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Mood sensitivity to estradiol predicts depressive symptoms in the menopause transition

Published online by Cambridge University Press:  11 March 2020

Jennifer L. Gordon*
Affiliation:
Department of Psychology, University of Regina, Regina, Saskatchewan, Canada
Bethany Sander
Affiliation:
Department of Psychology, University of Regina, Regina, Saskatchewan, Canada
Tory A. Eisenlohr-Moul
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
Laurie Sykes Tottenham
Affiliation:
Department of Psychology, University of Regina, Regina, Saskatchewan, Canada
*
Author for correspondence: Jennifer L. Gordon, E-mail: jennifer.gordon@uregina.ca

Abstract

Background

The risk for depression markedly rises during the 5–6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression.

Method

The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship.

Results

The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes.

Conclusion

Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

Type
Original Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Alder, E., Bancroft, J., & Livingstone, J. (1992). Estradiol implants, hormone levels and reported symptoms. Journal of Psychosomatic Obstetrics & Gynecology, 13, 223235.CrossRefGoogle Scholar
Avis, N. E., Crawford, S., Stellato, R., & Longcope, C. (2001). Longitudinal study of hormone levels and depression among women transitioning through menopause. Climacteric: The Journal of the International Menopause Society, 4, 243249.CrossRefGoogle ScholarPubMed
Avis, N. E., & McKinlay, S. M. (1995). The Massachusetts Women's Health Study: An epidemiologic investigation of the menopause. Journal of the American Medical Women's Association (1972), 50, 45.Google ScholarPubMed
Benjamini, Y. (2010). Discovering the false discovery rate. Journal of the Royal Statistical Society, Series B, 72, 405416.CrossRefGoogle Scholar
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Jounral of the Royal Statistical Society, 57, 289300.Google Scholar
Bishara, A. J., & Hittner, J. B. (2015). Reducing bias and error in the correlation coefficient due to nonnormality. Educational and Psychological Measurement, 75, 785804.CrossRefGoogle ScholarPubMed
Boyd, J. H., Weissman, M. M., Thompson, W. D., & Myers, J. K. (1982). Screening for depression in community sample. Archives of General Psychiatry, 39, 11951200.CrossRefGoogle ScholarPubMed
Bromberger, J. T., Kravitz, H. M., Chang, Y.-F., Cyranowski, J. M., Brown, C., & Matthews, K. A. (2011). Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN). Psychological Medicine, 41, 18791888.CrossRefGoogle Scholar
Bromberger, JT, Kravitz, HM, Matthews, K, Youk, A, Brown, C, & Feng, W. (2009). Predictors of first lifetime episodes of major depression in midlife women. Psychological medicine, 39, 5564.CrossRefGoogle ScholarPubMed
Bromberger, JT, Schott, L, Kravitz, HM, & Joffe, H. (2015). Risk factors for major depression during midlife among a community sample of women with and without prior major depression: are they the same or different? Psychological medicine, 45, 16531664.CrossRefGoogle ScholarPubMed
Cardoso, C., Ellenbogen, M. A., & Linnen, A. M. (2014). The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Emotion (Washington, D.C.), 14, 4350.CrossRefGoogle Scholar
Chiodera, P., Volpi, R., Capretti, L., Marchesi, C., d'Amato, L., De Ferri, A., … Coiro, V. (1991). Effect of estrogen or insulin-induced hypoglycemia on plasma oxytocin levels in bulimia and anorexia nervosa. Metabolism: Clinical and Experimental, 40, 12261230.CrossRefGoogle ScholarPubMed
Chowen, J. A., Torres-Aleman, I., & Garcia-Segura, L. M. (1992). Trophic effects of estradiol on fetal rat hypothalamic neurons. Neuroendocrinology, 56, 895901.CrossRefGoogle ScholarPubMed
Cohen, J. (1992). A power primer. Psychological Bulletin, 112, 155159.CrossRefGoogle Scholar
De Leo, V., Lanzetta, D., Morgante, G., De Palma, P., & D'Antona, D. (1997). Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women. Contraception, 55, 239243.CrossRefGoogle ScholarPubMed
Derman, R. J., Dawood, M., & Stone, S. (1994). Quality of life during sequential hormone replacement therapy – a placebo-controlled study. International Journal of Fertility and Menopausal Studies, 40, 7378.Google Scholar
Engel, S., Klusmann, H., Ditzen, B., Knaevelsrud, C., & Schumacher, S. (2019). Menstrual cycle-related fluctuations in oxytocin concentrations: A systematic review and meta-analysis. Frontiers in Neuroendocrinology, 52, 144155.CrossRefGoogle ScholarPubMed
Gavin, N. I., Gaynes, B. N., Lohr, K. N., Meltzer-Brody, S., Gartlehner, G., & Swinson, T. (2005). Perinatal depression: A systematic review of prevalence and incidence. Obstetrics & Gynecology, 106, 10711083.CrossRefGoogle ScholarPubMed
Gordon, J. L., Eisenlohr-Moul, T. A., Rubinow, D. R., Schrubbe, L., & Girdler, S. S. (2016a). Naturally occurring changes in estradiol concentrations in the menopause transition predict morning cortisol and negative mood in perimenopausal depression. Clinical Psychological Science, 4, 919935.CrossRefGoogle Scholar
Gordon, J. L., Girdler, S. S., Meltzer-Brody, S. E., Stika, C. S., Thurston, R. C., Clark, C. T., … Wisner, K. L. (2015). Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in perimenopausal depression: A novel heuristic model. American Journal of Psychiatry, 172, 227236.CrossRefGoogle ScholarPubMed
Gordon, J. L., Rubinow, D. R., Eisenlohr-Moul, T. A., Leserman, J., & Girdler, S. S. (2016b). Estradiol variability, stressful life events, and the emergence of depressive symptomatology during the menopausal transition. Menopause (New York, N.Y.), 23, 257266.CrossRefGoogle Scholar
Gordon, J. L., Rubinow, D. R., Eisenlohr-Moul, T. A., Xia, K., Schmidt, P. J., & Girdler, S. S. (2018). Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition: A randomized clinical trial. JAMA Psychiatry, 75, 149157.CrossRefGoogle ScholarPubMed
Greene, J. G. (2008). Constructing a standard climacteric scale. Maturitas, 61, 7884.CrossRefGoogle ScholarPubMed
Halbreich, U., Borenstein, J., Pearlstein, T., & Kahn, L. S. (2003). The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology, 28(Suppl 3), 123.Google Scholar
Hale, G. E., & Burger, H. (2009). Hormonal changes and biomarkers in late reproductive age, menopausal transition and menopause. Best Practice & Research Clinical Obstetrics & Gynaecology, 23, 723.CrossRefGoogle ScholarPubMed
Hale, G. E., Zhao, X., Hughes, C. L., Burger, H. G., Robertson, D. M., & Fraser, I. S. (2007). Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system. Journal of Clinical Endocrinology & Metabolism, 92, 30603067.CrossRefGoogle ScholarPubMed
Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., … de Villiers, T. J. (2012). Executive summary of the stages of reproductive aging workshop+ 10: Addressing the unfinished agenda of staging reproductive aging. Climacteric: The Journal of the International Menopause Society, 15, 105114.CrossRefGoogle ScholarPubMed
Hooper, L. M., Stockton, P., Krupnick, J. L., & Green, B. L. (2011). Development, use, and psychometric properties of the Trauma History Questionnaire. Journal of Loss & Trauma, 16, 258283.CrossRefGoogle Scholar
Leserman, J., Ironson, G., O'Cleirigh, C., Fordiani, J. M., & Balbin, E. (2008). Stressful life events and adherence in HIV. AIDS Patient Care and STDs, 22, 403411.CrossRefGoogle ScholarPubMed
Leserman, J., Petitto, J., Gu, H., Gaynes, B., Barroso, J., Golden, R., … Evans, D. (2002). Progression to AIDS, a clinical AIDS condition and mortality: Psychosocial and physiological predictors. Psychological Medicine, 32, 10591073.CrossRefGoogle ScholarPubMed
Leserman, J., Petitto, J. M., Perkins, D. O., Folds, J. D., Golden, R. N., & Evans, D. L. (1997). Severe stress, depressive symptoms, and changes in lymphocyte subsets in human immunodeficiency virus – infected men: A 2-year follow-up study. Archives of General Psychiatry, 54, 279285.CrossRefGoogle ScholarPubMed
Maki, P. M., Kornstein, S. G., Joffe, H., Bromberger, J. T., Freeman, E. W., Athappilly, G., … Soares, C. N. (2019). Guidelines for the evaluation and treatment of perimenopausal depression: Summary and recommendations. J Womens Health (Larchmt), 28, 117134.CrossRefGoogle ScholarPubMed
McTiernan, A., Wu, L., Chen, C., Chlebowski, R., Mossavar-Rahmani, Y., Modugno, F., … Women's Health Initiative, I. (2006). Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring), 14, 16621677.CrossRefGoogle ScholarPubMed
Meltzer-Brody, S., Boschloo, L., Jones, I., Sullivan, P. F., & Penninx, B. W. (2013). The EPDS-Lifetime: Assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women. Archives of Women's Mental Health, 16, 465473.CrossRefGoogle Scholar
Miro, F., Parker, S., Aspinall, L., Coley, J., Perry, P., & Ellis, J. (2004). Origins and consequences of the elongation of the human menstrual cycle during the menopausal transition: The FREEDOM study. Journal of Clinical Endocrinology & Metabolism, 89, 49104915.CrossRefGoogle ScholarPubMed
Mongraw-Chaffin, M. L., Anderson, C. A., Allison, M. A., Ouyang, P., Szklo, M., Vaidya, D., … Golden, S. H. (2015). Association between sex hormones and adiposity: Qualitative differences in women and men in the multi-ethnic study of atherosclerosis. Journal of Clinical Endocrinology and Metabolism, 100, E596E600.CrossRefGoogle ScholarPubMed
O'Connor, K. A., Brindle, E., Holman, D. J., Klein, N. A., Soules, M. R., Campbell, K. L., … Wood, J. W. (2003). Urinary estrone conjugate and pregnanediol 3-glucuronide enzyme immunoassays for population research. Clinical Chemistry, 49, 11391148.CrossRefGoogle ScholarPubMed
O'Connor, K. A., Ferrell, R., Brindle, E., Trumble, B., Shofer, J., Holman, D. J., & Weinstein, M. (2009). Progesterone and ovulation across stages of the transition to menopause. Menopause (New York, N.Y.), 16, 1178.CrossRefGoogle ScholarPubMed
Oldenhave, A., Jaszmann, L. J., Haspels, A. A., & Everaerd, W. T. A. (1993). Impact of climacteric on well-being: A survey based on 5213 women 39 to 60 years old. American Journal of Obstetrics and Gynecology, 168, 772780.CrossRefGoogle ScholarPubMed
Radloff, L. S. (1977). The CES-D scale a self-report depression scale for research in the general population. Applied Psychological Measurement, 1, 385401.CrossRefGoogle Scholar
Rubinow, D. R., Schmidt, P. J., & Roca, C. A. (1998). Estrogen–serotonin interactions: Implications for affective regulation. Biological Psychiatry, 44, 839850.CrossRefGoogle ScholarPubMed
Santoro, N., Brown, J. R., Adel, T., & Skurnick, J. H. (1996). Characterization of reproductive hormonal dynamics in the perimenopause. The Journal of Clinical Endocrinology and Metabolism, 81, 14951501.Google ScholarPubMed
Santoro, N., & Randolph, J. F Jr.. (2011). Reproductive hormones and the menopause transition. Obstetrics and Gynecology Clinics of North America, 38, 455.CrossRefGoogle ScholarPubMed
Sarason, I. G., & Johnson, J. H. (1976). The life experiences survey: preliminary findings (No. SCS-LS-001). Washington University Seattle Department of Psychology.CrossRefGoogle Scholar
Sarason, I. G., Johnson, J. H., & Siegel, J. M. (1978). Assessing the impact of life changes: Development of the life experiences survey. Journal of Consulting and Clinical Psychology, 46, 932.CrossRefGoogle ScholarPubMed
Schmidt, P. J., Ben, D. R., Martinez, P. E., Guerrieri, G. M., Harsh, V. L., Thompson, K., … Rubinow, D. R. (2015). Effects of estradiol withdrawal on mood in women with past perimenopausal depression: A randomized clinical trial. JAMA Psychiatry, 72, 714726.CrossRefGoogle ScholarPubMed
Schmidt, P. J., Martinez, P. E., Nieman, L. K., Koziol, D. E., Thompson, K. D., Schenkel, L., … Rubinow, D. R. (2017). Premenstrual dysphoric disorder symptoms following ovarian suppression: Triggered by change in ovarian steroid levels but not continuous stable levels. American Journal of Psychiatry, 174, 980989.CrossRefGoogle Scholar
Schmidt, P. J., Nieman, L. K., Danaceau, M. A., Adams, L. F., & Rubinow, D. R. (1998). Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. New England Journal of Medicine, 338, 209216.CrossRefGoogle ScholarPubMed
Schmidt, P. J., Nieman, L. K., Grover, G. N., Muller, K. L., Merriam, G. R., & Rubinow, D. R. (1991). Lack of effect of induced menses on symptoms in women with premenstrual syndrome. New England Journal of Medicine, 324, 11741179.CrossRefGoogle ScholarPubMed
Schneider, H. P., MacLennan, A. H., & Feeny, D. (2008). Assessment of health-related quality of life in menopause and aging. Climacteric: The Journal of the International Menopause Society, 11, 93107.CrossRefGoogle ScholarPubMed
Shideler, S., DeVane, G., Kalra, P., Benirschke, K., & Lasley, B. (1989). Ovarian-pituitary hormone interactions during the perimenopause. Maturitas, 11, 331339.CrossRefGoogle ScholarPubMed
Thomas, J. L., Jones, G. N., Scarinci, I. C., Mehan, D. J., & Brantley, P. J. (2001). The utility of the CES-D as a depression screening measure among low-income women attending primary care clinics. International Journal of Psychiatry in Medicine, 31, 2540.CrossRefGoogle ScholarPubMed
Tivis, L. J., Richardson, M. D., Peddi, E., & Arjmandi, B. (2005). Saliva versus serum estradiol: Implications for research studies using postmenopausal women. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 29, 727732.CrossRefGoogle ScholarPubMed
Treloar, A. E. (1981). Menstrual cyclicity and the pre-menopause. Maturitas, 3, 249264.CrossRefGoogle ScholarPubMed
Vegeto, E., Benedusi, V., & Maggi, A. (2008). Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases. Frontiers in Neuroendocrinology, 29, 507519.CrossRefGoogle ScholarPubMed
Wang, H., Ward, A. R., & Morris, J. F. (1995). Oestradiol acutely stimulates exocytosis of oxytocin and vasopressin from dendrites and somata of hypothalamic magnocellular neurons. Neuroscience, 68, 11791188.CrossRefGoogle ScholarPubMed
Watson, N. R., Studd, J. W., Riddle, A. F., & Savvas, M. (1988). Suppression of ovulation by transdermal oestradiol patches. BMJ, 297, 900901.CrossRefGoogle ScholarPubMed
Wittchen, H. U., Becker, E., Lieb, R., & Krause, P. (2002). Prevalence, incidence and stability of premenstrual dysphoric disorder in the community. Psychological Medicine, 32, 119132.CrossRefGoogle Scholar
Woods, N. F., Smith-DiJulio, K., Percival, D. B., Tao, E. Y., Mariella, A., & Mitchell, E. S. (2008). Depressed mood during the menopausal transition and early postmenopause: Observations from the Seattle Midlife Women's Health Study. Menopause (New York, N.Y.), 15, 223232.CrossRefGoogle ScholarPubMed
Woolley, C. S. (1998). Estrogen-mediated structural and functional synaptic plasticity in the female rat hippocampus. Hormones and Behavior, 34, 140148.CrossRefGoogle ScholarPubMed
Wyatt, K. M., Dimmock, P. W., Ismail, K. M., Jones, P. W., & O'Brien, P. M. (2004). The effectiveness of GnRHa with and without ‘add-back’ therapy in treating premenstrual syndrome: A meta analysis. BJOG: An International Journal of Obstetrics and Gynaecology, 111, 585593.CrossRefGoogle ScholarPubMed
Young, L. J., Wang, Z., Donaldson, R., & Rissman, E. F. (1998). Estrogen receptor alpha is essential for induction of oxytocin receptor by estrogen. Neuroreport, 9, 933936.CrossRefGoogle ScholarPubMed
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