Contraceptive use among women with cystic fibrosis: A pilot study linking reproductive health questions to the Cystic Fibrosis Foundation National Patient Registry

Godfrey, Emily M.; Mody, Sheila K.; Schwartz, Malaika; Heltshe, Sonya L.; Taylor‐Cousar, Jennifer L.; Jain, Raksha; Sufian, Sandy; Josephy, Tatiana; Aitken, Moira L.

doi:10.1016/j.contraception.2020.02.006

Cited by 23 publications

(20 citation statements)

References 24 publications

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“…Exploring whether a colonizing P. aeruginosa strain is responsive to hormonal stress may allow a more focused and tailored therapeutic approach based on sex steroids and gender, particularly in the era of antimicrobial resistance ( 55 , 56 ). A further interesting aspect of our work is improved mechanistic insight into why CF females taking oral contraceptive pills experience fewer exacerbations and need for antibiotics ( 8 , 57 , 58 ). In these women, synthetic exogenous ethinylestradiol ([EE2] logP, 4.15) suppresses the more polar and endogenous estradiol ([E2] logP, 2.70) ( 59 ), which based on our data, would have less effect on inducing P. aeruginosa virulence and potentially translate to better patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

Vidaillac

Yong

Aschtgen

et al. 2020

mBio

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Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in P. aeruginosa. This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting in vivo persistence of the bacteria. The steroid-induced P. aeruginosa response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and P. aeruginosa explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains. IMPORTANCE Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.

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Section: Discussionmentioning

confidence: 99%

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

Vidaillac

Yong

Aschtgen

et al. 2020

mBio

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“…Ideally, this information would be communicated to both the woman with CF and to her child’s pediatrician so that shared decision making could occur. First, although the partners of most women with CF undergo genetic testing for CF prior to pregnancy, not all may do so, and up to 50% of pregnancies in women with CF are reported to be unplanned [ 60 ]. Importantly, in the CF ferret animal model, when IVA was administered throughout pregnancy to ferrets with the IVA-responsive G551D (Gly551Asp) mutation, investigators demonstrated restoration of pancreatic function in kits [ 61 ].…”

Section: Pregnancymentioning

confidence: 99%

Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

Jain

Taylor‐Cousar

2021

JPM

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder impacting approximately 80,000 people of all races and ethnicities world-wide. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes a protein of the same name. Protein dysfunction results in abnormal chloride and bicarbonate transport in mucus membranes, including those in the respiratory, gastrointestinal and reproductive tracts. Abnormal anion transport causes viscous secretions at the site of involvement. The majority of people with CF succumb to respiratory failure following recurrent cycles of infection and inflammation in the airways. Historically, providers treated the signs and symptoms of CF, but since 2012, have been able to impact the basic defect for the subset of people with CF who have mutations that respond to the new class of drugs, CFTR protein modulators. With the improved health and longevity afforded by CFTR modulators, more women are interested in parenthood and are becoming pregnant. Furthermore, this class of drugs likely increases fertility in women with CF. However, the safety of CFTR modulators in pregnancy and lactation is only beginning to be established. We summarize available data on the impact of CFTR modulators on fertility, pregnancy and lactation in women with CF.

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“…Some limited data do exist on contraception and bone health in CF. A survey study of 150 females with CF linked participants’ reported contraceptive history to clinical outcomes from the CF Foundation Patient Registry [37] . In this study, use of DMPA was associated with 5 times greater odds of osteoporosis compared to never use, after adjusting for BMI.…”

Section: Contraception For Females With Cfmentioning

confidence: 99%

“…Contraceptive uptake is lower in patients with CF than in the general population, with only half of females with CF using any form of contraception [32] . The most common methods are the OCP and condoms [32] , [42] , although a recent survey indicates growing use of intrauterine devices [37] . Qualitative interviews with females with CF reveal that contraceptive decision-making can be complicated as they weigh possible health effects and medication interactions, and contraception is often a lower priority amidst their other health considerations [43] , [44] .…”

Section: Contraception For Females With Cfmentioning

confidence: 99%

Gynecologic health care for females with cystic fibrosis

Roe

Merjaneh

Oxman

et al. 2021

Journal of Clinical & Translational Endocrinology

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Contraceptive use among women with cystic fibrosis: A pilot study linking reproductive health questions to the Cystic Fibrosis Foundation National Patient Registry

Cited by 23 publications

References 24 publications

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

Gynecologic health care for females with cystic fibrosis

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