14 March, 2016: 

The effect of quitting smoking on hot flushes in women aged 45–54 years of age at baseline followed for 1–7 years was examined by Smith and his colleagues [1] in a longitudinal analysis published recently. A cohort study of hot flushes among women 45–54 years of age was conducted starting in 2006 among residents of Baltimore and its surrounding counties. Menopausal status was defined as follows: premenopausal women were those who experienced their last menstrual period within the past 3 months and reported 11 or more periods within the past year; perimenopausal women were those who experienced (1) their last menstrual period within the past year, but not within the past 3 months, or (2) their last menstrual period within the past 3 months and experienced 10 or fewer periods within the past year; postmenopausal women were those women who had not experienced a menstrual period within the past year. Participants were asked to complete a brief questionnaire during a clinic visit 3 weeks after the baseline visit, then annually after that. This questionnaire repeated all previous questions about hot flushes and smoking. Interestingly, they concluded that women who quit smoking were less likely to suffer from hot flushes, less likely to have severe hot flushes, and less likely to have frequent hot flushes than women who continued to smoke, but were more likely to suffer from any hot flushes, more severe hot flushes, and more frequent hot flushes than women who never smoked.

Comment

It is well known that the hot flush is the most distressing symptom of menopause. It is probably the symptom that is most widely recognized as being related to menopause. Hot flushes are extremely common, although their frequency and intensity will vary greatly between individuals. Their underlying physiological mechanisms are not completely understood [2], although several mechanisms have been implicated. The reduction in hot flushes with estrogen replacement therapy suggests a hormonal etiology. However, the levels of estrogens do not appear to correlate with hot flushes. It seems more likely that the rate of change of plasma estrogen concentrations influences the thermoregulatory system via the hypothalamus [3]. Cross-sectional studies have shown that cigarette smoking increases a woman's risk of hot flushes, especially those that are considered severe [4]; the mechanism by which smoking is associated with the risk of hot flushes is unknown. A common hypothesis is that cigarette smoking increases the risk of hot flushes through the lowering of endogenous estrogen concentrations in the body [4-6]. This hypothesis is supported by studies that have shown lower active estrogen levels, specifically estradiol and estrone, in smokers compared to non-smokers [7,8]. It has been suggested also that the risk from cigarette smoking is due to alterations in hormone levels [9,10]. The effect of quitting could be related to changes in metabolic pathways; evidence suggests that smoking cessation of just 6 weeks can improve hepatic metabolism [11]. Freedman in 2001 suggested that smoking interferes with thermoregulatory pathways associated with hot flushes [2], potentially through norepinephrine changes. Smoking has been found to increase norepinephrine levels via the monoamine oxidase pathway [12] and the effect appears to be long lasting [13],which would explain the lack of significant effect for women who quit smoking for less than 5 years. Rather, the effect of cigarette smoking on hot flushes could be due to the direct effect of nicotine on the hypothalamic nicotinic receptors. Further studies will be needed to shed light on more physiological mechanisms of hot flushes. Advice about changing lifestyle and quitting smoking early is an important part of the routine counseling of women before approaching menopausal age.

Randa Mostafa

President of Emirates Menopause Society, Professor of Clinical Physiology and Head of Basic Medical Sciences Department, College of Medicine, University of Sharjah, UAE

References

1. Smith RL, Flaws JA, Gallicchio L. Does quitting smoking decrease the risk of midlife hot flashes? A longitudinal analysis. Maturitas 2015;82:123-7
http://www.ncbi.nlm.nih.gov/pubmed/26149340 

2. Freedman RR. Physiology of hot flashes. Am J Hum Biol 2001;13:453-64
http://www.ncbi.nlm.nih.gov/pubmed/11400216 

3. Andrikoula M, Prelevic G. Menopausal hot flushes revisited. Climacteric 2009;12:3-15
http://www.ncbi.nlm.nih.gov/pubmed/19061056 

4. Whiteman MK, Staropoli CA, Benedict JC, Borgeest C, Flaws JA. Risk factors for hot flashes in midlife women. J Womens Health (Larchmt) 2003;12:459-72
http://www.ncbi.nlm.nih.gov/pubmed/12869293 

5. Li C, Samsioe G, Borgfeldt C, Lidfeldt J, Agardh CD, Nerbrand C. Menopause-related symptoms: what are the background factors? A prospective population-based cohort study of Swedish women (The Women's Health in Lund Area study). Am J Obstet Gynecol 2003;189:1646-53
http://www.ncbi.nlm.nih.gov/pubmed/14710092 

6. Whiteman MK, Staropoli CA, Langenberg PW, McCarter RJ, Kjerulff KH, Flaws JA. Smoking, body mass, and hot flashes in midlife women. Obstet Gynecol 2003;101:264-72
http://www.ncbi.nlm.nih.gov/pubmed/12576249 

7. Cassidenti DL, Vijod AG, Vijod MA, Stanczyk FZ, Lobo RA. Short-term effects of smoking on the pharmacokinetic profiles of micronized estradiol in postmenopausal women. Am J Obstet Gynecol 1990;163:1953-60
http://www.ncbi.nlm.nih.gov/pubmed/2256508 

8. Westhoff C, Gentile G, Lee J, Zacur H, Helbig D. Predictors of ovarian steroid secretion in reproductive-age women. Am J Epidemiol 1996;144:381-8
http://www.ncbi.nlm.nih.gov/pubmed/8712195

9. Kapoor D, Jones TH. Smoking and hormones in health and endocrine disorders. Eur J Endocrinol 2005;152:491-9
http://www.ncbi.nlm.nih.gov/pubmed/15817903 

10. Tanko LB, Christiansen C. An update on the antiestrogenic effect of smoking: a literature review with implications for researchers and practitioners. Menopause 2004;11:104-9
http://www.ncbi.nlm.nih.gov/pubmed/14716190 

11. O'Malley SS, Wu R, Mayne ST, Jatlow PI. Smoking cessation is followed by increases in serum bilirubin, an endogenous antioxidant associated with lower risk of lung cancer and cardiovascular disease. Nicotine Tob Res 2014;16:1145-9
http://www.ncbi.nlm.nih.gov/pubmed/24812024 

12. Rendu F, Peoc'h K, Berlin I, Thomas D, Launay JM. Smoking related diseases: the central role of monoamine oxidase. Int J Environ Res Public Health 2011;8:136-47
http://www.ncbi.nlm.nih.gov/pubmed/21318020 

13. Launay JM, Del Pino M, Chironi G, et al. Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. PLoS One 2009;4:e7959
http://www.ncbi.nlm.nih.gov/pubmed/19956754