Menopausal Mood and Anxiety Disorders: Treatment Options and the Role of Hormone Therapy

An increasing number of women are coming to clinic looking for treatment for menopausal depression and anxiety — and they also have questions about the use of menopausal hormone treatment. Dr. Ruta Nonacs, a psychiatrist at the MGH Center for Women’s Mental Health and editor of womensmentalhealth.org, describes a shift in medical practice: women are seeing more direct-to-consumer advertising about menopause hormone treatment, and the FDA and Health and Human Services have changed the wording around its use. One challenge is that it is difficult to find providers with expertise in hormonal therapies — most OBGYNs and primary care providers trained after the Women’s Health Initiative results came out in the early 2000s, when those studies suggested significant risks associated with hormone therapy in older women. Those studies were conducted with older preparations at much higher doses. More recently, using hormone therapy with estrogen and progestins is considered a reasonable option for younger perimenopausal women.

Understanding the Perimenopausal Window

Menopause is medically defined as 12 consecutive months without a menstrual period — the cessation of reproductive functioning — and typically occurs between the ages of 45 and 55. In the United States, the median age is around 51. Perimenopause, the time leading up to menopause, is more nebulous: it may begin in the early forties, last as little as six months, or extend over five to seven years or longer. During the perimenopause, estrogen levels are rising and falling — fluctuating rapidly and frequently — and can cause considerable disruption in functioning. Symptoms include irregular menstrual cycles, vasomotor symptoms such as hot flashes and night sweats, sleep disturbance, cognitive difficulties, changes in sexual functioning, and mood and anxiety symptoms.

Vulnerability to Depression

A clinically important observation: mood symptoms and sleep problems can emerge several years before vasomotor symptoms appear. It is possible to have mood changes in the absence of hot flashes or cycle irregularity — which can make it unclear whether a presentation reflects depression, perimenopause, or both. In terms of treatment this distinction matters less than it might seem, but it can complicate the question of which provider is best positioned to help.

Women are about two to four times more vulnerable to developing depression during the perimenopause than at other times in their lives. Most cases occur in women with a history of earlier depressive episodes. Postpartum depression is also a risk factor — another time of hormonal fluctuation — and severe vasomotor symptoms are an independent risk factor for depression. Some women present with new or worsening premenstrual symptoms: severe irritability, sleep disturbance, profound sadness, or dread that emerges in the week to ten days before the menstrual cycle and disappears quickly with the onset of the period.

Treatment Decision-Making

How symptoms are treated often depends on which provider a woman sees. A woman presenting to a psychiatrist with depression or anxiety is more likely to be treated with an antidepressant. A woman presenting to an OBGYN or primary care provider with a more mixed picture — including vasomotor or premenstrual symptoms — is more likely to be recommended hormone therapy. There is data to support the use of menopausal hormone therapies for moderate to severe vasomotor symptoms and premenstrual symptoms, and data to suggest that menopausal hormone replacement therapy may be beneficial for women with depression. Several randomized controlled trials suggest that estradiol can be effective for the treatment of depression, either alone or in combination with an antidepressant. However, hormonal treatments are not a first-line treatment for menopausal or perimenopausal depression. SSRIs and SNRIs are first-line. Serotonergic agents are preferred in this population because they tend to be better for treating comorbid anxiety — which is very common — and may also reduce the severity and frequency of vasomotor symptoms, not as strongly as estradiol but beneficially.

Hormone Therapy: Specifics and Safety

When menopausal hormone therapy is appropriate, transdermal estradiol is preferred over oral, as it is associated with lower risk of stroke, thromboembolism, and cardiovascular disease. Women with an intact uterus must combine estrogen with a progestogen, typically oral micronized progesterone. These options are reasonable for women under 60 and within ten years of menopause.

Managing Residual Symptoms

When SSRIs or SNRIs are initiated, partial response or residual symptoms are common — particularly sleep disturbance, which may persist during the two to four weeks before the antidepressant takes effect. Sleep problems affect multiple domains: difficulty falling asleep and difficulty staying asleep. In that setting, benzodiazepines may be used — lorazepam for problems with sleep onset, clonazepam for problems with sleep maintenance. Alternatives include trazodone or doxylamine, though these are considered less effective. Gabapentin, typically at 300 to 1200 milligrams at bedtime, can be helpful for both sleep and vasomotor symptoms. If depression is treated but significant vasomotor symptoms persist, augmentation with transdermal estradiol and a progestogen may be considered. At the MGH Center for Women’s Mental Health, this is typically done in collaboration with a gynecologist so that hormone therapy can be monitored closely, given the risks associated with its use in older women. This is a complex patient population, and the right approach is most likely to be a combination of various medications and interventions.

Treatment at a Glance

Resources

• MGH Center for Women’s Mental Health
• Essential Reads: A Primer on Menopausal Hormone Therapy for Mental Health Providers — Dr. Ruta Nonacs, MGH Center for Women’s Mental Health
• JCP Focus on Women’s Mental Health