Like many aspects of depression in women, the diagnosis of climacteric depression and its treatment remains controversial. Whereas gynecologists who deal with the menopause have no difficulty in accepting the role of estrogens in the causation and the treatment of this common disorder, psychiatrists seem to be implacably opposed to it. This may be because there is no real evidence of an excess of depression occurring after the menopause, nor any evidence that estrogens help postmenopausal depression or what used to be called ‘involutional melancholia. This is quite true and indeed many women with longstanding depression improve considerably when the periods stop. This is because the depression created by premenstrual syndrome, heavy painful periods, menstrual headaches and the exhaustion that attend excess blood loss disappears. Therefore, the longitudinal studies of depression carried out by many psychologists, particularly those as notable as Hunter, have shown no peak of depression in a large population of menopausal women. The depression that occurs in women around the time of the menopause is at its worst in the 2 or 3 years before the periods stop. This, of course, is perimenopausal depression and is, no doubt, related to premenstrual depression as it becomes worse with age and with falling estrogen levels.
The earliest placebo-controlled study that defined the precise menopausal syndrome showed that estrogens helped hot flushes, night sweats and vaginal dryness. They also had a mood-elevating effect. This work was further supported by that of Campbell and Whitehead, who used Premarin ®, and by the study of Montgomery and co-workers using higher-dose estradiol- and estradiol-plus-testosterone implants. This study of 90 peri-and postmenopausal women with depression showed considerable improvement in the treatment group compared with placebo but only in the perimenopausal women. There was no improvement in depression in the postmenopausal women with this treatment when compared with placebo. This effect is not transient and we have shown that the improvement in depression is maintained even at 23 months. By this stage, the placebo patients had dropped out and there was no placebo group in the study.
At last, after 15 years, psychiatrists, particularly in the USA, are coming round to the view that transdermal estrogens are effective in the treatment of depressed perimenopausal women. Soares and colleagues in 2001 studied 50 such women: 26 with major depressive disorder, 11 with dysthymic depression and 30 with minor depressive illness. They treated them with 100 µg e stradiol patches in a 12-week placebo-controlled study. There was a remission of depression in 17 of 25 treatment patients (68%), and only five of the 25 placebo patients (20%). This improvement occurred regardless of the Diagnostic and Statistics Manual IV (DSM-IV) diagnosis.
Rasgon and co-workers studied 16 perimenopausal women with unipolar major depressive disorder for an 8-week open protocol trial comparing low-dose 0.3 mg Premarin ® plus fluoxetine daily. There was a greater response with estrogen alone. All but two of the total patients responded but the response was greater in the estrogen replacement therapy (estrogen replacement therapy) patients, and it was significant that the reduction of depression scores began rapidly after the first week of treatment.
More recently, Harlow and co-workers studied a large number (976) of perimenopausal women with a history of major depression and others without. Those with a history of depression had higher follicle stimulating hormone levels and lower estradiol levels at enrolment to the study, and women with a history of antidepressant medication use had three times the rate of early menopause. A similar excess rate was found in perimenopausal women who had a history of severe depression.
It is reassuring for those ‘menopausologists’ who have been trying to persuade the world of psychiatry that estrogens have a place in the treatment of depressed women, and pleasing to read at last the view that ‘periods of intense hormonal fluctuations have been associated with the heightened prevalence and exacerbation of underlying psychiatric illness, particularly the occurrence of premenstrual dysphoria, puerperal depression and depressive treatment during the perimenopause. It is speculated that sex steroids such as estrogens, progestogens (sic), testosterone and dehydroepiandrosterone (dehydroepiandrosterone) have a significant modulatory effect on brain functioning. There are preliminary, but promising, data on the use of estradiol (particularly transdermal estradiol) to alleviate depression during the menopause. At last we are getting through!