TY - JOUR
T1 - A comparison of progestins within three classes
T2 - Differential effects on learning and memory in the aging surgically menopausal rat
AU - Braden, Brittany
AU - Andrews, Madeline G.
AU - Acosta, Jazmin I.
AU - Mennenga, Sarah E.
AU - Lavery, Courtney
AU - Bimonte-Nelson, Heather
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2017/3/30
Y1 - 2017/3/30
N2 - Introduction For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored. Methods In two studies, the present investigation evaluated the cognitive effects of norethindrone acetate (NETA), levonorgestrel (LEVO), and medroxyprogesterone acetate (MPA) on the water radial-arm maze (WRAM) and Morris water maze (MM) in middle-aged ovariectomized rats. Results In Study 1, six-weeks of a high-dose NETA treatment impaired learning and delayed retention on the WRAM, and impaired reference memory on the MM. Low-dose NETA treatment impaired delayed retention on the WRAM. In Study 2, high-dose NETA treatment was reduced to four-weeks and compared to MPA and LEVO. As previously shown, MPA impaired working memory performance during the lattermost portion of testing, at the highest working memory load, impaired delayed retention on the WRAM, and impaired reference memory on the MM. NETA also impaired performance on these WRAM and MM measures. Interestingly, LEVO did not impair performance, but instead enhanced learning on the WRAM. Conclusions The current study corroborates previous evidence that the most commonly prescribed FDA-approved progestin for HT, MPA, impairs learning and memory in the ovariectomized middle-aged rat. When progestins from two different additional subcategories were investigated, NETA impaired learning and memory similarly to MPA, but LEVO enhanced learning. Future research is warranted to determine LEVO's potential as an ideal progestin for optimal health in women, including for cognition.
AB - Introduction For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored. Methods In two studies, the present investigation evaluated the cognitive effects of norethindrone acetate (NETA), levonorgestrel (LEVO), and medroxyprogesterone acetate (MPA) on the water radial-arm maze (WRAM) and Morris water maze (MM) in middle-aged ovariectomized rats. Results In Study 1, six-weeks of a high-dose NETA treatment impaired learning and delayed retention on the WRAM, and impaired reference memory on the MM. Low-dose NETA treatment impaired delayed retention on the WRAM. In Study 2, high-dose NETA treatment was reduced to four-weeks and compared to MPA and LEVO. As previously shown, MPA impaired working memory performance during the lattermost portion of testing, at the highest working memory load, impaired delayed retention on the WRAM, and impaired reference memory on the MM. NETA also impaired performance on these WRAM and MM measures. Interestingly, LEVO did not impair performance, but instead enhanced learning on the WRAM. Conclusions The current study corroborates previous evidence that the most commonly prescribed FDA-approved progestin for HT, MPA, impairs learning and memory in the ovariectomized middle-aged rat. When progestins from two different additional subcategories were investigated, NETA impaired learning and memory similarly to MPA, but LEVO enhanced learning. Future research is warranted to determine LEVO's potential as an ideal progestin for optimal health in women, including for cognition.
KW - Aging
KW - Cognition
KW - Hormone therapy
KW - Memory
KW - Menopause
KW - Progestin
UR - http://www.scopus.com/inward/record.url?scp=84978897984&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978897984&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2016.06.053
DO - 10.1016/j.bbr.2016.06.053
M3 - Article
C2 - 27368418
AN - SCOPUS:84978897984
SN - 0166-4328
VL - 322
SP - 258
EP - 268
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -