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. 2021 Sep 9;16(9):e0257186. doi: 10.1371/journal.pone.0257186

Table 2. Steroid hormone z-scores in children from the placebo and metformin groups.

    a) Children of both sexes
The maternal PCOS effecta The metformin effectb
Placebo, n = 54 p Metformin, n = 63 Δ M-P (95% CI) p
Mean (95% CI) Mean (95% CI)
Androstenedione z-score 0.53 (0.27 to 0.79) .0001* 0.66 (0.41 to 0.91) 0.13 (-0.23 to 0.49) .470
Testosterone z-score 0.53 (0.29 to 0.77) < .0001* 0.53 (0.30 to 0.76) 0.00 (-0.33 to 0.33) .995
SHBG z-score -0.28 (-0.55 to 0.00) .051 -0.28 (-0.51 to -0.05) 0.01 (-0.36 to 0.34) .973
Cortisol z-score 0.34 (0.08 to 0.61) .012 0.69 (0.42 to 0.96) 0.35 (-0.03 to 0.72) .070
17-OH-progesterone z-score 0.42 (0.15 to 0.69) .003 0.83 (0.62 to 1.04) 0.41 (0.08 to 0.74) .015
11-deoxycortisol z-score 0.13 (-0.11 to 0.37) .269 0.46 (0.22 to 0.69) 0.32 (-0.01 to 0.66) .056
Free testosterone z-score 0.67 (0.38 to 0.96) < .0001* 0.63 (0.35 to 0.91) -0.04(-0.44 to 0.36) .841
    b) Boys
The maternal PCOS effecta The metformin effectb
Placebo, n = 24 p Metformin, n = 31 Δ M-P (95% CI) p
Mean (95% CI) Mean (95% CI)
Androstenedione z-score 0.27 (-0.15 to 0.69) .195 0.74 (0.45 to 1.02) 0.46 (-0.02 to 0.95) .058
Testosterone z-score 0.25 (-0.20 to 0.70) .264 0.54 (0.22 to 0.85) 0.29 (-0.23 to 0.81) .268
SHBG z-score 0.03 (-0.45 to 0.51) .905 -0.43 (-0.75 to -0.11) -0.46 (-0.99 to 0.08) .096
Cortisol z-score 0.51 (0.17 to 0.84) .005 0.82 (0.37 to 1.27) 0.31 (-0.27 to 0.89) .284
17-OH-progesterone z-score 0.40 (-0.07 to 0.87) .089 0.93 (0.61 to 1.24) 0.53 (-0.00 to 1.06) .052
11-deoxycortisol z-score 0.08 (-0.31 to 0.47) .670 0.74 (0.38 to 1.09) 0.65 (0.14 to 1.17) .014
Free testosterone z-score 0.25 (-0.23 to 0.73) .292 0.67 (0.34 to 1.00) 0.42 (-0.13 to 0.97) .133
    c) Girls
The maternal PCOS effecta The metformin effectb
Placebo, n = 30 p Metformin, n = 32
Mean (95% CI)
Δ M-P (95% CI) p
Mean (95% CI)
Androstenedione z-score 0.73 (0.41 to 1.06) < .0001* 0.59 (0.16 to 1.01) -0.15 (-0.68 to 0.38) .580
Testosterone z-score 0.76 (0.51 to 1.00) < .0001* 0.53 (0.18 to 0.88) -0.23 (-0.66 to 0.19) .280
SHBG z-score -0.51(-0.83 to-0.19) .003 -0.13 (-0.47 to 0.20) 0.37 (-0.08 to 0.83) .104
Cortisol z-score 0.21 (-0.19 to 0.61) .291 0.56 (0.24 to 0.89) 0.35 (-0.15 to 0.86) .165
17-OH-progesterone z-score 0.44 (0.11 to 0.76) .010 0.74 (0.44 to 1.03) 0.30 (-0.13 to 0.73) .162
11-deoxycortisol z-score 0.18 (-0.14 to 0.49) .291 0.19 (-0.11 to 0.48) 0.01 (-0.41 to 0.44) .952
Free testosterone z-score 0.99 (0.67 to 1.32) < .0001* 0.59 (0.12 to 1.06) -0.40 (-0.96 to 0.16) .157

*p-values statistically significant after Holm-Bonferroni adjustment.

aThe impact of maternal PCOS on steroid hormones was assessed by the deviation in z-scores between the placebo group and the reference population (z-score zero) by one sample t-tests.

bΔ M-P expresses the metformin effect on hormone mean z-scores, assessed by two sample t-tests.

All z-scores were calculated from the Bergen Growth Study 2 references, according to gender and age.

CI: confidence interval; SHBG: sex hormone binding globulin.