Low Estradiol Linked to Depression in Iranian Women Across Menopause Stages

Depression remains one of the most common and disabling mental health conditions affecting women worldwide, yet the biological forces that shape its risk across a woman’s reproductive life are still poorly understood. A new cross-sectional study from southeast Iran adds a striking piece to that puzzle, reporting that four in ten women screened in the city of Kerman showed elevated depressive symptoms, and that lower levels of the sex hormone estradiol were independently associated with greater odds of depression in both premenopausal and postmenopausal women. The research, published in BMC Psychology by Tania Dehesh of Kerman University of Medical Sciences, Mohammad Amin Mosleh-Shirazi of Shiraz University of Medical Sciences, and Paria Dehesh of Kerman University of Medical Sciences, offers one of the most detailed snapshots to date of how reproductive hormones and mood intersect in a Middle Eastern population.

The study enrolled 952 women aged 18 to 65 years, recruited randomly across four socioeconomic regions of Kerman in 2024. This stratified sampling approach was designed to capture women from different social and economic circumstances rather than relying on a single clinic or neighborhood, which strengthens the representativeness of the findings for the wider urban population. Each participant completed a validated Persian-language version of the Beck Depression Inventory-II, a widely used self-report screening instrument, and a cut-off score above 14 was used to identify women with elevated depressive symptoms. In addition to the psychological assessment, the researchers measured serum levels of four key hormones: progesterone, prolactin, estradiol, and testosterone. Demographic variables including age and body mass index were also recorded, allowing the team to disentangle hormonal effects from other well-known contributors to mood.

The headline result is the sheer scale of the burden. The overall prevalence of elevated depressive symptoms was 40 percent across the sample. When the researchers split the cohort by menopausal status, the figures were remarkably similar: 39 percent of premenopausal women and 41 percent of postmenopausal women screened positive. That narrow gap between the two groups is itself informative. It suggests that the transition through menopause, often assumed to be a period of heightened psychological vulnerability, does not dramatically change the prevalence of depressive symptoms in this population, even though the hormonal milieu shifts profoundly. Postmenopausal women were only slightly more likely to report elevated symptoms than their premenopausal counterparts.

The hormonal findings are where the study becomes technically compelling. In adjusted multivariable logistic regression models, stratified by menopausal status, lower estradiol levels were independently associated with greater odds of depressive symptoms in both groups. Among premenopausal women, the adjusted odds ratio was 0.63, with a 95 percent confidence interval of 0.18 to 0.92 and a p-value of 0.038. Among postmenopausal women, the adjusted odds ratio was 0.61, with a 95 percent confidence interval of 0.23 to 0.88 and a p-value of 0.034. Because these are odds ratios for the hormone variable expressed in a direction where values below one indicate a protective association, the results mean that women with higher estradiol had lower odds of screening positive for depression, and the relationship held after accounting for age, body mass index, and other covariates.

Estradiol is the most potent form of estrogen circulating in the human body, and its influence on the brain extends far beyond the reproductive system. The hormone modulates neurotransmitter systems, including serotonin and dopamine pathways, that are central to mood regulation. It also influences neuroplasticity, cerebral blood flow, and the stress response axis. A long-standing hypothesis in reproductive neuroscience holds that declines or fluctuations in estradiol, whether across the menstrual cycle, after childbirth, or during the menopausal transition, can destabilize mood in susceptible individuals. The new findings align with that framework: in both reproductive stages, women with elevated depressive symptoms had significantly lower estradiol levels than those without, even though the absolute hormone concentrations differ enormously between premenopausal and postmenopausal women.

Equally notable is what did not predict depression. After adjustment, there were no significant associations between progesterone, prolactin, or testosterone and elevated depressive symptoms in either group. Progesterone metabolites interact with inhibitory GABA receptors in the brain and have been implicated in premenstrual mood disorders, while prolactin and testosterone have each been linked to mood in previous research with mixed results. The fact that only estradiol emerged as a significant independent predictor, consistently across both menopausal strata, sharpens the focus on estrogen signaling as the hormonal thread most tightly woven into depressive symptomatology in this cohort. It also underscores the value of measuring multiple hormones simultaneously rather than studying them in isolation, since a single-hormone analysis could easily have produced a misleading picture.

Beyond the hormonal story, the study identified demographic risk factors that echo patterns seen globally. Older age and higher body mass index were independently associated with elevated depressive symptoms in both premenopausal and postmenopausal women. The link between adiposity and depression is well documented in the international literature and is thought to involve chronic low-grade inflammation, insulin resistance, and social and psychological factors related to body image and health status. The age association is consistent with the cumulative burden of life stressors and chronic disease, although cross-sectional data cannot determine whether aging itself, or the conditions that accompany it, drives the relationship. Marital status added a further layer of nuance: divorced or widowed marital status was an additional significant predictor of elevated depressive symptoms in premenopausal women, with an adjusted odds ratio of 1.36, a 95 percent confidence interval of 1.17 to 1.59, and a p-value of 0.043. This association was not reported as significant in the postmenopausal group.

The methodological choices of the study deserve scrutiny. The Beck Depression Inventory-II is a screening tool, not a diagnostic instrument, so the 40 percent figure reflects the prevalence of elevated depressive symptoms rather than clinically confirmed major depressive disorder. Self-report measures can be influenced by somatic symptoms, cultural expression of distress, and response bias, although the Persian-language version used has been validated for Iranian populations. The cross-sectional design is the study’s principal limitation: it captures a single moment in time and cannot establish whether low estradiol causes depression, whether depression alters hormone levels, or whether both are shaped by a common underlying factor. Longitudinal designs, in which hormone trajectories are tracked alongside mood over months or years, would be needed to establish temporal direction. The authors also note that the study was not registered in a clinical trial registry, which is not mandatory for observational cross-sectional designs under current Iranian research regulations, and that the work received no external funding.

Nevertheless, the consistency of the estradiol signal across two very different hormonal contexts is what makes the study worth attention. Premenopausal women experience cyclical estradiol fluctuations at concentrations many times higher than those seen after menopause, yet in both groups the same directional relationship with depressive symptoms appeared after adjustment. This suggests that estradiol’s relevance to mood may operate relative to a woman’s own hormonal baseline rather than at any absolute threshold. For clinicians, the findings hint that reproductive hormonal status could be a meaningful consideration when assessing depression risk in women, alongside established factors such as age, body weight, and social circumstances. For researchers, they set the stage for intervention studies and mechanistic work exploring whether maintaining estradiol within physiological ranges can buffer mood, and for longitudinal cohorts that can finally separate cause from correlation in the intricate dialogue between the ovaries and the brain.

Subject of Research: Prevalence of depression in Iranian premenopausal and postmenopausal women and its association with sex hormone levels

Article Title: Prevalence of depression in Iranian premenopausal and postmenopausal women and its association with sex hormone levels

Article References: Dehesh, T., Mosleh-Shirazi, M. A., & Dehesh, P. (2026). Prevalence of depression in Iranian premenopausal and postmenopausal women and its association with sex hormone levels. BMC Psychology. https://doi.org/10.1186/s40359-026-05692-y

Image Credits: AI Generated

DOI: 10.1186/s40359-026-05692-y

Keywords: Prevalence, depression, Iranian, premenopausal, postmenopausal, women, association, hormone, levels, scientific research