Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study.
BACKGROUND
Childhood cancer survivors who retain ovarian function after completing cancer treatment are at increased risk of developing premature menopause, defined as cessation of menses before age 40 years. However, published data pertaining to the risk and frequency of premature menopause are limited.


METHODS
We assessed the incidence of and risk factors for premature menopause in 2819 survivors of childhood cancer who were older than 18 years and were participants in the multicenter Childhood Cancer Survivor Study (CCSS). The comparison group was 1065 female siblings of participants in the CCSS. A multiple Poisson regression model was constructed to determine risk factors for nonsurgical premature menopause. All statistical tests were two-sided.


RESULTS
A total of 126 childhood cancer survivors and 33 control siblings developed premature menopause. Of these women, 61 survivors (48%) and 31 siblings (94%) had surgically induced menopause (rate ratio [RR] = 0.8, 95% confidence interval [CI] = 0.52 to 1.23). However, the cumulative incidence of nonsurgical premature menopause was higher for survivors than for siblings (8% versus 0.8%; RR = 13.21, 95% CI = 3.26 to 53.51; P<.001). A multiple Poisson regression model showed that risk factors for nonsurgical premature menopause included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score (based on number of alkylating agents and cumulative dose), and a diagnosis of Hodgkin lymphoma. For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30%.


CONCLUSIONS
The results of this study will facilitate counseling current survivors about their future risk of premature menopause and aid in designing new regimens that seek to diminish late ovarian toxicity.
Sklar
Charles A
CA
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA. sklarc@mskcc.org
Mertens
Ann C
AC
Mitby
Pauline
P
Whitton
John
J
Stovall
Marilyn
M
Kasper
Catherine
C
Mulder
Jean
J
Green
Daniel
D
Nicholson
H Stacy
HS
Yasui
Yutaka
Y
Robison
Leslie L
LL
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D015994:Incidence; D008594:Menopause, Premature / Q000187:drug effects* / Q000528:radiation effects*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D016017:Odds Ratio; D010053:Ovary / Q000187:drug effects* / Q000528:radiation effects*; D010902:Pituitary Gland / Q000187:drug effects* / Q000528:radiation effects*; D016012:Poisson Distribution; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012307:Risk Factors; D011795:Surveys and Questionnaires; D017741:Survivors / Q000706:statistics & numerical data
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating