The effect of combination chemotherapy on ovarian function in women treated for hodgkin's disease

Abstract

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy‐induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy‐induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.

Post-treatment parenthood in Hodgkin's lymphoma survivors

“…For males, these analyses are a relatively appropriate parameter of fertility, whereas regular post-treatment menstruation does not equal ovulation and the possibility of pregnancy. Some authors have reported the number of childbirths achieved in HLSs, but often in small series (Schilsky et al, 1981;Whitehead et al, 1983;Bonadonna et al, 1984;Anselmo et al, 1990), and rarely with those attempting post-treatment parenthood as a denominator (Aisner et al, 1993;Hodgson et al, 2006).…”

“…Earlier reports have shown that female post-treatment fertility depends on the degree of gonadotoxicity of the treatment given and age at diagnosis (Schilsky et al, 1981;Whitehead et al, 1983;Bonadonna et al, 1984;Behringer et al, 2005). In a recent publication, the 12-month pregnancy rate was 70% in 36 female HLSs attempting pregnancy after treatment with ABVD, with no significant difference compared to the control group (n ¼ 29) (Hodgson et al, 2006).…”

“…Although the number of achieved pregnancies and childbirths is sometimes reported in small series (Schilsky et al, 1981;Whitehead et al, 1983;Bonadonna et al, 1984;Anselmo et al, 1990), the selection of survivors attempting parenthood is not reported, with a few exceptions (Aisner et al, 1993;Hodgson et al, 2006).…”

Oncofertility and preservation of reproductive capacity in children and young adults

“…It is interesting to note that early puberty is often reported, particularly in females treated with cranial radiation doses of < 24 Gy. 14 However, it has been shown that after lowdose cranial radiotherapy (18)(19)(20)(21)(22)(23)(24), there is a subtle decline in hypothalamic-pituitary-ovarian function as characterized by decreased luteinizing hormone (LH) secretion, an attenuated LH surge, and shorter luteal phases that are likely to herald incipient ovarian failure or be associated with early pregnancy loss. 15 …”

“…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. Cyclophosphamide is widely used in combination chemotherapy regimens, in which its effect on ovarian function is related to both the dose used and the age of the patient.…”