By CYNTHIA GORNEY
Here we are, two fast-talking women on estrogen, staring at a wall of live mitochondria from the brain of a rat. Mitochondria are cellular energy generators of unfathomably tiny size, but these are vivid and big because they were hit with dye in a petri dish and enlarged for projection purposes. They’re winking and zooming, like shooting stars. “Oh, my God,” Roberta Diaz Brinton said. “Look at that one. I love these. I love shooting mitochondria.”
Lindsay Hutchens for The New York Times
Brinton is a brain scientist. Estrogen, particularly in its relationship to the health of the brain, is her obsession. At present it is mine too, but for more selfish reasons. We’re inside a darkened lab room in a research facility at the University of Southern California, where Brinton works. We are both in our 50s. I use estrogen, by means of a small oval patch that adheres to my skin, because of something that began happening to me nine years ago — to my brain, as a matter of fact. Brinton uses estrogen and spends her work hours experimenting with it because of her own brain and also that of a woman whose name, Brinton will say, was Dr. A. She’s dead now, this Dr. A. But during the closing years of her life she had Alzheimer’s, and Brinton would visit her in the hospital. Dr. A. was a distinguished psychotherapist and had vivid stories she could still call to mind about her years in Vienna amid the great European psychologists. “We’d spend hours, me listening to her stories, and I’d walk out of the room,” Brinton told me. “Thirty seconds later, I’d walk back in. I’d say, ‘Dr. A., do you remember me?’ And she was so lovely. She’d say: ‘I’m so sorry. Should I?’ ”
The problem with the estrogen question in the year 2010 is that you set out one day to ask it in what sounds like a straightforward way — Yes or no? Do I or do I not go on sticking these patches on my back? Is hormone replacement as dangerous in the long term as people say it is? — and before long, warring medical articles are piling up, researchers are raising their voices and gesticulating excitedly and eventually you’re in Los Angeles staring at a fluorescent rodent brain in the dark. “You want a statistic?” Brinton asked softly. Something about the shooting mitochondria has made us reverent. “Sixty-eight percent of all victims of Alzheimer’s are women. Is it just because they live longer? Let’s say it is, for purposes of discussion. Let’s say it’s just because these ladies get old. Do we just say, ‘Who cares?’ and move them into a nursing home? Or alternatively, maybe they are telling us something.”
With their brains, she means. Their sputtering, fading Alzheimer’s brains, which a few decades earlier were maybe healthy brains that might have been protected from eventual damage if those women had taken estrogen, and taken it before they were long past their menopause, while their own neural matter still looked as vigorous as those rat cells on the wall. This proposition, that estrogen’s effects on our minds and our bodies may depend heavily upon when we first start taking it, is a controversial and very big idea. It has a working nickname: “the timing hypothesis.” Alzheimer’s is only one part of it. Because the timing hypothesis adds another layer of complication to the current conventional wisdom on hormone replacement, it has implications for heart disease, bone disease and the way all of us women now under 60 or so — the whole junior half of the baby boomers, that is, and all our younger sisters — could end up re-examining, again, everything the last decade was supposed to have taught us about the wisdom of taking hormones.
I first met Brinton at a scientific symposium at Stanford University in January that was entirely devoted to the timing hypothesis. The meeting was called Window of Opportunity of Estrogen Therapy for Neuroprotection, and it drew research scientists and physicians from all over the country. When I asked to listen in, the organizers hesitated; these are colleagues around a conference table, they pointed out. They’re probing, interrogating, poking holes in one another’s work in progress.
But I was finally permitted to take a chair in a corner, and as the day went on, I became aware of my patch, in a distracted, hallucinatory sort of way, as if I had started fixating on a smallish scar. One after another, their notes and empty coffee cups piling up around them, heart experts and brain experts and mood experts got up to talk about estrogen — experiments, clashing data, suppositions, mysteries. There are new hormone trials under way that are aimed at the 40-year-old to 60-year-old cohort, with first results due in 2012 and 2013. There are depression studies involving estrogen. There are dementia studies involving estrogen. There are menopausal lab monkeys taking estrogen, ovariectomized lab mice taking estrogen and young volunteers undergoing pharmaceutically induced menopause so researchers at the National Institutes of Health can study exactly what happens when the women’s estrogen and progesterone are then cranked back up. I typed notes into my laptop for hours, imagining the patch easing its molecules into the skin of my back, and the whole time I was typing, working hard to follow the large estrogen-replacement thoughts of the scientists around the table, I had one small but persistent estrogen-replacement thought of my own: If I make the wrong decision about this, I am so screwed.
I started taking estrogen because I was under the impression that I was going crazy, which turns out to be not as unusual a reaction to midlife hormonal upheaval as I thought. This was in 2001. The year is significant, because the prevailing belief about hormone replacement in 2001 was still, as it had been for a quarter century, the distillation of extensive medical and pharmaceutical-company instruction: that once women start losing estrogen, taking replacement hormones protects against heart disease, cures hot flashes, keeps the bones strong, has happy effects on the skin and sex life and carries a breast-cancer risk that’s worth considering but not worrying about too much, absent some personal history of breast cancer or a history of breast cancer in the immediate family.
At first, as I was trying to locate a psychiatrist who would take me on, I wasn’t aware I had reason to pay attention to advice about hormones at all. That year I turned 47, a normal age for beginning the drawn-out hormonal-confusion period called perimenopause, but I had none of the familiar signs. Menopausal holdouts run in the family; one of my grandmothers was nearly 60 by the time hers finally kicked in. My only problem was a new tendency to wake up some mornings with a great dark weight shoving my shoulders toward the floor and causing me to weep inside my car and basically haul myself around as if it were the world’s biggest effort to stand up straight and carry on a conversation. Except for its having shown up so arbitrarily and then coming and going in waves, there was nothing interesting about my version of what my husband and I came to think of as the Pit; anybody who has been through a depression knows what a stretch of semidisabling despair feels like, and for my part I had a very nice life, a terrific family and a personal interior chorus of quarreling voices demanding to know why I didn’t pull up my socks and carry on, which in fact was the first question I planned to ask a psychiatrist.