Nicotine May Block Estrogen in Women’s Brains, Making It Harder to Quit Smoking
November 01, 2022

Nicotine May Block Estrogen in Women’s Brains, Making It Harder to Quit Smoking

  • Studies have shown that women have a harder time quitting smoking than men do.
  • New research indicates that nicotine blocks the production of estrogen in women’s brains, which could explain why it’s more difficult for them to quit.
  • While more research is needed to fully understand the underlying mechanisms, the findings suggest that nicotine may also impact other aspects of female biology.

The sex and gender differences in smoking cessation have been explored in research studies, with some evidence showing that women may be less likely to stop smoking compared to men.

Now, new research indicates that nicotine blocks estrogen production in the female brain, which could explain why it’s more difficult for women to quit smoking.

In fact, the findings show that the amount of nicotine found in just a single cigarette could be enough to block estrogen production.

According to researchers, the results could explain several behavioral differences in women who smoke, including being less likely to quit smoking. These differences were observed in the thalamus, part of the brain’s limbic system involved in behavioral and emotional responses.

“Estrogen, through its widespread receptors in brain areas of relevance to the addiction circuitry, can influence neurotransmission,” lead researcher Erika Comasco, PhD, assistant professor in the Department of Women’s and Children’s Health, Neuropsychopharmacology at Uppsala University in Sweden, told Healthline.

“Our study shows that nicotine binds to the enzyme responsible for the synthesis of estrogen in the thalamus — the brain region with the highest expression of this enzyme and of receptors for nicotine.”

Comasco said her team was surprised by how powerful nicotine was on areas of the brain targeted by addictive substances and added that they aren’t yet sure what the behavioral or cognitive outcomes are.

The research was presented on October 17 at the 35th annual European College of Neuropsychopharmacology (ECNP) Congress in Vienna.

Studying the synthesis of estrogen in the brain

The study looked at a group of 10 healthy female volunteers who were given a commercially available nicotine dose intra-nasally.

They were also injected with a radioactive tracer attached to a molecule that binds to the enzyme aromatase, also known as “estrogen synthase,” which is the enzyme responsible for the production of estrogen.

MRI and PET brain scans allowed researchers to see the quantity of aromatase and where it was in the brain. They found a single dose moderately reduced the amount of aromatase in the brain.

The study draws attention to what researchers already know; that women show more resistance to nicotine replacement therapy and a greater tendency to relapse when trying to quit smoking.

But the biological basis for these differences isn’t understood.

Comasco said this is the first time this inhibitory effect on aromatase production was shown in humans, though noted that the effect wasn’t studied on men.

“Our study does not assess resistance to quit smoking or treatment for nicotine addiction,” she explained. “It rather highlights another mechanism through which nicotine influences the brain.”

Effects of nicotine on the female body

Comasco said the study leads researchers to believe nicotine’s effect on estrogen could also affect other areas of female biology.

“It is known that nicotine has peripheral effects on the reproductive system; for instance, women who smoke do enter menopause significantly earlier,” she said.

Comasco noted that women also show a 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,” she said.

“Of course, this is a comparatively small group of women, we need a larger sample to confirm these findings.”

Implications for smoking cessation

Dr. Wim van den Brink, Ph.D., emeritus professor of psychiatry and addiction at the Academic Medical Center at the University of Amsterdam, told Healthline the findings of the new study are important. He said that it’s still too early to tell if adding estrogen to the equation could help women quit smoking.

“It may help, but we do not know,” Dr. van den Brink said. “What we do know now is that nicotine seems to have a strong effect on estrogen production in healthy women.”

Dr. Monty Ghosh, an addiction specialist and assistant clinical professor at the University of Alberta Hospital in Canada, told Healthline the study could show connections between nicotine and fatigue, energy, and overall wellness.

“Indeed, nicotine’s impact on estrogen production can cause side effects such as osteoporosis and increased cardiac disease, both of which are related to estrogen loss and smoking, but this study shows the relationship clearer,” Dr. Ghosh told Healthline.

“While (it’s) a small sample size and more work needs to be done, this study may demonstrate [a] potential need to evaluate [or] screen for estrogen deficiency in women and to potentially treat this as well,” Ghosh said.

“I think if further research substantiates these findings, we would need to screen for estrogen deficiency more and potentially use estrogen replacement, although this may have additional concerns by causing an increase in DVT [deep vein thrombosis] when combined with smoking.”

Tips to help you quit

While smoking cessation is no easy feat, there are several methods you can try to help you cut back and eventually quit.

For instance, both Comasco and van den Brink suggested a combination of medication and cognitive behavioral therapy.

There are also a number of medications and patches available to help you quit gradually.

“The most effective medication is varenicline,” van den Brink said. “Other effective medications are nicotine replacements (gum, patches, spray), bupropion, and nortriptyline.”

Ghosh noted that quitting smoking is based on the individual.

“Some people do well with medication support like Chantix [Champix] or Wellbutrin. Others do better with nicotine replacement therapy such as patches, gum, sprays, or a combination of short and long-acting replacement.”


Smoking cessation can be difficult, regardless of gender or biological sex.

But new research builds on existing evidence showing that women may find it more difficult to quit smoking than men do.

According to the study, smoking just a single cigarette blocks the production of estrogen in the brain, which may result in several differences in women who smoke versus men.

These effects were observed in the thalamus, the part of the brain’s limbic system involved in behavioral and emotional responses.

While more studies are still needed to better understand the clinical implications of smoking cessation among females, the findings may present a need for specialized medical attention and care for women who are trying to quit.