Characterizing the effects of tonic 17β-estradiol administration on spatial learning and memory in the follicle-deplete middle-aged female rat

Koebele, Stephanie V.; Mennenga, Sarah E.; Poisson, Mallori L.; Hewitt, Lauren T.; Patel, Shruti; Mayer, Loretta P.; Dyer, Cheryl A.; Bimonte‐Nelson, Heather A.

doi:10.1016/j.yhbeh.2020.104854

Cited by 19 publications

(36 citation statements)

References 121 publications

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“…Compared to the VCD-Vehicle group, the VCD-E2 group had significantly fewer primordial follicles [F (1 , 16) = 6.10, p < 0.05] and fewer primary follicles [F (1 , 16) = 9.89, p < 0.01] (Figures 13A,B), an effect we have previously observed in follicle-depleted rats with tonic E2 treatment (Koebele et al, 2020a). Secondary follicles, antral follicles, and corpora lutea counts did not differ between VCD-Vehicle and VCD-E2 groups, although both groups exhibited substantial follicle decline, indicating successful VCD-induced follicular depletion.…”

Section: How Does Daily E2-only Treatment Affect Ovarian Follicle Profiles With Transitional Menopause?mentioning

confidence: 57%

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Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

Koebele

Hiroi

Plumley

et al. 2021

Front. Behav. Neurosci.

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A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17β-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.

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Section: How Does Daily E2-only Treatment Affect Ovarian Follicle Profiles With Transitional Menopause?mentioning

confidence: 57%

“…Based on prior data from our and other laboratories, normal estrous cyclicity is disrupted approximately 4 months after VCD injection administration, and vaginal cytology can be modified by a given hormone therapy regimen (Koebele et al, 2020a).…”

Section: Vaginal Cytologymentioning

confidence: 99%

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

Koebele

Hiroi

Plumley

et al. 2021

Front. Behav. Neurosci.

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“…As with all animal models some limitations associated with the model system should be mentioned. First, although well-established, 23 particularly in cognitive and cardiology research 24,110,111 and believed to be non-toxic/ovarian follicle specific, 24,112 the VCD menopause induction may introduce as yet unidentified off-target impacts. The timing of the VCD and cognitive assessment (ie, middle-aged animals) could have resulted in some sham animals being spontaneously acyclic.…”

Section: Discussionmentioning

confidence: 99%

APOE4 genotype exacerbates the impact of menopause on cognition and synaptic plasticity in APOE‐TR mice

et al. 2021

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“…Our laboratory has also systematically tested E2 HT in surgical (Ovx) and transitional (VCD) rodent menopause models, whereby strong working memory benefits were observed with E2 treatment following surgical menopause [70]. In contrast, in the transitional model of menopause, both learning benefits and retention deficits were observed with E2 treatment [54]. These divergent cognitive effects depending upon menopause history have also been observed with CEE.…”

Section: Use Of E2 or Conjugated Equine Estrogens As The Estrogenic Component In Hormone Therapymentioning

confidence: 97%

“…Furthermore, Daniel and colleagues performed an elegant series of experiments highlighting the importance of HT timing and duration, demonstrating that immediate, but not delayed, E2 treatment benefits attentional processes [47], and that transient E2 exposure in midlife can have long-lasting memory benefits and enhance hippocampal estrogen receptor expression, even after E2 treatment is discontinued in an Ovx model [48,49]. It is important to note that preclinical cognitive and neurobiological effects of estrogen are not always consistent, even when given in this critical window; menopause type, HT type and behavior testing account for some variations in outcomes [44,[50][51][52][53][54][55][56][57][58].…”

Section: Timing Of Hormone Therapy Relative To Menopause and Age: Insights From Preclinical Researchmentioning

confidence: 99%

Menopause, hormone therapy and cognition: maximizing translation from preclinical research

2021

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Menopause-associated and hormone-associated cognitive research has a rich history built from varied disciplines and species. This review discusses landmark rodent and human work addressing cognitive outcomes associated with varied experiences of menopause and hormone therapy. Critical variables in menopause and cognitive aging research are considered, including menopause etiology, background hormone milieu and parameters of exposure to estrogens and progestogens. Recent preclinical research has identified that menopause and ovarian hormone fluctuations across many neurobiological systems affect cognitive aging, mapping novel avenues for future research. Preclinical models provide insight into complex interdisciplinary relationships in a systematic and highly controlled fashion. We highlight that acknowledging the strengths and weaknesses for both preclinical and clinical research approaches is vital to accurate interpretation, optimal translation and the direction of future research. There is great value in collaboration and communication across preclinical and clinical realms, especially regarding reciprocal feedback of findings to advance preclinical models, improve experimental designs and enrich basic science translation to the clinic. In searching for biological mechanisms underlying the cognitive consequences of menopause and hormone therapies, it is noteworthy that clinical and preclinical scientists are grounded in the same fundamental goal of optimizing health outcomes for women across the lifespan.

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Characterizing the effects of tonic 17β-estradiol administration on spatial learning and memory in the follicle-deplete middle-aged female rat

Cited by 19 publications

References 121 publications

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

APOE4 genotype exacerbates the impact of menopause on cognition and synaptic plasticity in APOE‐TR mice

Menopause, hormone therapy and cognition: maximizing translation from preclinical research

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