Iatrogenic Ovarian Failure

Prepubertal girls treated with radiation therapy or chemotherapy may present gonadal failure with delayed puberty or primary or secondary amenorrhea.

In cases of abdominal or pelvic radiotherapy, the ovaries must be surgically removed from the radiation field. Chemotherapy induces follicular atresia, especially when alkylant agents are used or in association with radiotherapy.
Cryopreservation of ovarian fragments will be possible in the near future.

Hypogonadotropic Hypogonadism
Delayed puberty may be related to gonadotropin deficiency: FSH and LH plasma levels are low, as are urinary gonadotropins. This insufficiency may be caused by a pituitary defect of the gonadotropic cells, isolated or associated with other pituitary cell deficiencies, by a lesion of the pituitary stalk or by a defect of the hypothalamic center with altered pulsatile secretion of LHRH.

Theoretically, the origin of the defect can be differentiated by an LHRH stimulation test (100μg IVD). However, even with normal gonadotropic function, preliminary priming with pulsatile LHRH may be necessary to obtain a positive response to LHRH stimulation. LHRH pulsatile secretion cannot be explored directly but it can be assessed indirectly by measuring LH pulsatility every 10 min for 6 or 8 h during the night.

Gonadotropin deficiency may be secondary due to a direct organic lesion of the hypothalamo-pituitary axis (tumoral, inflammatory, vascular or traumatic origin), or to an indirect functional inhibition of the pulsatile LHRH secretion (chronic disease, negative energetic imbalance). Gonadotropin deficiency may also be primitive, caused by a genetic or developmental defect present at birth but unremarkable before puberty. Finally, in absence of any deficiency, delayed puberty may be simply due to a constitutional idiopathic delay in puberty usually associated with growth delay.

Gonadotropin deficiency may be associated with other pituitary defects, especially GH secretion. Impaired growth is suggested by decreased growth velocity and short stature and confirmed by a negative response to dynamic exploration of the somatotropic axis. In cases of isolated gonadotropin deficiency, height is usually normal for age but bone age is retarded in accordance with the delayed puberty and very low or absent response to LHRH. In contrast, girls with functional delayed puberty or constitutional delay are short for chronological age, with normal growth rate for bone age and plasmatic and urinary gonadotropins not so low. If bone age has reached 11 years, gonadotropic deficiency is likely; if not, functional or constitutive delayed of growth and puberty is more likely.

Provided by ArmMed Media
Revision date: June 18, 2011
Last revised: by Janet A. Staessen, MD, PhD