Vol 92, No 4 (2021)
Research paper
Published online: 2021-03-04
A crosscut survey on reproductive health in Lithuanian childhood cancer survivors
Abstract
Objectives: Sexual dysfunction was reported to compromise the quality of life in childhood cancer survivors. The aim of
our study was to evaluate the reproductive health in long-term pediatric cancer survivors by conducting a crosscut survey.
Material and methods: Childhood cancer survivors over 18 years of age, who were in remission for more than 5 years,
were invited to complete a gender-specific questionnaire surveying on their reproductive health. Demographic and treatment
data were retrieved from their medical records. Treatment modalities were reviewed for its potential gonadotoxicity.
Results: 34 (17 males and 17 females, respectively) from 346 addressed survivors (9.8%) completed the questionnaire. Median
age and follow-up after diagnosis was 27 (18–35) and 14 (3–25) years, respectively. Some respondents reported sexual
concerns: 11.8% males experienced problems with penetration, two males (11.8%) who underwent semen analysis were
found to be azoospermic. Similarly, 11.8% females reported delayed puberty, the average age of menarche was 14 (12–17)
years, 29.4% females reported irregular menstrual cycles. Cyclophosphamide equivalent dose (CED) differed significantly
between the patients treated for leukemia, lymphoma and solid tumors (3000 vs 4352 vs 6660 mg/m2, respectively, p = 0.014).
Conclusions: Low prevalence of sexual dysfunction, fertility related disorders or delayed puberty in childhood cancer
survivors was found. However, the results should be interpreted with caution taking into account a low response rate.
Keywords: late effectslong-term survivorspediatric cancerreproductive healthsexual dysfunction
References
- Winther JF, Kenborg L, Byrne J, et al. Childhood cancer survivor cohorts in Europe. Acta Oncol. 2015; 54(5): 655–668.
- Ness K, Armstrong G, Kundu M, et al. Frailty in childhood cancer survivors. Cancer. 2014; 121(10): 1540–1547.
- Zebrack BJ, Foley S, Wittmann D, et al. Sexual functioning in young adult survivors of childhood cancer. Psychooncology. 2010; 19(8): 814–822.
- Lee SH, Shin CHo. Reduced male fertility in childhood cancer survivors. Ann Pediatr Endocrinol Metab. 2013; 18(4): 168–172.
- Žulpaitė R, Bumbulienė Ž. Reproductive health of female childhood cancer survivors. Ginekol Pol. 2018; 89(5): 280–286.
- Kim J, Mersereau JE. A pilot study about female adolescent/young childhood cancer survivors' knowledge about reproductive health and their views about consultation with a fertility specialist. Palliat Support Care. 2015; 13(5): 1251–1260.
- Lehmann V, Keim MC, Nahata L, et al. Fertility-related knowledge and reproductive goals in childhood cancer survivors: short communication. Hum Reprod. 2017; 32(11): 2250–2253.
- van Dorp W, Haupt R, Anderson RA, et al. Reproductive Function and Outcomes in Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Review. J Clin Oncol. 2018; 36(21): 2169–2180.
- Chow EJ, Stratton KL, Leisenring WM, et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2016; 17(5): 567–576.
- Reinmuth S, Hohmann C, Rendtorff R, et al. Impact of chemotherapy and radiotherapy in childhood on fertility in adulthood: the FeCt-survey of childhood cancer survivors in Germany. J Cancer Res Clin Oncol. 2013; 139(12): 2071–2078.
- Kenney LB, Laufer MR, Grant FD, et al. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer. 2001; 91(3): 613–621, doi: 10.1002/1097-0142(20010201)91:3<613::aid-cncr1042>3.0.co;2-r.
- Green DM, Nolan VG, Goodman PJ, et al. The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2014; 61(1): 53–67.
- Chemaitilly W, Li Z, Krasin MJ, et al. Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort. J Clin Endocrinol Metab. 2017; 102(7): 2242–2250.
- Green DM, Zhu L, Wang M, et al. Effect of cranial irradiation on sperm concentration of adult survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude Lifetime Cohort Study†. Hum Reprod. 2017; 32(6): 1192–1201.
- Tutkuviene J. Growth and development criteria for Lithuanian children of various ages. Studies in Human Biology Edited by Bodzsar EB, Susanne C Budapest. ; 1996: 157–64.
- Ploug T, Holm S. Meta Consent - A Flexible Solution to the Problem of Secondary Use of Health Data. Bioethics. 2016; 30(9): 721–732.
- Gilleland Marchak J, Seidel KD, Mertens AC, et al. Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study. J Cancer Surviv. 2014; 8(3): 437–447.
- Yoon JuY, Park HJ, Ju HY, et al. Gonadal and Sexual Dysfunction in Childhood Cancer Survivors. Cancer Res Treat. 2017; 49(4): 1057–1064.
- van den Berg MH, Overbeek A, Lambalk CB, et al. DCOG LATER-VEVO study group. Long-term effects of childhood cancer treatment on hormonal and ultrasound markers of ovarian reserve. Hum Reprod. 2018; 33(8): 1474–1488.
- Ritenour CWM, Seidel KD, Leisenring W, et al. Erectile Dysfunction in Male Survivors of Childhood Cancer-A Report From the Childhood Cancer Survivor Study. J Sex Med. 2016; 13(6): 945–954.
- Benedict C, Thom B, Friedman D, et al. Young Adult Female Survivors’ Unmet Information Needs and Reproductive Concerns Contribute to Decisional Conflict about Post-treatment Fertility Preservation. Cancer. 2016; 122(13): 2101–9.
- Angarita AM, Johnson CA, Fader AN, et al. Fertility Preservation: A Key Survivorship Issue for Young Women with Cancer. Front Oncol. 2016; 6: 102.
- Chapple A, Salinas M, Ziebland S, et al. Fertility issues: the perceptions and experiences of young men recently diagnosed and treated for cancer. J Adolesc Health. 2007; 40(1): 69–75.
- Haavisto A, Henriksson M, Heikkinen R, et al. Sexual function in male long-term survivors of childhood acute lymphoblastic leukemia. Cancer. 2016; 122(14): 2268–2276.
- Gunn HM, Rinne I, Emilsson H, et al. Primary Gonadal Insufficiency in Male and Female Childhood Cancer Survivors in a Long-Term Follow-Up Clinic. J Adolesc Young Adult Oncol. 2016; 5(4): 344–350.
- Haupt R, Essiaf S, Dellacasa C, et al. PanCareSurFup, ENCCA Working Group, ExPo-r-Net Working Group. The 'Survivorship Passport' for childhood cancer survivors. Eur J Cancer. 2018; 102: 69–81.
- Matulevicius V, Ostrauskas R, Preikša T, et al. Sexual function of Lithuanian males aged 26–36 years. Sexual Medicine. 2013; 1(1): 7–14.
- Yoon JuY, Park HJ, Ju HY, et al. Gonadal and Sexual Dysfunction in Childhood Cancer Survivors. Cancer Res Treat. 2017; 49(4): 1057–1064.
- Ritenour CWM, Seidel KD, Leisenring W, et al. Erectile Dysfunction in Male Survivors of Childhood Cancer-A Report From the Childhood Cancer Survivor Study. J Sex Med. 2016; 13(6): 945–954.
- Datta J, Palmer MJ, Tanton C, et al. Prevalence of infertility and help seeking among 15 000 women and men. Hum Reprod. 2016; 31(9): 2108–2118.
- WHO | Global prevalence of infertility, infecundity and childlessness [updated 2020/03/02/18:30:01]. Available from: https://www who int/reproductivehealth/topics/infertility/burden/en.
- Gerstl B, Sullivan E, Koch J, et al. Reproductive outcomes following a stem cell transplant for a haematological malignancy in female cancer survivors: a systematic review and meta-analysis. Support Care Cancer. 2019; 27(12): 4451–4460.
- Silva C, Ribeiro Rama AC, Reis Soares S, et al. Adverse reproductive health outcomes in a cohort of young women with breast cancer exposed to systemic treatments. J Ovarian Res. 2019; 12(1): 102.
- La Vignera S, Cannarella R, Duca Y, et al. Hypogonadism and Sexual Dysfunction in Testicular Tumor Survivors: A Systematic Review. Front Endocrinol (Lausanne). 2019; 10: 264.
- Huang SM, Tseng LM, Lai JCY, et al. Infertility-related knowledge in childbearing-age women with breast cancer after chemotherapy. Int J Nurs Pract. 2019; 25(5): e12765.
- Erenpreiss J, Punab M, Zilaitiene B, et al. Semen quality of young men from the general population in Baltic countries. Hum Reprod. 2017; 32(6): 1334–1340.
- Meistrich ML, Wilson G, Brown BW, et al. Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer. 1992; 70(11): 2703–2712, doi: 10.1002/1097-0142(19921201)70:11<2703::aid-cncr2820701123>3.0.co;2-x.
- Noorda EM, Somers R, Leeuwen FEv, et al. Adult height and age at menarche in childhood cancer survivors. European Journal of Cancer. 2001; 37(5): 605–612.
- Mills J, Fears T, Robison L, et al. Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. The Journal of Pediatrics. 1997; 131(4): 598–602.
- Armstrong GT, Whitton JA, Gajjar A, et al. Abnormal timing of menarche in survivors of central nervous system tumors: A report from the Childhood Cancer Survivor Study. Cancer. 2009; 115(11): 2562–2570.
- Barton SE, Najita JS, Ginsburg ES, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2013; 14(9): 873–881.
- Sklar CA, Mertens AC, Mitby P, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst. 2006; 98(13): 890–896.
- De Bruin ML, Huisbrink J, Hauptmann M, et al. Treatment-related risk factors for premature menopause following Hodgkin lymphoma. Blood. 2008; 111(1): 101–108.
- Levine JM, Whitton JA, Ginsberg JP, et al. Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer. 2018; 124(5): 1044–1052.
- Thomas-Teinturier C, Allodji RS, Svetlova E, et al. Ovarian reserve after treatment with alkylating agents during childhood. Hum Reprod. 2015; 30(6): 1437–1446.
- Elchuri SV, Patterson BC, Brown M, et al. Low Anti-Müllerian Hormone in Pediatric Cancer Survivors in the Early Years after Gonadotoxic Therapy. J Pediatr Adolesc Gynecol. 2016; 29(4): 393–399.
- Lie Fo, Laven JSE, Hakvoort-Cammel FG, et al. Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone. Human Reproduction (Oxford, England. 2009; 24(4): 982–90.
- Brougham MFH, Crofton PM, Johnson EJ, et al. Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study. J Clin Endocrinol Metab. 2012; 97(6): 2059–2067.
- van Dijk EM, van Dulmen-den Broeder E, Kaspers GJL, et al. Psychosexual functioning of childhood cancer survivors. Psychooncology. 2008; 17(5): 506–511.
- Langeveld NE, Stam H, Grootenhuis MA, et al. Quality of life in young adult survivors of childhood cancer. Support Care Cancer. 2002; 10(8): 579–600.
