Bone mineral density in women with cytotoxic-induced ovarian failure.
OBJECTIVE
Premature ovarian failure is associated with a reduction in bone mineral density. As survival rates following treatment for haematological malignancies improve, chemotherapy-induced ovarian failure is becoming more common. However, there are few data concerning the impact of this on bone mineral density (BMD). We have therefore measured the BMD in 33 women with ovarian failure following treatment with cytotoxic chemotherapy.


METHODS
We studied 33 women who received combination chemotherapy for Hodgkin's disease (n = 27), non-Hodgkin's lymphoma (n = 4), sarcoma (n = 1) and acute myeloid leukaemia (n = 1). The mean (range) age of the subjects at the time of BMD measurement was 37.5 (24-50) years and the mean (median: range) duration of amenorrhoea was 49 (24: 5-277) months. Eleven women had received hormone replacement therapy (HRT) for a mean (range) duration of 25 (1-62) months. BMD was measured by single photon absorptiometry or single X-ray absorptiometry, and dual energy X-ray absorptiometry at the distal and proximal radius, the femoral neck and the lumbar spine, respectively. BMD was expressed as Z-scores and statistical analysis was performed using the Wilcoxon matched-pairs signed-rank test.


RESULTS
There was no significant reduction in BMD at the hip, spine or a forearm in the cohort as a whole, although there was a trend to reduce bone density at all sites. When patients who had received HRT were excluded from the analysis there were small reductions in mean BMD at all sites, but this was only statistically significant at the proximal forearm (Z-score = -0.65; P = 0.03). Mean BMD of the HRT-treated patients was normal at all sites. Only seven patients (21%) had a BMD Z-score < -2 at any site.


CONCLUSIONS
It is inappropriate to assume that ovarian failure from different aetiologies has a similar deleterious impact on the skeleton. Untreated premature ovarian failure following cytotoxic chemotherapy results in some reduction in bone mineral density, but this is of a minor degree and is less than that observed in other hypo-oestrogenic states. The reason for this is unclear but studies of residual hormone production in the cytotoxic-damaged ovary may provide an answer.
Howell
S J
SJ
Department of Endocrinology, Christie Hospital NHS Trust, Manchester.
Berger
G
G
Adams
J E
JE
Shalet
S M
SM
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000503:physiopathology; D020249:Hormone Replacement Therapy; D006801:Humans; D007951:Leukemia, Myeloid / Q000503:physiopathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000503:physiopathology; D008875:Middle Aged; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy / Q000503:physiopathology; D018709:Statistics, Nonparametric