Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement

Abstract

Objective To study the effect of total body irradiation (14.4 Gray) in childhood and adolescence on ovarian and uterine characteristics, and to investigate the response to physiological sex steroid serum concentrations.Design All long term post-pubertal female survivors of total body irradiation who had been treated in paediatric centres in Scotland were identified. Their ovarian and uterine characteristics were studied.Setting Recruitment was from follow up oncology clinics.Sample Nine women were identified, eight of whom were assessed and five progressed to detailed investigation. A control population of 12 women treated for acute leukaemia, but not treated with total body irradiation, and five healthy women with no history of childhood malignancy were recruited as controls.Methods Ovarian function was determined by measurement of serum gonadotrophins and sex steroids. Uterine response to physiological sex steroid replacement was investigated in women with ovarian failure, and to endogenous sex steroid production in women with ovarian function by ultrasound scan. The physiological sex steroid replacement was achieved with transdermal oestradiol patches and self administered vaginal progesterone pessaries. Main outcome measuresDetermination of ovarian function and uterine response to physiological sex steroid serum concentrations.Results Six of eight women treated with total body irradiation had ovarian failure; preservation of function was seen in two girls treated pre-pubertally who had biochemical evidence of incipient ovarian failure. Four women with ovarian failure had reduced uterine volume, undetectable blood supply and absent endometrium at baseline assessment; after three months of physiological sex steroid replacement treatment uterine blood supply and endometrial response were not significantly different from controls; uterine volume improved but remained significantly smaller than controls and correlated with age at total body irradiation.Conclusions Ovarian failure after total body irradiation is common and risk relates to age at treatment. Physiological sex steroid replacement improved uterine measures and these women may benefit from assisted reproductive technology.

Oncofertility and preservation of reproductive capacity in children and young adults

“…10 The number of primordial follicles present at the time of treatment, together with the dose received by the ovaries, will determine the fertility ''window'' and influence the age of premature ovarian failure. Ovarian failure has been reported in 90% of patients followed long term after TBI (10-15.75 Gy) and in 97% of females treated with total abdominal irradiation (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Gy) during childhood. 11,12 Using our knowledge and understanding of the radiosensitivity of human oocytes, it is now possible to predict the estimated sterilizing dose after any given dose of radiotherapy at any given age based on the application of the mathematical solution to our model for natural oocyte decline (Fig.…”

“…27 Even lower dose of irradiation, as in TBI, have been reported to cause impaired growth and blood flow. 27 Efforts to improve uterine function have been tried, with limited success. In young adult women previously treated with TBI, physiological sex steroid replacement therapy was found to improve uterine function (blood flow and endometrial thickness) and may potentially enable these women to benefit from assisted reproductive technologies.…”

“…In young adult women previously treated with TBI, physiological sex steroid replacement therapy was found to improve uterine function (blood flow and endometrial thickness) and may potentially enable these women to benefit from assisted reproductive technologies. 27 Larsen et al studied uterine volume in 100 childhood cancer survivors and assessed uterine response to high-dose estrogen replacement in 3 patients with ovarian failure and reduced uterine volume after abdominal and/or pelvic irradiation. 28 There was no significant difference noted with regard to uterine volume, endometrial thickness, or uterine artery blood flow after sex steroid therapy.…”

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…Even with spontaneous puberty and/or normal progression of development, premature menopause may still occur. Women having normal menstrual cycles and those able to become pregnant despite a history of exposure to TBI experience high rates of miscarriage that have been attributed to adverse effects on the uterus and/ or its blood supply (130,152,153 I-MIBG for neuroblastoma was also reported to be a risk factor of POI (161). Data on fertility outcomes off-therapy and long-term for novel targeted chemotherapy agents are limited (8, 140).…”

Effect of Radiation on Age at Menopause among Atomic Bomb Survivors

“…Exposure to ionizing radiation has been thought to induce ovarian failure and premature menopause based on the follow-up of female patients who underwent radiotherapy (1)(2)(3)(4)(5). Since most of those effects were observed in patients with high-dose radiotherapy, the effects of low-dose radiation are still unclear.…”