A symptom of estrogen deficiency that many women fear is the decline in memory and mental concentration. Our mothers and grandmothers often accepted this as a necessary consequence of aging. Postmenopausal women often describe it as “brain fog” and “fuzzy thinking.” They especially notice problems with word retrieval and remembering names and phone numbers they could easily recall before menopause.
When women learn I’m a physician specializing in menopause, they usually tell me their stories. Earlier this year, I sat next to Jane, a PhD researcher, who works for a prominent east coast research institution. She had been menopausal for 3 years and was terrified of taking hormones because she was fearful of breast cancer. Jane lamented, “Dr. Johnson, I can’t remember articles I’ve just read. I have to read and re-read them to make any sense of them. I keep incessant lists of everything to keep me on task. I’m afraid I’m going to lose my job!” I reassured her about the risk-benefit ratio for estrogen, told her about topical HRT and advised her to follow-up with a menopause specialist.
On another trip this month, I sat next to Jackie, a woman in her 60s who told me about her experience when she became menopausal 10 years ago. Jackie said,
“I was having awful hot flashes and could not think straight. I became paranoid and frightened, and I was afraid to be in any social situations. I asked my young doctor for help but he just told me that was something normal that would eventually pass. I relied on advice from an older woman friend, long menopausal. I coped by refusing to go out of my house for six months and staying in bed most of the that time. My husband was worried sick about me until finally I felt a little better.”
I submit to you in the 21st century, this is not an acceptable way to treat fifty percent of our population who will all eventually go through this life stage. In addition to the suffering of these women, think of the lost productivity. When you don’t have your mind, your quality of life is severely compromised.
When estrogen deficiency continues long-term, there is an increased risk for the development of Alzheimer’s disease. In June 2008, the Centers for Disease Control and Prevention reported that AD is now the sixth leading cause of death in the United States, surpassing diabetes. There are currently five million Americans with AD or dementia and more than half of them are women. This total figure is expected to increase to 10 million as the Baby Boomers age.
Estrogen has the following effects on the brain:
1. Modulation of synapses, the special junctions where nerve cells communicate with each other
2. Increase of cerebral blood flow
3. Mediation of important neurotransmitters and hormones
4. Protection against apoptosis (programmed cell death)
5. Increase in anti-inflammatory actions
6. Antioxidant effects
There are estradiol receptors throughout the brain especially in the basal forebrain located near the bottom of the front of the brain. This area includes the hippocampus that is important for memory and learning.
There is clearly an association between the length of time a woman maintains her own estrogen production and her ability to have normal mental focus and memory. When women undergo surgical menopause at an early age and do not take estrogen, they have a sharper decline in these mental functions than women who undergo natural menopause. A Mayo Clinic study of 3000 women followed for 30 years found that women who had one or both ovaries removed before menopause and did not take estrogen were more likely to develop dementia and Parkinson’s Disease.
Despite the biologic importance of estradiol in a woman’s mental function, studies in women receiving HRT have been less conclusive. The Nurses’ Health Study of 13,087 postmenopausal women followed for eight years showed no appreciable mental benefits in women who took oral estrogen or estrogen/ synthetic progestin as compared to those on no HRT. On the contrary, they showed an actual increased risk of mental decline in those women who started HRT at an older age. A possible mechanism for this is that oral estrogen increases C-reactive protein that has been associated with increased dementia. A few smaller studies have shown a modest benefit in improving cognitive function. The WHI Memory Study showed worsening of dementia in women taking Prempro; however, the dementia appears to be related to the use of continuous combined estrogen plus medroxyprogesterone acetate (MPA). MPA has been found to reduce mental performance in both animal and human studies. See previous chapter on Risks of Adding Oral Synthetic Progestins.
Achieving The Optimal Protective Effect of Estrogen
To achieve the optimal brain protective effect of estrogen, women are advised to start on topical estrogen soon after menopause. In light of the lack of protection seen in the WHI Memory Study, it seems prudent to initiate topical estradiol. In women with an intact uterus, cyclic progesterone should be used over a synthetic progestin. Women who start estrogen after age 60 have no reduction in their risk of AD probably because they have already developed degenerative brain loss.
The Cache Study on Memory Health and Aging: Estrogen Use Reduced Alzheimer’s Risk by 50%
The Cache County Study on Memory, Health and Aging has been following a group of 5,092 seniors in rural, northeastern Utah since 1995 to determine the development of Alzheimer’s disease. In 2005 they published findings showing an increased risk of developing AD when you carry a gene called Apolipo- protein E (ApoE4.) If you inherit an ApoE4 gene from each parent, your gene type is called ApoE 4/4. If you only receive one ApoE4, your type is ApoE 3/4 or ApoE 2/4.
The Cache study also reported medications that may reduce the risk of developing Alzheimer’s disease. Use of aspirin and non-steroidal anti-inflammatory agents (NSAIDS) like ibuprofen were associated with a reduced prevalence of AD by about 50%. Use of Vitamin E and vitamin C showed a decreased prevalence of AD but only if they were both used in combination. Estrogen use reduced AD risk by 50%, and in women without dementia, estrogen use improved cognitive performance.
Future Research on Treatment For Alzheimer’s Disease
While estrogen has been shown to prevent the occurrence of Alzheimer’s disease, in studies specifically evaluating the effect of oral estrogen in women with established AD, no effect on progression of the disease was seen. A few small studies have shown topical estrogen positively influences postmenopausal memory and may offer some protective effect against the mental decline seen in AD.
Future research on treatment for AD should focus on such variables as the route of estrogen administration, the form of estrogen (conjugated estrogens versus estradiol), when estrogen is initiated following menopause, duration of estrogen treatment, and the effects of opposed versus unopposed estrogen to define which HRT regimens may have a benefit.
Excerpt from “Outliving Your Ovaries” © 2012 by Marina Johnson MD.
To obtain a copy of “Outliving Your Ovaries” click here
Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, et al, Cache County Memory Study Investigators., Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study, JAMA (2002) 288(17):2123-9