Over the last few years, the concept of menopause has hit the national radar screen with a vengeance. One of the reasons for the onslaught of publicity was a nasty bit of research news released in 2002, when the initial results of the Women's Health Initiative Study were made public (JAMA. 2002; 288:321-333).

The study showed that hormone replacement therapy (HRT) is much more dangerous than anybody realized. Prempro, which is a combination of estrogen (0.625 mg) and progesterone (2.5 mg), was associated with an increased risk for heart attacks, strokes, blood clots, and breast cancer. This news dealt a huge blow to estrogen. Prescriptions of Prempro and other HRT treatments plummeted from 91 million in 2001 to 57 million in 2003, and they have surely decreased even more by now (JAMA 2004; 291:47-53).

How is all this affecting our psychiatric practices? Well, if your practice is anything like mine, you have been seeing an influx of estrogen refugees--peri- and post-menopausal women who had felt great on HRT, discontinued the treatment because of the bad press, and now are suffering insomnia, hot flashes, and all around dysphoria. What can we offer such women?

First, a quick lesson in menopause. Occurring at an average age of 51, it is typically defined as the cessation of menstruation for 12 consecutive months. Perimenopause (also termed "menopausal transition") is defined as the few years leading up to menopause, during which periods become irregular and various menopausal symptoms emerge, such as hot flashes. The perimenopause lasts 4-5 years on average.

What is happening biologically is that as the ovaries age, they become less and less responsive to gonadotrophic hormones such as FSH, and therefore produce less and less estrogen. Without sufficient estrogen, there can be no thickening of the uterine lining, and hence, no menstrual bleeding. Low estrogen also causes hot flashes and night sweats, followed by later symptoms such as vaginal dryness and thinning, bladder problems, and dryness of the hair and skin. In addition, low estrogen leads to several major health risks, including an increased risk of osteoporosis, cardiovascular disease, and possibly even Alzheimer's dementia (see Am J Psychiatry 1997; 154:1641-1647 for a review of some of this data).

A frequent question from patients transitioning to menopause is, "Am I at greater risk to develop a major depression?" The answer is, "Possibly." Studies that survey groups of women referred to menopause clinics report high rates of depressive disorders (nearly 30% in one study--see Arch Gen Psychiatry 2001; 58:306), but such clinics may attract a more severely affected group of women. A recent study showed that depressive symptoms appear to increase during the perimenopause, are especially common in women with hot flashes, and then decrease in prevalence after menopause (Arch Gen Psychiatry 2004;61:62-70).

What works for perimenopausal depression? Estrogen, for one, especially when given as the transdermal 17ßestradiol patch (100 μg QD), as reported in a successful placebo-controlled trial (Arch Gen Psychiatry. 2001; 58:529- 534). Yes, many physicians still prescribe estrogen, notwithstanding recent research findings, but this depends on a complicated assessment of risks vs. benefits for a particular patient (JAMA 2004; 291:1621-1625). These days, it is the rare psychiatrist who feels up to this task, and most of us would be wise to ask the neighborhood OB/GYN to take care of any estrogen prescriptions.

Not surprisingly, SSRIs also appear to work for perimenopausal depression. A recent uncontrolled study reported 90% remission rates when Celexa (20- 60 mg QD) was either added to the estradiol patch or used as monotherapy (J Clin Psychiatry 2003; 64: 473-479).

In addition to depressive symptoms, your patients will likely ask you for help with specific symptoms of menopause, especially hot flashes. While estrogen is the gold standard treatment, typically reducing hot flash frequency and severity by 80%, both SSRIs and Effexor have been proven helpful, causing a 60% improvement in clinical trials (see JAMA 2003; 289:2827-34 for the data on Paxil CR).

Finally, if you are inclined toward natural medications, try black cohosh, shown effective for the treatment of hot flashes and mild depressive symptoms in controlled trials (Ann Intern Med 2002; 137:805-813).

TCR VERDICT:
Menopause symptoms: Try SSRIs, SNRIs, and black cohosh.