Identifying Patients at Risk for Depression After Menopause

Frank J. Domino, MD

Review

Freeman EW, Sammel MD, Boorman DW, Zhang R. Longitudinal pattern of depressive symptoms around natural menopause. JAMA Psychiatry. 2013 Nov 13. http://archpsyc.jamanetwork.com/article.aspx?articleID=1772342.

Study Methods

This was an observational study of a randomly identified, population-based sample of 203 late-reproductive-age women who were premenopausal at baseline, but later reached natural menopause and were followed for more than 14 years.

Assessments were conducted approximately every 9 months in the first 5 years, and then annually for 14 years with a 2-year gap between assessments 10 and 11. During each assessment, data was collected at 2 in-home visits that were timed to the early follicular phase of the menstrual cycle for 2 consecutive menstrual cycles. For non-cycling women, the in-home visits were approximately 1 month apart.

Trained interviewers obtained menstrual dates, data on overall health, blood samples for the hormone assays, and anthropometric measures. Participants completed a set of validated self-reporting measures to assess health and other behavioral measures of the study at each assessment period.

The final menstrual period (FMP) was defined as the point after 12 or more months without menstrual bleeding. FMP was identified for all women and was used as an assessment point to study the comparison of the patients’ data.

Time in years from 12 years before FMP to 11 years after FMP was evaluated in relation to FMP (designated as time “0” for each participant), in order to allow longitudinal evaluation of within-woman changes in depressive symptoms for each year before and after menopause.

Variables measured include age, age at FMP, body mass index (BMI), Center for Epidemiologic Studies Depression Scale (CES-D) score, estradiol level, follicle-stimulating hormone (FSH) level, inhibin B level, current smoking status, history of depression, and race.

The primary outcome of depressed mood was assessed by CES-D, a standard measure that evaluates current depressive symptoms in the past week. The CES-D asked participants to rate 20 items on a 4-point scale at each assessment. A total score of 16 or greater was defined as the high depressive symptom group, though a score of 25 or greater — which has greater specificity for a clinical diagnosis of depression — was also examined.

In the postmenopausal predictive models, depression status was categorized by 4 different groups:

1. History of depression as identified at enrollment
2. Depressive symptoms that first occurred during the study while premenopausal
3. Depression in the menopause transition
4. No depression or depression history before FMP

Patient Demographics

At enrollment, all cohort participants were premenopausal, defined by regular menstrual cycles. All participants were aged between 35-48 years old and had an intact uterus and at least 1 ovary. Exclusion criteria included current use of any hormone or psychotropic medication, alcohol or drug abuse, a major psychiatric disorder in the past year, pregnancy or breastfeeding, serious health problems known to compromise ovarian function, or uncontrolled hypertension.

Results and Outcomes

The overall prevalence of high CES-D scores decreased from 10 years before FMP to 8 years after FMP, with an overall decrease of approximately 15% per year (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.81-0.89; P< .001). Additionally, the risk of depressive symptoms was higher throughout each year before FMP and lower throughout each year after FMP. Repeating those models with a CES-D score of 25 or greater yielded similar results. Overall, the mean decrease in risk of depressive symptoms was approximately 12% per year (OR,0.88; 95% CI, 0.83-0.93; P< .001).

The pattern of depressive symptoms was strongly modified by a history of depression, as women with a history of depression before enrollment were more than 13 times more likely to have high depressive symptoms than women with no history of depression (OR, 13.62; 95% CI, 7.20-25.80; P< .001). Those who had a history of depression before menopause were also 8 times more likely to have depressive symptoms after menopause, compared to women who did not have depression before their FMP (OR, 8.39; 95% CI, 3.66-19.24; P< .001).

Current smokers were approximately twice as likely to report high CES-D scores in the study compared to nonsmokers (OR, 2.18; 95% CI, 0.99-4.79; P= .05). Race, age at menopause, and BMI were not significantly associated with CES-D scores.

FSH alone seemed to predict depressive symptoms after FMP, as the risk decreased by 35% for each logarithmic increase in FSH by multivariable analysis (OR, 0.65; 95% CI, 0.46-0.91; P= .01). There was no significant association between the rate of change of estradiol or inhibin B and depressive symptoms after FMP.

Conclusion

The risk for depression exists in the years prior to menopause, but declines as a woman approaches her FMP and decreases even further after FMP. For women who do not have a history of depression prior to their FMP, the risk of subsequently developing depression is very low. However, a history of depression prior to FMP increases the risk of recurrence or persistence after FMP, and this heightened risk seems to correlate with an increase in serum FSH.

Commentary

By using each woman as her own comparator, this study helps to clarify who is at risk for depression during the menopausal years. The rate at which FSH rose prior to menopause predicted this even further, with a faster rate implying a lower risk.

Though this study makes several assumptions, it demonstrates that a very small set of variables can assist clinicians in identifying ways to potentially improve this transitional phase of life. Even so, one weakness of this study is its exclusion of women with a history of major depressive disorder (MDD) within the year prior to enrollment.

A useful follow-up to this study would involve measuring CES-D scores and FSH levels in all women — including those with history of depression &mdash; in order to identify those at greatest risk for developing depression prior to menopause, and then attempting a variety of methods to prevent depressive events. Exercise, medications, yoga, and meditation have all been used to treat depressive symptoms during menopause, but their effectiveness has only been studied after symptoms appear. Finding an intervention to further lower the risk of developing depression would be of great value and may help providers tailor their treatments.

What’s encouraging in this data set is that the rate of depression declines in the years after menopause for both women with depression prior to menopause and those without it. This finding is especially encouraging for those who have suffered with depression in adulthood, and it may empower everyone to appreciate the disease’s physiologic basis.

About the Author

Frank J. Domino, MD, is Professor and Pre-Doctoral Education Director for the Department of Family Medicine and Community Health at the University of Massachusetts Medical School in Worcester, MA. Domino is Editor-in-Chief of the 5-Minute Clinical Consult series (Lippincott Williams & Wilkins). Additionally, he is Co-Author and Editor of the Epocrates LAB database, and author and editor to the MedPearls smartphone app. He presents nationally for the American Academy of Family Medicine and serves as the Family Physician Representative to the Harvard Medical School’s Continuing Education Committee.