Hydroxyurea and Sperm Abnormalities in Patients with Sickle Cell Disease
*Dr. Salma M. AlDallal
Haematology & Blood Bank Department, Amiri Hospital, Kuwait Ministry of Health, Sharq, Kuwait
*Corresponding author
*Dr. Salma M. AlDallal, Haematology & Blood Bank Department, Amiri Hospital, Kuwait Ministry of Health,
Sharq, Kuwait
Email: dr.s.aldallal@outlook.com
DOI: 10.55920/JCRMHS.2022.01.001014
- Luban, N.L., Leikin, S.L., August, G.A. (1982): “Growth and development in sickle cell anemia: preliminary report”. Pediatr. Hematol. Oncol., 4(1):61-65. https://pubmed.ncbi.nlm.nih.gov/7091577/
- Zemel, B.S., Kawchak, D.A., Ohene-Frempong, K., Schall, J.I., Stallings, V.A. (2007): “Effects of delayed pubertal development, nutritional status, and disease severity on longitudinal patterns of growth failure in children with sickle cell disease”. Pediatr. Res, 61(5):607-613. https://doi.org/10.1203/pdr.0b013e318045bdca
- Taddesse, A., Woldie, I.L., Khana, P., Swerdlow, P.S., Chu, J.W., Abrams, J., Abou-Samra A.B. (2012): “Hypogonadism in patients with sickle cell disease: central or peripheral?” Acta Haematol, 128(2):65-68. https://doi.org/10.1159/000337344
- National Toxicology Program (2008): “NTP-CERHR monograph on the potential human reproductive and developmental effects of hydroxyurea”. NTP Cerhr Mon, 21:vii-viiiv-ixIII1.
- Brawley, O.W., Cornelius, L.J., Edwards, L.R., Gamble, V.N., Green, B.L., Inturrisi, C., James, A.H., Laraque, D., Mendez, M., Montoya, C.J., Pollock, B.H. (2008): “National Institutes of Health Consensus Development Conference Statement: hydroxyurea treatment for sickle cell disease”. Ann. Intern. Med, 148(12):932-938. https://doi.org/10.7326/0003-4819-148-12-200806170-00220
- Berthaut, I., Guignedoux, G., Kirsch-Noir, F., de Larouziere, V., Ravel, C., Bachir, D., Galactéros, F., Ancel, P.Y., Kunstmann, J.M., Levy, L., Jouannet, P. (2008): “Influence of sickle cell disease and treatment with hydroxyurea on sperm parameters and fertility of human males”. Haematologica, 93(7):988-993. https://doi.org/10.3324/haematol.11515
- Modebe, O., Ezeh, U.O. (1995): “Effect of age on testicular function in adult males with sickle cell anemia”. Fertil. Steril, 63(4):907-912. https://doi.org/10.1016/S0015-0282(16)57500-1
- Friedman, G., Freeman, R., Bookchin, R. (1974): “Testicular function in sickle cell disease”. Fertil. Steril, 25(12):1018‒1021. https://doi.org/10.1016/s0015-0282(16)40809-5
- Adeyoju, A.B., Olujohungbe, A.B., Morris, J., Yardumian, A., Bareford, D., Akenova, A., Akinyanju, O., Cinkotai, K., O'reilly, P.H. (2002): “Priapism in sickle-cell disease; incidence, risk factors and complications-an international multicentre study”. BJU Int, 90(9):898-902. https://doi.org/10.1046/j.1464-410X.2002.03022.x
- Emond, A.M., Holman, R., Hayes, R.J., Serjeant, G.R. (1980): “Priapism and impotence in homozygous sickle cell disease”. Arch. Intern. Med, 140(11):1434-1437. 10.1001/archinte.1980.00330220022011
- Madu, A.J., Ubesie, A., Ocheni, S., Chinawa, J., Madu, K.A., Ibegbulam, O.G., Nonyelu, C., Eze, A. (2014): “Priapism in homozygous sickle cell patients: important clinical and laboratory associations”. Med Princ Pract, 23(3):259-263. https://doi.org/10.1159/000360608
- Agbaraji, V.O., Scott, R.B., Leto, S., Kingslow, L.W. (1988): “Fertility studies in sickle cell disease: semen analysis in adult male patients”. Int. J. Fertil, 33(5):347-352.
- Lanzkron, S., Strouse, J.J., Wilson, R., Beach, M.C., Haywood, C., Park, H., Witkop, C., Bass, E.B., Segal, J.B. (2008): “Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease”. Ann. Intern. Med., 148(12):939-955. https://doi.org/10.7326/0003-4819-148-12-200806170-00221
- Fiscor, G., Ginsberg, L.C. (1980): “The effect of hydroxyurea and mitomycin C on sperm motility in mice”. MUTAT RES-FUND MOL M, 70(3):383-387. https://doi.org/10.1016/0027-5107(80)90028-7
- Evenson, D.P., Jost, L.K. (1993): “Hydroxyurea exposure alters mouse testicular kinetics and sperm chromatin structure”. Cell Prolif, 26(2):147-159. https://doi.org/10.1111/j.1365-2184.1993.tb00015.x
- Wiger, R., Hongslo, J.K., Evenson, D.P., De Angelis, P., Schwarze, P.E., Holme, J.A. (1995): “Effects of acetaminophen and hydroxyurea on spermatogenesis and sperm chromatin structure in laboratory mice”. Reprod. Toxicol, 9(1):21-33. https://doi.org/10.1016/0890-6238(94)00052-X
- Abbasi, A.A., Prasad, A.S., Ortega, J. (1976): “Gonadal function abnormalities in sickle cell anemia; studies in male adult patients”. Ann. Intern. Med, 85:601-605. https://doi.org/10.7326/0003-4819-85-5-601
- Osegbe, N., Akinyanju, O.O. (1987): “Testicular dysfunction in men with sickle cell disease”. Postgrad. Med. J, 63(736):95-98. http://dx.doi.org/10.1136/pgmj.63.736.95
- Abdulwaheed, O.O., Abdulrasaq, A.A., Sulaiman, A.K., Abdulgafar, A.J., Munirdeen, A.I. (2002): “The hormonal assessment of the infertile male in Ilorin, Nigeria”. African J Clin Endocrinol Metab, 3:62-64. http://dx.doi.org/10.1136/pgmj.63.736.95
- Gofrit, O.N., Rund, D., Shapiro, A., Pappo, O., Landau, E.H., Pode, D. (1998): “Segmental testicular infarction due to sickle cell disease”. J Urol, 160(3):835-836. https://doi.org/10.1097/00005392-199809010-00059
- Prasad, A.S., Schoomaker, E.B., Ortega, J., Brewer, G.J., Oberleas, D., Oelshlegel, Jr F.J. (1975): “Zinc deficiency in sickle cell disease”. Clin. Chem, 21(4):582-587. https://doi.org/10.1093/clinchem/21.4.582
- Prasad, A.S., Cossack, Z.T. (1984): “Zinc supplementation and growth in sickle cell disease”. Ann. Intern. Med, 100(3):367-371. https://doi.org/10.7326/0003-4819-100-3-367
- Landefeld, C.S., Schambelan, M., Kaplan, S.L., Embury, S.H. (1983): “Clomiphene-responsive hypogonadism in sickle cell anemia”. Ann. Intern. Med, 99(4):480-483. https://doi.org/10.7326/0003-4819-99-4-480
- Lu, C.C., Meistrich, M.L. (1979): “Cytotoxic effects of chemotherapeutic drugs on mouse testis cells”. Cancer Res, 39(9):3575-3582.
- Ficsor, G., Ginsberg, L.C. (1980): “The effect of hydroxyurea and mitomycin C on sperm motility in mice”. MUTAT RES-FUND MOL M, 70(3):383-387. https://doi.org/10.1016/0027-5107(80)90028-7
- Singh, H., Taylor, C. (1981): “Effects of Thio-TEPA and hydroxyurea on sperm production in Lakeview hamsters”. J. Toxicol. Environ. Health Part A, 8(1-2):307-316. https://doi.org/10.1080/15287398109530071
- Saez, J.M. (1994): “Leydig cells: endocrine, paracrine, and autocrine regulation”. Endocr. Rev.,15(5):574-626. https://doi.org/10.1210/edrv-15-5-574
- Garozzo, G., Disca, S., Fidone, C., Bonomo, P. (2000): “Azoospermia in a patient with sickle cell disease treated with hydroxyurea”. Haematologica, 85(11):1216-1218. https://www.haematologica.org/article/view/1870/7772
- Grigg, A. (2007): “Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease”. Intern. Med. J., 37:190-192. https://doi.org/10.1111/j.1445-5994.2006.01290.x
- Lukusa, A.K., Vermylen, C. (2008): “Use of hydroxyurea from childhood to adult age in sickle cell disease: semen analysis”. Haematologica, 93(11): e67discussion-e68. https://doi.org/10.3324/haematol.13659
- Lukusa, A.K., Vermylen, C., Vanabelle, B., Curaba, M., Brichard, B., Chantrain, C., Dupont, S., Ferrant, A., Wyns, C. (2009): “Bone marrow transplantation or hydroxyurea for sickle cell anemia: long-term effects on semen variables and hormone profiles”. Pediatr. Hematol. Oncol., 26(4):186-194. https://doi.org/10.1080/07357900902892780
- Nahoum, C.R., Fontes, E.A., Freire, F.R. (1980): “Semen analysis in sickle cell disease”. Andrologia, 12(6):542-45. https://doi.org/10.1111/j.1439-0272.1980.tb01347.x
- Osegbe, D.N., Akinyanju, O., Amaku, E.O. (1981): “Fertility in males with sickle cell disease”. Lancet, 318(8241):275-276. https://doi.org/10.1016/S0140-6736(81)90525-0
- Claudino, M.A., Franco-Penteado, C.F., Corat, M.A., Gimenes, A.P., Passos, L.A., Antunes, E., Costa, F.F. (2009): “Increased cavernosal relaxations in sickle cell mice priapism are associated with alterations in the NO-cGMP signalling pathway”. J Sex Med, 6(8):2187-2196. https://doi.org/10.1111/j.1743-6109.2009.01337.x
- Bivalacqua, T.J., Ross, A.E., Strong, T.D., Gebska, M.A., Musicki, B., Champion, H.C., Burnett, A.L. (2010): “Attenuated RhoA/Rho-kinase signaling in penis of transgenic sickle cell mice”. Urology, 76(2):510-e7. https://doi.org/10.1016/j.urology.2010.02.050
- Wen, J., Jiang, X., Dai, Y., Zhang, Y., Tang, Y., Sun, H., Mi, T., Kellems, R.E., Blackburn, M.R., Xia, Y. (2010): “Adenosine deaminase enzyme therapy prevents and reverses the heightened cavernosal relaxation in priapism”. J Sex Med, 7(9):3011-3022. https://doi.org/10.1111/j.1743-6109.2009.01552.x
- Wen, J., Jiang, X., Dai, Y., Zhang, Y., Tang, Y., Sun, H., Mi, T., Phatarpekar, P.V., Kellems, R.E., Blackburn, M.R, Xia, Y. (2010): “Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling”. FASEB J, 24(3):740-749. https://doi.org/10.1096/fj.09-144147
- Ohene-Frempong, K., Steinberg, M.H. (2001): “Clinical aspects of sickle cell anemia in adults and children”. DisordersofHemoglobin: Genetics, Pathophysiology and Clinical Management, 611-70.
- Rogers, Z.R. (2005): “Priapism in sickle cell disease”. Hematol. Oncol. Clin., 19(5):917-928. https://doi.org/10.1016/j.hoc.2005.08.003
- Habibi, A., Foïs, E., Cannas, G. (2017): “Management of Male Fertility in Sickle Cell Disease before and after Hydroxycarbamide”. Blood, 130:2260. https://doi.org/10.1182/blood.V130.Suppl_1.2260.2260
- de Montalembert, M., Voskaridou, E., Oevermann, L., Cannas, G., Habibi, A., Loko, G., Joseph, L., Colombatti, R., Bartolucci, P., Brousse, V., Galactéros, F. (2021): “Real‐Life experience with hydroxyurea in patients with sickle cell disease: Results from the prospective ESCORT‐HU cohort study”. Am. J. Hematol, 96(10):1223-1231. https://doi.org/10.1002/ajh.26286
- Sickle Cell Disease News. (2018): “Hydroxyurea Treatment in Men with SCA Leads to Drop in Total Sperm Count”. https://sicklecellanemianews.com/2018/02/01/hydroxyurea-treatment-men-sickle-cell-anemia-found-to-have-lower-total-sperm-count/
- Abudu, E.K., Akanmu, S.A., Soriyan, O.O., Akinbami, A.A., Adediran, A., Adeyemo, T.A., Okany, C.C. (2011): “Serum testosterone levels of HbSS (sickle cell disease) male subjects in Lagos, Nigeria”. BMC Res. Notes, 4(1):1-5. https://doi.org/10.1186/1756-0500-4-298
- Lukusa, A., Vermylen, C. (2008): “Use of hydroxyurea from childhood to adult age in sickle cell disease: semen analysis”. Haematologica, 93(11):e67-e67. https://doi.org/10.3324/haematol.13659
- Stukenborg, J.B., Alves-Lopes, J.P., Kurek, M., Albalushi, H., Reda, A., Keros, V., Töhönen, V., Bjarnason, R., Romerius, P., Sundin, M., Norén Nyström, U. (2018): “Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy”. Hum. Reprod, 33(9):1677-1683. https://doi.org/10.1093/humrep/dey240
- Joseph, L., Jean, C., Manceau, S., Chalas, C., Arnaud, C., Kamdem, A., Pondarre, C., Habibi, A., Bernaudin, F., Allali, S., De Montalembert, M. (2021): “Effect of hydroxyurea exposure before puberty on sperm parameters in males with sickle cell disease”. Blood, 137(6):826-829. https://doi.org/10.1182/blood.2020006270
- Fallat, M.E., Hutter, J., Committee on Bioethics. (2008): “Preservation of fertility in pediatric and adolescent patients with cancer”. Pediatrics, 121()5:e1461-e1469. https://doi.org/10.1542/peds.2008-0593
- Saraf, A.J., Nahata, L. (2017): “Fertility counseling and preservation: considerations for the pediatric endocrinologist”. Transl. Pediatr, 6(4):313-322. https://dx.doi.org/10.21037%2Ftp.2017.07.02