Effects of Endogenous Sex Hormones on Lung Function and Symptom Control in Adolescents With Asthma

Mark D. DeBoer; Brenda R. Phillips; David T. Mauger; Joe Zein; Serpil C. Erzurum; Anne M. Fitzpatrick; Benjamin M. Gaston; Ross Myers; Kristie R. Ross; James Chmiel; Min Jie Lee; John V. Fahy; Michael Peters; Ngoc P. Ly; Sally E. Wenzel; Merritt L. Fajt; Fernando Holguin; Wendy C. Moore; Stephen P. Peters; Deborah Meyers; Eugene R. Bleecker; Mario Castro; Andrea M. Coverstone; Leonard B. Bacharier; Nizar N. Jarjour; Ronald L. Sorkness; Sima Ramratnam; Anne-Marie Irani; Elliot Israel; Bruce Levy; Wanda Phipatanakul; Jonathan M. Gaffin; W. Gerald Teague

Disclosures

BMC Pulm Med. 2018;18(58) 

In This Article

Background

The prevalence of current asthma in the U.S. is higher in children than in adults, and from pre-school to age 14 years is greater in boys than it is in girls.[1] Both asthma severity and hospitalizations start to decrease in late childhood and remain relatively low into young adulthood.[2,3] After age 18 years, in young men, current asthma prevalence is lower than in childhood; in young women although lower than in childhood, current asthma prevalence is higher than it is in young men, and remains higher in women through middle-age.[1] Surges in endogenous sex hormones across adolescence could affect the "gender switch" in asthma status.[2] For example, DHEA-S, a circulating androgen that increases with puberty, inhibits human airway smooth muscle and airway fibroblast proliferation[4,5] and may influence airway epithelial-to-mesenchymal transition.[6] Testosterone promotes airway smooth muscle relaxation.[7] In women both with and without asthma, FEV1% peaks at the end of the luteal phase to the beginning of menstruation, and then decreases when circulating estrogen and progesterone decrease.[8] Accordingly, the fall in circulating estrogen and progesterone from the luteal to the follicular phase of the menstrual cycle is accompanied by a reduction in lymphocyte β2 adrenoceptor density[9] and increased bronchial responsiveness in women with asthma.[10] Recent studies of dysanapsis (differential growth of airway caliber and lung volume) in healthy subjects suggest that, by adulthood, women develop more small airways resistance than do men.[11] Thus these studies support interdependent effects of sex and endogenous sex hormones on lung growth, and airways responsiveness that likely inform asthma status from puberty to middle-age.

Puberty is a dynamic process regulated by hormonal signals from the central nervous system that results in sexual maturation. Assessment of the stage of pubertal maturation is different in boys than girls.[12] In boys, androgen production gradually increases both from testes producing testosterone and the adrenal glands producing weaker androgens—ultimately leading to pubarche. Girls experience increases in the production of estrogen from the ovaries (driving thelarche and ultimately menarche) and androgens such as androstenedione and DHEA-S from the adrenal glands (driving pubarche in girls).[13] In children studies of pubertal maturation and asthma status furthermore may be affected by corticosteroid treatment.[14] The primary purpose of the current studies was to do a cross-sectional analysis of the effects of pubertal maturation and sex hormone levels on asthma features in a sample of children enrolled in SARP. We found important differences in phenotypic features according to sex and pubertal stage. In boys higher DHEA-S levels positively associated with greater FEV1% predicted and improved 4 week symptoms, whereas in girls, breast development, signifying estradiol effects, weakly associated with lower lung function.

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