Insight

Is menopause associated with accelerated lung function decline?
Katrina Mountfort, Senior Medical Writer, Touch Medical Media, UK
Christina Mackins-Crabtree, Managing Editor, touchRESPIRATORY, UK
Insights into the European Respiratory Health Survey (ECRHS), discussed at the ATS Annual Meeting, Washington DC, May 19–24, 2017

The hormonal changes that accompany menopause have been linked to a range of physiological changes, including osteoporosis, insomnia, and an increased risk of developing diabetes and cardiovascular disease.1 Low levels of 17β-estradiol are associated with increased systemic inflammation and inflammation in the lungs.2,3 The inflammatory markers C-reactive protein and interleukin-6 are known to reduce forced vital capacity (FVC) and forced vital expiratory volume (FEV1), important measures of lung function.4,5 It is, therefore, logical to assume that menopause might affect the lungs.

A recent population-based study, investigated lung function decline over a 20-year period, using data from a large European cohort, the European Respiratory Health Survey (ECRHS).6 Each of the women, who were aged between 25 and 48 years at baseline, were assessed three times during separate study waves: ECRHS1 (1991–1994), ECRHS 2 (1998–2002) and ECRHS 3 (2010–2012). The study assessed FVC and FEV1, as well as measuring serum levels of follicle-stimulating hormone and luteinising hormone. Participants also provided information about menstrual patterns, respiratory and reproductive health, and were then classified as non-menopausal, transitional or post-menopausal. Analyses were performed among never-smokers, ever-smokers and BMI categories.

Results from 1,438 women showed that the mean decline in FVC was -10.2 ml per year in transitional women and -12.5 ml per year in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml per year in transitional women and -5.2 ml per year in post-menopausal women. The effect size for FEV1 was equivalent to smoking 20 cigarettes per day for two years, and for FVC to smoking 20 cigarettes per day for ten years. Such a decline may manifest as symptoms such as shortness of breath, reduced work capacity and fatigue. The severity of symptoms depends upon how much lung capacity is reduced, and a few women may actually develop respiratory failure as a result of this decline.

The decline was slower in women with higher BMI, which may be due to the fact that circulating androgens are converted to oestrogen in adipose tissue, and higher in women who had ever smoked, probably a combined effect of smoking on the lungs and its anti-oestrogenic effects. Further analysis showed that the results were not driven by a history of asthma, by gynecological disorders, by hypertension or cardiovascular disorders, or by surgical or premature menopause. The menopause-related decline was more pronounced for FVC than for FEV1, which suggests a restrictive rather than an obstructive pattern.

In addition to the inflammatory effect, the authors suggested that the decline might also be related to the accelerated osteoporosis seen after menopause, which leads to reduced height of the thoracic vertebrae. This may reduce the expansion of the thoracic cage during inspiration and place the diaphragm in a suboptimal position.7 They did emphasize, however, that further study is needed the fully elucidate the mechanisms underlying this effect.

These data support previous reports of a relationship between menopause and reduced lung function. One study has found an increased onset of asthma in menopause.8 A UK Biobank study analysed FVC and FEV1 data in 141,076 women who had provided spirometry measurements and information on menstrual status, and found an association between lower lung function and cessation of menstruation.9

Two small studies have found that hormone replacement therapy (HRT) appears to improve lung function in postmenopausal women,10,11 although more data is needed before prescribing HRT on the basis of lung function alone.

Women are now living longer and it is important for them to maintain their respiratory health long after menopause. The findings of the ECRHS study are important and should alert physicians to respiratory symptoms that are vital for health and quality of life in a growing patient population.

References

1. Dennerstein L, Dudley EC, Hopper JL, et al., A prospective population-based study of menopausal symptoms, Obstet Gynecol, 2000;96:351–8.
2. Tam A, Morrish D, Wadsworth S, et al., The role of female hormones on lung function in chronic lung diseases, BMC Womens Health, 2011;11:24.
3. Zhao J, Jiang CQ, Lam TH, et al., Genetically predicted 17beta-estradiol and systemic inflammation in women: a separate-sample Mendelian randomisation analysis in the Guangzhou Biobank Cohort Study, J Epidemiol Community Health, 2014;68:780–5.
4. Gimeno D, Delclos GL, Ferrie JE, et al., Association of CRP and IL-6 with lung function in a middle-aged population initially free from self-reported respiratory problems: the Whitehall II study, Eur J Epidemiol, 2011;26:135–44.
5. Chang SS, Vaz Fragoso CA, Van Ness PH, et al., Association between combined interleukin-6 and C-reactive protein levels and pulmonary function in older women: results from the Women's Health and Aging Studies I and II, J Am Geriatr Soc, 2011;59:113–9.
6. Triebner K, Matulonga B, Johannessen A, et al., Menopause is associated with accelerated lung function decline, Am J Respir Crit Care Med, 2017;195:1058–65.
7. Raisz LG, Pathogenesis of osteoporosis: concepts, conflicts, and prospects, J Clin Invest, 2005;115:3318–25.
8. Triebner K, Johannessen A, Puggini L, et al., Menopause as a predictor of new-onset asthma: A longitudinal Northern European population study, J Allergy Clin Immunol, 2016;137:50–7 e6.
9. Amaral AF, Strachan DP, Gomez Real F, et al., Lower lung function associates with cessation of menstruation: UK Biobank data, Eur Respir J, 2016;48:1288–97.
10. Cevrioglu AS, Fidan F, Unlu M, et al., The effects of hormone therapy on pulmonary function tests in postmenopausal women, Maturitas, 2004;49:221–7.
11. Pata O, Atis S, Utku Oz A, et al., The effects of hormone replacement therapy type on pulmonary functions in postmenopausal women, Maturitas, 2003;46:213–8.