Sexual and reproductive health behaviors and experiences reported by young women with cystic fibrosis

  • Traci M. Kazmerski
    Correspondence
    Corresponding author at: Division of Respiratory Diseases, Boston Children's Hospital, 1 Autumn St. Box #16, Boston, MA 02215, United States.
    Affiliations
    Division of Respiratory Diseases, Department of Medicine, Boston Children's Hospital, Boston, MA, United States

    Institute for Healthcare Improvement, Cambridge, MA, United States
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  • Gregory S. Sawicki
    Affiliations
    Division of Respiratory Diseases, Department of Medicine, Boston Children's Hospital, Boston, MA, United States
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  • Elizabeth Miller
    Affiliations
    Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

    Center for Women's Health Research and Innovation (CWHRI), University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
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  • Kelley A. Jones
    Affiliations
    Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
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  • Kaleab Z. Abebe
    Affiliations
    Department of Medicine, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, United States

    Center for Research on Health Care Data Center, Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA, United States
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  • Lisa K. Tuchman
    Affiliations
    Division of Adolescent and Young Adult Medicine, Children's National Health System, Washington, DC, United States
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  • Sigrid Ladores
    Affiliations
    University of Alabama-Birmingham, School of Nursing, Birmingham, AL, United States
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  • Ronald C. Rubenstein
    Affiliations
    Division of Pulmonary Medicine, Cystic Fibrosis Center, The Children's Hospital of Philadelphia, Philadelphia, PA, United States

    Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
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  • Scott D. Sagel
    Affiliations
    Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, United States
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  • Daniel J. Weiner
    Affiliations
    Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
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  • Joseph M. Pilewski
    Affiliations
    Department of Medicine, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, United States
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  • David M. Orenstein
    Affiliations
    Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
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  • Sonya Borrero
    Affiliations
    Center for Women's Health Research and Innovation (CWHRI), University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

    Department of Medicine, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, United States

    VA Pittsburgh Center for Health Equity Research and Promotion, Pittsburgh, PA, United States
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Open ArchivePublished:August 01, 2017DOI:https://doi.org/10.1016/j.jcf.2017.07.017

      Abstract

      Background

      The prevalence of general and disease-specific sexual and reproductive health (SRH) concerns is unknown in the United States (U.S.) female CF population. This study aimed to describe and compare the SRH experiences and behaviors of young women with CF with the general U.S. population.

      Methods

      Young women with CF ages 15–24 years from five geographically diverse U.S. CF centers participated in a survey investigating SRH. Results were summarized and compared to the U.S. National Survey of Family Growth (NSFG) using logistic regression adjusting for confounders.

      Findings

      A total of 188 young women with CF (mean age 19.7 ± 2.7 years) completed the survey; data were compared to 1997 NSFG respondents (mean age 19.6 ± 0.10 years). Fifty-four percent of women with CF reported having had vaginal sex with a male partner compared to 66% of U.S. women (p = 0.55). Women with CF were less likely to have ever used contraception (55% vs. 74%, p = 0.0001) or have been tested for sexually transmitted infections in the past year (19% vs. 34%, p = 0.001) compared to the general population. Two percent of women with CF reported having ever been pregnant compared to 24% of U.S. women (p < 0.0001). One-third of young women with CF reported perceived pubertal delay, 16% urinary incontinence, 16% sexual dysfunction, and 49% yeast infections.

      Interpretation

      Young women with CF face significant SRH concerns and appear to be experiencing gaps in SRH care provision. Opportunities exist for intervention development around this aspect of comprehensive CF care.

      Funding

      CF Foundation ( KAZMER15A0 ); U.S. National Institutes of Health ( UL1TR000005 ).

      Keywords

      1. Introduction

      Advances in therapy and chronic disease management have led to dramatic increases in the life expectancy for people with cystic fibrosis (CF) [
      ]. However, despite these improvements, females with CF have a lower median survival relative to males despite accounting for nutritional status, pulmonary function, and airway microbiology [
      • Rosenfeld M.
      • Davis R.
      • FitzSimmons S.
      • Pepe M.
      • Ramsey B.
      Gender gap in cystic fibrosis mortality.
      ,
      • McIntyre K.
      Gender and survival in cystic fibrosis.
      ,
      • Harness-Brumley C.L.
      • Elliott A.C.
      • Rosenbluth D.B.
      • Raghavan D.
      • Jain R.
      Gender differences in outcomes of patients with cystic fibrosis.
      ].
      In addition to this gender disparity, young women with CF experience a variety of sexual and reproductive health (SRH) concerns. In the United States (U.S.), young women age 15–24 years old endure the highest rates of sexually transmitted infections (STIs), unintended pregnancy, and intimate partner violence (IPV) [
      • Finer L.B.
      • Zolna M.R.
      Shifts in intended and unintended pregnancies in the United States, 2001-2008.
      ,
      • Centers for Disease Control and Prevention (CDC)
      Sexually transmitted disease surveillance: STDs in adolescents and young adults.
      ,
      • Miller E.
      • et al.
      Pregnancy coercion, intimate partner violence, and unintended pregnancy.
      ]. Along with these general SRH challenges, young women with CF face several disease-specific SRH issues, including pubertal delay, high rates of vulvovaginal candidiasis with frequent antibiotic use, urinary incontinence (UI), sexual dysfunction, concerns regarding contraceptive choice, decreased fertility, and adverse effects of pregnancy [
      • Levine S.B.
      • Stern R.C.
      Sexual function in cystic fibrosis. Relationship to overall health status and pulmonary disease severity in 30 married patients.
      ,
      • Sawyer S.M.
      • Bowes G.
      • Phelan P.D.
      Vulvovaginal candidiasis in young women with cystic fibrosis.
      ,
      • Sawyer S.M.
      • Phelan P.D.
      • Bowes G.
      Reproductive health in young women with cystic fibrosis: knowledge, behavior, and attitudes.
      ,
      • Nixon G.M.
      • Glazner J.A.
      • Martin J.M.
      • Sawyer S.M.
      Urinary incontinence in female adolescents with cystic fibrosis.
      ,
      • Roberts S.
      • Green P.
      The sexual health of adolescents with cystic fibrosis.
      ,
      • Tsang A.
      • Moriarty C.
      • Towns S.
      Contraception, communication and counseling for sexuality and reproductive health in adolescents and young adults with CF.
      ,
      • Roe A.H.
      • Traxler S.
      • Schreiber C.A.
      Contraception in women with cystic fibrosis: a systematic review of the literature.
      ]. The prevalence of such SRH issues in the U.S. female CF population is unknown. Defining the SRH experiences and behaviors of young female patients with CF is important both to improve comprehensive clinical care and serve as a gateway to explore the contribution of SRH on CF-specific health outcomes.
      The purpose of this study is to describe the general and disease-specific SRH experiences and behaviors of young women with CF and to compare these findings to the general U.S. population. We hypothesized that young women with CF would have similar SRH behaviors compared to their healthy counterparts, yet would have gaps in SRH care provision. Findings from this study will define the unique healthcare needs of this population and will inform the development of future SRH interventions that improve the overall health for female patients with CF.

      2. Methods

      Young women with CF ages 15–24 years were recruited to participate in a survey investigating SRH topics including sexual history, STIs, IPV and reproductive coercion (RC), contraceptive use, and pregnancy experiences and attitudes. CF-specific SRH concerns examined included puberty and menstruation, UI, vulvovaginal candidiasis, sexual functioning, CF disclosure to sexual partners, and concerns regarding pregnancy/parenthood. Participants also completed general demographics and self-reported CF health status items (see Online Data Supplement-Patient Survey). Survey content was informed by our prior qualitative work [
      • Kazmerski T.M.
      • Borrero S.
      • Tuchman L.
      • Weiner D.J.
      • Pilewski J.
      • Orenstein D.M.
      • et al.
      Patient and provider attitudes regarding sexual health in young women with cystic fibrosis.
      ,
      • Kazmerski T.M.
      • Gmelin T.
      • Slocum B.
      • Borrero S.
      • Miller E.
      Attitudes and decision making related to pregnancy in young women with cystic fibrosis.
      ]. Select survey items were derived from the National Survey of Family Growth (NSFG), prior patient-based surveys, the Female Sexual Functioning Index-6 (FSFI-6), and validated IPV and RC measures [
      • Sawyer S.M.
      • Phelan P.D.
      • Bowes G.
      Reproductive health in young women with cystic fibrosis: knowledge, behavior, and attitudes.
      ,
      • Nixon G.M.
      • Glazner J.A.
      • Martin J.M.
      • Sawyer S.M.
      Urinary incontinence in female adolescents with cystic fibrosis.
      ,
      • National Survey for Family Growth (NSFG)
      ,
      • Isidori A.M.
      • Pozza C.
      • Esposito K.
      • Giugliano D.
      • Morano S.
      • Vignozzi L.
      • et al.
      Development and validation of a 6-item version of the female sexual function index (FSFI) as a diagnostic tool for female sexual dysfunction.
      ,
      • Kazmerski T.
      • McCauley H.L.
      • Jones K.A.
      • Borrero S.
      • Silverman J.G.
      • Decker M.R.
      • et al.
      Use of reproductive and sexual health services among female family planning clinic patients exposed to partner violence and reproductive coercion.
      ].
      The survey was administered from June 2015 to September 2016 at five CF centers, including both adult and pediatric centers (2 from two different states in the Northeast, 1 in the Southeast, 1 in the West, and 1 in the Mid-Atlantic region). Participants completed the survey during a clinic visit or hospitalization. Data were collected anonymously to encourage disclosure of SRH behaviors/experiences. Study data were collected and managed using REDCap electronic data capture tools [
      • Harris P.A.
      • Taylor R.
      • Thielke R.
      • Payne J.
      • Gonzalez N.
      • Conde J.G.
      Research electronic data capture (REDCap) - a metadata-driven methodology and workflow process for providing translational research informatics support.
      ]. The Institutional Review Board of each site approved this study.
      Descriptive statistics were used to summarize demographics and SRH issues. Demographics and general SRH experiences/behaviors were compared to data for 15–24 year old women from the NSFG, a nationally representative survey of people age 15–44 years conducted by the CDC [
      • National Survey for Family Growth (NSFG)
      ]. The NSFG data was downloaded in its raw form to conduct these analyses and recommended NSFG guidelines on survey design and weighting were applied to account for its complex sampling design. Continuous variables were represented using means and standard deviations for the CF sample and weighted mean and standard errors for the NSFG; similarly, categorical variables were represented with percentages for the CF sample, and weighted percentages for the NSFG. To account for any missing data, percentages were calculated based on total n = 188 in the CF sample. Differences in demographics between young women with CF and the NSFG sample were explored via Wald log linear chi-squared testing for categorical variables and linear regression for continuous variables, which allowed for incorporation of NSFG sampling design. To account for observed significant demographic differences between the groups, multivariable logistic regression examining relationships between the samples and SRH outcomes (such as sexual activity or contraception use) was performed adjusting for race, ethnicity, highest level of education and current work/school status.
      Using the women in the CF sample only, SRH issues were explored across self-reported markers of CF disease; differences were explored using the Chi-square test for categorical outcomes and unbalanced ANOVA for continuous outcomes. Fisher exact tests were used when cell counts were 5 or less. Statistical analyses were conducted using SAS Version 9.3 (SAS II; SAS, 9 ed., SAS Institute, Cary, NC, USA; 2003).

      3. Results

      3.1 Demographic and CF-related health characteristics

      A total of 188 young women with CF (mean age 19.7 ± 2.7 years) completed the survey out of 206 eligible participants approached (91% response rate). Table 1 describes the sample's demographics and CF health characteristics. Data were compared to women age 15–24 years from the NSFG survey (n = 1997; mean age 19.6 ± 0.10 years). Significant differences between the samples were found for race, ethnicity, level of education, current work or school status, and self-reported health status.
      Table 1Demographics.
      Characteristics
      a Denominator varies by variable (n ranges from 180 to 188); percentages calculated based on total n = 188 to include missing data.
      Comparison groupWald log-linear χ2 p-value
      CF (n = 188)

      % (n)
      NSFG (n = 1997)

      Weighted %
      Age (mean, SD/mean, standard error of mean)19.7 (2.7)19.6 (0.10)0.56
      b Proc surveyreg was used to compare continuous outcomes by sample.
      Marital status0.58
       Single91 (172)91
       Married or living as married6 (12)8
       Separated or divorced1 (2)1
      Race/ethnicity<0.001
       Black/African-American3 (5)18
       White91 (172)69
       Other5 (10)13
      Hispanic ethnicity6 (12)22<0.001
      Highest level of education<0.001
       Some high school or less38 (71)38
       High school degree or GED15 (28)24
       Some college or vocational school34 (64)29
       College degree or higher13 (24)9
      Current work or school status<0.001
       Attending school62 (116)26
       Working full or part time24 (46)52
       Homemaker1 (2)10
       Not working due to health
      c “Not working due to health” was combined with the “seeking work/not working for other reasons category” in the CF sample for the comparison to NSFG.
      6 (11)n/a
       Seeking work/not working for other reasons6 (12)13
      Current health status (self-report)<0.001
       Excellent14 (27)31
       Very good24 (46)39
       Good32 (60)24
       Fair25 (47)5
       Poor4 (8)1
      CF severity (self-report)
       Mild37 (70)n/a
       Moderate55 (103)n/a
       Severe7 (13)n/a
      Baseline FEV1 (self-report)
       >70%71 (133)n/a
       41–70%16 (31)n/a
       <40%9 (16)n/a
      Number of hospitalizations in past year
       None41 (77)n/a
       One or two times38 (71)n/a
       >2 times21 (40)n/a
      Presence of G tube13 (24)n/a
      CF-related diabetes
       Diabetes31 (59)n/a
       Impaired glucose tolerance8 (15)n/a
      CF-related liver disease10 (18)n/a
      a Denominator varies by variable (n ranges from 180 to 188); percentages calculated based on total n = 188 to include missing data.
      b Proc surveyreg was used to compare continuous outcomes by sample.
      c “Not working due to health” was combined with the “seeking work/not working for other reasons category” in the CF sample for the comparison to NSFG.

      3.2 General SRH behaviors and experiences

      While nearly all women with CF and in the NSFG sample had reached menarche, the mean age at which women with CF reported menarche was later (13.1 ± 1.3 years compared to 12.4 ± 0.05 years in the NSFG sample, p < 0.0001). Fifty-four percent of young women with CF reported a history of vaginal sex with a male partner compared to 66% of women in the NSFG, but this difference was not statistically significant (p = 0.55). The average age at first vaginal sex with a male partner was 16.9 ± 1.9 years for young women with CF and 16.2 ± 0.11 years for NSFG women (p = 0.001). Similar to the NSFG sample, young women with CF reported an average of 4.7 ± 4.9 lifetime male vaginal sex partners with 1.5 ± 1.8 partners in the prior 12 months (p = 0.61 and p = 0.90, respectively). Regarding STIs (gonorrhea, chlamydia, herpes, HIV, syphilis, and/or genital warts), 19% of women with CF reported undergoing testing in the past year compared to 34% in the NSFG sample (p = 0.001). Fourteen percent of women with CF reported experiencing IPV and 4% reported experiencing RC. Table 2 further details both groups' SRH experiences.
      Table 2CF vs. NSFG sexual and reproductive health experiences and behaviors.
      OutcomesCF

      % (n)
      NSFG

      Weighted %
      p value
      d Adjusted for race, ethnicity, level of education and current work/school status.
      (n = 188)(n = 1997)
      Reached menarche98 (184)99.70.42
      Age of menarche (in years) (mean, SD/mean, standard error of mean)13.1 (1.3)12.4 (0.05)<0.001
      Sexual orientation
      a n = 187; percentages calculated based on total n = 188 to include missing data.
      0.22
       Heterosexual or straight87 (164)90
       Homosexual, gay, or lesbian2 (4)2
       Bisexual10 (19)9
      History of vaginal sex with male partner54 (101)660.55
      History of performing oral sex
       Male partner50 (94)590.08
       Female partner11 (20)9<0.01
      History of receiving oral sex
       Male partner52 (97)620.07
       Female partner10.6 (20)110.02
      History of anal sex12 (22)22<0.001
      History of any sexual experience with female partner14 (26)160.26
      Age at first vaginal sex with male partner
      b Of participants who have had vaginal sex (n = 101 CF, n = 1334 NSFG).
      (mean, SD/mean, standard error of mean)
      16.9 (1.9)16.2 (0.11)<0.01
      Number of male vaginal sex partners
      b Of participants who have had vaginal sex (n = 101 CF, n = 1334 NSFG).
      (mean, SD; median/mean, standard error of mean; median)
       Lifetime4.7 (4.9); 34.9 (0.21); 2.60.61
       Past 12 months1.5 (1.8); 11.4 (0.06); 0.60.90
      STI testing in past year
      c NSFG data has past-year diagnosis of chlamydia and gonorrhea and lifetime diagnosis of herpes, genital warts, and syphilis.
      19 (35)34<0.001
      STI treatment in past year4 (8)50.86
      History of pelvic inflammatory disease0.5 (1)2<.01
      Ever pregnant2 (3)24<0.001
      a n = 187; percentages calculated based on total n = 188 to include missing data.
      b Of participants who have had vaginal sex (n = 101 CF, n = 1334 NSFG).
      c NSFG data has past-year diagnosis of chlamydia and gonorrhea and lifetime diagnosis of herpes, genital warts, and syphilis.
      d Adjusted for race, ethnicity, level of education and current work/school status.
      Fifty-five percent of women with CF had ever used contraception compared to 74% of women in the NSFG (p < 0.0001). Among participants who reported sex in the prior three months (CF n = 83, 44%; NSFG n = 1058, 53%), 35% of young women with CF were not using any form of contraception compared to 26% of women in the NSFG (p < 0.0001). Table 3 summarizes the rates of use of both groups' current contraceptive methods. A higher percentage of women with CF were using a long-acting reversible contraceptive (LARC) (intrauterine device or implant) compared to NSFG women (17% vs. 8%, p < 0.0001). Women with CF currently using contraception had a mean age of contraceptive initiation of 16.8 ± 2.1 years compared to 16.2 ± 0.13 years in the NSFG (p = 0.001). In the previous year, women with CF were more likely to consistently report condom use with male partners compared to women in the NSFG (31% vs. 26%, p < 0.0001). Fewer women with CF (17%) reported a history of emergency contraception use compared to women in the NSFG (29%, p < 0.0001) (Table 3).
      Table 3Contraceptive use.
      OutcomesComparison groupp value
      e Adjusted for race, ethnicity, level of education and current work/school status.
      CF

      % (n)
      NSFG

      Weighted %
      History of contraceptive use55 (103)74<0.001
      Current contraceptive method
      a Among participants who report recent sex in the past three months (n = 83 CF, n = 1058 NSFG); can select multiple methods.
       None35 (29)26<0.001
       Intrauterine device11 (9)6<0.001
       Subdermal implant6 (5)2<0.001
       Injection (i.e., Depo-Provera)8 (7)60.04
       Vaginal ring1 (1)20.16
       Contraceptive patch1 (1)0.80.02
       Oral contraceptives29 (24)31<0.001
       Male condom24 (20)33<0.01
       Withdrawal (“pulling out”)14 (12)160.32
      Current use of long-acting reversible contraception (IUD or implant)
      a Among participants who report recent sex in the past three months (n = 83 CF, n = 1058 NSFG); can select multiple methods.
      17 (14)8<0.001
      Age of initiation of contraceptive use for current users (mean, SD/SE)
      b Among participants who currently use contraception (n = 76 CF, n = 852 NSFG).
      16.8 (2.1)16.2 (0.13)<0.001
      Reasons for current contraceptive non-use
      c n = 24; percentages calculated based on participants who currently do not use contraception (n = 25 CF, n = 1058 NSFG) to include missing data; can select multiple choices.
      <0.001
       You do not expect to have sex52 (13)14
       You do not think you can get pregnant8 (2)10
       You don't really mind if you get pregnant16 (4)22
       You are worried about the side effects of birth control20 (5)32
      Condom use, past 12months
      d n = 185; percentages calculated based on total n = 188 to include missing data.
      <0.001
       Every time20 (38)15
       Most of the time11 (21)11
       About half of the time2 (3)4
       Some of the time5 (10)12
       None of the time14 (27)20
       I have not had sexual intercourse46 (86)39
      History of emergency contraception use17 (32)29<0.001
      a Among participants who report recent sex in the past three months (n = 83 CF, n = 1058 NSFG); can select multiple methods.
      b Among participants who currently use contraception (n = 76 CF, n = 852 NSFG).
      c n = 24; percentages calculated based on participants who currently do not use contraception (n = 25 CF, n = 1058 NSFG) to include missing data; can select multiple choices.
      d n = 185; percentages calculated based on total n = 188 to include missing data.
      e Adjusted for race, ethnicity, level of education and current work/school status.
      Three women with CF (2%) reported ever being pregnant (resulting in one miscarriage, one abortion, and one ongoing pregnancy), whereas 24% of NSFG women had ever been pregnant (p < 0.0001) (Table 2).

      3.3 CF-specific SRH experiences and behaviors

      Twenty-nine percent of young women with CF perceived pubertal delay compared to other girls their age. Sixteen percent of women with CF had a history of UI and 49% had a history of yeast infections. Forty-nine percent of women with CF always disclose their CF diagnosis to sexual partners; 29% disclose their CF when they are in a committed relationship (Table 4).
      Table 4CF-specific SRH experience and behaviors.
      Outcomes
      a Denominator varies by variable (n ranges from 177 to 188); percentages calculated based on total n = 188 to include missing data.
      CF women

      % (n)
      (n = 188)
      Age of adrenarche, mean (SD)12.0 (1.4)
      Age of menarche, mean (SD)13.1 (1.3)
      Perceived timing of puberty
       Earlier than other girls my age13 (24)
       The same as other girls my age57 (107)
       Later than other girls my age29 (54)
      History of urinary incontinence (UI)16 (30)
       Age of onset, mean (SD)15.7 (4.5)
       Frequency of UI
      Once a day or more27 (8)
      1–4 times per week13 (4)
      2–4 times per month13 (4)
      A few times per year20 (6)
      Very rarely27 (8)
      History of yeast infections
       Never51 (95)
       Yes, once a year or less25 (47)
       Yes, a couple of times a year19 (36)
       Yes, once a month or more5 (10)
      Disclosure of CF diagnosis to sexual partners
       No4 (8)
       Yes, sometimes9 (17)
       Yes, when I am in a committed relationship29 (55)
       Yes, always49 (92)
       Don't know8 (14)
      Sexual functioning
      b Among participants who report sex in the past month (n = 81); n ranges from 80 to 81; percentages calculated based on total n = 81 to include missing data.
       Sexual dysfunction
      b Among participants who report sex in the past month (n = 81); n ranges from 80 to 81; percentages calculated based on total n = 81 to include missing data.
      c Determined by composite score of <19 on Female Sexual Functioning Index-6 scale (mean score 23.1 ± 4.7).
      16 (13)
      Coughing during or after sex
      b Among participants who report sex in the past month (n = 81); n ranges from 80 to 81; percentages calculated based on total n = 81 to include missing data.
      Almost never or never33 (27)
      A few times (less than half the time)32 (26)
      Half the time or most times21 (17)
      Almost always or always12 (10)
      Hemoptysis during or after sex
      b Among participants who report sex in the past month (n = 81); n ranges from 80 to 81; percentages calculated based on total n = 81 to include missing data.
      Almost never or never95 (77)
      A few times (less than half the time)1 (1)
      Half the time or most times1 (1)
      Almost always or always1 (1)
      Excessive flatulence during or after sex
      b Among participants who report sex in the past month (n = 81); n ranges from 80 to 81; percentages calculated based on total n = 81 to include missing data.
      Almost never or never79 (64)
      A few times (less than half the time)16 (13)
      Half the time or most times3 (2)
      Almost always or always1 (1)
      Pain with vaginal penetration
      d n = 100; percentages calculated based on participants who ever had vaginal sex (n = 101) to include missing data.
      Almost never or never47 (47)
      A few times (less than half the time)22 (22)
      Half the time or most times14 (14)
      Almost always or always2 (2)
      Have not recently attempted vaginal penetration15 (15)
      Informed or told of infertility due to CF1 (2)
      Concerned future children may have CF72 (136)
      Would elect to do genetic testing for CF for future child79 (148)
      Desire to have future child
       Definitely yes44 (83)
       Probably yes34 (63)
       Probably no11 (20)
       Definitely no6 (11)
      Feelings regarding prospect of pregnancy at this time
       Very upset59 (111)
       A little upset22 (42)
       A little pleased8 (14)
       Very pleased6 (12)
       Would not care2 (3)
      a Denominator varies by variable (n ranges from 177 to 188); percentages calculated based on total n = 188 to include missing data.
      b Among participants who report sex in the past month (n = 81); n ranges from 80 to 81; percentages calculated based on total n = 81 to include missing data.
      c Determined by composite score of <19 on Female Sexual Functioning Index-6 scale (mean score 23.1 ± 4.7).
      d n = 100; percentages calculated based on participants who ever had vaginal sex (n = 101) to include missing data.
      Sixteen percent of young women with CF who had sexual experiences in the past month had a composite score on the FSFI-6 signaling sexual dysfunction (n = 13 out of 81 women; mean score 23.1 ± 4.7). One-third of women with CF reported coughing during or after sex half the time or more. Sixteen percent of respondents with a history of vaginal penetration (n = 16 out of 101 women) reported pain with vaginal penetration half the time or more (Table 4).
      Seventy-two percent of women with CF were concerned that future children might have CF; 79% would elect to do genetic testing for CF for future children. Seventy-eight percent of all surveyed women with CF wanted to have a child in the future; however, 81% would feel upset regarding pregnancy at the current time. Similar proportions of women across age cohorts (15–18, 19–21, and 22–24 years old), expressed a desire for future children (>75% in each age cohort). Two women in the sample reported that a healthcare provider had told them that they were infertile due to their CF (Table 4).

      3.4 SRH outcomes by CF health status

      Women who rated their CF disease as “severe” reported a lower age of initial sex (16 ± 1.2 years) compared to women who rated their CF as “mild” (18 ± 1.9 years) or “moderate” (17 ± 1.9 years) (p = 0.03). All women with CF used similar methods of contraception with the exception of women who rated their CF as “severe” being less likely to use oral contraceptives (p = 0.035). Women with CF-related liver disease and/or a gastrostomy tube reported later menarche compared to other women with CF (14 ± 1.5 years/14 ± 1.4 years vs. 13 ± 1.3 years; p = 0.003 and p = 0.006). Women with liver disease were also significantly more likely to have had vaginal sex (78% vs. 51%; p = 0.035) compared to those without liver disease. Full data on the effect of CF health markers on SRH outcomes is available in Supplement 1.

      4. Discussion

      This is the first study to identify and compare the SRH experiences and behaviors of young women with CF to the general U.S. population. Despite reporting similar levels of sexual activity, young women with CF in this sample appear to be experiencing gaps in SRH care, specifically regarding preventive services including STI testing and contraception. Over a third of recently sexually active women in the sample are not using any form of contraception, but are experiencing lower pregnancy rates compared to U.S. women. The majority of young women with CF surveyed desire future children. Finally, young women with CF are experiencing many disease-specific SRH concerns, including pubertal delay, UI, yeast infections, and sexual dysfunction.
      The significant divergence in pregnancy rates between young women with CF in this sample and the general U.S. population deserves attention. This may be partly explained by the increased use of LARCs (the most effective forms of reversible contraception) in the CF population. However, the degree of difference in LARC use (17% vs. 8%) likely cannot fully explain the difference in pregnancy rates reported (2% vs. 24%). The stark contrast in pregnancy rates between the two groups may indicate decreased fertility in the CF population, especially given that women with CF who were currently sexually active were also less likely to be using any contraception. Fertility may be affected in CF through a variety of mechanisms, including thickened cervical mucus, decreased sperm motility and capacitation, and poor nutrition [
      • Lyon A.
      • Bilton D.
      Fertility issues in cystic fibrosis.
      ,
      • Chan H.C.
      • Shi Q.X.
      • Zhou C.X.
      • Wang X.F.
      • Xu W.M.
      • Chen W.Y.
      • et al.
      Critical role of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm.
      ]. However, understanding of fertility and pregnancy in CF is limited and, while female patients indicate that CF is a major factor in their pregnancy decision-making, they have expressed confusion about how CF actually affects their reproductive futures [
      • Kazmerski T.M.
      • Gmelin T.
      • Slocum B.
      • Borrero S.
      • Miller E.
      Attitudes and decision making related to pregnancy in young women with cystic fibrosis.
      ]. Although the U.S. CF Foundation patient registry inquires whether a patient had a pregnancy in the past year, no formalized collection of maternal-fetal outcomes or need for fertility interventions exists [
      ]. Registry data may be skewed to include only pregnancies that result in live births, as patients may not disclose miscarriage or abortion to their care team. Incorporating additional SRH items into the registry may facilitate understanding the interplay between these elements and CF disease. As nearly 80% of our sample desire future children, research regarding fertility and pregnancy is imperative to provide adequate preconception counseling and care for the increasing numbers of young women with CF who desire children [
      • Edenborough F.P.
      • Borgo G.
      • Knoop C.
      • Lannefors L.
      • MacKenzie W.E.
      • Madge S.
      • et al.
      Guidelines for the management of pregnancy in women with cystic fibrosis.
      ].
      Female sex hormones, particularly estrogen, are believed to modulate key components of CF physiology and negatively affect infection, inflammation, and mucociliary clearance [
      • Sweezey N.B.
      • Ratjen F.
      The cystic fibrosis gender gap: potential roles of estrogen.
      ,
      • Wang Y.
      • Cela E.
      • Gagnon S.
      • Sweezey N.B.
      Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice.
      ,
      • Whitacre C.C.
      • Reingold S.C.
      • O'Looney P.A.
      A gender gap in autoimmunity.
      ,
      • Sutton S.
      • Rosenbluth D.
      • Raghavan D.
      • Zheng J.
      • Jain R.
      Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.
      ]. Over 50% of women with CF in this sample currently using contraception reported using a hormonal method, a potentially useful treatment modality for shrinking the gender gap as it regulates these physiologic hormonal shifts. Despite limited data, oral contraception appears to be safe for use in women with CF14 and a review of the Cystic Fibrosis Registry of Ireland revealed that the use of oral contraceptives was associated with a decreased need for antibiotics [
      • Chotirmall S.H.
      • Smith S.G.
      • Gunaratnam C.
      • Cosgrove S.
      • Dimitrov B.D.
      • O'Neill S.J.
      • et al.
      Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis.
      ]. However, adoption of new therapies that alter the CFTR defect, such as ivacaftor and lumacaftor/ivacaftor, may limit the use of hormonal contraceptives as a treatment. These new drugs may affect metabolism and reduce efficacy of oral hormonal contraceptives [
      Vertex pharmaceuticals. Lumacaftor-ivacaftor: patient information.
      ] and current product information states that hormonal contraception should avoided. To complicate matters, these new therapies may have positive effects on female fertility through changes in cervical mucus consistency, yet their effects during pregnancy and lactation are incompletely understood [
      • Jones G.H.
      • Walshaw M.J.
      Potential impact on fertility of new systemic therapies for cystic fibrosis.
      ].
      Because young female patients with CF are engaging in SRH behaviors and have many SRH concerns, improved SRH care is needed. Many CF patients view their CF providers as “de facto” primary care physicians (PCPs) [
      • Kazmerski T.M.
      • Borrero S.
      • Tuchman L.
      • Weiner D.J.
      • Pilewski J.
      • Orenstein D.M.
      • et al.
      Patient and provider attitudes regarding sexual health in young women with cystic fibrosis.
      ,
      • Britto M.T.
      • Garrett J.M.
      • Dugliss M.A.
      • et al.
      Preventive services received by adolescents with cystic fibrosis and sickle cell disease.
      ] and, thus, may use the CF care setting for SRH care and counseling. CF providers should be comfortable discussing SRH concerns and providing appropriate referrals/resources. Unfortunately, providers do not routinely address SRH in the CF setting. A recent national survey of primary CF care providers found that routine discussion of SRH topics in clinical practice was low, although most believed that these topics were important [
      • Kazmerski T.M.
      • Borrero S.
      • Sawicki G.S.
      • Abebe K.Z.
      • Jones K.A.
      • Tuchman L.K.
      • et al.
      Provider attitudes and practices toward sexual and reproductive health care for young women with cystic fibrosis.
      ].
      Standardization of SRH care in the CF care model may help to advance this aspect of comprehensive care. Frayman and Sawyer have described a framework in which the CF provider also assumes the primary role in SRH discussions [
      • Frayman K.B.
      • Sawyer S.M.
      Sexual and reproductive health in cystic fibrosis: a life-course perspective.
      ]. This approach emphasizes communication and coordination of care among the CF team, PCPs, and women's health services. Prior research supports this model as it has elucidated a patient desire for individualized SRH discussions with CF providers [
      • Kazmerski T.M.
      • Borrero S.
      • Tuchman L.
      • Weiner D.J.
      • Pilewski J.
      • Orenstein D.M.
      • et al.
      Patient and provider attitudes regarding sexual health in young women with cystic fibrosis.
      ,
      • Kazmerski T.M.
      • Gmelin T.
      • Slocum B.
      • Borrero S.
      • Miller E.
      Attitudes and decision making related to pregnancy in young women with cystic fibrosis.
      ]. Investigating SRH care utilization patterns and preferences of this population is a crucial next step. By understanding the patient experience, the CF community can work to develop ways to facilitate SRH care provision. Future interventions should include patient educational resources, training for the multidisciplinary CF team, and the development of tools that facilitate patient-provider SRH communication.
      This study has several limitations. This survey utilized a convenience sample that provided self-reported assessments and is not necessarily generalizable to all women with CF. SRH behaviors and practices are influenced by cultural, educational, and societal differences; thus, a similar study may yield different results in other countries or in a larger U.S. sample. Obtaining objective clinical data on an international group of patients with CF affected by certain disease-specific SRH complications may help further define the effect of SRH on the gender gap and allow for targeted screening and management strategies. Moreover, we did not assess some relevant factors (i.e., insurance status, religious/personal preferences, genotype, and use of targeted CFTR therapies) that could potentially influence SRH care decisions and outcomes. We did not formally adjust for multiplicity in this work; thus, some statistically significant findings may be spurious. A Bonferroni correction for 31 tests yields a significance cut-off of p ≤ 0.002, which does not affect the significance of the majority of this study's findings. Finally, the ability to detect statistically significant associations between CF health status and SRH outcomes may have been limited by the relatively small sample sizes of women with severe CF disease. As disease severity and complications may greatly affect SRH decisions, a future, larger study of these issues is warranted.
      In conclusion, this study found that young female patients with CF are sexually active and face a variety of both general and disease-specific SRH concerns in the modern treatment era regardless of disease severity. Thus, health providers should routinely address SRH as part of comprehensive CF care. Opportunities exist for the development of interventions that will improve this important aspect of health. Understanding the unique interplay between the female sex and CF is vital, as the reasons for the gender gap in CF-related morbidity and mortality remain unclear. Whether the SRH concerns identified in this study contribute to worsening overall health outcomes in the female CF population should be explored. Future research should focus on understanding and modifying the complex interplay between being female and having CF.
      The following are the supplementary data related to this article.

      Authors' contributions

      Dr. Kazmerski conceptualized and designed the survey, performed data analysis, drafted the initial manuscript, revised the manuscript and approved the final manuscript as submitted. Drs. Sawicki, Miller, Weiner, and Tuchman aided in the design of survey, critically revised the manuscript, and approved the final manuscript as submitted. Drs. Pilewski and Orenstein reviewed and revised the survey, critically revised the manuscript, and approved the final manuscript as submitted. Drs. Ladores, Rubenstein, and Sagel served as site co-investigators, revised the manuscript, and approved the final manuscript as submitted. Drs. Abebe and Jones aided in the data analysis plan, performed data analysis, revised the manuscript, and approved the final manuscript as submitted. Dr. Borrero provided mentorship to Dr. Kazmerski throughout the project, aided in the design of the project and survey, critically revised the manuscript, and approved the final manuscript as submitted.

      Conflicts of interest

      No significant conflicts of interest exist for the authors of this work.

      Acknowledgements

      The authors would like to acknowledge the diligent research coordinators and assistants that ensured the recruitment and enrollment of this study: Elizabeth Hartigan, KC Little, Sandra Hurban, Kathy Iurlano, Jonathan Greenberg, Kelsey Hill, Erin Donnelly, Alden Dewey, Meg Anthony, and Leigh Anne Bray.

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