Cancer Res Treat.  2017 Oct;49(4):1057-1064. 10.4143/crt.2016.197.

Gonadal and Sexual Dysfunction in Childhood Cancer Survivors

• Yoon JY
• Park HJ
• Ju HY
• Yoon JH
• Chung JS
• Hwang SH
• Lee DO
• Shim HY
• Park BK

• KMID: 2394824
• DOI: http://doi.org/10.4143/crt.2016.197

Abstract

PURPOSE
Few studies have addressed gonadal and sexual dysfunctions in childhood cancer survivors. We evaluated the prevalence rates and risk factors for gonadal failure among adolescent/young adult childhood cancer survivors and their sexual function.
MATERIALS AND METHODS
Subjects were childhood cancer survivors aged 15-29 years who had completed therapy more than 2 years ago. Demographic and medical characteristics were obtained from the patients' medical records. In addition, hormonal evaluation and semen analysis were performed and sexual function was evaluated via questionnaire.
RESULTS
The study included 105 survivors (57 males, 48 females), of which 61 were adults (age > 19 years) and 44 were adolescents. In both males and females, the proportion of survivors with low sex hormone levels did not differ among age groups or follow-up period. Thirteen female subjects (27.1%) needed sex hormone replacement, while five males subjects (8.8%) were suspected of having hypogonadism, but none were receiving sex hormone replacement. Of 27 semen samples, 14 showed azospermia or oligospermia. The proportion of normospermia was lower in the high cyclophosphamide equivalent dose (CED) group (CED ≥ 8,000 mg/m2) than the low CED group (27.3% vs. 62.5%, p=0.047). Among adults, none were married and only 10 men (35.7%) and eight women (34.3%) were in a romantic relationship. Though a significant proportion (12.0% of males and 5.3% of females) of adolescent survivors had experienced sexual activity, 13.6% had not experienced sex education.
CONCLUSION
The childhood cancer survivors in this study showed a high prevalence of gonadal/sexual dysfunction; accordingly, proper strategies are needed to manage these complications.

Keyword

Gonads; Sexual dysfunction; Survivors; Child; Neoplasms

MeSH Terms

Adolescent
Adult
Child
Cyclophosphamide
Female
Follow-Up Studies
Gonads*
Humans
Hypogonadism
Male
Medical Records
Oligospermia
Prevalence
Risk Factors
Semen
Semen Analysis
Sex Education
Sexual Behavior
Survivors*
Cyclophosphamide

Reference

References

1. Park HJ, Moon EK, Yoon JY, Oh CM, Jung KW, Park BK, et al. Incidence and survival of childhood cancer in Korea. Cancer Res Treat. 2016; 48:869–82.

2. Hamre H, Kiserud CE, Ruud E, Thorsby PM, Fossa SD. Gonadal function and parenthood 20 years after treatment for childhood lymphoma: a cross-sectional study. Pediatr Blood Cancer. 2012; 59:271–7.

3. Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol. 2009; 27:2374–81.

4. Green DM, Liu W, Kutteh WH, Ke RW, Shelton KC, Sklar CA, et al. Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Lancet Oncol. 2014; 15:1215–23.

5. Green DM, Nolan VG, Goodman PJ, Whitton JA, Srivastava D, Leisenring WM, 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; 61:53–67.

6. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010; 16:231–45.

7. Ahn TY, Lee DS, Kang WC, Hong JH, Kim YS. Validation of an abridged Korean version of the International Index of ErectileFunction (IIEF-5) as a diagnostic tool for erectile dysfunction. Korean J Urol. 2001; 42:535–40.

8. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999; 11:319–26.

9. Kim HY, So HS, Park KS, Jeong SJ, Lee JY, Ryu SB. Development of the Korean-version of Female Sexual Function Index (FSFI). Korean J Androl. 2002; 20:50–6.

10. Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, et al. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000; 26:191–208.

11. Ministry of Education, Science and Technology; Ministry of Health and Welfare; Korea Centers for Disease Control and Prevention. The eighth Korea Youth Risk Behavior Web-based Survey, 2012. Seoul: Korea Centers for Disease Control and Prevention;2012.

12. Korea Centers for Disease Control and Prevention. The statistics of 2015 Korea Youth Health Risk Behavior Online Survey 2015 [Internet]. Cheongju: Centers for Disease Control and Prevention;2015. [cited 2016 May 10]. Available from: http://yhs.cdc.go.kr.

13. Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y, et al. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab. 2006; 91:1723–8.

14. Sklar CA, Mertens AC, Mitby P, Whitton J, Stovall M, Kasper C, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst. 2006; 98:890–6.

15. Lunsford AJ, Whelan K, McCormick K, McLaren JF. Antimullerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril. 2014; 101:227–31.

16. Yoo JH, Kim HO, Cha SW, Park CW, Yang KM, Song IO, et al. Age specific serum anti-Mullerian hormone levels in 1,298 Korean women with regular menstruation. Clin Exp Reprod Med. 2011; 38:93–7.

17. Sakamoto H, Yajima T, Nagata M, Okumura T, Suzuki K, Ogawa Y. Relationship between testicular size by ultrasonography and testicular function: measurement of testicular length, width, and depth in patients with infertility. Int J Urol. 2008; 15:529–33.

18. Aribarg A, Kenkeerati W, Vorapaiboonsak V, Leepipatpaiboon S, Farley TM. Testicular volume, semen profile and serum hormone levels in fertile Thai males. Int J Androl. 1986; 9:170–80.

19. Arai T, Kitahara S, Horiuchi S, Sumi S, Yoshida K. Relationship of testicular volume to semen profiles and serum hormone concentrations in infertile Japanese males. Int J Fertil Womens Med. 1998; 43:40–7.

20. Greenfield DM, Walters SJ, Coleman RE, Hancock BW, Eastell R, Davies HA, et al. Prevalence and consequences of androgen deficiency in young male cancer survivors in a controlled cross-sectional study. J Clin Endocrinol Metab. 2007; 92:3476–82.

21. Howell SJ, Radford JA, Adams JE, Shalet SM. The impact of mild Leydig cell dysfunction following cytotoxic chemotherapy on bone mineral density (BMD) and body composition. Clin Endocrinol (Oxf). 2000; 52:609–16.

22. Romerius P, Stahl O, Moell C, Relander T, Cavallin-Stahl E, Wiebe T, et al. Hypogonadism risk in men treated for childhood cancer. J Clin Endocrinol Metab. 2009; 94:4180–6.

23. Shalet SM, Tsatsoulis A, Whitehead E, Read G. Vulnerability of the human Leydig cell to radiation damage is dependent upon age. J Endocrinol. 1989; 120:161–5.

24. Kenney LB, Cohen LE, Shnorhavorian M, Metzger ML, Lockart B, Hijiya N, et al. Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children's Oncology Group. J Clin Oncol. 2012; 30:3408–16.

25. Zebrack BJ, Foley S, Wittmann D, Leonard M. Sexual functioning in young adult survivors of childhood cancer. Psychooncology. 2010; 19:814–22.

26. Ahn TY, Park JK, Lee SW, Hong JH, Park NC, Kim JJ, et al. Prevalence and risk factors for erectile dysfunction in Korean men: results of an epidemiological study. J Sex Med. 2007; 4:1269–76.

27. Bresters D, Emons JA, Nuri N, Ball LM, Kollen WJ, Hannema SE, et al. Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood. Pediatr Blood Cancer. 2014; 61:2048–53.