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,