Estrogen and Smoking: Whats the connection?

The connection between nicotine and estrogen is likely connected with its metabolism. There is a metabolic pathway called the cytochrome P450 and is responsible for the metabolism of substrates in our body. There are many varieties of this enzymes and each with its own function in the metabolism of substrates. The relationship between these substrates and enzymes are further complex in that they have different effects depending on the substrate in question. But in general, these substates can either be a substrate, inhibitor, or inducer. Substrates are the substances being metabolized. Inhibitors are things that decrease the activity of the P450 enzyme in question and the inducers increase the activity of the enzyme whereby decreasing or increasing the metabolism of the substrate in question, respectively. Estrogen is thought to be an inducer of a cytochrome P450 enzyme called CYP2A6, which so happens to the metabolism enzyme of nicotine. Hypothetically the more inducer activity there is, the more the metabolic clearance of the substrate. In this case the more estrogen there is the less of nicotine there is at any given time. Now this is an oversimplification since there are multiple confounding factors (known and unknown) about these types of relationships between the substrates and inducers/inhibitors. For example, enzymes like CYP2A6 have variations in itself due to polymorphisms in our genes, which means that there are individual differences when it comes to metabolism due to these genetic variations. So female 1 may have greater activity of the enzyme and female 2 might have very poor activity, which has different implications when it comes to smoking cessation. Another confounding factors are that there are many different things we consume including food and medication that has various impacts on these enzymes. For example if estrogen is an inducer of the enzyme, then technically why wouldn’t someone just eat a grapefruit which is known to be an inhibitor (though this is an over-simplification).

Adding estrogen to aid in smoking cessation is not advised as it increases the women’s risk of cardiovascular disease, strokes, and venous thromboembolism (VTE).

Socio-economic and environmental factors may have stronger influence on smoking cessation than estrogen alone. For example, I see many older patients who are post-menopausal and do not have much circulating estrogen, yet they still smoke and have difficult time quitting. Additionally on the other spectrum are pregnancy. Women who are pregnant have much higher circulating estrogen to support their gestation, however many women quit before and during pregnancy for the health of their child.

There are many risks associated with smoking and reproductive health. Some of those include difficulty in fertility (both male and female), low fetal birth weight, ectopic pregnancy, spontaneous abortions, and premature menopause. It’s clear that smoking cessation helps with maternal and fetal outcomes.

Best way to quit smoking is really a multimodal approach with involvement by multiple stakeholders including his or her physician. Even a brief counseling by the physician has shown to improve cessation rates in individuals. Once the individual is ready to quit, the best approach is usually a combination of behavioral intervention and medication. The combination approach is better than any one of those alone.

When the partners of women smoke, they are less likely to be able to quit. So partners are encouraged to avoid smoking before, during and after pregnancy to avoid risk of their female partner from smoking.