Nicotine blocks estrogen production in women’s brains

The amount of nicotine in one cigarette inhibits women’s brains from producing estrogen. This may explain a variety of behavioral differences in smokers, including the reason why women have a higher resistance to quitting than males. The ECNP Congress in Vienna will mark the debut of this work.

Lead researcher, Associate Professor Erika Comasco (Uppsala University, Sweden) said: “For the first time, we can see that nicotine works to shut down the estrogen production mechanism in the brain of women. We were surprised to see that this effect could be seen even with a single dose of nicotine, equivalent to just one cigarette, showing how powerful the effects of smoking are on a woman’s brain. This is a newly-discovered effect, and it’s still preliminary work. We’re still not sure what the behavioral or cognitive outcomes are; only that nicotine acts on this area of the brain, however, we note that the affected brain system is a target for addictive drugs, such as nicotine”.

The thalamus, a brain region part of the limbic system, has demonstrated the effect. This system is involved in regulating behavior and emotions.

Ten healthy female volunteers participated in the study with the help of researchers from Uppsala University in Sweden. In addition to receiving an intranasal dose of nicotine from a commercial source, the women received an injection of a radioactive tracer bound to an enzyme called aromatase, also known as estrogen synthase, which binds to estrogen. Aromatase is the enzyme that produces estrogen. The researchers were able to visualize the amount of aromatase present in the brain as well as its location using MRI and PET brain images. Researchers discovered that a single dose slightly decreased the brain-based aromatase level.

It has long been recognized that men and women react to nicotine differently, with women being more resistant to NRT and more likely than men to relapse when trying to give up smoking. However, it is unclear what biological factors led to these variations. This is the first instance where the production of aromatase has been inhibited in humans. The impact on guys wasn’t investigated.

Professor Comasco continued “This discovery leads us to believe that nicotine’s effect on estrogen production has a significant impact on the brain, but perhaps also on other functions, such as the reproductive system – we don’t know that yet. There are significant differences in the way men and women react to smoking. Women seem to be more resistant to nicotine replacement therapy, they experience more relapses, show greater vulnerability to the heritability of smoking, and are at greater risk of developing primary smoking-related illnesses, such as lung cancer and heart attacks. We need now to understand if this action of nicotine on the hormonal system is involved in any of these reactions.”

Commenting, Professor Wim van den Brink, Emeritus Professor of Psychiatry and Addiction at the Academic Medical Center, University of Amsterdam said:

“This is indeed an important first finding. Smoking has many adverse effects on men and women, but this particular effect of nicotine on the reduction of estrogen production in women was not known before. It should be noted, however, that tobacco addiction is a complex disorder with many contributing factors. It’s unlikely that this specific effect of nicotine on the thalamus (and the production of estrogen) explains all the observed differences in the development, treatment, and outcomes between male and female smokers. It is still a long way from a nicotine-induced reduction in estrogen production to a reduced risk of nicotine addiction and negative effects of treatment and relapse in female cigarette smokers, but this work merits further investigation”.