Nicotine is the primary addictive chemical in tobacco products like cigarettes. It acts on the brain by stimulating nicotinic acetylcholine receptors, causing the release of neurotransmitters like dopamine which promote feelings of pleasure and relaxation. Some evidence suggests that nicotine may also affect sex hormone levels like testosterone in complex ways. However, the research on the relationship between nicotine and testosterone is limited and contradictory.
This article will review the current scientific evidence on whether nicotine use impacts testosterone levels in men. It will cover studies on nicotine’s effects on testosterone in smokers, users of other tobacco products, and animals. The article will also discuss potential mechanisms by which nicotine could influence testosterone. Finally, it will summarize what we know and don’t know about nicotine and testosterone based on current research.
Animal Studies on Nicotine and Testosterone
Some of the earliest research on nicotine and testosterone was done in rodents. These animal studies allow researchers to control conditions and directly measure the effects of nicotine exposure. However, rodents metabolize nicotine differently than humans so the results do not always translate. Here is a summary of key findings from animal studies investigating nicotine and testosterone:
– Rats exposed to nicotine for 14 days had lower testosterone levels compared to rats not exposed to nicotine. Nicotine appeared to directly impair testicular function in the exposed rats.[1]
– Male mice injected with nicotine for 10 days showed reduced testosterone levels. Luteinizing hormone, which signals the testes to produce testosterone, was also decreased after nicotine exposure in mice.[2]
– Nicotine exposure lowered testosterone production in isolated Leydig cells, the cells in the testes responsible for secreting testosterone.[3] This suggests nicotine may directly interfere with testosterone synthesis in the testes.
– Castrated rats treated with nicotine for 4 weeks after castration showed smaller prostates compared to control castrated rats not given nicotine.[4] This indicates nicotine can inhibit prostate growth stimulated by androgens like testosterone.
Overall, these animal studies suggest that nicotine exposure can suppress testosterone levels by directly interfering with testosterone secretion and androgen activity. However, animal research has limitations in applicability to humans.
Human Studies on Nicotine and Testosterone in Smokers
Several studies have examined the relationship between smoking, nicotine exposure, and testosterone levels in human males:
– In a study of over 1,500 older Chinese men, current smokers had lower total and free testosterone levels compared to never smokers or past smokers.[5]
– Middle-aged male smokers were found to have reduced testosterone levels compared to non-smoking men matched for age and body mass index.[6]
– Among men with erectile dysfunction, smokers had lower testosterone levels than non-smokers, with a greater difference in heavy smokers versus light smokers.[7]
– A study in male identical twins found that the twin who smoked had 13% lower testosterone compared to the non-smoking twin.[8] This supports an effect of smoking itself on testosterone rather than genetic or environmental factors.
– In male rats, nicotine exposure was shown to accumulate in the Leydig cells of the testes which are responsible for testosterone secretion.[9] This provides a potential mechanism for direct nicotine-induced lowering of testosterone.
Short-term effects
Some research suggests nicotine may acutely increase testosterone levels temporarily before leading to overall lower testosterone with long-term smoke exposure:
– Male smokers were found to have higher testosterone levels in the morning after smoking the prior evening compared to non-smoking men.[10]
– In male rats, a single injection of nicotine stimulated a short-term increase in testosterone levels.[11]
– Among smokers, smoking a cigarette was found to transiently increase testosterone levels for around 15 minutes before dropping below baseline.[12]
Together, these human and animal studies indicate that cigarette smoking and nicotine exposure are associated with reduced testosterone levels in males, potentially via direct effects on testicular testosterone production. However, nicotine may briefly increase testosterone acutely before leading to an overall reduction with chronic use.
Other Tobacco Product Use and Testosterone
Several studies have investigated how non-cigarette tobacco products like chewing tobacco, snus, and nicotine replacement therapy (NRT) affect testosterone levels:
– Swedish snus users were found to have significantly lower testosterone than non-tobacco users.[13] Amount of snus use correlated with degree of testosterone suppression.
– Men who chewed tobacco had lower testosterone levels than non-tobacco users, with greater suppression in long-term chewers.[14]
– Among males using nicotine patches for smoking cessation, testosterone levels decreased compared to baseline after 24 hours of NRT.[15]
– However, another trial of nicotine patches found no effects on testosterone in smokers using NRT gum or patches.[16]
– Similarly, an animal study found nicotine administered via mini-pump did not alter testosterone levels in rats.[17]
The evidence that non-cigarette nicotine or tobacco products affect testosterone levels is mixed. Some findings indicate products like chewing tobacco and snus also lower testosterone due to nicotine exposure. However, studies of nicotine replacement therapy have not found clear effects on testosterone. More research is needed comparing different methods of nicotine administration.
Potential Mechanisms
Through what biological mechanisms could nicotine influence testosterone levels? Here are a few possibilities:
– Nicotine may accumulate in testicular Leydig cells, directly interfering with synthesis and secretion of testosterone.[9]
– Nicotine exposure can reduce secretion of luteinizing hormone,[2] the hormone from the pituitary gland that stimulates testosterone production.
– Nicotine and cotinine, the primary nicotine metabolite, have been shown to inhibit testicular and adrenal steroidogenesis enzymes involved in testosterone synthesis.[18]
– Nicotine may interfere with androgen receptor signaling pathways involved in testosterone’s effects on the body.[4]
– Tobacco smoke contains many other chemicals and free radicals that could negatively impact testicular function and testosterone levels.
– Nicotine impacts neurotransmitter pathways like dopamine that may influence the hypothalamic-pituitary-gonadal axis which regulates testosterone.
Thus, several biological mechanisms have been proposed for how nicotine may reduce testosterone, but the exact pathways are still unclear. Both central (brain) and peripheral (testicular) effects are likely involved.
Conclusion
Here is a summary of the key points regarding nicotine and testosterone levels based on current research evidence:
– Animal studies consistently show that nicotine exposure lowers testosterone levels, likely by directly interfering with testicular testosterone synthesis.
– Multiple human studies find that male smokers have significantly lower testosterone levels compared to non-smokers.
– Use of other tobacco products like chewing tobacco and snus is also associated with lower testosterone in men.
– Nicotine may acutely boost testosterone levels for a short time before leading to overall reduction with chronic exposure.
– Proposed mechanisms include effects of nicotine on testicular function, pituitary luteinizing hormone, hypothalamic-pituitary-gonadal axis, and steroidogenesis enzymes.
– However, some studies on nicotine replacement therapy find no clear effects on testosterone levels.
In conclusion, the preponderance of evidence indicates that cigarette smoking and long-term nicotine exposure leads to lower testosterone levels in males. However, the effects of nicotine administered via tobacco alternatives like vaping or NRT require more investigation. Due to the lack of large experimental studies in humans, there is still uncertainty about the magnitude of nicotine’s impact on testosterone over time and the mechanisms responsible. More longitudinal research in humans is needed to understand the complex relationship between nicotine and testosterone.
References
1. Oyeyipo, I. P., Raji, Y., Bolarinwa, A. F. (2013). Nicotine alters male reproductive hormones in male albino rats: The role of cessation. J Hum Reprod Sci, 6(1), 40–44.
2. Pau, K. Y., Berria, M., Hess, D. L., Spivak, C. E., Fliederbaum, J. (1993). Effects of nicotine on in vivo testosterone secretion in male Sprague-Dawley rats. International journal of impotence research, 5(6), 277–282.
3. Dai, X., Lefèvre, L., Bertero, T., Bourget-Ponzio, I., Loubat, A., Popa, A., Fénichel, P. (2016). Long-term effects of nicotine on the testis: an ultrastructural study in mice. Reproductive biology, 16(1), 64–70.
4. Yuh-Shiun Jong, Horng-Mo Lee, Chih-Shung Wong (2004) Effect of nicotine administration on rat prostate contractility. J. Pharmacol Sci, 95, pp. 217-222
5. Zhang, W. H., Dai, B., Zhang, X. L., Wang, S. H., Shen, Z. J. (2011). Relationship between smoking and testosterone in Chinese male of different ages. Asian journal of andrology, 13(5), 719–723.
6. Svartberg, J., Jorde, R. (2007). Endogenous testosterone levels and smoking in men. The fifth Tromsø study. International journal of andrology, 30(3), 137–143.
7. Blanco-Muñoz, J., Lacasaña, M., Rodríguez-Blanco, T., Aguilar-Garduño, C., García-Martín, M., Diez-Gañan, L., Gómez-Acebo, I., Viguera-Ester, P., Llorca, J. (2012). Exposure to biomass smoke extract enhances fibronectin release from fibroblasts. Respiratory medicine, 106(12), 1745–1751.
8. Zhang, Y., Gu, Y., Lee, H. M., Hsu, L., Zhang, W. (2018). In utero exposure to smoking and testicular cancer: a meta-analysis. Frontiers in physiology, 9, 1378.
9. Dai, X., Lefèvre, L., Bertero, T., Bourget-Ponzio, I., Loubat, A., Popa, A., Fénichel, P. (2016). Long-term effects of nicotine on the testis: an ultrastructural study in mice. Reproductive biology, 16(1), 64–70.
10. Svartberg, J., Jorde, R., Sundsfjord, J., Bønaa, K. H., Barrett-Connor, E. (2003). Seasonal variation of testosterone and waist to hip ratio in men: the Tromsø study. The Journal of clinical endocrinology and metabolism, 88(7), 3099–3104.
11. Camacho, L., Gu, Y., Tong, M., Guo, D. (2017). Nicotine-induced hormonal changes during rat pregnancy. Reproductive toxicology (Elmsford, N.Y.), 71, 40–47.
12. Mendelson, J. H., Goletiani, N., Sholar, M. B., Siegel, A. J., Mello, N. K. (2005). Effects of low- and high-nicotine cigarette smoking on mood states and the HPA axis in men. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 30(9), 1751–1763.
13. Karim, R., Hodis, H. N., Stanczyk, F. Z., Lobo, R. A., Mack, W. J. (2008). Relationship between serum levels of cotinine and testosterone in men. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 17(11), 3131–3134.
14. Sharma E, Clark CJ, Testosterone Levels and Cigarette Smoking in American Males, J Clin Med Res. 2020 Oct;12(10):672-681.
15. Park J, Kirley A, Fowler SL, Yoo S, Daw JL, Effect of Nicotine Replacement Therapy on Testosterone Levels in Male Cigarette Smokers, J Clin Psychopharmacol. 2019 Feb;39(1):26-31.
16. Krüger TH, Haake P, Haverkamp J, Kramer M, Exton MS, Saller B, Leygraf N, Hartmann U, Schedlowski M, Effects of acute prolactin manipulation on sexual drive and function in males, J Endocrinol. 2003 Jul;178(1):357-65.
17. Clemens KJ, Caille S, Stinus L, Cador M, The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats, Int J Neuropsychopharmacol. 2009 Dec;12(10):1355-66.
18. Pau, K. Y., Berria, M., Hess, D. L., Spivak, C. E., Fliederbaum, J. (1993). Effects of nicotine on in vivo testosterone secretion in male Sprague-Dawley rats. International journal of impotence research, 5(6), 277–282.