TY - JOUR
T1 - Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause
AU - Koebele, Stephanie V.
AU - Hiroi, Ryoko
AU - Plumley, Zachary M.T.
AU - Melikian, Ryan
AU - Prakapenka, Alesia V.
AU - Patel, Shruti
AU - Carson, Catherine
AU - Kirby, Destiney
AU - Mennenga, Sarah E.
AU - Mayer, Loretta P.
AU - Dyer, Cheryl A.
AU - Bimonte-Nelson, Heather A.
N1 - Funding Information:
Dr. Michael Edwards is thanked for his valuable discussions regarding the statistical analyses in this manuscript. Alicia M. Quihuis is thanked for her assistance with VCD injections. Funding. HB-N, NIA (AG028084), state of Arizona, Arizona Department of Health Services (ADHS14-052688), NIH Alzheimer’s Disease Core Center (P30AG019610), and Arizona State University Office of Knowledge Enterprise Development, College of Liberal Arts and Sciences, and Department of Psychology.
Publisher Copyright:
© Copyright © 2021 Koebele, Hiroi, Plumley, Melikian, Prakapenka, Patel, Carson, Kirby, Mennenga, Mayer, Dyer and Bimonte-Nelson.
PY - 2021/7/21
Y1 - 2021/7/21
N2 - 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.
AB - 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.
KW - VCD
KW - anxiety
KW - depression
KW - estrogen
KW - levonorgestrel
KW - memory
KW - menopause
KW - progesterone
UR - http://www.scopus.com/inward/record.url?scp=85111903345&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111903345&partnerID=8YFLogxK
U2 - 10.3389/fnbeh.2021.696838
DO - 10.3389/fnbeh.2021.696838
M3 - Article
AN - SCOPUS:85111903345
SN - 1662-5153
VL - 15
JO - Frontiers in Behavioral Neuroscience
JF - Frontiers in Behavioral Neuroscience
M1 - 696838
ER -