Table 1 Sex-related differences in anthracycline-induced cardiomyopathy in pediatric cancer patients

Silber et al. [20]

150

0.23–21, mean 9.5 years

0.09–18 years, average 4.7

50–750 mg/m²

Mean = 307 mg/m²

Female sex was a significant risk factor for cardiac abnormality (OR = 3.2)

Lipshultz et al. [21]

120

0.6–28.9

2–14.6

244–550 mg/m²

Median = 390 and 395 mg/m² for osteogenic sarcoma and acute lymphoblastic leukemia, respectively

Female sex was an independent risk factor for cardiac abnormality after DOX therapy.

Krischer et al. [26]

6493

< 1 year to > 15 years

1 year

From < 99 mg/m² to > 500 mg/m²

No specific doses were stated

Female sex increased the risk of anthracycline-associated cardiotoxicity (RR = 1.9)

Review of protocols records

Ewer et al. [27]

113

1–17

Mean, 10.6;

Median, 11

4–180 months

113–506 mg/m²

Mean = 341 mg/m²

More girls than boys developed cardiac dysfunction (not statistically significant, small sample size)

Green et al. [28]

2710

< 16

Up to 20 years

59–691 mg/m²

Females are at 4 times higher risk of congestive heart failure after

Review of medical records

Pein et al. [34]

229

0–21

> 15 years

40–600 mg/m²

Mean = 344 mg/m²

Sex was not a significant risk factor

Van Dalen et al. [35]

830

0.1–18.0 years, median 8.7 years

0.01–28.4 years, median 7.1 years

15–900 mg/m²

Mean = 288 mg/m²

Median = 280 mg/m²

Sex was not a significant risk factor for clinical heart failure (female RR = 1.46, 95% CI 0.62–3.43 p value = 0.39)

Review of medical records/registry charts

Hudson et al. [36]

217

5 years

3–21.7 years

25–510 mg/m²

Median = 202 mg/m²

Sex was not a significant risk factor for abnormal non-invasive cardiac testing

Armstrong et al. [29]

20,483

0–20 years

> 5 years

NA

Female sex was a risk factor for mortality due to cardiac disease (RR = 1.4).

Reviewing of national death index and death certificates

Mulrooney et al. [10]

14,358

0–20

> 5 years

NA

Female sex was a risk factor for congestive heart failure (HR = 1.4)

Retrospective cohort study

Lipshultz et al. [30]

66 (out of 100 enrolled patients)

Mean age 7.8 years

5 years

300 mg/m²

Reduction in left ventricular fractional shortening was significantly greater in DOX-treated girls than boys

Rathe et al. [37]

80

0.8–13.4

Median of 4 years

1.1– 20.6

Median of 8.2 years

120–300 mg/m²

Sex was not a significant risk factor for subclinical decline in cardiac function (less than 300 mg/m² DOX)

Longitudinal follow-up

Amigoni et al. [31]

62

0–13

6–19 years

120–280 mg/m²

Mean = 228 mg/m²

Left ventricular mass and dimensions were reduced only in female ALL survivors (less than 300 mg/m² DOX)

Andolina et al. [38]

308

< 1 year to > 5 years

≥ 5 years

Mean = 210 mg/m²

Median = 190 mg/m²

Sex was not a significant risk factor

Retrospective medical record and echocardiography review

Van der Pal et al. [39]

525

9

≥ 5 years

33–720 mg/m²

Median = 250 mg/m²

Sex was not a significant risk factor

Brouwer et al. [40]

277

≤ 20 years

Median 8.8

5–31 years

Median 18.2

50–600 mg/m²

Median = 183 mg/m²

Female sex was protective from diastolic dysfunction (OR = 0.3). Sex was not a risk factor for systolic dysfunction

Vandecruys et al. [18]

37

0.2–12.2

Median 4.8

10.6–18.3

Median 13.3

180–240 mg/m²

Subclinical echocardiographic abnormalities were found more frequently in male ALL survivors who had received less than 250 mg/m² DOX

Toro-Salazar et al. [32]

46

Mean of 11 ± 5.1

2.5–26.9

200–600 mg/m²

Mean = 328 mg/m²

Higher extracellular volume was detected in female than in male survivors who had received 200 mg/m² or more

Ylanen et al. [41]

62

0–13.8

4.9–18

80–419 mg/m²

Median = 222 mg/m²

There was a trend toward a male predominance among those with abnormal left ventricular ejection fraction and those with abnormal right ventricular ejection fraction

Tham et al. [33]

30

7–19 years

7.6 ± 4.5

80–375 mg/m²

Mean = 197.2 mg/m²

Higher non-contrast myocardial T1 and extra-cellular volume (ECV) was observed in female subjects