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Reproductive health in young women with cystic fibrosis: Knowledge, behavior and attitudes
/ o u RNAL OF ADOLESCENT HEALTH 1995;17:46-50
INTERNATIONAL
ARTICLE
Reproductive Health in Young Women with Cystic Fibrosis: Knowledge, Behavior and Attitudes S.M. S A W Y E R , M.B.B.S., M . D . , P.D. P H E L A N ,
B . S c . , M . D . A N D G. B O W E S , M.B.B.S., P h . D .
P u r p o s e : The improved life-expectancy in cystic fibrosis (CF) results in the fact that the majority of affected young women now survive to face the same reproductive health decisions as other women, in addition to those that specifically relate to CF. The aim of this study was to assess the reproductive health knowledge of women with CF, to investigate the range of their reproductive health problems, and to review their reproductive health attitudes and behaviors. M e t h o d s : Women aged 18 years and over attending CF services in the state of Victoria, Australia were invited to complete a reproductive health questionnaire. Comparison subjects (n = 76) were enrolled from 2 primary care practices. R e s u l t s : Fifty-five women participated (89%), with a median age of 22 years (range 18-50). There was no significant difference in marital status between the two groups and a similar proportion were sexually active, yet wmnen with CF were less likely to use contraception. A majority of women with CF believed that fertility was reduced, and there was poor knowledge of the potentially deleterious effect of pregnancy. A relatively high proportion were planning to become pregnant in the near future. Twenty-two percent had tried to conceive, with a success rate of 67%. C o n c l u s i o n s : Women with CF are currently lacking important information about reproductive health that potentially has a major impact on their health and their lives.
l'rout the Dcparttm'l#s ¢!f rlTloI'acic Medicine aml Pm'dizdrics, Ccpttrc h'" Adoh'stcHt Ih'alth, Royal Chihtrc~Fs ffosFihd, I)mkvillc, Victoria, real LhHvcrsity ~!fiMclbourm', l~arkPilh ', Vi~ toria, Aush'alia. Add~vs; corFesFomtcmc t(,: Dr. 5.M. Sawyer, DcFartmcnt ~!fiEIIviromi1c~thll fh'alth ? 1302, t tarvard Scll~,ol o.t I~tthlic th,ollh, 665 Huuti,~to,1 Avcmlc, Bostou, M A 02115 Mtmus('ript acccFtcd ]ldy 15, 1994 1 0 5 4 - 1 3 9 X J95/$9.50 SSDI 1054-139X(94J00096-W
KEY W O R D S :
Cystic fibrosis Female reproductive health Pregnancy Fertility
The d r a m a t i c i m p r o v e m e n t in life-expectancy in CF o v e r the past few d e c a d e s (1) n o w results in suvival to a d u l t life for the majority of w o m e n with CF. These w o m e n n o w face the s a m e sexual a n d reprod u c t i v e o p t i o n s as other w o m e n and will n e e d to m a k e decisions a b o u t the onset of sexual intercourse, the control of fertility t h r o u g h c o n t r a c e p t i o n , and the choice a n d t i m i n g of h a v i n g children. There are, h o w e v e r , a d d i t i o n a l r e p r o d u c t i v e health p r o b l e m s that are r e p o r t e d to be faced b y w o m e n with CF: m e n a r c h a l d e l a y (2,3), increased risk for v u l v o v a g i n a l candidiasis, c o n c e r n s a b o u t the safety of the oral c o n t r a c e p t i v e pill in CF (4,5), a n d the relationship b e t w e e n p r e g n a n c y in w o m e n with CF and r e s p i r a t o r y f u n c t i o n (6-8). It has also been r e p o r t e d that w o m e n w i t h CF h a v e r e d u c e d fertility (9), a l t h o u g h the increasing n u m b e r of p r e g nancies r e p o r t e d (6-8) calls this early f i n d i n g into question. Despite this b r o a d a r r a y of r e c o g n i z e d c o n c e r n s and potential problems, this area of health in w o m e n with CF has received minimal investigation. The aim of this s t u d y was to assess the r e p r o d u c t i v e health k n o w l e d g e of w o m e n with CF, to investigate the range of r e p r o d u c t i v e health problems that they face, and to review their r e p r o d u c t i v e health behaviors. Methods
All w o m e n with CF in Victoria a g e d 18 y e a r s a n d o v e r a t t e n d i n g the CF services at either the R o y a l
© Society for Adolescent Medicine, V-~95 I'ublished bv Elsevier Science Inc., 655 Avenue of tile Americas, Newr York, NY 10010
July 1995
Children's Hospital or the Alfred Hospital were invited to participate in the study. These two clinics, one pediatric and adolescent, the other adult, coordinate the management of over 95% of all people with CF in the state of Victoria, which has a population of approximately 4 million. The study was approved by both the Royal Children's Hospital Research in Human Ethics Committee and the Ethics Review Committee at Alfred Hospital. The study consisted of a self-administered questionnaire covering a wide range of reproductive health topics. The background to the study was explained individually by one of the investigators (SMS), a copy of the questionnaire was given, and participants were asked to complete it at home and return it by prepaid mail.
Development of the Reproductive Health Questionnaire The reproductive health questionnaire was developed and pilot-tested to cover a wide range of reproductive health concerns. The reproductive health questionnaire was developed from the known and anticipated reproductive health problems faced by women with CF. Construct validity of the questions was tested by two gynecologists experienced with the reproductive health of women with CF and a social biologist with particular experience of sexuality and chronic illness. A group of 5 young women with CF was convened to test face validity. The questionnaire consisted of 52 questions and took approximately 20 minutes to complete. The internal validity of the questionnaire was examined by checking the logical consistency of individual questions, which was present in all cases when cross-tabulation of specific responses was performed. For other questions the same information was sought using different wording and the responses were the same in all of cases. Medical details (pattern of antibiotic use, diabetes mellitus) were obtained from each patient's medical record including recent pulmonary function tests, which were expressed as percent predicted (10). In the absence of population surveys and a validated reproductive health questionnaire, it was necessary to generate comparison subjects to provide baseline data for key items. This group of women aged 18 years and over was enrolled from 2 general practices in Victoria, one urban and one rural. A modified questionnaire was administered to consecutive, eligible subjects that omitted CF-related ques-
REPRODUCTIVE HEALTH AND CYSTIC FIBROSIS
47
tions but sought details of all medical conditions and regular medications. Much of the data are descriptive, but the twosample Student's t-test was used to compare the two groups when appropriate. P values < .05 were considered significant.
Results Fifty-five of sixty-two eligible women with CF completed the reproductive health questionnaire, a response rate of 89%. Four women were unable to be contacted during the study period, 2 were not approached because of terminal disease and major psychiatric illness, and one chose not to participate. There were 76 comparison subjects. The mean age of women with CF was 23.7 years (median 22; range 18-50 years), while the mean age of the comparison group was 23.9 years (median 23; range 18-52 years). The mean age (SD) of menarche was 14.9 (2.1) years, which was 2.0 years delayed in comparison to the comparison group menarche of 12.9 (1.4) years (p < 0.001). Ten women with CF (18%) had diabetes mellitus, 39 (71%) took daily oral antibiotics and 19 (35%) regularly used the contraceptive pill. Respondents with CF were asked to self-rate the severity of their disease on a linear scale ranging from mild to moderate to severe without further instruction. Thirty (55%) self-rated as mild CF, 20 (36%) as moderate CF, and 5 (9%) as severe. The self-ratings correlated well with pulmonary function test results, such that the mean forced vital capacity (percent predicted) of the self-rated "mild" group was 91%, "moderate" was 73% and "severe" was 51%. There was no difference in prevalence of sexual intercourse in the previous 12 months, age at onset of sexual intercourse, or marital status between the two groups. Twenty-nine percent of women with CF were married (24% comparison group), 7% were living in a "de facto" relationship (9% comparison group), 35% were single but had a relationship involving regular sexual intercourse (32% comparison group), and 29% were single without such a relationship (34% comparison group). Sexually active women with CF were less likely to use contraception than the comparison group (p < .05), and although the contraceptive pill was the most commonly used method in both groups, women with CF were less likely to use it (p < .005). A very high rate of vulvovaginal candidiasis was reported, with 24% reporting that they suffered
48
SAWYER ET AL
from vulvovaginal candidiasis either once a m o n t h or almost all the time (11). Fifty-seven percent of w o m e n with CF w h o reported episodes of vulvovaginal candidiasis recognized an association between oral antibiotics and vulvovaginal candidiasis (p < .05). There was no significant association with diabetes (p = 0.18). W o m e n with CF had a reasonable u n d e r s t a n d i n g of male infertility in CF, with 87% correctly stating that males had either reduced fertility, or were nearly always infertile. Only 13% r e s p o n d e d that they "didn't k n o w " h o w CF affected male fertility. This contrasts with k n o w l e d g e of their o w n fertility. Nine percent thought that w o m e n with CF had normal fertility, 65% thought that they had reduced fertility, 4% thought they were nearly always infertile, and 22% did not know. There was a poor level of knowledge of the risk of having a child with CF, yet 16% of respondants specifically stated that they would not want a child if it had CF. In particular, when asked about the risk of a w o m a n with CF having a child who was also affected (assuming no history of CF in the partner's family), only 15% correctly reported the risk as approximately 1 in 50. Thirty-one percent overestimated the risk; 13% thought the risk to be 1 in 4 and 18% considered it to be ] in 25. Sixteen percent considered the risk to be 1 in 2500, and 38% didn't know how the risk may be altered from the risk for unaffected women. When asked about the importance or relevance of their partner's carrier status, 15% did not consider that carrier status was important, 20% considered it important, and 65% considered it very important to them in making decisions about having children. A large proportion of w o m e n did not k n o w about the possible deleterious effects of p r e g n a n c y on respiratory health in w o m e n with CF. Two percent thought that pregnancy m a y improve lung disease, 2% thought pregnancy had no effect, 49% considered that pregnancy w o u l d make lung disease worse, 13% thought it w o u l d be m u c h worse, and 34% did not know. Fifty-one percent of w o m e n with CF reported that they wanted to have children in the near future, and 4 w o m e n were currently trying to conceive. Specific concerns raised about p r e g n a n c y included the fact that their health m a y be deleteriously affected during pregnancy and also focused on the impact on their o w n health of the time c o m m i t m e n t and energy required to care for a y o u n g child. H o w e v e r , these statements were m a d e by a minority of women. Nine w o m e n openly stated that they did not want to have a child with CF.
JOURNAL OF ADOLESCENT HEALTH Vol. 17, No. 1
There was no difference in the n u m b e r of w o m e n w h o had tried to conceive and the frequency of conception in either g r o u p of w o m e n . T w e n t y - t w o percent of w o m e n with CF had at some time tried to conceive, with a conception rate of 67%. An additional 4 w o m e n conceived without planning to (unplanned pregnancy), which was similar to the healthy group. There was no difference in the rates of spontaneous abortion and termination of pregnancy in the two groups.
Discussion This s t u d y suggests that w o m e n with CF have insufficient information to make informed decisions about some aspects of their reproductive and sexual life. Specifically, they lack important information (such as the potential for p r e g n a n c y to be associated with a significant deterioration of health) and seem u n d u l y concerned about other aspects (such as the risk of having a child with CF, which was overstated by 1 in 3 women). This is a concern w h e n the results of this study suggest that apart from menarchal delay, the onset and rate of sexual intercourse in y o u n g w o m e n with CF is no different from that of other y o u n g women, and that m a n y w o m e n with CF are planning to have children in the near future. It is reported that in general, w o m e n with CF have a lower pregnancy rate than the expected 85% per year for normal, child-bearing w o m e n using no contraception (12) and estimates of fertility in CF range from 0-20% (10,13). Kopito et al. studied the cervical mucus of w o m e n with CF and s h o w e d that it is more d e h y d r a t e d than in healthy w o m e n and lacks the normal mid-cycle increase in hydration, a possible cause of reduced fertility (10). H o w e v e r , these authors failed to demonstrate that ovulation had occurred in these w o m e n at the time that cervical specimens were studied. The usual mid-cycle increase in hydration coincides with ovulation and the lack of studies demonstrating cervical m u c u s abnormalities at ovulation means that the situation in w o m e n with CF linking abnormal cervical mucus with reduced fertility is still unknown. The small numbers in this study (n = 3) is a further reason not to overinterpret these results. There are additional explanations for reduced fertility in w o m e n with CF, which include amenorrhea as a complication of weight loss and reduced b o d y weight (14), as well as the chronic stress of illness (15). An alternative explanation is that these w o m e n use appropriate contraception, but this is not s u p p o r t e d b y this study. Despite the theoretical
July 1995
reasons for reduced fertility in these w o m e n , this s t u d y does not suggest that reduced fertility is as extensive a problem as suggested in the literature. It is of concern that w o m e n with CF are less likely to use contraception. The 33% of pregnancies that were u n p l a n n e d underscores this concern, given the possibility of deterioration of health with p r e g n a n c y (6-8). The w i d e s p r e a d lack of k n o w l e d g e about h o w respiratory disease m a y deteriorate during p r e g n a n c y is worrisome, as is the lack of ack n o w l e d g m e n t of the additional time and energy required in looking after a y o u n g child by more than a minority of respondents. This is especially concerning given the n u m b e r of w o m e n with CF w h o stated they are planning to have children. Alt h o u g h p r e g n a n c y is generally considered safe for w o m e n with mild to moderate respiratory disease, it is preferable that it be planned at a time w h e n health is g o o d (7,8). There have been concerns raised about the safety of oral contraceptives in w o m e n with CF because of the possibility that progesterone increases viscosity of bronchial secretions, just as it thickens cervical m u c u s in the post-luteal phase (4). FitzPatrick (16) studied the short term effect of the contraceptive pill in 10 w o m e n with CF and failed to s h o w any deterioration in respiratory function after 6 m o n t h s of use. To our k n o w l e d g e there have been no published follow-up studies. The differential rate of decline in respiratory function between males and females, with more females than males d y i n g from CF at all ages after adolescence (17), suggests that there m a y be an interaction of sex h o r m o n e s with respiratory function, either positively (testosterone) or negatively (estrogen), and it is critical that this area be investigated further. Other concerns regarding the contraceptive pill in w o m e n with CF relate to unfavourable d r u g interactions with concurrent antibiotic use. Hepatic enz y m e induction from antibiotics can cause substantial reductions in circulating contraceptive steroid levels (18), and b r o a d spectrum antibiotics m a y reduce the a m o u n t of bacterial hydrolysis, which prevents the enterohepatic circulation of ethinylestradiol (19). Both mechanisms m a y result in a reduction in efficacy of oral contraceptives and the risk of pill failure (20,21). A l t h o u g h a s t u d y by Stead et al. (22) suggested that there was no difference in the pharmacokinetics of contraceptive steroids in w o m e n with CF and healthy controls, none had received antibiotics in the 10 days prior to the study. This s t u d y questions the notion that w o m e n with CF have significantly reduced fertility. Using con-
REPRODUCTIVEHEALTHAND CYSTICFIBROSIS
49
traception to prevent u n w a n t e d p r e g n a n c y should be as high a priority for these w o m e n as for other y o u n g women. A l t h o u g h it is not clear w h e t h e r oral contraceptives are entirely safe or effective in w o m e n with CF, there is currently no firm evidence of contraindications (5). Health professionals need to assist y o u n g w o m e n with CF to avoid u n p l a n n e d pregnancies b y providing appropriate contraceptive advice. The challenge for health care professionals is to generate appropriate reproductive health research, p r o v i d e superior communication, and ensure the provision of truly comprehensive health care for w o m e n with CF if the deficiencies exposed by this s t u d y are to be rectified. A c o p y of the reproductive health questionnaire is available on request from the authors. Dr. Sawyer was supported by an Australian NH&MRC postgraduate scholarship. The authors with to acknowledgement the assistance of Dr. Trevor Williams and Ms. Libby Francis, Alfred Hospital, for facilitating patient access, and Dr. Janet Duke and Dr. Chris Bayley for helpful discussions.
References 1. Elborn JS, Shale DJ, Britton JR. Cystic fibrosis: current survival and population estimates to the year 2000. Thorax 1991;46:881-5.
2. Mitchell-Heggs P, Mearns M, Batten JC. Cystic tibrosis in adolescents and adults. Quart J Med 1976;179:479-504. 3. Neinstein LS, Stewart D, Wang CI, et al. Menstrual dysfunction in cystic fibrosis. J Adolesc Health Care 1983;4;153-7. 4. Dooley RR, Braunstein H, Osher AB. Polypoid cervicitis in cystic fibrosis patients receiving oral contraceptives. Am J Obstet Gynecol 1974;118:971-4. 5. Neinstein LS, Katz B. Contraceptive use in the chronically ill adolescent female: Part 1. J Adolesc Health Care 1986;7:123-33. 6. Cohen LF, di Sant'Agnese PA, Friedlander J. Cystic fibrosis and pregnancy. A national survey. Lancet 1980;2:842-4. 7. CorkeyCWB, Newth CJL, Corey M, et al. Pregnancy in cystic fibrosis: A better prognosis in patients with pancreatic function? Am J Obstet Gynecol 1981;140:737-42. 8. Palmer J, Dillon-Baker C, Tecklin JS, et al. Pregnancy in patients with cystic fibrosis. Ann lnt Med 1983;99:596-600. 9. Kopito LE, Kosasky HJ, Shwachman H. Water and electrolytes in cervical mucus from patients with cystic fibrosis. Fertil Steril 1973;24:512-6. 10. Zapletal A, Samanek TP. Lung Function in children and adolescents: methods and reference values. Karger, BaselMunchen, 1987. 11. Sawyer SM, Bowes G, Phelan PD. Vulvovaginal candidiasis in young women with cystic fibrosis: a previously unrecognised problem. BMJ 1994;308:1609. 12. Brugman SM, Taussig LM. The reproductive system. In Taussig LM, ed: Cystic Fibrosis. New York, Thieme-Stratton, 1984.
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13, Shwachman H, Kulczycki LL, Khaw KT. Studies in cystic fibrosis: report on 65 patients over 17 years of age. Pediatrics 1965;36:689-99. 14, Frisch RE. Food intake, fatness, a~d reproductive ability. In Vigersky RA, ed: Anorexia Nervosa. New York, Raven Press, 1977:14~. 15, Morgan A, London S. Effects of excessive exercise and weight loss on adolescent menstrual cyclicity. Adolesc Pediatr Gynecol 19911;6:63-70. 16. FitzPatrick SB, Stokes DC, Rosenstein BJ, et al. Use of contraceptives in women with cystic fibrosis. Chest 1984;86:863-7. 17. Gurwit,, D, Corer M, Francis PWJ, et al. Perspectives in cystic fibrosis. Pediatr Clin North Am 1979;26:603-15.
JOURNAL OF ADOLESCENT HEALTH Vol. 17, No. 1
18. Back DJ, Breckenbridge AM, Gay FE, et al. The pharmacokinetics of norethisterone during single and multiple dosing in women and changes caused by rifampicin. Acta Endo Supp 1977;212:149P. 19. Orme ML, Back DJ. Therapy with oral contraceptive steroids and antibiotics. J Antimicrob Chemother 1979;5:124-6. 20. Dossetor J. Drug interactions with oral contraceptives. Br Med J 1975;4:467-8. 21. Hughes BR, Cunliffe WJ. Interactions between the oral contraceptive pill and antibiotics. Br J Dermatol 1990;122:717-8. 22. Stead RJ, Grimmer SFM, Rogers SM, et al. Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis. Thorax 1987;42:59-64.
INTERNATIONAL
ARTICLE
Reproductive Health in Young Women with Cystic Fibrosis: Knowledge, Behavior and Attitudes S.M. S A W Y E R , M.B.B.S., M . D . , P.D. P H E L A N ,
B . S c . , M . D . A N D G. B O W E S , M.B.B.S., P h . D .
P u r p o s e : The improved life-expectancy in cystic fibrosis (CF) results in the fact that the majority of affected young women now survive to face the same reproductive health decisions as other women, in addition to those that specifically relate to CF. The aim of this study was to assess the reproductive health knowledge of women with CF, to investigate the range of their reproductive health problems, and to review their reproductive health attitudes and behaviors. M e t h o d s : Women aged 18 years and over attending CF services in the state of Victoria, Australia were invited to complete a reproductive health questionnaire. Comparison subjects (n = 76) were enrolled from 2 primary care practices. R e s u l t s : Fifty-five women participated (89%), with a median age of 22 years (range 18-50). There was no significant difference in marital status between the two groups and a similar proportion were sexually active, yet wmnen with CF were less likely to use contraception. A majority of women with CF believed that fertility was reduced, and there was poor knowledge of the potentially deleterious effect of pregnancy. A relatively high proportion were planning to become pregnant in the near future. Twenty-two percent had tried to conceive, with a success rate of 67%. C o n c l u s i o n s : Women with CF are currently lacking important information about reproductive health that potentially has a major impact on their health and their lives.
l'rout the Dcparttm'l#s ¢!f rlTloI'acic Medicine aml Pm'dizdrics, Ccpttrc h'" Adoh'stcHt Ih'alth, Royal Chihtrc~Fs ffosFihd, I)mkvillc, Victoria, real LhHvcrsity ~!fiMclbourm', l~arkPilh ', Vi~ toria, Aush'alia. Add~vs; corFesFomtcmc t(,: Dr. 5.M. Sawyer, DcFartmcnt ~!fiEIIviromi1c~thll fh'alth ? 1302, t tarvard Scll~,ol o.t I~tthlic th,ollh, 665 Huuti,~to,1 Avcmlc, Bostou, M A 02115 Mtmus('ript acccFtcd ]ldy 15, 1994 1 0 5 4 - 1 3 9 X J95/$9.50 SSDI 1054-139X(94J00096-W
KEY W O R D S :
Cystic fibrosis Female reproductive health Pregnancy Fertility
The d r a m a t i c i m p r o v e m e n t in life-expectancy in CF o v e r the past few d e c a d e s (1) n o w results in suvival to a d u l t life for the majority of w o m e n with CF. These w o m e n n o w face the s a m e sexual a n d reprod u c t i v e o p t i o n s as other w o m e n and will n e e d to m a k e decisions a b o u t the onset of sexual intercourse, the control of fertility t h r o u g h c o n t r a c e p t i o n , and the choice a n d t i m i n g of h a v i n g children. There are, h o w e v e r , a d d i t i o n a l r e p r o d u c t i v e health p r o b l e m s that are r e p o r t e d to be faced b y w o m e n with CF: m e n a r c h a l d e l a y (2,3), increased risk for v u l v o v a g i n a l candidiasis, c o n c e r n s a b o u t the safety of the oral c o n t r a c e p t i v e pill in CF (4,5), a n d the relationship b e t w e e n p r e g n a n c y in w o m e n with CF and r e s p i r a t o r y f u n c t i o n (6-8). It has also been r e p o r t e d that w o m e n w i t h CF h a v e r e d u c e d fertility (9), a l t h o u g h the increasing n u m b e r of p r e g nancies r e p o r t e d (6-8) calls this early f i n d i n g into question. Despite this b r o a d a r r a y of r e c o g n i z e d c o n c e r n s and potential problems, this area of health in w o m e n with CF has received minimal investigation. The aim of this s t u d y was to assess the r e p r o d u c t i v e health k n o w l e d g e of w o m e n with CF, to investigate the range of r e p r o d u c t i v e health problems that they face, and to review their r e p r o d u c t i v e health behaviors. Methods
All w o m e n with CF in Victoria a g e d 18 y e a r s a n d o v e r a t t e n d i n g the CF services at either the R o y a l
© Society for Adolescent Medicine, V-~95 I'ublished bv Elsevier Science Inc., 655 Avenue of tile Americas, Newr York, NY 10010
July 1995
Children's Hospital or the Alfred Hospital were invited to participate in the study. These two clinics, one pediatric and adolescent, the other adult, coordinate the management of over 95% of all people with CF in the state of Victoria, which has a population of approximately 4 million. The study was approved by both the Royal Children's Hospital Research in Human Ethics Committee and the Ethics Review Committee at Alfred Hospital. The study consisted of a self-administered questionnaire covering a wide range of reproductive health topics. The background to the study was explained individually by one of the investigators (SMS), a copy of the questionnaire was given, and participants were asked to complete it at home and return it by prepaid mail.
Development of the Reproductive Health Questionnaire The reproductive health questionnaire was developed and pilot-tested to cover a wide range of reproductive health concerns. The reproductive health questionnaire was developed from the known and anticipated reproductive health problems faced by women with CF. Construct validity of the questions was tested by two gynecologists experienced with the reproductive health of women with CF and a social biologist with particular experience of sexuality and chronic illness. A group of 5 young women with CF was convened to test face validity. The questionnaire consisted of 52 questions and took approximately 20 minutes to complete. The internal validity of the questionnaire was examined by checking the logical consistency of individual questions, which was present in all cases when cross-tabulation of specific responses was performed. For other questions the same information was sought using different wording and the responses were the same in all of cases. Medical details (pattern of antibiotic use, diabetes mellitus) were obtained from each patient's medical record including recent pulmonary function tests, which were expressed as percent predicted (10). In the absence of population surveys and a validated reproductive health questionnaire, it was necessary to generate comparison subjects to provide baseline data for key items. This group of women aged 18 years and over was enrolled from 2 general practices in Victoria, one urban and one rural. A modified questionnaire was administered to consecutive, eligible subjects that omitted CF-related ques-
REPRODUCTIVE HEALTH AND CYSTIC FIBROSIS
47
tions but sought details of all medical conditions and regular medications. Much of the data are descriptive, but the twosample Student's t-test was used to compare the two groups when appropriate. P values < .05 were considered significant.
Results Fifty-five of sixty-two eligible women with CF completed the reproductive health questionnaire, a response rate of 89%. Four women were unable to be contacted during the study period, 2 were not approached because of terminal disease and major psychiatric illness, and one chose not to participate. There were 76 comparison subjects. The mean age of women with CF was 23.7 years (median 22; range 18-50 years), while the mean age of the comparison group was 23.9 years (median 23; range 18-52 years). The mean age (SD) of menarche was 14.9 (2.1) years, which was 2.0 years delayed in comparison to the comparison group menarche of 12.9 (1.4) years (p < 0.001). Ten women with CF (18%) had diabetes mellitus, 39 (71%) took daily oral antibiotics and 19 (35%) regularly used the contraceptive pill. Respondents with CF were asked to self-rate the severity of their disease on a linear scale ranging from mild to moderate to severe without further instruction. Thirty (55%) self-rated as mild CF, 20 (36%) as moderate CF, and 5 (9%) as severe. The self-ratings correlated well with pulmonary function test results, such that the mean forced vital capacity (percent predicted) of the self-rated "mild" group was 91%, "moderate" was 73% and "severe" was 51%. There was no difference in prevalence of sexual intercourse in the previous 12 months, age at onset of sexual intercourse, or marital status between the two groups. Twenty-nine percent of women with CF were married (24% comparison group), 7% were living in a "de facto" relationship (9% comparison group), 35% were single but had a relationship involving regular sexual intercourse (32% comparison group), and 29% were single without such a relationship (34% comparison group). Sexually active women with CF were less likely to use contraception than the comparison group (p < .05), and although the contraceptive pill was the most commonly used method in both groups, women with CF were less likely to use it (p < .005). A very high rate of vulvovaginal candidiasis was reported, with 24% reporting that they suffered
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from vulvovaginal candidiasis either once a m o n t h or almost all the time (11). Fifty-seven percent of w o m e n with CF w h o reported episodes of vulvovaginal candidiasis recognized an association between oral antibiotics and vulvovaginal candidiasis (p < .05). There was no significant association with diabetes (p = 0.18). W o m e n with CF had a reasonable u n d e r s t a n d i n g of male infertility in CF, with 87% correctly stating that males had either reduced fertility, or were nearly always infertile. Only 13% r e s p o n d e d that they "didn't k n o w " h o w CF affected male fertility. This contrasts with k n o w l e d g e of their o w n fertility. Nine percent thought that w o m e n with CF had normal fertility, 65% thought that they had reduced fertility, 4% thought they were nearly always infertile, and 22% did not know. There was a poor level of knowledge of the risk of having a child with CF, yet 16% of respondants specifically stated that they would not want a child if it had CF. In particular, when asked about the risk of a w o m a n with CF having a child who was also affected (assuming no history of CF in the partner's family), only 15% correctly reported the risk as approximately 1 in 50. Thirty-one percent overestimated the risk; 13% thought the risk to be 1 in 4 and 18% considered it to be ] in 25. Sixteen percent considered the risk to be 1 in 2500, and 38% didn't know how the risk may be altered from the risk for unaffected women. When asked about the importance or relevance of their partner's carrier status, 15% did not consider that carrier status was important, 20% considered it important, and 65% considered it very important to them in making decisions about having children. A large proportion of w o m e n did not k n o w about the possible deleterious effects of p r e g n a n c y on respiratory health in w o m e n with CF. Two percent thought that pregnancy m a y improve lung disease, 2% thought pregnancy had no effect, 49% considered that pregnancy w o u l d make lung disease worse, 13% thought it w o u l d be m u c h worse, and 34% did not know. Fifty-one percent of w o m e n with CF reported that they wanted to have children in the near future, and 4 w o m e n were currently trying to conceive. Specific concerns raised about p r e g n a n c y included the fact that their health m a y be deleteriously affected during pregnancy and also focused on the impact on their o w n health of the time c o m m i t m e n t and energy required to care for a y o u n g child. H o w e v e r , these statements were m a d e by a minority of women. Nine w o m e n openly stated that they did not want to have a child with CF.
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There was no difference in the n u m b e r of w o m e n w h o had tried to conceive and the frequency of conception in either g r o u p of w o m e n . T w e n t y - t w o percent of w o m e n with CF had at some time tried to conceive, with a conception rate of 67%. An additional 4 w o m e n conceived without planning to (unplanned pregnancy), which was similar to the healthy group. There was no difference in the rates of spontaneous abortion and termination of pregnancy in the two groups.
Discussion This s t u d y suggests that w o m e n with CF have insufficient information to make informed decisions about some aspects of their reproductive and sexual life. Specifically, they lack important information (such as the potential for p r e g n a n c y to be associated with a significant deterioration of health) and seem u n d u l y concerned about other aspects (such as the risk of having a child with CF, which was overstated by 1 in 3 women). This is a concern w h e n the results of this study suggest that apart from menarchal delay, the onset and rate of sexual intercourse in y o u n g w o m e n with CF is no different from that of other y o u n g women, and that m a n y w o m e n with CF are planning to have children in the near future. It is reported that in general, w o m e n with CF have a lower pregnancy rate than the expected 85% per year for normal, child-bearing w o m e n using no contraception (12) and estimates of fertility in CF range from 0-20% (10,13). Kopito et al. studied the cervical mucus of w o m e n with CF and s h o w e d that it is more d e h y d r a t e d than in healthy w o m e n and lacks the normal mid-cycle increase in hydration, a possible cause of reduced fertility (10). H o w e v e r , these authors failed to demonstrate that ovulation had occurred in these w o m e n at the time that cervical specimens were studied. The usual mid-cycle increase in hydration coincides with ovulation and the lack of studies demonstrating cervical m u c u s abnormalities at ovulation means that the situation in w o m e n with CF linking abnormal cervical mucus with reduced fertility is still unknown. The small numbers in this study (n = 3) is a further reason not to overinterpret these results. There are additional explanations for reduced fertility in w o m e n with CF, which include amenorrhea as a complication of weight loss and reduced b o d y weight (14), as well as the chronic stress of illness (15). An alternative explanation is that these w o m e n use appropriate contraception, but this is not s u p p o r t e d b y this study. Despite the theoretical
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reasons for reduced fertility in these w o m e n , this s t u d y does not suggest that reduced fertility is as extensive a problem as suggested in the literature. It is of concern that w o m e n with CF are less likely to use contraception. The 33% of pregnancies that were u n p l a n n e d underscores this concern, given the possibility of deterioration of health with p r e g n a n c y (6-8). The w i d e s p r e a d lack of k n o w l e d g e about h o w respiratory disease m a y deteriorate during p r e g n a n c y is worrisome, as is the lack of ack n o w l e d g m e n t of the additional time and energy required in looking after a y o u n g child by more than a minority of respondents. This is especially concerning given the n u m b e r of w o m e n with CF w h o stated they are planning to have children. Alt h o u g h p r e g n a n c y is generally considered safe for w o m e n with mild to moderate respiratory disease, it is preferable that it be planned at a time w h e n health is g o o d (7,8). There have been concerns raised about the safety of oral contraceptives in w o m e n with CF because of the possibility that progesterone increases viscosity of bronchial secretions, just as it thickens cervical m u c u s in the post-luteal phase (4). FitzPatrick (16) studied the short term effect of the contraceptive pill in 10 w o m e n with CF and failed to s h o w any deterioration in respiratory function after 6 m o n t h s of use. To our k n o w l e d g e there have been no published follow-up studies. The differential rate of decline in respiratory function between males and females, with more females than males d y i n g from CF at all ages after adolescence (17), suggests that there m a y be an interaction of sex h o r m o n e s with respiratory function, either positively (testosterone) or negatively (estrogen), and it is critical that this area be investigated further. Other concerns regarding the contraceptive pill in w o m e n with CF relate to unfavourable d r u g interactions with concurrent antibiotic use. Hepatic enz y m e induction from antibiotics can cause substantial reductions in circulating contraceptive steroid levels (18), and b r o a d spectrum antibiotics m a y reduce the a m o u n t of bacterial hydrolysis, which prevents the enterohepatic circulation of ethinylestradiol (19). Both mechanisms m a y result in a reduction in efficacy of oral contraceptives and the risk of pill failure (20,21). A l t h o u g h a s t u d y by Stead et al. (22) suggested that there was no difference in the pharmacokinetics of contraceptive steroids in w o m e n with CF and healthy controls, none had received antibiotics in the 10 days prior to the study. This s t u d y questions the notion that w o m e n with CF have significantly reduced fertility. Using con-
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traception to prevent u n w a n t e d p r e g n a n c y should be as high a priority for these w o m e n as for other y o u n g women. A l t h o u g h it is not clear w h e t h e r oral contraceptives are entirely safe or effective in w o m e n with CF, there is currently no firm evidence of contraindications (5). Health professionals need to assist y o u n g w o m e n with CF to avoid u n p l a n n e d pregnancies b y providing appropriate contraceptive advice. The challenge for health care professionals is to generate appropriate reproductive health research, p r o v i d e superior communication, and ensure the provision of truly comprehensive health care for w o m e n with CF if the deficiencies exposed by this s t u d y are to be rectified. A c o p y of the reproductive health questionnaire is available on request from the authors. Dr. Sawyer was supported by an Australian NH&MRC postgraduate scholarship. The authors with to acknowledgement the assistance of Dr. Trevor Williams and Ms. Libby Francis, Alfred Hospital, for facilitating patient access, and Dr. Janet Duke and Dr. Chris Bayley for helpful discussions.
References 1. Elborn JS, Shale DJ, Britton JR. Cystic fibrosis: current survival and population estimates to the year 2000. Thorax 1991;46:881-5.
2. Mitchell-Heggs P, Mearns M, Batten JC. Cystic tibrosis in adolescents and adults. Quart J Med 1976;179:479-504. 3. Neinstein LS, Stewart D, Wang CI, et al. Menstrual dysfunction in cystic fibrosis. J Adolesc Health Care 1983;4;153-7. 4. Dooley RR, Braunstein H, Osher AB. Polypoid cervicitis in cystic fibrosis patients receiving oral contraceptives. Am J Obstet Gynecol 1974;118:971-4. 5. Neinstein LS, Katz B. Contraceptive use in the chronically ill adolescent female: Part 1. J Adolesc Health Care 1986;7:123-33. 6. Cohen LF, di Sant'Agnese PA, Friedlander J. Cystic fibrosis and pregnancy. A national survey. Lancet 1980;2:842-4. 7. CorkeyCWB, Newth CJL, Corey M, et al. Pregnancy in cystic fibrosis: A better prognosis in patients with pancreatic function? Am J Obstet Gynecol 1981;140:737-42. 8. Palmer J, Dillon-Baker C, Tecklin JS, et al. Pregnancy in patients with cystic fibrosis. Ann lnt Med 1983;99:596-600. 9. Kopito LE, Kosasky HJ, Shwachman H. Water and electrolytes in cervical mucus from patients with cystic fibrosis. Fertil Steril 1973;24:512-6. 10. Zapletal A, Samanek TP. Lung Function in children and adolescents: methods and reference values. Karger, BaselMunchen, 1987. 11. Sawyer SM, Bowes G, Phelan PD. Vulvovaginal candidiasis in young women with cystic fibrosis: a previously unrecognised problem. BMJ 1994;308:1609. 12. Brugman SM, Taussig LM. The reproductive system. In Taussig LM, ed: Cystic Fibrosis. New York, Thieme-Stratton, 1984.
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13, Shwachman H, Kulczycki LL, Khaw KT. Studies in cystic fibrosis: report on 65 patients over 17 years of age. Pediatrics 1965;36:689-99. 14, Frisch RE. Food intake, fatness, a~d reproductive ability. In Vigersky RA, ed: Anorexia Nervosa. New York, Raven Press, 1977:14~. 15, Morgan A, London S. Effects of excessive exercise and weight loss on adolescent menstrual cyclicity. Adolesc Pediatr Gynecol 19911;6:63-70. 16. FitzPatrick SB, Stokes DC, Rosenstein BJ, et al. Use of contraceptives in women with cystic fibrosis. Chest 1984;86:863-7. 17. Gurwit,, D, Corer M, Francis PWJ, et al. Perspectives in cystic fibrosis. Pediatr Clin North Am 1979;26:603-15.
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18. Back DJ, Breckenbridge AM, Gay FE, et al. The pharmacokinetics of norethisterone during single and multiple dosing in women and changes caused by rifampicin. Acta Endo Supp 1977;212:149P. 19. Orme ML, Back DJ. Therapy with oral contraceptive steroids and antibiotics. J Antimicrob Chemother 1979;5:124-6. 20. Dossetor J. Drug interactions with oral contraceptives. Br Med J 1975;4:467-8. 21. Hughes BR, Cunliffe WJ. Interactions between the oral contraceptive pill and antibiotics. Br J Dermatol 1990;122:717-8. 22. Stead RJ, Grimmer SFM, Rogers SM, et al. Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis. Thorax 1987;42:59-64.