Hold that thought AND the box

I'd inched my way down the first step with a heavy box of books when I noticed that I felt off-balance on looking down. Ah, still had my reading glasses on. Set the books down on the landing with a heavy thump, pulled off the glasses, and scratched the tip of my nose. Gathered box and books back in my arms, and resumed my careful descent.

Dang, still dizzy. While my nose was no longer itchy, I was once again wearing the glasses.

The benefits of progesterone

I woke up this morning, made coffee as usual, then sat down with the Sunday paper. I realized by page 10 that the smell of the ink (something I'd never noticed before) was grossing me out. I had to leave steaming coffee and paper or risk throwing up. Whoa, thought I, this feels like morning sickness.

Lying miserably in bed, I remembered that I was on the day 2 of the progesterone cycle of my combined hormone therapy. And, indeed, as morning sickness is probably caused by the high levels of progesterone in early pregnancy, this a.m.'s passing upset may well have been the menopausal equivalent.

I am not alone in my ambivalence towards progesterone; other women find they too are woozy and sleepy on natural progesterone. The research of Emory University's Dr. Donald Stein reassures me that progesterone is not without benefits to brain even if the acute effects include sedation and dizziness.

A major problem with head injuries is that not only does the part of the brain injured by the blow lose neurons, but the adjacent brain cells are also at risk of dying off as a wave of inflammation caused by the trauma spreads laterally. Dr. Stein and his colleagues in the Emory's Emergency Department, frustrated by their inability to prevent this devastating secondary injury to unharmed gray matter, set out to test whether or not progesterone could benefit traumatic brain injury (TBI) patients.

Until recently, the primary treatment for TBI was high dose steroids, but the evidence for the efficacy of this approach was sparse. In fact, a 2004 study compared the outcomes for thousands of head-injured patients, half treated with steroids and half not(1). The trial was abruptly terminated when it was found that 2 weeks after injury, the steroid-treated patients had a greatly increased risk of death.

Testing on both human and animal subjects suggest that memory, executive, and spatial functioning is best during mid-cycle (ovulation) when progesterone levels are highest. Animal models of TBI and stroke show that progesterone reduces brain swelling and greatly protects neurons surrounding the primary area of injury from dying. Stein and company found that rats treated at the time of injury had quicker and more complete recoveries of brain function. Initial trials on humans (and progesterone is a non-feminizing hormone that can be used in men who are more likely than women to experience TBI) suggested that the early use of progesterone after head trauma improved odds of being undead one month post-injury by more than 50% and those progesterone-treated survivors had a trend towards better functional recovery(2).

So why does progesterone lead to sedation and, in some, such a morning hangover? Stein notes that progesterone binds to GABA receptors in the brain --the same ones targeted by Valium, Xanax, and other such tranquilizers-- causing temporary sedation. These effects are passing, and the net effect of progesterone on brain is neuroprotective.
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1. Sauerland, S, et al. 2004. A CRASH landing in severe head injury. Lancet. 2004 364: 1291-1292.
2. Stein, D, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007 Apr;49(4):391-402,

Shady business

My patient was in today about her chronic insomnia. Like so many women, her sleep changed with the menopausal transition and never returned to the good old ways.

As we sat talking, she fiddled with her sunglasses in her lap. Midway through the appointment, she put them on. A puzzled look crossed her face for a moment as if she wondered, briefly, why the room had dimmed. She pulled them off, and we both had a laugh over that.

As we bent over her test results together, she opened her purse and got out her reading glasses. Not a minute later, she lifted the sunglasses and attempted to put them on over her readers.

Sleep deprivation or just a plain old menopause moment?

If you can't say anything right...

Don't say anything at all!

Shopping with spouse, he comparing the price per square foot of paper towels, me wondering if this outing is materially affecting the length of my remaining life.

Along comes a patient who greets me "Hi Dr. P!"

Argh, dig deep, it's a big leap from towels to names. The details of her last visit come up on the mental screen, but there's a hole where her name lives.

"Uh, hi....Irene." I smile uneasily. She hurries her cart and her partner out of the aisle.

Dang, I realize immediately that's Ilene. Perhaps she thinks she heard me wrong. Perhaps not.

Losing my buttons!

I sat at my desk today, retrieving patient messages on my cell phone. One of those push 1 for this and 2 for that sort of voice mail systems. I pushed 2 to get the new message. Nothing. No beep, no response, nothing. So I pushed it again, harder! Nothing. Then I realized that I was pushing the 2 button on my desk top phone while holding my cell phone to my ear.

And you are...????

Ah, it's....you. I'm always on my toes at the grocery store, ready to recognize and greet patients that I may have met only once in my life. I usually remember the faces and something personal, like where their children go to school, or where they work. But names? That's a problem mostly because new names seem to me like random tags without any associated memories to link them with a face.

What, however, of persons who can't recognize faces? This problem, dubbed prosopagnosia, can be so severe that these people have trouble identifying their nearest and dearest. Once thought to be rare as can be, researchers now believe that 2% of the general population have face blindness severe enough to affect their daily lives.

Are you in the facial know? Check out Faceblind for two little recognition quizzes. The first presents an array of famous faces that does require a certain visual knowledge of the famous and the infamous. During the second, you will have a small amount of time to familiarize yourself with twenty women, then will be asked to recognize them as they appear on your screen amonst the unknown. It's fun!

DNA loves company

We can't change them into the happy, laughing life of the party, but we can keep them out of the coffin.
---Steve Cole, genomics researcher at UCLA

The chronically lonely are known to be more likely to suffer from ill health. A recent study suggests that this state of mind actually affects gene action in a way that decreases immune response and increases inflammation.

Dr. Cole and his colleagues set out to find the biological basis for the detrimental effects of loneliness on health. They studied the DNA of a group of 153 volunteers, looking for abnormal gene expression as related to the self-expressed degree of loneliness in their subjects.

The UCLA Loneliness Scale was used to determine just how isolated these folks felt. Then DNA gleaned from white blood cells of the 8 top lonely scorers was compared with the DNA from the 6 subjects most connected to others. The researchers found 209 genes abnormally expressed in the lonely genome, many involved in activation of the immune system and production of inflammation. The genes in charge of inflammation were overexpressed, and those that regulate the production of antibodies against bacteria and viruses were underexpressed.

These results may explain why isolation and loneliness increases vulnerability to infection and cardiovascular disease. Dr. Cole theorizes that strategies that decrease inflammation may promote better health amongst the isolated.

Verbal fluency

Verbal fluency (VF) is defined as the ease with which a person can find the right word and use it at the right time. Verbal fluency tests generally involve a timed interval in which a person is asked to name as many animals (fruits, vegetables, words that start with Q, etc) as they can during that time.

I test my verbal fluency every day in the consultation room as I explain this, that, or the other medical condition to a patient with more or less ease. Progesterone definitely slows down my VF as does a lack of estrogen. Progesterone is known to have sedating effects on the brain, and my frontal lobe is clearly affected by my periodic use of Prometrium, a proprietary formulation of natural progesterone. A dose at bedtime gives me a great, dream-filled sleep but leaves me fumble-mouthed on the job the following day.

Likewise, estrogen has a strong influence on verbal memory, and some of my patients who choose to motor into menopause without HRT find their word-finding abilities seriously impaired. Estrogen supports the function of cholinergic neurons in the brain (those brain cells that communicate one to another via a neurotransmitter called acetylcholine). Cells in charge of verbal memory and executive functioning are cholinergic neurons and thus affected by lack of estrogen. Likewise, anticholinergic medication such as antihistamines (which are used as over-the-counter sleep aids) also can leave the user tongue-tied with respect to VF.

Not only does dementia cause decrease in verbal fluency, so often do head injuries (as the frontal lobe sitting just behind the forehead, is often first to hit the windshield in accidents), Parkinson's disease, schizophrenia, diabetes, and alcoholism. Persons with chronic lung disease are known to have cognitive troubles whether or not they're running short on oxygen levels. Ohio investigators found that 20 minute exercise sessions significantly increased verbal fluency scores on patients with COPD.