The goals of the current study were to examine depression as well as depression in combination with psychological stress in relation to ovarian aging as indexed by AFC, a validated marker of ovarian reserve. In cross-sectional analyses of 683 pre-menopausal women, results indicated that independently of covariates, AFC decline across women was greater in women with lower positive affect as measured by the positive affect subscale of the CESD. The average follicle decline across women was − 0.990 follicles per year in women with low positive affect compared to − 0.773 follicles per year in women with high positive affect. In addition, among women with low positive affect, AFC decline across women was greater in women reporting higher levels of psychological stress. That is, the average follicle decline across women was − 1.112 follicles per year in women with low positive affect who reported high levels of stress compared to − 0.920 follicles per year and − 0.747 follicles per year in women with low positive affect who reported mid and low levels of stress, respectively. Also, there was a significant main effect of greater stress on higher AFC estimated at the mean age of the sample. In contrast, among women with high positive affect, there was no effect of psychological stress on AFC decline. In summary, cross-sectional evidence suggests that 1) women with low positive affect may experience accelerated AFC decline and 2) low positive affect may be a vulnerability factor, or, alternatively, high positive affect may be a protective factor, in moderating the negative effects of psychological stress on AFC decline.
Among the CESD-derived variables, only low positive affect emerged as a potential psychological risk factor for accelerated ovarian aging. Depressive symptomatology more generally (as represented by the total score of the CESD) as well as other depressive symptom types (i.e., depressed affect, somatic, interpersonal difficulties) were unrelated to AFC decline. A prior literature suggests that low positive affect or the lack of positive emotion is a prominent symptom in depression. In a recent review, positive affect, even compared to DSM-IV symptoms of depression, showed the strongest correlation with depression diagnoses compared to other types of psychopathology.54
In addition, outside the depression literature, dimensional variability in positive affect has been shown to predict a variety of physical health outcomes (for a review see Pressman & Cohen, 2005).55
For example, among studies that have used the CESD positive affect subscale, low positive affect has been related prospectively to all-cause mortality,56
reduced survival in AIDS patients,58
and poorer physical functioning following a major health event (e.g., myocardial infarction).59
Although these studies varied methodologically, results generally showed positive affect but not the other CESD subscales predicted the indicated health outcome, supporting the contribution of positive affect uniquely. Lastly, the current findings are also consistent with models suggesting that individuals with low positive affect may be especially vulnerable to psychological stress and concomitant physiological alterations (e.g., autonomic nervous system activation; hypothalamic-pituitary-adrenal axis activation) commonly implicated in explaining stress effects on health and disease.55,60–61
How similar stress-related mechanisms may be operative in the context of ovarian aging, however, is not known.
Secondarily, results also indicated that among the covariates, a history of using hormone-containing medication for birth control was related independently to lower AFC. Findings from previous studies examining oral contraceptive (OC) use in relation to menopausal timing have been mixed, showing OC use related to later age at menopause62–63
or showing no relation at all64–65
. The suggestion in the current study that hormone-containing birth control may actually have an inhibitory effect on antral follicle count was described in a previous report also from the OVA Study66
; however, no other study to our knowledge has reported such a link. Future studies are necessary to determine whether this association is reproducible in an independent sample as well as whether OC use is related to AFC decline over time
. Future studies are also necessary to further evaluate the significant main effect found in the current study in which greater stress was related to higher AFC in the context of a significant age-x-stress interaction among women with low positive affect. Interestingly, the possibility that stress may relate to the enhancement of fertility marked by having a higher AFC is not inconsistent with life history models which have proposed that adverse environments may promote biological preparation for current versus longer term reproduction to avert risks associated with a delay in reproduction.67–68
A primary weakness of the current study was the single assessment of depression, psychological stress, and AFC, limiting analyses to the cross-sectional examination of these psychological factors in relation to AFC decline across
women. Whether depression and psychological stress relate to intra-individual change in AFC over time
remains untested. The cross-sectional nature of the analyses also precluded characterization of the temporal relationship between depression and psychological stress. This may be particularly problematic in light of prior research suggesting the relationship between psychological stress and depression may change over time.14–15
A second primary weakness of the current study concerned the measurement of depression and psychological stress which was limited to assessments of current, self-reported symptoms of depression and perceptions of stress. Greater detail regarding depression diagnoses and depression history as well as exposures to specific psychosocial stressors, their timing, and severity is necessary to begin to more fully characterize the role of psychological factors in ovarian aging. Finally, the current findings should be considered preliminary due the relatively large number of analyses performed from which only results related to positive affect were statistically significant; and due to limitations in the generalizability of results as evidenced by significant differences on race/ethnicity, socioeconomic status, and body size between women who completed the self-report measures and those who did not return the questionnaire packet.
A primary strength of the current study was its novel focus on depression in relation to ovarian aging. Although prior research has suggested MDD may accelerate biological aging, there has been a paucity of research investigating the effects of depression on ovarian aging in particular. In addition, the current study makes an important contribution by assessing depression as well as psychological stress in connection with ovarian aging in order to begin to more fully characterize how these commonly inter-related psychological dimensions may act synergistically to impact AFC decline. Other notable strengths of the current study were its emphasis on the pre-menopausal period; its assessment of AFC; and its recruitment of a relatively large and diverse sample. The study’s emphasis on examining risk factors for ovarian aging among young, pre-menopausal women is important in potentially generating novel intervention opportunities to prolong ovarian function in women at-risk for accelerated ovarian aging and early menopause. The study’s use of AFC as a marker of ovarian reserve is superior to conventional methods of staging reproductive age which rely on menstrual cycle and hormonal characteristics which do not appreciably change until reproductive aging is more advanced.69
Lastly, the current sample was relatively large in size, well-characterized in terms of its reproductive and general health, and unique in its representation of five, approximately equal, race/ethnic groups.