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Turns into a man. Scientists uncover the effect of nicotine on the female brain

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MOSCOW, November 5, Vladislav Strekopytov. Swedish biologists have found that nicotine blocks the production of estrogen, the female sex hormone. According to scientists, this explains some of the “male” behavior of smoking women. About the molecular mechanisms of changes in the brain under the influence of tobacco and their consequences for health – in the article .

Smoker's metabolism

The effect of nicotine on humans is well studied. It is known that long-term use of cigarettes causes diseases such as hyperglycemia, arterial hypertension, atherosclerosis, tachycardia, arrhythmia, angina pectoris, coronary heart disease, heart failure and myocardial infarction. In combination with tar, nicotine contributes to the development of cancer of the lungs, tongue and larynx. Smoking also reduces blood flow throughout the body, which in turn damages the nerves. Smoke also contains free radicals – molecules that attack all organs and tissues of the body.

According to the US Centers for Disease Control and Prevention (CDC), smoking is the leading cause of preventable death in the US. More people die each year from cigarettes than from HIV, drugs, alcohol, car accidents and gunshot wounds combined. At the same time, the United States is far from the most smoking country.

In general, the physiological effects of nicotine on the body do not depend on gender, but there are some differences. Knownthat women get used to it faster and have a harder time quitting smoking. This is usually attributed to a more mobile psyche and dependence on mood, as well as anxiety about gaining weight when quitting cigarettes. However, scientists think that the reasons lie deeper – at the level of metabolism.

Nicotine is metabolized in the liver through a series of biochemical reactions. Approximately 80 percent is converted to cotinine, which persists in plasma for up to 16 hours, and the rest to other metabolites that are excreted in the urine. A few years ago, American scientists establishedthat female hormones speed up the metabolism of nicotine, due to which toxins leave the body faster. Thanks to this, women tolerate the effects of smoking more easily, and they develop addiction earlier.
The authors also explain other differences between men and women in matters related to smoking by the peculiarities of hormonal reactions. In particular, women are more resistant to nicotine replacement therapy, they more often experience relapses when trying to quit smoking, and the factor of heredity is more clearly manifested. In addition, they are at greater risk of developing diseases directly related to tobacco use, such as lung cancer and heart disease.It is known that nicotine negatively affects cerebral circulation, induces the formation of blood clots, disrupts the protective function of the blood-brain barrier and endothelial cells lining the walls of blood vessels, which causes inflammation. In women, in addition to these common detrimental effects, nicotine addiction lowers levels of the sex hormone estrogen. This leads to disruption of the normal periodicity of the menstrual cycle, early onset of menopause and other hormonal disruptions.

There are three types of estrogens: estradiol, estrone and estriol. They are formed in the body from androgens – male sex hormones produced by the testes in men and the ovaries in women. Under the action of the aromatase enzyme, which is produced in the thalamus (a section in the central part of the brain), the male hormone testosterone is converted to female estradiol, and androstenedione to estrone. Of these, at the next stage, the third female hormone, estriol, is formed. In men, the thalamus produces significantly less aromatase than in women, so estrogen synthesis is not active in them.

Recently, Swedish scientists for the first time established in an experiment involving people that nicotine suppresses the production of estrogen in the female brain. They presented the results at the 35th Congress of the European College of Neuropsychopharmacology (ECNP), held in October 2022 in Vienna.
“The effect can be observed even after a single dose of nicotine equivalent to one cigarette, which shows how much smoking affects a woman’s brain,” the study’s leader, Associate Professor Erika Komasko from Uppsala University, is quoted in a college press release. “Maybe the decrease in estrogen production is spreading and other functions, such as the female reproductive system.”

The authors worked with a group of ten healthy female volunteers. They were injected intranasally with a dose of nicotine, which smokers usually consume, and with it a radioactive tracer in the composition of a molecule that binds to aromatase. Thanks to this, scientists using the methods of magnetic resonance (MRI) and positron emission (PET) tomography were able to track how much of the enzyme is produced and in which part of the brain.
Scanning showed that before the start of the experiment, aromatase was present in various parts of the diencephalon – the thalamus, hypothalamus and amygdala. These areas of the limbic system are important control centers for endocrine processes and many basic bodily functions. After the introduction of nicotine, the amount of aromatase in the thalamus decreased sharply. Thus, for the first time, scientists directly saw where the enzyme necessary for the synthesis of estrogen is produced, and received confirmation that nicotine inhibits its formation.
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Hormone games

It turns out that in hormonal terms, with each cigarette, a woman becomes a little man, since a smaller amount of male hormones is converted into female ones. This, according to scientists, can explain the appearance of masculine traits in the behavior of smoking women, as well as some physiological changes – for example, a rough voice.that neuronal networks responsible for mood, aggression, and sexual behavior are associated with aromatase expression. In experiments on primates, experts observed how the behavior and neurophysiology of animals change after a dose of nicotine.
The role of estrogens is not limited to this. It is known that female sex hormones provide normal blood circulation in the brain, so women are much less susceptible to strokes, and the weakening of their production makes the brain more susceptible to ischemic damage.
But there is also good news. If you stop smoking in time, the hormonal background is restored. True, if the changes have not gone too far. In addition, it is unlikely that everything depends on a single factor.
“Tobacco addiction is a complex disorder,” Wim van den Brink: It is unlikely that a specific effect of nicotine on the thalamus and estrogen production explains all the observed differences in development, treatment, and outcomes between male and female smokers, but this direction certainly deserves further study. Question: Is it possible to replenish estrogen stores with hormone replacement therapy (HRT)? Doctors do not recommend doing this, at least without consulting a doctor, because of the risk of developing cardiovascular diseases. In addition, HRT is incompatible with smoking. So you still have to break up with a bad habit.

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