initiative because of increased rates of breast cancer, acute MI, and stroke has for now squelched interest in identifying new indications for estrogen therapy in any form. That is particularly the case for conditions such as depression, for which numerous therapeutic options already exist.

But the antidepressant effect of transdermal estradiol is worth noting. That's because the Women's Health Initiative looked at the use of one particular oral formulation of estrogen with progestin. When the dust clears surrounding this issue, if it turns out that the serious adverse effects of estrogen are limited to oral combination therapy, transdermal estradiol may yet have a future in the treatment of depression in perimenopausal women, said Dr. Hensley, a psychiatrist who is clinical director of the general clinic at the University of New Mexico Mental Health Center, Albuquerque.

The transdermal estradiol antidepressant study was conducted by Dr. Claudio de Navaes Soares and colleagues at Harvard Medical School, Boston, and the University of Sao Paolo, Brazil.

The trial involved 50 perimenopausal women aged 40-55 with an FSH level greater than 25 IU/L and irregular menstrual periods. Twenty-six women met DSM-IV diagnostic criteria for major depressive disorder, 13 met the criteria for minor depressive disorder, and 11 for dysthymic disorder.

Participants were randomized in double-blind fashion to 12 weeks of transdermal patches containing 100 µg of 17 -estradiol or placebo followed by a 4-week washout period.

Full remission of depression as documented by a reduction in the Montgomery-Asberg Depression Rating Scale to below 10 was achieved in 17 of 25 women (68%) on transdermal estradiol, compared with just 5 (20%) on placebo. The estradiol patch appeared to be equally effective regardless of which DSM-IV depressive diagnosis a woman carried.

The response to transdermal estradiol was “quite rapid,” compared with conventional antidepressants, Dr. Hensley said. Depressive symptoms improved noticeably within the first 2-4 weeks. Moreover, transdermal estradiol's antidepressant effect remained significant during the 4-week washout period at the end of the 12-week study period.

The estradiol patch therapy was well tolerated. Like depressive symptoms, menopausal symptoms also showed significant improvement with transdermal estradiol therapy as evidenced by improved scores on the Blatt-Kupperman Menopausal Index.

However, somatic complaints increased in frequency and intensity during the 4-week post treatment washout phase of the study, unlike depressive symptoms (Arch. Gen. Psychiatry 58[6]:537-38, 2001).

In a recent review of Dr. Soares' trial, Dr. Holly L. Thacker of the Cleveland Clinic Foundation hailed it as “a landmark study” (ACP J. Club 136[1]:26, 2002).

“We are moving beyond viewing estrogen as only a reproductive hormone to viewing it as a neural hormonal agent with effects on mood and cognition,” Dr. Thacker said.