ArticleNeurobiology of aging2018
Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two.
Article in Neurobiology of aging, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Testing an increasing social working memory load in the female rat.Brain research · 2026Article
- Contraceptive hormone ethinyl estradiol but not levonorgestrel modulates the role of reinforcer-enhancement in nicotine self-administration in ovary-intact female Sprague-Dawley rats.Neuropharmacology · 2025Article
- Chronic 17β-estradiol treatment improves negative valence, anhedonic profile, and social interactions in ovariectomized, middle-aged female rats.Frontiers in behavioral neuroscience · 2025Article
- Gynecological surgery in adulthood imparts cognitive and brain changes in rats: A focus on hysterectomy at short-, moderate-, and long-term intervals after surgery.Hormones and behavior · 2023Article
- Evaluations of memory, anxiety, and the growth factor IGF-1R after post-surgical menopause treatment with a highly selective progestin.Behavioural brain research · 2023Article
- Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer's disease: three key timepoints through middle-age in females.Scientific reports · 2022Article
- Evaluating the Cognitive Impacts of Drospirenone, a Spironolactone-Derived Progestin, Independently and in Combination With Ethinyl Estradiol in Ovariectomized Adult Rats.Frontiers in neuroscience · 2022Article
- GABA System Modifications During Periods of Hormonal Flux Across the Female Lifespan.Frontiers in behavioral neuroscience · 2022Review
- Oestrogen treatment modulates the impact of cognitive experience and task complexity on memory in middle-aged surgically menopausal rats.Journal of neuroendocrinology · 2021Article
- Menopause, hormone therapy and cognition: maximizing translation from preclinical research.Climacteric : the journal of the International Menopause Society · 2021Review
- Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause.Frontiers in behavioral neuroscience · 2021Article
- Age Impacts the Burden That Reference Memory Imparts on an Increasing Working Memory Load and Modifies Relationships With Cholinergic Activity.Frontiers in behavioral neuroscience · 2021Article
- Surgical Menopause and Estrogen Therapy Modulate the Gut Microbiota, Obesity Markers, and Spatial Memory in Rats.Frontiers in cellular and infection microbiology · 2021Article
- Adolescent Development of Biological Rhythms in Female Rats: Estradiol Dependence and Effects of Combined Contraceptives.Frontiers in physiology · 2021Article
- Intranasal 17β-Estradiol Modulates Spatial Learning and Memory in a Rat Model of Surgical Menopause.Pharmaceutics · 2020Article
- Characterizing the effects of tonic 17β-estradiol administration on spatial learning and memory in the follicle-deplete middle-aged female rat.Hormones and behavior · 2020Article
- Oestradiol as a neuromodulator of learning and memory.Nature reviews. Neuroscience · 2020Review
- A long-term cyclic plus tonic regimen of 17β-estradiol improves the ability to handle a high spatial working memory load in ovariectomized middle-aged female rats.Hormones and behavior · 2020Article
- Poly(lactic-co-glycolic Acid) Nanoparticle Encapsulated 17β-Estradiol Improves Spatial Memory and Increases Uterine Stimulation in Middle-Aged Ovariectomized Rats.Frontiers in behavioral neuroscience · 2020Article
- The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats.Frontiers in endocrinology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Most estrogen-based hormone therapies are administered in combination with a progestogen, such as Levonorgestrel (Levo). Individually, the estrogen 17β-estradiol (E2) and Levo can improve cognition in preclinical models. However, although these hormones are often given together clinically, the impact of the E2 + Levo combination on cognitive function has yet to be methodically examined. Thus, we investigated E2 + Levo treatment on a cognitive battery in middle-aged, ovariectomized rats. When administered alone, E2 and Levo treatments each enhanced spatial working memory relative to vehicle treatment, whereas the E2 + Levo combination impaired high working memory load performance relative to E2 only and Levo only treatments. There were no effects on spatial reference memory. Mitogen-activated protein kinases/extracellular signal-regulated kinases pathway activation, which is involved in memory formation and estrogen-induced memory effects, was evaluated in 5 brain regions implicated in learning and memory. A distinct relationship was seen in the E2-only treatment group between mitogen-activated protein kinases/extracellular signal-regulated kinases pathway activation in the frontal cortex and working memory performance. Collectively, the results indicate that the differential neurocognitive effects of combination versus sole treatments are vital considerations as we move forward as a field to develop novel, and to understand currently used, exogenous hormone regimens across the lifespan.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.