Authors: Tina Kabir, PhD Student, University of Toronto, CAMH| Editors: Romina Garcia de leon, Janielle Richards (Blog Co-Coordinators) | Reviewer: Tanisse Epp
Published: September 5th, 2025
Over the last few decades, fewer people are smoking cigarettes worldwide. However, 3.5 million Canadians aged 15 and older smoked in 2022, including 1.5 million women. Tobacco smoking remains the leading preventable cause of cancer death in Canada, and is a risk factor for 16 types of cancer. In 2025, most people would probably agree that smoking is “bad for you,” as there is a lot of evidence on the health effects of tobacco smoking. However, there is limited accessible information that differentiates the effects of nicotine from other less/non-addictive components of tobacco, particularly in understanding how smoking and nicotine addiction affect different populations, including women.
When we think about the main perpetrator of smoking-related disease, we often think about nicotine, but this is not entirely true. Burning of tobacco leaves releases over 7,000 different chemicals, many of which, unlike nicotine, are well-known direct carcinogens – polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines. Although fewer women smoke than men, women continue to face substantial rates of smoking-related cancers. In 2015, 15% of all cancer diagnoses in Canadian women were attributable to tobacco smoking, including 69% of lung cancer cases and 26% of cervical cancer cases. Of note, women may be more susceptible to lung disease and have a higher risk of coronary heart disease, as a result of smoking, than men.
Nonetheless, the health burdens of smoking would not be so significant, if tobacco was not addictive. Tobacco use disorder remains one of the most common substance use disorders in North America, and nicotine is to blame for addictive properties of tobacco. Once nicotine is absorbed into the bloodstream, more dopamine – the “feel-good” neurotransmitter associated with feelings of pleasure and satisfaction – is released in the reward circuits of the brain. Over time and with repeated use, the cycle of addiction strengthens. Due to the desensitization of nicotinic receptors in the brain, people that use tobacco start smoking more abundantly and frequently to achieve the same intensity of the rewarding and stimulating nicotine effects. When abstinent for a few hours, people who smoke regularly experience withdrawal symptoms – anxiety, irritability, increased perception of stress – which serve as additional motivators to smoke. These biological effects of nicotine, combined with behavioural and social cues (e.g., stress at work, interpersonal problems, friends who smoke, daily ritual of smoking a cigarette with coffee) reinforce smoking.
Quitting smoking is the best way to reduce the risks of smoking-related disease. Quitting is beneficial at any age, but women who quit smoking before age 45 avoid approximately 90% of lung cancers and 85% of overall mortality seen among those who continue to smoke. While quitting smoking is hard for everyone, women have greater difficulty abstaining from smoking than men. In Ontario, Canada, women that try to quit using behavioural support and nicotine replacement therapy (NRT, i.e., nicotine patches, gum, lozenge, and inhaler, that can reduce urges to smoke) are significantly less successful at 6-month follow-up than men that participated in the same quit smoking program. NRT is one of the more accessible smoking cessation treatments, as it is available over the counter. NRT, especially its long-acting formulations, such as the patch, have low addictive potential due to a slower rise in blood plasma nicotine and the slower onset of stimulating effects.
Why is it harder for women to quit smoking? Like many questions in science, this one does not have a linear answer. There are likely a multitude of contributing factors, including biological, behavioural, and social. Ovarian hormones and their fluctuations within menstrual cycle and across lifespan could provide some explanation to why it is harder for women to quit. Both estradiol and progesterone play a role in substance use. Estradiol potentiates dopamine release in the reward pathway of the brain after drug administration, thus increasing reward. Progesterone effects are slightly more complicated. It can both enhance estradiol-induced dopamine release and counteract estradiol effects by negatively modulating nicotinic receptors, and therefore reducing reward from smoking.
In the context of menstrual cycle, the interplay of these hormones regulates addiction-related brain pathways and nicotine use behaviours in a cyclical pattern. A recent study found that brain responses to smoking cues versus non-smoking cues were highest during the late follicular phase (high estradiol), less strong in the luteal (high estradiol + progesterone in mid-luteal phase), and lowest in the early follicular phase (low estradiol + progesterone). Nonetheless, significantly greater nicotine withdrawal, and a trend for greater craving, was reported by women during the luteal phase (days 25-28) compared to the follicular phase (days 1-14) of their menstrual cycle.
How could we use these findings to help women quit smoking? A few research groups have studied whether timing of a quit attempt to a specific time within the menstrual cycle could make quitting easier. Thus far, the findings have been inconclusive. As part of my doctoral research at the INTREPID Lab, CAMH, I am conducting a randomized controlled trial to investigate whether coordinating the start of quit attempt to either the follicular, or the luteal phase will have any benefit over usual care (no consideration for menstrual cycle). If supported by evidence, menstrual cycle phase timing could be a low-cost and accessible way to improve efficacy of existing smoking treatments.
