title: A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ, United States; Arizona Alzheimer's Consortium, United States.
authors.forename: B Blair
authors.initials: BB
authors.lastname: Braden
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ, United States.
authors.forename: Madeline G
authors.initials: MG
authors.lastname: Andrews
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ, United States.
authors.forename: Jazmin I
authors.initials: JI
authors.lastname: Acosta
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Mennenga
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ, United States.
authors.forename: Courtney
authors.initials: C
authors.lastname: Lavery
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ, United States; Arizona Alzheimer's Consortium, United States. Electronic address: bimonte.nelson@asu.edu.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Bimonte-Nelson
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D016912:Levonorgestrel / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D009640:Norethindrone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010052:Ovariectomy; D011372:Progestins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011581:Psychological Tests; D011897:Random Allocation; D011916:Rats, Inbred F344
chemical_list: D011372:Progestins; D016912:Levonorgestrel; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone
keywords: Aging; Cognition; Hormone therapy; Memory; Menopause; Progestin