Ovarian Hormone Fluctuation, Neurosteroids, and HPA Axis Dysregulation in Perimenopausal Depression: A Novel Heuristic Model

In this conceptual review, we propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition (a.k.a. perimenopausal depression) involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation

A higher sense of purpose in life is associated with sexual enjoyment in midlife women.

OBJECTIVE: The aim of this study was to understand the association between sense of purpose in life and sexual well-being in a cohort of midlife women. METHODS: Participation in partnered sexual activities and indicators of sexual well-being (the engagement in and enjoyment of sexually intimate activities) were measured in a longitudinal cohort of 677 eligible women aged 40 to 65 years. At a single time point, women completed the Life Engagement Test, a measure of life purpose. Univariable and multivariable mixed models were used to assess the association between the Life Engagement Test and longitudinal sexual well-being. RESULTS: A higher sense of purpose in life was associated with higher levels of enjoyment (coefficient = 2.89, P CONCLUSIONS: Higher sense of purpose in life is associated with more enjoyment of sexually intimate activities, adjusting for other known factors that influence sexual well-being and independent of demographic factors and menopause or hormone therapy status.</p

Ovarian Hormone Fluctuation, Neurosteroids, and HPA Axis Dysregulation in Perimenopausal Depression: A Novel Heuristic Model

OBJECTIVE: In this conceptual review, we propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition (a.k.a. perimenopausal depression) involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation. METHODS: The relevant literature in perimenopausal depression was reviewed, including its prevalence, predictors, and treatment with estrogen therapy. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development. RESULTS: The rate of major depressive disorder and of clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growing evidence from basic and clinical research suggests that fluctuations in ovarian hormones and their derived neurosteroids result in altered GABAergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Our heuristic model suggests that for some women, failure of the GABA(A) receptor to regulate overall GABAergic tone in the face of shifting levels of these neurosteroids may induce HPA axis dysfunction, thereby increasing sensitivity to stress, and generating a period of greater vulnerability to depression. CONCLUSIONS: The proposed model provides a basis for understanding the mechanisms by which the changing hormonal environment of the menopause transition may interact with the psychosocial environment of mid-life to contribute to perimenopausal depression risk. Future research investigating this model may inform the development of novel pharmacological treatments for perimenopausal depression and related disorders such as postpartum depression and premenstrual dysphoric disorder