M a y 2 0 0 6 • w w w. c l i n i c a l e n d o c r i n o l o g y n ew s . c o m Reproductive Endocrinology 19

Menopausal Change Linked

To Depression Symptoms

B Y M A RY A N N M O O N

Contributing Writer

The “changing hormonal milieu” ofmenopause is strongly associatedwith new-onset major depression

as well as depressive symptoms in womenwith no history of mood disturbance, re-ported Ellen W. Freeman, Ph.D., of the de-partments of ob.gyn. and psychiatry at theUniversity of Pennsylvania, Philadelphia,and her associates in the Penn Ovarian Ag-ing Study.

Women are significantly more likely todevelop a depressive disorder when theirlevels of estradiol fluctuate, levels of FSHand LH increase,and levels of inhib-in B decrease, ashappens during thetransition tomenopause. It ap-pears that the hor-monal changescharacteristic ofovarian aging pro-duce “destabilizingeffects” that contribute to depression, theinvestigators said.

This finding should make a substantialcontribution to what has been only “lim-ited evidence” in the literature aboutmood symptoms in the perimenopausalyears.

“Whether mood symptoms increase inthe perimenopausal years and whetherthe occurrence of depressed mood is in-dependently associated with ovarianchanges or is secondary to vasomotor orother bothersome symptoms” has beencontroversial, they noted.

Dr. Freeman and her associates exam-ined the issue by assessing fluctuations inreproductive hormone levels in 231 pre-menopausal women aged 35-47 years atbaseline who were followed for 8 years.During that interval, 43% of the womenentered the transition to menopause.

Hormone assays were conducted in 10assessment periods, the first 6 at 8-monthintervals. Blood samples were collected atthe start of menstrual cycles, and subjectsalso were interviewed concerning theiroverall health, demographic factors, andmenopausal symptoms.

Depressive symptoms were assessed us-ing the CES-D (Center for Epidemiologi-cal Studies–Depression) scale; either thePRIME-MD (Primary Care Evaluation ofMental Disorders) or the PHQ (PatientHealth Questionnaire) was used to detectmajor depressive disorder.

A total of 116 women (50%) was foundto have depressive symptoms on the CES-D during follow-up.

Of these, 16 women had depressivesymptoms on two consecutive assess-ments and 35 had them on three or moreconsecutive assessments.

Of the 231 women, 59 (26%) werefound to have depressive disorders on thePRIME-MD or PHQ; 26 had major de-pressive disorder and 33 had other de-pressive disorders. Nine of the women had

depressive disorders on two consecutiveassessments and four had them on threeor more consecutive assessments.

A total of 108 women (47%) showed nodepressive symptoms on either measure,the researchers said (Arch. Gen. Psychia-try 2006;63:375-82).

Changes in individual women’s levels ofFSH, LH, and inhibin B were significant-ly associated with depressive symptomsand with major depression.

Similarly, variability in a woman’s meanlevels of estradiol, FSH, and LH also werelinked to depression and depressive symp-toms.

“On average, the women were 4.58 timesmore likely to havehigher FSH levels ...3 times more likelyto have higher LHlevels ... and 63%more likely to havelower inhibin B lev-els ... at the time ofhigh [depression]scores” comparedwith the time be-

fore high scores, the investigators said.After the data were adjusted for several

other depression risk factors, includingchange in employment status or maritalstatus, the researchers found that a womanwas, on average, more than five times“more likely to be in menopausal transi-tion at the time of reporting high [de-pression] scores than she was before theonset of depressive symptoms.”

The “strongest risk factor for the newonset of diagnosed depressive disorderswas the increased variability of estradiol(around the woman’s own mean levels) atthe time of the diagnosed disorder,” Dr.Freeman and her associates said.

However, other health and demo-graphic factors also significantly affecteddepression risk, “confirming ... the multi-factorial nature of depressive symptoms.”These factors included hot flashes, bodymass index, smoking status, and the pres-ence or absence of PMS.

The researchers also observed that on-sets of both major depression and de-pressive symptoms were more common inthe earlier years of their study, raising thequestion of “whether [depressed] womenentered the menopausal transition at anearlier age.” The study couldn’t answerthat question because it was “designed toexamine all women starting at a similarpremenopausal baseline,” they noted. ■

The strongest riskfactor for new-onset depressionwas increasedvariability ofestradiol at thetime of diagnosis.

DR. FREEMAN

V E R B A T I M

‘The very low RDA for

vitamin D is the main

problem regarding

issues of vitamin D

and health.’

Dr. Edward Giovannucci, p. 24