Losing Your Keys and other “signs” of Menopause

One of my professors during my fellowship stated emphatically there is a big difference between women under the age of 50 and over the age of 50 when it comes to losing their car keys. Those under 50 tend to make a joke about the experience or enlist others around to help in locating the missing keys. Those over 50 just keep very quiet and search frantically themselves.


Forgetfulness, or “brain fog” as my hormone patients like to phrase this one, can be one of the most commonly reported symptoms of menopause. There are a number of mechanisms through which changes in hormones affect brain function and memory.

Estrogens have direct effects in the brain by increasing the number of synapses in the hippocampus, the region of the brain where transferring short term memories to long term memories is believed to occur. Estrogen and progesterone both help to protect the brain from exogenous and endogenous toxins including glutamate-induced excitotoxicity. Progesterone is a potent anti-inflammatory agent in the central nervous system, working to rebuild the blood-brain barrier, reduce edema and down-regulate the inflammatory cascade in the event of physical or ischemic trauma.

Another important mechanism through which hormones enhance memory is by increasing acetylcholine activity. Acetylcholine is an important neurotransmitter involved in learning and encoding new memories and its production is greatly decreased in conditions of compromised memory including Alzheimer’s disease. Estrogen increases the activity of the enzyme choline-

acetyl transferase, which stimulates the synthesis of acetylcholine.

Maintaining optimal hormone levels throughout the menopausal transition can not only aide in the management of classically “menopausal symptoms” such as hot flashes and night sweats, but can prevent and treat “brain fog” and protect the brain from chemical and physical assault. As always, discuss these concerns, symptoms and possible treatment options with your physician.

1.       McEwen BS. Invited review: Estrogens effects on the brain: Multiple sites and molecular mechanisms. J Appl Physiol 2001;91:2785-801.
2.       Norbury R, Cutter WJ, Compton J, Robertson DM, Craig M, Whitehead M, Murphy DG. The
neuroprotective effects of estrogen on the aging brain. Experim Geront. 2003. 38:109-117.
3.       Prokai L, Prokai-Tatrai K, Perjesi P, Zharikova AD, Perez EJ, Liu R, Simpkins JW. Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11741-6.
4.       Green PS, Simpkins JW. Neuroprotective effects of estrogens: potential mechanisms of action. Int J Dev Neurosci. 2000 Jul-Aug;18(4-5):347-58.
5.       Brann DW, Dhandapani K, Wakade C, Mahesh VB, Khan MM. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids. 2007 May;72(5):381-405. Epub 2007 Feb 21.
6.       Kaur P, Jodhka PK, Underwood WA, Bowles CA, de Fiebre NC, Singh M. Progesterone increases brain-derived neurotrophic factor expression and protects against glutamate toxicity in a mitogen-activated
protein kinase- and phosphoinositide-3 kinase-dependent manner in cerebral cortical explants. J Neurosci Res. 2007 Aug 15:85(11):2441-9.
7.       Stein DG. Progesterone exerts neuroprotective effects after brain injury. Brain Res Rev. 2008 Mar:57(2): 386-397.
8.       Bartus RT, Dean RL, 3rd, Beer B, Lippa AS 1982 The cholinergic hypothesis of geriatric memory
dysfunction. Science 217:408-414
9.       Gabor R, Nagle R, Johnson DA, Gibbs RB. Estrogen enhances potassium-stimulated acetylcholine release in the rat hippocampus. Brain Res. 2003 Feb 7;962(1-2):244-7.
10.    Van Amelsvoort T, Murphy DGM, Robertson D, Daly E, Whitehead M, Abel K. Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmenopausal women. Psychoneuroendocrinology. 2003. 28,101-112.
This entry was posted in Hormones. Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *