Gonadal function after combination chemotherapy for Hodgkin's disease in childhood.

Whitehead, E; Shalet, Stephen M; Jones, Patricia B.; Beardwell, Colin G; Deakin, DP

doi:10.1136/adc.57.4.287

Cited by 100 publications

(38 citation statements)

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“…A number of previous studies have reported on reproductive function following treatment for Hodgkin's disease in childhood with MOPP (Whitehead et al, 1982b;Ortin et al, 1990) and OPPA/COPP (Bramswig et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Infertility appears to be almost inevitable in adult males with Hodgkin's disease treated by six or more courses of MOPP or MVPP (mustine, vincristine/vinblastine, procarbazine, prednisolone) (Whitehead et al, 1982a). Chemotherapy induced testicular damage in patients treated for Hodgkin's disease in childhood was first reported by Sherins et al, in 1978. Whitehead et al (1982b reported 15 males treated with MOPP for Hodgkin's disease in childhood and concluded that severe testicular damage is common, with azoospermia, but normal pubertal development.…”

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confidence: 99%

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Testicular function following the treatment of Hodgkin's disease in childhood

Shafford

Kingston²,

Malpas³

et al. 1993

Br J Cancer

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Summary Testicular function was studied in 40 males treated in childhood for Hodgkin's disease at St Bartholomew's Hospital, and the Hospital for Sick Children, London, between 1971-1985. All patients were 16 years or over at evaluation, and off treatment more than 6 years. Basal FSH, LH and testosterone levels were measured. Testicular size was measured using a Prader orchidometer, and all patients were offered a seminal analysis. Twenty-eight patients were treated with chemotherapy, usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm. Twelve patients were treated with radiotherapy alone (five below the diaphragm). Twenty-six of 28 patients treated with chemotherapy and three of five patients treated with radiotherapy alone below the diaphragm have elevated basal FSH levels, and 18 of these also have elevated basal LH levels. Median testicular volume is 11 ml (range 5-25 ml). Eleven With a current 5 year event free survival of 90%, there is increasing interest in the late effects of treatment in patients with Hodgkin's disease. Decreased sitting height due to extended field irradiation including the spine (Wilimas et al., 1980) and abnormalities of thyroid function after neck radiotherapy have been well documented (Shalet et al., 1977). Infertility appears to be almost inevitable in adult males with Hodgkin's disease treated by six or more courses of MOPP or MVPP (mustine, vincristine/vinblastine, procarbazine, prednisolone) (Whitehead et al., 1982a). Chemotherapy induced testicular damage in patients treated for Hodgkin's disease in childhood was first reported by Sherins et al., in 1978. Whitehead et al. (1982b reported 15 males treated with MOPP for Hodgkin's disease in childhood and concluded that severe testicular damage is common, with azoospermia, but normal pubertal development. More recently Bramswig et al. (1990) evaluated testicular function in 75 boys treated for Hodgkin's disease with involved or extended field irradiation and chemotherapy with OPPA (vincristine, prednisone, procarbazine, doxorubicin) or COPP (cyclophosphamide, vincristine, prednisone, procarbazine). Testicular dysfunction was observed in boys treated before as well as during puberty. Abnormal basal FSH/LH levels were found more frequently in patients who had received higher cumulative doses of chemotherapy.We have studied testicular function in 40 males treated in childhood for Hodgkin's disease with chemotherapy (usually chlorambucil, vincristine, procarbazine, prednisolone -ChlVPP) (Robinson et al., 1984) and/or radiotherapy to assess the effect of this treatment on subsequent fertility. range 6-18 years). Basal FSH, LH and testosterone levels were measured. FSH and LH levels were measured by standard immunoradiometric assays with intra-inter-assay coefficient of variation (CV) of < 5% for both assays. Testosterone was measured by radioimmunoassay with a CV of <5%. Testicular size was measured using a Prader orchidometer, and all patients were given the opportunity to have a seminal analysis performed...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Testicular function following the treatment of Hodgkin's disease in childhood

Shafford

Kingston²,

Malpas³

et al. 1993

Br J Cancer

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“…16,17 Ovarian damage is Original Article drug and dose dependent and is related to the patient's age at time of treatment, with progressively smaller doses required to produce ovarian failure with increasing age. 18 It is important to emphasize that there is no evidence that the prepubertal ovary is protected from chemotherapy or radiotherapy.…”

Section: Cancer Treatment and Ovarian Functionmentioning

confidence: 99%

Oncofertility and preservation of reproductive capacity in children and young adults

Wallace

2011

Cancer

168

114

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With increasing numbers of survivors from cancer at a young age, the issue of fertility preservation has assumed greater importance. This review describes normal ovarian and testicular function and summarizes what is known about the effect of chemotherapy and radiotherapy on the gonads and uterus. All young patients with cancer or leukemia should have their fertility prognosis discussed before the initiation of treatment. Sperm and embryo cryopreservation should be considered standard practice and be widely available for those at significant risk of infertility. For prepubertal girls, ovarian tissue cryopreservation should be considered if the risk of premature menopause is high, but for the prepubertal boy there are no established techniques in current practice. Cancer 2011;117(10 suppl):2301–10. © 2011 American Cancer Society.

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“…In one study of long-term survivors of childhood cancer, 6 of 13 patients treated prepubertally had a normal or near-normal reproductive state compared to 7 of 14 treated postpubertally (129). Interestingly, tests to detect abnormal testicular function, such as basal levels of gonadotropins and gonadotropin response to GnRH, are unlikely to detect testicular damage in prepubertal boys (130). This is illustrated by the case of a 6-year-old boy who received chemotherapy and had normal FSH levels prepubertally but then had abnormally high levels of FSH in early puberty (130).…”

Section: Prenatal Exposuresmentioning

confidence: 99%

“…Interestingly, tests to detect abnormal testicular function, such as basal levels of gonadotropins and gonadotropin response to GnRH, are unlikely to detect testicular damage in prepubertal boys (130). This is illustrated by the case of a 6-year-old boy who received chemotherapy and had normal FSH levels prepubertally but then had abnormally high levels of FSH in early puberty (130). Leydig cell function is generally not affected by chemotherapy in the prepubertal male, as assessed by mean baseline and GnRH-stimulated LH levels and onset of puberty (131).…”

Section: Prenatal Exposuresmentioning

confidence: 99%

Critical Windows of Exposure for Children's Health: The Reproductive System in Animals and Humans

Pryor¹,

Hughes²,

Foster³

et al. 2000

Environmental Health Perspectives

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Drugs and environmental chemicals can adversely affect the reproductive system. Currently, available data indicate that the consequences of exposure depend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. The reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundreds of millions of spermatozoa are generated daily by most adult male mammals, yet very few of these germ cells succeed in transmitting their genetic material to the next generation. Although the number of oocytes produced in mammalian females is more limited, and their production occurs only during fetal life, most ovaries contain several orders of magnitude more oocytes than ever will be fertilized. Toxicant exposures may affect critical events in the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, external genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usual animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach to the identification of reproductive toxicants; and the development of sensitive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during embryonic, postnatal, and adult life.

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Gonadal function after combination chemotherapy for Hodgkin's disease in childhood.

Cited by 100 publications

References 14 publications

Testicular function following the treatment of Hodgkin's disease in childhood

Testicular function following the treatment of Hodgkin's disease in childhood

Oncofertility and preservation of reproductive capacity in children and young adults

Critical Windows of Exposure for Children's Health: The Reproductive System in Animals and Humans

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